Molecules

23 pages, 651 KiB

Open AccessReview

Essential Oils as an Alternative to Pyrethroids’ Resistance against Anopheles Species Complex Giles (Diptera: Culicidae)

by Olivier Gnankiné¹ and Imaël Henri Nestor Bassolé^2,*

¹ Laboratoire d’entomologie fondamentale et appliquée (Lefa), Université Ouaga I Pr Joseph KI-ZERBO, 03 P.O. 7021 Ouagadougou, Burkina Faso

² Laboratoire de biologie moléculaire, d’épidémiologie et de surveillance des bactéries et virus transmis par les aliments (Labesta), Université Ouaga I Pr Joseph KI-ZERBO, 03 P.O. 7021 Ouagadougou, Burkina Faso

Molecules 2017, 22(10), 1321; https://doi.org/10.3390/molecules22101321 - 22 Sep 2017

Cited by 57 | Viewed by 9130

Abstract

Widespread resistance of Anopheles sp. populations to pyrethroid insecticides has led to the search for sustainable alternatives in the plant kingdom. Among many botanicals, there is great interest in essential oils and their constituents. Many researchers have explored essential oils (EOs) to determine [...] Read more.

Widespread resistance of Anopheles sp. populations to pyrethroid insecticides has led to the search for sustainable alternatives in the plant kingdom. Among many botanicals, there is great interest in essential oils and their constituents. Many researchers have explored essential oils (EOs) to determine their toxicity and identify repellent molecules that are effective against Anopheles populations. Essential oils are volatile and fragrant substances with an oily consistency typically produced by plants. They contain a variety of volatile molecules such as terpenes and terpenoids, phenol-derived aromatic components and aliphatic components at quite different concentrations with a significant insecticide potential, essentially as ovicidal, larvicidal, adulticidal, repellency, antifeedant, growth and reproduction inhibitors. The current review provides a summary of chemical composition of EOs, their toxicity at different developmental stages (eggs, larvae and adults), their repellent effects against Anopheles populations, for which there is little information available until now. An overview of antagonist and synergistic phenomena between secondary metabolites, the mode of action as well as microencapsulation technologies are also given in this review. Finally, the potential use of EOs as an alternative to current insecticides has been discussed. Full article

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17 pages, 3287 KiB

Open AccessArticle

In Vitro Assessment of the Effect of Antiepileptic Drugs on Expression and Function of ABC Transporters and Their Interactions with ABCC2

by Gurpreet Kaur Grewal^1,2, Samiksha Kukal^1,2, Neha Kanojia^1,2, Krateeka Madan², Luciano Saso³

and Ritushree Kukreti^1,2,*

¹ Academy of Scientific and Innovative Research (AcSIR), CSIR-Institute of Genomics and Integrative Biology (CSIR-IGIB) Campus, Delhi 110007, India

² Genomics and Molecular Medicine Unit, Institute of Genomics and Integrative Biology (IGIB), Council of Scientific and Industrial Research (CSIR), Mall Road, Delhi 110007, India

³ Department of Physiology and Pharmacology “Vittorio Erspamer”, Sapienza University of Rome, P. le Aldo Moro 5, 00185 Rome, Italy

Molecules 2017, 22(10), 1484; https://doi.org/10.3390/molecules22101484 - 29 Sep 2017

Cited by 28 | Viewed by 5547

Abstract

ABC transporters have a significant role in drug disposition and response and various studies have implicated their involvement in epilepsy pharmacoresistance. Since genetic studies till now are inconclusive, we thought of investigating the role of xenobiotics as transcriptional modulators of ABC transporters. Here, [...] Read more.

ABC transporters have a significant role in drug disposition and response and various studies have implicated their involvement in epilepsy pharmacoresistance. Since genetic studies till now are inconclusive, we thought of investigating the role of xenobiotics as transcriptional modulators of ABC transporters. Here, we investigated the effect of six antiepileptic drugs (AEDs) viz. phenytoin, carbamazepine, valproate, lamotrigine, topiramate and levetiracetam, on the expression and function of ABCB1, ABCC1, ABCC2 and ABCG2 in Caco2 and HepG2 cell lines through real time PCR, western blot and functional activity assays. Further, the interaction of AEDs with maximally induced ABCC2 was studied. Carbamazepine caused a significant induction in expression of ABCB1 and ABCC2 in HepG2 and Caco2 cells, both at the transcript and protein level, together with increased functional activity. Valproate caused a significant increase in the expression and functional activity of ABCB1 in HepG2 only. No significant effect of phenytoin, lamotrigine, topiramate and levetiracetam on the transporters under study was observed in either of the cell lines. We demonstrated the interaction of carbamazepine and valproate with ABCC2 with ATPase and 5,6-carboxyfluorescein inhibition assays. Thus, altered functionality of ABCB1 and ABCC2 can affect the disposition and bioavailability of administered drugs, interfering with AED therapy. Full article

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13 pages, 820 KiB

Open AccessArticle

Immobilization of Moniliella spathulata R25L270 Lipase on Ionic, Hydrophobic and Covalent Supports: Functional Properties and Hydrolysis of Sardine Oil

by Lívia T. de A. Souza^1,*, Sonia Moreno-Perez², Gloria Fernández Lorente³, Eliane P. Cipolatti⁴

, Débora De Oliveira⁴, Rodrigo R. Resende^1,5,* and Benevides C. Pessela^3,6,*

¹ Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, Avenida Presidente Antônio Carlos, 6627, Caixa Postal 486, Belo Horizonte MG 31270-901, Brazil

² Pharmacy and Biotechnology Department, School of Biomedical Sciences, Universidad Europea, Villaviciosa de Odón, 28670 Madrid, Spain

³ Departamento de Biotecnología y Microbiología de Alimentos, Instituto de Investigación en Ciencias de la Alimentación CIAL (CSIC-UAM), Campus de la Universidad Autónoma de Madrid, Nicolás Cabrera 9, 28049 Madrid, Spain

⁴ Departamento de Engenharia Química e Engenharia de Alimentos, Universidade Federal de Santa Catarina (UFSC), P.O. Box 476, Florianópolis SC 88040-900, Brazil

⁵ Instituto Nanocell, Divinópolis MG 35500-041, Brazil

⁶ Departamento de Engenharia e Tecnologías, Instituto Superior Politécnico de Tecnologías e Ciências (ISPTEC) Av. Luanda Sul, Rua Lateral Via S10, P.O. Box 1316, Talatona-Luanda Sul, Angola

Molecules 2017, 22(10), 1508; https://doi.org/10.3390/molecules22101508 - 25 Sep 2017

Cited by 19 | Viewed by 4546

Abstract

The oleaginous yeast Moniliella spathulata R25L270 was the first yeast able to grow and produce extracellular lipase using Macaúba (Acrocomia aculeate) cake as substrate. The novel lipase was recently identified, and presented promising features for biotechnological applications. The M. spathulata R25L270 [...] Read more.

The oleaginous yeast Moniliella spathulata R25L270 was the first yeast able to grow and produce extracellular lipase using Macaúba (Acrocomia aculeate) cake as substrate. The novel lipase was recently identified, and presented promising features for biotechnological applications. The M. spathulata R25L270 lipase efficiently hydrolyzed vegetable and animal oils, and showed selectivity for generating cis-5,8,11,15,17-eicosapentaenoic acid from sardine oil. The enzyme can act in a wide range of temperatures (25–48 °C) and pH (6.5–8.4). The present study deals with the immobilization of M. spathulata R25L270 lipase on hydrophobic, covalent and ionic supports to select the most active biocatalyst capable to obtain omega-3 fatty acids (PUFA) from sardine oil. Nine immobilized agarose derivatives were prepared and biochemically characterized for thermostability, pH stability and catalytic properties (K_M and V_max). Ionic supports improved the enzyme–substrate affinity; however, it was not an effective strategy to increase the M. spathulata R25L270 lipase stability against pH and temperature. Covalent support resulted in a biocatalyst with decreased activity, but high thermostability. The enzyme was most stabilized when immobilized on hydrophobic supports, especially Octyl-Sepharose. Compared with the free enzyme, the half-life of the Octyl-Sepharose derivative at 60 °C increased 10-fold, and lipase stability under acidic conditions was achieved. The Octyl-Sepharose derivative was selected to obtain omega-3 fatty acids from sardine oil, and the maximal enzyme selectivity was achieved at pH 5.0. Full article

(This article belongs to the Special Issue Lipases and Lipases Modification)

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10 pages, 1021 KiB

Open AccessArticle

Antimicrobial Effects of Violacein against Planktonic Cells and Biofilms of Staphylococcus aureus

by Andressa H. M. Batista^1,*

, Anne C. D. Moreira¹, Rafael M. De Carvalho¹, Gleilton W. P. Sales¹

, Patrícia C. N. Nogueira², Thalles B. Grangeiro³

, Suelen C. Medeiros³, Edilberto R. Silveira²

and Nádia A. P. Nogueira¹

¹ Clinical Department of Toxicological Analysis, Faculty of Pharmacy, Federal University of Ceará, Fortaleza 60356000, Brazil

² Organic Chemistry Department, Federal University of Ceará, Fortaleza 60356000, Brazil

³ Biology Department, Federal University of Ceará, Fortaleza 60356000, Brazil

Molecules 2017, 22(10), 1534; https://doi.org/10.3390/molecules22101534 - 25 Sep 2017

Cited by 29 | Viewed by 6149

Abstract

Violacein is an indole compound, produced by Chromobacterium violaceum, a bacteria present in tropical and subtropical areas. Among its numerous biological activities, its antimicrobial potential stands out. This study aims to determine the antimicrobial activity of VIO on S. aureus in planktonic [...] Read more.

Violacein is an indole compound, produced by Chromobacterium violaceum, a bacteria present in tropical and subtropical areas. Among its numerous biological activities, its antimicrobial potential stands out. This study aims to determine the antimicrobial activity of VIO on S. aureus in planktonic culture and biofilms. VIO showed excellent antimicrobial activity in inhibiting and killing S. aureus in planktonic cultures and biofilm formation. The minimum bactericidal concentration (5 μg/mL) of VIO caused the death of S. aureus after 3–4 h of exposure and the minimum inhibitory concentration (1.25 μg/mL) of VIO inhibited bacterial growth within the first 8 h of contact. Biofilm formation was also strongly inhibited by VIO (1.25 μg/mL), in contrast to the higher resistance verified for S. aureus in mature biofilm (40 μg/mL). The high bacterial metabolic activity favored VIO activity; however, the good activity observed during phases of reduced metabolism indicates that VIO action involves more than one mechanism. Thus, VIO is a promising molecule for the development of an antimicrobial drug for the eradication of S. aureus infections. Full article

(This article belongs to the Special Issue Emerging Drug Discovery Approaches against Infectious Diseases)

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20 pages, 1109 KiB

Open AccessReview

Current Development Status of MEK Inhibitors

by Ying Cheng

and Hongqi Tian^*

Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin 300192, China

Molecules 2017, 22(10), 1551; https://doi.org/10.3390/molecules22101551 - 26 Sep 2017

Cited by 205 | Viewed by 13726

Abstract

The current development status of mitogen-activated protein kinase kinase (MEK) inhibitors, including the preclinical data and clinical study progress, has been summarized in this review. Different MEK inhibitors, possessing specific physicochemical properties and bioactivity characteristics, may provide different options for patients seeking treatment [...] Read more.

The current development status of mitogen-activated protein kinase kinase (MEK) inhibitors, including the preclinical data and clinical study progress, has been summarized in this review. Different MEK inhibitors, possessing specific physicochemical properties and bioactivity characteristics, may provide different options for patients seeking treatment for cancer. Moreover, the combination of the MEK inhibitors with other therapies—such as chemotherapy, targeted therapy, and immunotherapy—may be a promising approach for clinical use. Full article

(This article belongs to the Special Issue Kinase Inhibitors)

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12 pages, 1327 KiB

Open AccessArticle

Novel Anti-Tuberculosis Nanodelivery Formulation of Ethambutol with Graphene Oxide

by Bullo Saifullah^1,2,3

, Alina Chrzastek^1,†, Arundhati Maitra^1,†

, Bullo Naeemullah⁴, Sharida Fakurazi^3,5, Sanjib Bhakta¹

and Mohd Zobir Hussein^2,*

¹ Mycobacteria Research Laboratory, Department of Biological Sciences, Institute of Structural and Molecular Biology (ISMB), Birkbeck, University of London, Malet Street, London WC1E 7HX, UK

² Material Synthesis and Characterization Laboratory, Institute of Advanced Technology (ITMA), Universiti Putra Malaysia (UPM), Serdang 43400, Selangor, Malaysia

³ Laboratory for Vaccine and Immunotherapeutics, Institute of Biosciences, Universiti Putra Malaysia (UPM), Serdang 43400, Selangor, Malaysia

⁴ Department of Neurology (Ward No. 18) Jinnah Postgraduate Medical Center/Jinnah Sindh Medical, University Karachi, Karachi 75510, Pakistan

⁵ Department of Human Anatomy Faculty of Medicine and Health Sciences, University Putra Malaysia (UPM), Serdang 43400, Selangor, Malaysia

^† These authors contributed equally to this work.

Molecules 2017, 22(10), 1560; https://doi.org/10.3390/molecules22101560 - 12 Oct 2017

Cited by 28 | Viewed by 8001

Abstract

Tuberculosis (TB) is a bacterial disease responsible for millions of infections and preventable deaths each year. Its treatment is complicated by patients’ noncompliance due to dosing frequency, lengthy treatment, and adverse side effects associated with current chemotherapy. However, no modifications to the half-a-century [...] Read more.

Tuberculosis (TB) is a bacterial disease responsible for millions of infections and preventable deaths each year. Its treatment is complicated by patients’ noncompliance due to dosing frequency, lengthy treatment, and adverse side effects associated with current chemotherapy. However, no modifications to the half-a-century old standard chemotherapy have been made based on a nanoformulation strategy to improve pharmacokinetic efficacy. In this study, we have designed a new nanodelivery formulation, using graphene oxide as the nanocarrier, loaded with the anti-TB antibiotic, ethambutol. The designed formulation was characterized using a number of molecular analytical techniques. It was found that sustained release of the drug resulted in better bioavailability. In addition, the designed formulation demonstrated high biocompatibility with mouse fibroblast cells. The anti-TB activity of the nanodelivery formulation was determined using whole-cell resazurin microtiter plate assay, modified-spot culture growth inhibition assay, and biofilm inhibition assay. The nanodelivery formulation showed good anti-mycobacterial activity. The anti-mycobacterial activity of Ethambutol was unaffected by the drug loading and release process. The results of this study demonstrated the potential of this new nanodelivery formulation strategy to be considered for modifying existing chemotherapy to yield more efficacious antibiotic treatment against TB. Full article

(This article belongs to the Collection Nanomedicine)

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9 pages, 1108 KiB

Open AccessArticle

Cytotoxic and Hypoglycemic Activity of Triterpenoid Saponins from Camellia oleifera Abel. Seed Pomace

by Tai-Mei Di¹, Shao-Lan Yang¹, Feng-Yu Du², Lei Zhao¹

, Tao Xia³

and Xin-Fu Zhang^1,*

¹ College of Horticulture, Qingdao Agricultural University, Qingdao 266109, China

² College of Chemistry and Pharmacy, Qingdao Agricultural University, Qingdao 266109, China

³ State Key Laboratory of Tea Plant Biology and Utilization, Anhui Agricultural University, Hefei 230036, China

Molecules 2017, 22(10), 1562; https://doi.org/10.3390/molecules22101562 - 21 Sep 2017

Cited by 45 | Viewed by 5979

Abstract

One new and three known triterpenoid saponins were isolated and identified from Camellia oleifera seeds through IR, NMR, HR-ESI-MS and GC-MS spectroscopic methods, namely oleiferasaponin A₃, oleiferasaponin A₁, camelliasaponin B₁, and camelliasaponin B₂. The structure [...] Read more.

One new and three known triterpenoid saponins were isolated and identified from Camellia oleifera seeds through IR, NMR, HR-ESI-MS and GC-MS spectroscopic methods, namely oleiferasaponin A₃, oleiferasaponin A₁, camelliasaponin B₁, and camelliasaponin B₂. The structure of oleiferasaponin A₃ was elucidated as 16α-hydroxy-21β-O-angeloyl-22α-O-cinnamoyl-23α-aldehyde-28-dihydroxymethylene-olean-12-ene-3β-O-[β-d-galactopyranosyl-(1→2)]-[β-d-xylopyranosyl-(1→2)-β-d-galactopyranosyl-(1→3)]-β-d-gluco-pyranosiduronic acid. Camelliasaponin B₁ and camelliasaponin B₂ exhibited potent cytotoxic activity on three human tumour cell lines (human lung tumour cells (A549), human liver tumour cells (HepG2), cervical tumour cells (Hela)). The hypoglycemic activity of oleiferasaponin A₁ was testified by protecting pancreatic β-cell lines from high-glucose damage. Full article

(This article belongs to the Collection Natural Products: Anticancer Potential and Beyond)

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13 pages, 3639 KiB

Open AccessArticle

Molecular Dynamic Simulation of Space and Earth-Grown Crystal Structures of Thermostable T1 Lipase Geobacillus zalihae Revealed a Better Structure

by Siti Nor Hasmah Ishak^1,6, Sayangku Nor Ariati Mohamad Aris^1,2, Khairul Bariyyah Abd Halim³, Mohd Shukuri Mohamad Ali^1,4, Thean Chor Leow^1,2,5

, Nor Hafizah Ahmad Kamarudin^1,2, Malihe Masomian^1,6 and Raja Noor Zaliha Raja Abd Rahman^1,6,5,7,*

¹ Enzyme and Microbial Technology Research Centre, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia

² Department of Cell and Molecular Biology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia

³ Department of Biotechnology, Kuliyyah of Science, International Islamic University Malaysia, Bandar Indera Mahkota, 25200 Kuantan, Pahang, Malaysia

⁴ Department of Biochemistry, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia

⁵ Institute of Bioscience, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia

⁶ Department of Microbiology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia

⁷ Laboratory of Halal Science Research, Halal Products Research Institute, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia

Molecules 2017, 22(10), 1574; https://doi.org/10.3390/molecules22101574 - 25 Sep 2017

Cited by 30 | Viewed by 8159

Abstract

Less sedimentation and convection in a microgravity environment has become a well-suited condition for growing high quality protein crystals. Thermostable T1 lipase derived from bacterium Geobacillus zalihae has been crystallized using the counter diffusion method under space and earth conditions. Preliminary study using [...] Read more.

Less sedimentation and convection in a microgravity environment has become a well-suited condition for growing high quality protein crystals. Thermostable T1 lipase derived from bacterium Geobacillus zalihae has been crystallized using the counter diffusion method under space and earth conditions. Preliminary study using YASARA molecular modeling structure program for both structures showed differences in number of hydrogen bond, ionic interaction, and conformation. The space-grown crystal structure contains more hydrogen bonds as compared with the earth-grown crystal structure. A molecular dynamics simulation study was used to provide insight on the fluctuations and conformational changes of both T1 lipase structures. The analysis of root mean square deviation (RMSD), radius of gyration, and root mean square fluctuation (RMSF) showed that space-grown structure is more stable than the earth-grown structure. Space-structure also showed more hydrogen bonds and ion interactions compared to the earth-grown structure. Further analysis also revealed that the space-grown structure has long-lived interactions, hence it is considered as the more stable structure. This study provides the conformational dynamics of T1 lipase crystal structure grown in space and earth condition. Full article

(This article belongs to the Special Issue Computational Analysis for Protein Structure and Interaction)

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29 pages, 1670 KiB

Open AccessReview

Function Oriented Molecular Design: Dendrimers as Novel Antimicrobials

by Sandra García-Gallego^1,2, Gianluigi Franci^3,4, Annarita Falanga⁵, Rafael Gómez^1,2, Veronica Folliero³, Stefania Galdiero^4,5,6

, Francisco Javier De la Mata^1,2,* and Massimiliano Galdiero^3,4,*

¹ Organic and Inorganic Chemistry Department, Universidad de Alcalá, Campus Universitario, E-28871 Alcalá de Henares, Spain

² Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), 28029 Madrid, Spain

³ Department of Experimental Medicine, II University of Naples, Via Costantinopoli 16, 80138 Naples, Italy

⁴ Interuniversity Research Centre on Bioactive Peptides (CiRPEB), University of Naples “Federico II”, Via Mezzocannone 16, 80134 Naples, Italy

⁵ Department of Pharmacy, University of Naples “Federico II”, Via Mezzocannone 16, 80134 Napoli, Italy

⁶ John Felice Rome Center, Loyola University Chicago, Via Massimi 114, 00136 Roma, Italy

Molecules 2017, 22(10), 1581; https://doi.org/10.3390/molecules22101581 - 21 Sep 2017

Cited by 55 | Viewed by 8751

Abstract

In recent years innovative nanostructures are attracting increasing interest and, among them, dendrimers have shown several fields of application. Dendrimers can be designed and modified in plentiful ways giving rise to hundreds of different molecules with specific characteristics and functionalities. Biomedicine is probably [...] Read more.

In recent years innovative nanostructures are attracting increasing interest and, among them, dendrimers have shown several fields of application. Dendrimers can be designed and modified in plentiful ways giving rise to hundreds of different molecules with specific characteristics and functionalities. Biomedicine is probably the field where these molecules find extraordinary applicability, and this is probably due to their multi-valency and to the fact that several other chemicals can be coupled to them to obtain desired compounds. In this review we will describe the different production strategies and the tools and technologies for the study of their characteristics. Finally, we provide a panoramic overview of their applications to meet biomedical needs, especially their use as novel antimicrobials. Full article

(This article belongs to the Special Issue Dendrimers in Medicine)

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17 pages, 1249 KiB

Open AccessArticle

N-Halamine Biocidal Materials with Superior Antimicrobial Efficacies for Wound Dressings

by Buket Demir¹, Roy M. Broughton², Mingyu Qiao³, Tung-Shi Huang³ and S. D. Worley^1,*

¹ Department of Chemistry and Biochemistry, Auburn University, Auburn, AL 36849, USA

² Center for Polymers and Advanced Composites, Department of Mechanical Engineering, Auburn University, Auburn, AL 36849, USA

³ Department of Poultry Science, Auburn University, Auburn, AL 36849, USA

Molecules 2017, 22(10), 1582; https://doi.org/10.3390/molecules22101582 - 21 Sep 2017

Cited by 65 | Viewed by 10422

Abstract

This work demonstrated the successful application of N-halamine technology for wound dressings rendered antimicrobial by facile and inexpensive processes. Four N-halamine compounds, which possess different functional groups and chemistry, were synthesized. The N-halamine compounds, which contained oxidative chlorine, the source of antimicrobial activity, [...] Read more.

This work demonstrated the successful application of N-halamine technology for wound dressings rendered antimicrobial by facile and inexpensive processes. Four N-halamine compounds, which possess different functional groups and chemistry, were synthesized. The N-halamine compounds, which contained oxidative chlorine, the source of antimicrobial activity, were impregnated into or coated onto standard non-antimicrobial wound dressings. N-halamine-employed wound dressings inactivated about 6 to 7 logs of Staphylococcus aureus and Pseudomonas aeruginosa bacteria in brief periods of contact time. Moreover, the N-halamine-modified wound dressings showed superior antimicrobial efficacies when compared to commercially available silver wound dressings. Zone of inhibition tests revealed that there was no significant leaching of the oxidative chlorine from the materials, and inactivation of bacteria occurred by direct contact. Shelf life stability tests showed that the dressings were stable to loss of oxidative chlorine when they were stored for 6 months in dark environmental conditions. They also remained stable under florescent lighting for up to 2 months of storage. They could be stored in opaque packaging to improve their shelf life stabilities. In vitro skin irritation testing was performed using a three-dimensional human reconstructed tissue model (EpiDerm™). No potential skin irritation was observed. In vitro cytocompatibility was also evaluated. These results indicate that N-halamine wound dressings potentially can be employed to prevent infections, while at the same time improving the healing process by eliminating undesired bacterial growth. Full article

(This article belongs to the Special Issue Antibacterial Materials and Coatings)

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10 pages, 1259 KiB

Open AccessCommunication

Anti-Inflammatory Phenolic Metabolites from the Edible Fungus Phellinus baumii in LPS-Stimulated RAW264.7 Cells

by Seulah Lee¹, Dahae Lee^1,2, Tae Su Jang³, Ki Sung Kang², Joo-Won Nam⁴

, Hae-Jeung Lee⁵

and Ki Hyun Kim^1,*

¹ School of Pharmacy, Sungkyunkwan University, Suwon 16419, Korea

² College of Korean Medicine, Gachon University, Seongnam 13120, Korea

³ Institute of Green Bio Science & Technology, Seoul National University, Pyeong Chang 232-916, Korea

⁴ College of Pharmacy, Yeungnam University, Gyeongsan, Gyeongbuk 38541, Korea

⁵ Department of Food and Nutrition, Gachon University, Seongnam 13120, Korea

Molecules 2017, 22(10), 1583; https://doi.org/10.3390/molecules22101583 - 21 Sep 2017

Cited by 43 | Viewed by 7452

Abstract

The edible fungus Phellinus baumii Pilat (Hymenochaetaceae) has been used in Korean traditional medicines for strengthening health and prolonging life. An extract of the fruiting bodies of P. baumii was subjected to bioassay-guided fractionation based on its anti-inflammatory effects in lipopolysaccharide (LPS)-stimulated RAW264.7 [...] Read more.

The edible fungus Phellinus baumii Pilat (Hymenochaetaceae) has been used in Korean traditional medicines for strengthening health and prolonging life. An extract of the fruiting bodies of P. baumii was subjected to bioassay-guided fractionation based on its anti-inflammatory effects in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. The resulting fractions were chemically investigated, leading to isolation of three phenolic compounds (1–3), a sesquiterpene (4), two steroids (5–6), a fatty acid (7), and a cerebroside (8). Spectroscopic analyses including 1D and 2D NMR spectroscopy and LC/MS were used to determine their chemical structures. Compounds 2, 4, 5, 7 and 8 were identified in P. baumii for the first time. Since all compounds were isolated from active fractions with anti-inflammatory activity, their ability to inhibit LPS-stimulated nitric oxide (NO) production in RAW264.7 cells were evaluated in vitro. Compounds 1, 2, 3, 5 and 7 inhibited LPS-stimulated NO production, and compounds 1–3 had IC₅₀ values <10 μM. Treatment of LPS-stimulated RAW264.7 cells with compounds 1–3 inhibited phosphorylation of IKKα and IκBα. In addition, treatment of compounds 1–3 reduced LPS-induced increases of nuclear factor-kappa B (NF-κB) p65, iNOS and COX-2 protein expressions. Collectively, compounds 1–3 inhibited NF-κB-dependent inflammation in RAW264.7 cells. Thus, P. baumii is a potential source of natural anti-inflammatory agents, and active compounds 1–3 could be promising lead compounds for the development of novel anti-inflammatory agents. Full article

(This article belongs to the Collection Bioactive Compounds)

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21 pages, 6055 KiB

Open AccessArticle

The Recognition of Calmodulin to the Target Sequence of Calcineurin—A Novel Binding Mode

by Chia-Lin Chyan^*, Deli Irene and Sin-Mao Lin

Department of Chemistry, National Dong Hwa University, Hualien 974, Taiwan

Molecules 2017, 22(10), 1584; https://doi.org/10.3390/molecules22101584 - 21 Sep 2017

Cited by 7 | Viewed by 6353

Abstract

Calcineurin (CaN) is a Ca²⁺/calmodulin-dependent Ser/Thr protein phosphatase, which plays essential roles in many cellular and developmental processes. CaN comprises two subunits, a catalytic subunit (CaN-A, 60 kDa) and a regulatory subunit (CaN-B, 19 kDa). CaN-A tightly binds to CaN-B in [...] Read more.

Calcineurin (CaN) is a Ca²⁺/calmodulin-dependent Ser/Thr protein phosphatase, which plays essential roles in many cellular and developmental processes. CaN comprises two subunits, a catalytic subunit (CaN-A, 60 kDa) and a regulatory subunit (CaN-B, 19 kDa). CaN-A tightly binds to CaN-B in the presence of minimal levels of Ca²⁺, but the enzyme is inactive until activated by CaM. Upon binding to CaM, CaN then undergoes a conformational rearrangement, the auto inhibitory domain is displaced and thus allows for full activity. In order to elucidate the regulatory role of CaM in the activation processes of CaN, we used NMR spectroscopy to determine the structure of the complex of CaM and the target peptide of CaN (CaNp). The CaM/CaNp complex shows a compact ellipsoidal shape with 8 α-helices of CaM wrapping around the CaNp helix. The RMSD of backbone and heavy atoms of twenty lowest energy structures of CaM/CaNp complex are 0.66 and 1.14 Å, respectively. The structure of CaM/CaNp complex can be classified as a novel binding mode family 1–18 with major anchor residues Ile³⁹⁶ and Leu⁴¹³ to allocate the largest space between two domains of CaM. The relative orientation of CaNp to CaM is similar to the CaMKK peptide in the 1–16 binding mode with N- and C-terminal hydrophobic anchors of target sequence engulfed in the hydrophobic pockets of the N- and C-domain of CaM, respectively. In the light of the structural model of CaM/CaNp complex reported here, we provide new insight in the activation processes of CaN by CaM. We propose that the hydrophobic interactions between the Ca²⁺-saturated C-domain and C-terminal half of the target sequence provide driving forces for the initial recognition. Subsequent folding in the target sequence and structural readjustments in CaM enhance the formation of the complex and affinity to calcium. The electrostatic repulsion between CaM/CaNp complex and AID may result in the displacement of AID from active site for full activity. Full article

(This article belongs to the Special Issue Recent Advances in Biomolecular NMR Spectroscopy)

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7 pages, 1794 KiB

Open AccessLetter

Concentration Effect on Quenching of Chlorophyll a Fluorescence by All-Trans-β-Carotene in Photosynthesis

by Chen Chen¹, Nan Gong¹, Zuowei Li¹, Chenglin Sun^2,* and Zhiwei Men^1,*

¹ Coherent Light and Atomic and Molecular Spectroscopy Laboratory, College of Physics, Jilin University, Changchun 130012, China

² Key Laboratory of Physics and Technology for Advanced Batteries, College of Physics, Jilin University, Changchun 130012, China

Molecules 2017, 22(10), 1585; https://doi.org/10.3390/molecules22101585 - 21 Sep 2017

Cited by 16 | Viewed by 8244

Abstract

Absorption, fluorescence spectra of chlorophyll a (Chl-a) and all-trans-β-carotene (β-Car) mixing solution are investigated in different polarity and polarizability solvents. The carotenoids regulate the energy flow in photosynthesis by interaction with chlorophyll, leading to an observable reduction of Chl-a fluorescence. The fluorescence red [...] Read more.

Absorption, fluorescence spectra of chlorophyll a (Chl-a) and all-trans-β-carotene (β-Car) mixing solution are investigated in different polarity and polarizability solvents. The carotenoids regulate the energy flow in photosynthesis by interaction with chlorophyll, leading to an observable reduction of Chl-a fluorescence. The fluorescence red shifts with the increasing solvent polarizability. The energy transfer in the Chl-a and β-Car system is proposed. The electron transfer should be dominant in quenching Chl-a fluorescence rather than the energy transfer in this system. Polar solvent with large polarizability shows high quenching efficiency. When dissolved in carbon tetrachloride, Chl-a presents red shift of absorption and blue shift of fluorescence spectra with increasing β-Car concentration, which implies a Chl-a conformational change. Full article

(This article belongs to the Special Issue Artificial Photosynthesis: Recent Progress in Solar Energy Utilization)

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14 pages, 2482 KiB

Open AccessFeature PaperReview

Applications of PNA-Based Artificial Restriction DNA Cutters

by Narumi Shigi^1,2, Jun Sumaoka^2,3 and Makoto Komiyama^1,2,*

¹ World Premier International (WPI) Research Center for Materials Nanoarchitectonics (MANA), National Institute for Materials Science (NIMS), 1-1 Namiki, Tsukuba, Ibaraki 305-0044, Japan

² Life Science Center of Tsukuba Advanced Research Alliance, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki 305-8577, Japan

³ Department of Applied Chemistry, School of Engineering, Tokyo University of Technology, 1404-1 Katakuramachi, Hachioji, Tokyo 192-0982, Japan

Molecules 2017, 22(10), 1586; https://doi.org/10.3390/molecules22101586 - 21 Sep 2017

Cited by 14 | Viewed by 8268

Abstract

More than ten years ago, artificial restriction DNA cutters were developed by combining two pseudo-complementary peptide nucleic acid (pcPNA) strands with either Ce(IV)/EDTA or S1 nuclease. They have remarkably high site-specificity and can cut only one predetermined site in the human genome. In [...] Read more.

More than ten years ago, artificial restriction DNA cutters were developed by combining two pseudo-complementary peptide nucleic acid (pcPNA) strands with either Ce(IV)/EDTA or S1 nuclease. They have remarkably high site-specificity and can cut only one predetermined site in the human genome. In this article, recent progress of these man-made tools have been reviewed. By cutting the human genome site-selectively, desired fragments can be clipped from either the termini of chromosomes (telomeres) or from the middle of genome. These fragments should provide important information on the biological functions of complicated genome system. DNA/RNA hybrid duplexes, which are formed in living cells, are also site-selectively hydrolyzed by these cutters. In order to further facilitate the applications of the artificial DNA cutters, various chemical modifications have been attempted. One of the most important successes is preparation of PNA derivatives which can form double-duplex invasion complex even under high salt conditions. This is important for in vivo applications, since the inside of living cells is abundant of metal ions. Furthermore, site-selective DNA cutters which require only one PNA strand, in place of a pair of pcPNA strands, are developed. This progress has opened a way to new fields of PNA-based biochemistry and biotechnology. Full article

(This article belongs to the Special Issue Molecular Properties and the Applications of Peptide Nucleic Acids)

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11 pages, 5047 KiB

Open AccessArticle

Influence of Jiegeng on Pharmacokinetic Properties of Flavonoids and Saponins in Gancao

by Yancao Mao^1,2,†, Linxiu Peng^2,†, An Kang², Tong Xie¹, Jianya Xu¹, Cunsi Shen¹, Jianjian Ji¹, Liuqing Di², Hao Wu^2,* and Jinjun Shan^1,2,*

¹ Jiangsu Key Laboratory of Pediatric Respiratory Disease, Institute of Pediatrics, Nanjing University of Chinese Medicine, Nanjing 210023, China

² Jiangsu Engineering Research Center for Efficient Delivery System of TCM, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China

^† The first two authors contributed equally to this work.

Molecules 2017, 22(10), 1587; https://doi.org/10.3390/molecules22101587 - 21 Sep 2017

Cited by 26 | Viewed by 6159

Abstract

Jiegeng Gancao decoction, which is composed of Jiegeng and Gancao at a weight ratio of 1:2, was widely used for treating pharyngalgia and cough for thousands of years. Our previous work indicated that Gancao could increase the systemic exposure of platycodin D and [...] Read more.

Jiegeng Gancao decoction, which is composed of Jiegeng and Gancao at a weight ratio of 1:2, was widely used for treating pharyngalgia and cough for thousands of years. Our previous work indicated that Gancao could increase the systemic exposure of platycodin D and deapio-platycodin D, two main components in Jiegeng. However, whether Jiegeng could alter the pharmacokinetics of the main compounds in Gancao is still unknown. Thus, the purpose of this study was to compare the oral pharmacokinetics of flavonoids and saponins from Gancao alone vs. after co-administration with Jiegeng. Furthermore, Caco-2 cell transport and fecal hydrolysis were investigated to explain the altered pharmacokinetic properties. Pharmacokinetics results suggested that the bioavailability of liquiritin, isoliquiritin, glycyrrhizin and its metabolite, glycyrrhetinic acid, could be improved while bioavailability of liquiritigenin and isoliquiritigenin deteriorated when co-administered with Jiegeng. The Caco-2 transport study showed no significant difference of the P_app values of the main components in Jiegeng Gancao decoction when compared with those in Gancao decoction (p > 0.05). The in vitro metabolism study suggested that saponins and flavonoids glycosides in Gancao were influenced and the metabolic characteristics of most ingredients were consistent with pharmacokinetic results, such as liquiritin and glycyrrhetinic acid. The hydrolysis of liquiritigenin and glycyrrhizin observed with fecal lysate in vitro appeared consistent with the oral pharmacokinetics. Based on experiments, the pharmacokinetic profiles of six components in Gancao were influenced by Jiegeng. The metabolic process might partially contribute to the altered pharmacokinetic behavior. The metabolism of some components of Gancao appeared to be inhibited when coadministered with Jiegeng, possibly by the Jiegeng constituent platycodin. Full article

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16 pages, 7314 KiB

Open AccessArticle

Novel FXa Inhibitor Identification through Integration of Ligand- and Structure-Based Approaches

by Carlos F. Lagos^1,2

, Gerardine F. Segovia³, Nicolás Nuñez-Navarro³, Mario A. Faúndez⁴ and Flavia C. Zacconi^3,5,*

¹ Department of Endocrinology, School of Medicine, Pontificia Universidad Católica de Chile, Lira 85, Santiago 8330074, Chile

² Facultad de Ciencia, Universidad San Sebastián, Campus Los Leones, Lota 2465, Providencia, Santiago 7510157, Chile

³ Departamento de Química Orgánica, Facultad de Química, Pontificia Universidad Católica de Chile, Av. Vicuña Mackenna 4860, Macul, Santiago 7820436, Chile

⁴ Departamento de Farmacia, Facultad de Química, Pontificia Universidad Católica de Chile, Av. Vicuña Mackenna 4860, Macul, Santiago 7820436, Chile

⁵ Centro de Investigación en Nanotecnología y Materiales Avanzados, CIEN-UC, Pontificia Universidad Católica de Chile, Av. Vicuña Mackenna 4860, Macul, Santiago 7820436, Chile

Molecules 2017, 22(10), 1588; https://doi.org/10.3390/molecules22101588 - 22 Sep 2017

Cited by 11 | Viewed by 6684

Abstract

Factor Xa (FXa), a vitamin K-dependent serine protease plays a pivotal role in the coagulation cascade, one of the most interesting targets for the development of new anticoagulants. In the present work, we performed a virtual screening campaign based on ligand-based shape and [...] Read more.

Factor Xa (FXa), a vitamin K-dependent serine protease plays a pivotal role in the coagulation cascade, one of the most interesting targets for the development of new anticoagulants. In the present work, we performed a virtual screening campaign based on ligand-based shape and electrostatic similarity search and protein-ligand docking to discover novel FXa-targeted scaffolds for further development of inhibitors. From an initial set of 260,000 compounds from the NCI Open database, 30 potential FXa inhibitors were identified and selected for in vitro biological evaluation. Compound 5 (NSC635393, 4-(3-methyl-4H-1,4-benzothiazin-2-yl)-2,4-dioxo-N-phenylbutanamide) displayed an IC₅₀ value of 2.02 nM against human FXa. The identified compound may serve as starting point for the development of novel FXa inhibitors. Full article

(This article belongs to the Section Medicinal Chemistry)

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14 pages, 3117 KiB

Open AccessArticle

Aspalathin Reverts Doxorubicin-Induced Cardiotoxicity through Increased Autophagy and Decreased Expression of p53/mTOR/p62 Signaling

by Rabia Johnson^1,2,*

, Samukelisiwe Shabalala^1,3

, Johan Louw^1,3, Abidemi Paul Kappo³

and Christo John Frederick Muller^1,2,3

¹ Biomedical Research and Innovation Platform (BRIP), South African Medical Research Council (MRC), Tygerberg 7505, South Africa

² Division of Medical Physiology, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg 7505, South Africa

³ Department of Biochemistry and Microbiology, University of Zululand, Kwadlangezwa 3886, South Africa

Molecules 2017, 22(10), 1589; https://doi.org/10.3390/molecules22101589 - 22 Sep 2017

Cited by 62 | Viewed by 8665

Abstract

Doxorubicin (Dox) is an effective chemotherapeutic agent used in the treatment of various cancers. Its clinical use is often limited due to its potentially fatal cardiotoxic side effect. Increasing evidence indicates that tumour protein p53 (p53), adenosine monophosphate-activated protein kinase (AMPK), nucleoporin p62 [...] Read more.

Doxorubicin (Dox) is an effective chemotherapeutic agent used in the treatment of various cancers. Its clinical use is often limited due to its potentially fatal cardiotoxic side effect. Increasing evidence indicates that tumour protein p53 (p53), adenosine monophosphate-activated protein kinase (AMPK), nucleoporin p62 (p62), and the mammalian target of rapamycin (mTOR) are critical mediators of Dox-induced apoptosis, and subsequent dysregulation of autophagy. Aspalathin, a polyphenolic dihydrochalcone C-glucoside has been shown to activate AMPK while decreasing the expression of p53. However, the role that aspalathin could play in the inhibition of Dox-induced cardiotoxicity through increased autophagy flux remained unexplored. H9c2 cardiomyocytes and Caov-3 ovarian cancer cells were cultured in Dulbecco’s Modified Eagle’s medium and treated with or without Dox for five days. Thereafter, cells exposed to 0.2 µM Dox were co-treated with either 20 µM Dexrazozane (Dexra) or 0.2 µM aspalathin (ASP) daily for 5 days. Results obtained showed that ASP mediates its cytoprotective effect in a p53-dependent manner, by increasing the Bcl-2/Bax ratio and decreasing apoptosis. The latter effect was diminished through ASP-induced activation of autophagy-related genes (Atgs) with an associated decrease in p62 through induction of AMPK and Fox01. Furthermore, we showed that ASP was able to potentiate this effect without decreasing the anti-cancer efficacy of Dox, as could be observed in Caov-3 ovarian cancer cells. Taken together, the data presented in this study provides a credible mechanism by which ASP co-treatment could protect the myocardium from Dox-induced cardiotoxicity. Full article

(This article belongs to the Collection Phytochemicals: Biosynthesis, Metabolism and Biological Activities)

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8 pages, 1194 KiB

Open AccessArticle

Inhibitory Effect of Selaginellins from Selaginella tamariscina (Beauv.) Spring against Cytochrome P450 and Uridine 5′-Diphosphoglucuronosyltransferase Isoforms on Human Liver Microsomes

by Jae-Kyung Heo¹, Phi-Hung Nguyen², Won Cheol Kim¹, Nguyen Minh Phuc¹ and Kwang-Hyeon Liu^1,*

¹ BK21 Plus KNU Multi-Omics Based Creative Drug Research Team, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University, 80 Daehakro, Bukgu, Daegu 41566, Korea

² Institute of Natural Products Chemistry, Vietnam Academy of Science and Technology, 18-Hoang Quoc Viet, Cau Giay, Hanoi 122100, Vietnam

Molecules 2017, 22(10), 1590; https://doi.org/10.3390/molecules22101590 - 21 Sep 2017

Cited by 13 | Viewed by 5049

Abstract

Selaginella tamariscina (Beauv.) has been used for traditional herbal medicine for treatment of cancer, hepatitis, and diabetes in the Orient. Numerous bioactive compounds including alkaloids, flavonoids, lignans, and selaginellins have been identified in this medicinal plant. Among them, selaginellins having a quinone methide [...] Read more.

Selaginella tamariscina (Beauv.) has been used for traditional herbal medicine for treatment of cancer, hepatitis, and diabetes in the Orient. Numerous bioactive compounds including alkaloids, flavonoids, lignans, and selaginellins have been identified in this medicinal plant. Among them, selaginellins having a quinone methide unit and an alkylphenol moiety have been known to possess anticancer, antidiabetic, and neuroprotective activity. Although there have been studies on the biological activities of selaginellins, their modulatory potential of cytochrome P450 (P450) and uridine 5′-diphosphoglucuronosyltransferase (UGT) activities have not been previously evaluated. In this study, we investigated the drug interaction potential of two selaginellins on ten P450 isoforms (CYP1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, 2J2 and 3A) and six UGT isoforms (UGT1A1, 1A3, 1A4, 1A6, 1A9 and 2B7) using human liver microsomes and liquid chromatography-tandem mass spectrometry. Selaginellin and selaginellin M had high inhibitory potential for CYP2C8-mediated amodiaquine O-demethylation with IC₅₀ values of 0.5 and 0.9 μM, respectively. Selaginellin and selaginellin M also showed medium inhibitory potential against CYP2C9, CYP2J2, UGT1A1, and UGT1A3 (1 μM < IC₅₀ < 5 μM). These two selaginellins had low inhibitory potential against CYP1A2, CYP2A6, CYP2E1, and UGT1A6 (IC₅₀ > 25 μM). This information might be helpful to predict possible drug interaction potential of between selaginellins and co-administered drugs. Full article

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9 pages, 756 KiB

Open AccessFeature PaperArticle

One-Pot Multi-Enzymatic Synthesis of the Four Stereoisomers of 4-Methylheptan-3-ol

by Elisabetta Brenna^1,*, Michele Crotti^1,†, Francesco G. Gatti¹

, Daniela Monti²

, Fabio Parmeggiani¹

and Andrea Pugliese¹

¹ Politecnico di Milano, Dipartimento di Chimica, Materiali, Ingegneria Chimica, Via Mancinelli 7, I-20131 Milano, Italy

² Istituto di Chimica del Riconoscimento Molecolare—CNR, Via M. Bianco 9, I-20131 Milano, Italy

^† Authors are listed in alphabetical order. M. C. is the principal author of the publication.

Molecules 2017, 22(10), 1591; https://doi.org/10.3390/molecules22101591 - 22 Sep 2017

Cited by 15 | Viewed by 7343

Abstract

The use of pheromones in the integrated pest management of insects is currently considered a sustainable and environmentally benign alternative to hazardous insecticides. 4-Methylheptan-3-ol is an interesting example of an insect pheromone, because its stereoisomers are active towards different species. All four possible [...] Read more.

The use of pheromones in the integrated pest management of insects is currently considered a sustainable and environmentally benign alternative to hazardous insecticides. 4-Methylheptan-3-ol is an interesting example of an insect pheromone, because its stereoisomers are active towards different species. All four possible stereoisomers of this compound were prepared from 4-methylhept-4-en-3-one by a one-pot procedure in which the two stereogenic centres were created during two sequential reductions catalysed by an ene-reductase (ER) and an alcohol dehydrogenase (ADH), respectively. Full article

(This article belongs to the Collection Recent Advances in Flavors and Fragrances)

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27 pages, 2679 KiB

Open AccessArticle

Synthesis of 2,4-Diaminopyrimidine Core-Based Derivatives and Biological Evaluation of Their Anti-Tubercular Activities

by Yifan Ouyang^1,†, Hao Yang^1,†, Peng Zhang¹, Yu Wang¹, Sargit Kaur², Xuanli Zhu¹, Zhe Wang¹, Yutong Sun¹, Wei Hong^3,*, Yun Fong Ngeow^2,* and Hao Wang^1,4,*

¹ School of Pharmacy, Ningxia Medical University, Yinchuan 750004, China

² Department of Pre-Clinical Sciences, Faculty of Medicine and Health Sciences, Universiti Tunku Abdul Rahman, Sungai Long campus, Kajang 43000, Selangor, Malaysia

³ School of Chemistry and Chemical Engineering, North Minzu University, Yinchuan 750021, China

⁴ KeyLaboratory of Hui Ethnic Medicine Modernization, Ministry of Education, Ningxia Medical University, Yinchuan 750004, China

^† These authors contributed equally to this work.

Molecules 2017, 22(10), 1592; https://doi.org/10.3390/molecules22101592 - 22 Sep 2017

Cited by 26 | Viewed by 10219

Abstract

Tuberculosis (TB) is a chronic, potentially fatal disease caused by Mycobacterium tuberculosis (Mtb). The dihyrofolate reductase in Mtb (mt-DHFR) is believed to be an important drug target in anti-TB drug development. This enzyme contains a glycerol (GOL) binding site, [...] Read more.

Tuberculosis (TB) is a chronic, potentially fatal disease caused by Mycobacterium tuberculosis (Mtb). The dihyrofolate reductase in Mtb (mt-DHFR) is believed to be an important drug target in anti-TB drug development. This enzyme contains a glycerol (GOL) binding site, which is assumed to be a useful site to improve the selectivity towards human dihyrofolate reductase (h-DHFR). There have been previous attempts to design drugs targeting the GOL binding site, but the designed compounds contain a hydrophilic group, which may prevent the compounds from crossing the cell wall of Mtb to function at the whole cell level. In the current study, we designed and synthesized a series of mt-DHFR inhibitors that contain a 2,4-diaminopyrimidine core with side chains to occupy the glycerol binding site with proper hydrophilicity for cell entry, and tested their anti-tubercular activity against Mtb H37Ra. Among them, compound 16l showed a good anti-TB activity (MIC = 6.25 μg/mL) with a significant selectivity against vero cells. In the molecular simulations performed to understand the binding poses of the compounds, it was noticed that only side chains of a certain size can occupy the glycerol binding site. In summary, the novel synthesized compounds with appropriate side chains, hydrophobicity and selectivity could be important lead compounds for future optimization towards the development of future anti-TB drugs that can be used as monotherapy or in combination with other anti-TB drugs or antibiotics. These compounds can also provide much information for further studies on mt-DHFR. However, the enzyme target of the compounds still needs to be confirmed by pure mt-DHFR binding assays. Full article

(This article belongs to the Section Medicinal Chemistry)

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11 pages, 2908 KiB

Open AccessArticle

Polyyne-Enriched Extract from Oplopanax elatus Significantly Ameliorates the Progression of Colon Carcinogenesis in Apc^Min/+ Mice

by Xin Qiao¹, Wei Sun¹, Chongzhi Wang², Li Zhang¹, Ping Li¹, Xiaodong Wen^1,*, Jie Yang^1,* and Chunsu Yuan²

¹ State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 211198, China

² Tang Center for Herbal Medicine Research and Department of Anesthesia & Critical Care, The Pritzker School of Medicine, The University of Chicago, Chicago, IL 60601, USA

Molecules 2017, 22(10), 1593; https://doi.org/10.3390/molecules22101593 - 22 Sep 2017

Cited by 11 | Viewed by 5559

Abstract

Colorectal cancer (CRC) is the third most common cancer in the world. Oplopanax elatus is widely used in traditional medicine. However, little is known about its pharmacological effects and bioactive compounds. We evaluated the effects of the polyyne-enriched extract from O. elatus (PEO) [...] Read more.

Colorectal cancer (CRC) is the third most common cancer in the world. Oplopanax elatus is widely used in traditional medicine. However, little is known about its pharmacological effects and bioactive compounds. We evaluated the effects of the polyyne-enriched extract from O. elatus (PEO) on the progression of colon carcinogenesis in Apc^Min/+ mice. In addition, these effects were also investigated in HCT116 and SW480 cells. After PEO oral administration (0.2% diet) for 12 weeks, PEO significantly improved body weight changes and reduced the tumor burden and tumor multiplicity compared with the untreated mice. Meanwhile, western blot and immunohistochemistry results showed PEO significantly reduced the expression of β-catenin and cyclinD1 in both small intestine and the colon tissues compared with the untreated mice. In addition, PEO treatment significant decreased the cell viability in both HCT116 and SW480 cell lines. It also decreased the levels of β-catenin, cyclinD1, c-myc and p-GSK-3β in HCT116 and SW480 cells at 25 μM. These results indicate that PEO may have potential value in prevention of colon cancer by down-regulating Wnt-related protein. Full article

(This article belongs to the Collection Natural Products: Anticancer Potential and Beyond)

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13 pages, 1788 KiB

Open AccessArticle

Therapeutic Mechanisms of Vernonia amygdalina Delile in the Treatment of Prostate Cancer

by William Johnson, Paul B. Tchounwou^*

and Clement G. Yedjou^*

Natural Chemotherapeutics Research Laboratory, NIH-RCMI Center for Environmental Health College of Science, Engineering and Technology, Jackson State University, 1400 Lynch Street, P.O. Box 18540, Jackson, MS 39217, USA

Molecules 2017, 22(10), 1594; https://doi.org/10.3390/molecules22101594 - 22 Sep 2017

Cited by 22 | Viewed by 8375

Abstract

Prostate cancer patients have been suffering from limited treatment options due to late diagnosis, poor drug tolerance, and multi-drug resistance to almost all the current drug treatments. Therefore, it is important to seek a new alternative therapeutic medicine that can effectively prevent the [...] Read more.

Prostate cancer patients have been suffering from limited treatment options due to late diagnosis, poor drug tolerance, and multi-drug resistance to almost all the current drug treatments. Therefore, it is important to seek a new alternative therapeutic medicine that can effectively prevent the disease and even eradicate the progression and metastasis of prostate cancer. Vernonia amygdalina Delile (VAD) is a common edible vegetable in Cameroon that has been used as a traditional medicine for some human diseases. However, to the best of our knowledge, no previous reports have explored its therapeutic efficacy against human prostate cancer. The objective of the present study was to assess the anticancer activities of VAD methanolic extracts in the prevention and treatment of prostate cancer using human androgen-independent prostate cancer (PC-3) cells as a test model. To achieve our objective, PC-3 cells were treated with various doses of VAD for 48 h. Data generated from the trypan blue test and MTT assay demonstrated that VAD extracts exhibited significant growth-inhibitory effects on PC-3 cells. Collectively, we established for the first time the antiproliferative effects of VAD on PC-3 cells, with an IC₅₀ value of about 196.6 µg/mL. Further experiments, including cell morphology, lipid peroxidation and comet assays, and apoptosis analysis showed that VAD caused growth-inhibitory effects on PC-3 cells through the induction of cell growth arrest, DNA damage, apoptosis, and necrosis in vitro and may provide protection from oxidative stress diseases as a result of its high antioxidant content. These results provide useful data on the anticancer activities of VAD for prostate cancer and demonstrate the novel possibilities of this medicinal plant for developing prostate cancer therapies. Full article

(This article belongs to the Collection Natural Products: Anticancer Potential and Beyond)

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11 pages, 446 KiB

Open AccessArticle

Antifungal Activity of Thapsia villosa Essential Oil against Candida, Cryptococcus, Malassezia, Aspergillus and Dermatophyte Species

by Eugénia Pinto^1,2,*, Maria-José Gonçalves³, Carlos Cavaleiro³

and Lígia Salgueiro³

¹ Laboratory of Microbiology, Biological Sciences Department, Faculty of Pharmacy of University of Porto, Rua Jorge Viterbo Ferreira n° 228, 4050-313 Porto, Portugal

² Interdisciplinary Centre of Marine and Environmental Research (CIIMAR/CIMAR), University of Porto, Terminal de Cruzeiros do Porto de Leixões Av. General Norton de Matos s/n, 4450-208 Matosinhos, Portugal

³ CNC.IBILI, Faculty of Pharmacy, University of Coimbra, Azinhaga de S. Comba, 3000-354 Coimbra, Portugal

Molecules 2017, 22(10), 1595; https://doi.org/10.3390/molecules22101595 - 22 Sep 2017

Cited by 56 | Viewed by 7921

Abstract

The composition of the essential oil (EO) of Thapsia villosa (Apiaceae), isolated by hydrodistillation from the plant’s aerial parts, was analysed by GC and GC-MS. Antifungal activity of the EO and its main components, limonene (57.5%) and methyleugenol (35.9%), were evaluated against clinically [...] Read more.

The composition of the essential oil (EO) of Thapsia villosa (Apiaceae), isolated by hydrodistillation from the plant’s aerial parts, was analysed by GC and GC-MS. Antifungal activity of the EO and its main components, limonene (57.5%) and methyleugenol (35.9%), were evaluated against clinically relevant yeasts (Candida spp., Cryptococcus neoformans and Malassezia furfur) and moulds (Aspergillus spp. and dermatophytes). Minimum inhibitory concentrations (MICs) were measured according to the broth macrodilution protocols by Clinical and Laboratory Standards Institute (CLSI). The EO, limonene and methyleugenol displayed low MIC and MFC (minimum fungicidal concentration) values against Candida spp., Cryptococcus neoformans, dermatophytes, and Aspergillus spp. Regarding Candida species, an inhibition of yeast–mycelium transition was demonstrated at sub-inhibitory concentrations of the EO (MIC/128; 0.01 μL/mL) and their major compounds in Candida albicans. Fluconazole does not show this activity, and the combination with low concentrations of EO could associate a supplementary target for the antifungal activity. The association of fluconazole with T. villosa oil does not show antagonism, but the combination limonene/fluconazole displays synergism. The fungistatic and fungicidal activities revealed by T. villosa EO and its main compounds, associated with their low haemolytic activity, confirm their potential antimicrobial interest against fungal species often associated with human mycoses. Full article

(This article belongs to the Special Issue Medicinal Chemistry in Europe)

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14 pages, 2263 KiB

Open AccessArticle

Separation and Enrichment of Lectin from Zihua Snap-Bean (Phaseolus vulgaris) Seeds by PEG 600–Ammonium Sulfate Aqueous Two-Phase System

by Bin Jiang

, Yongqiang Yuan, Xiaoqing Zhang, Zhibiao Feng^* and Chunhong Liu

Department of Applied Chemistry, Northeast Agricultural University, No. 600 Changjiang Road, Xiangfang District, Harbin 150030, China

Molecules 2017, 22(10), 1596; https://doi.org/10.3390/molecules22101596 - 22 Sep 2017

Cited by 12 | Viewed by 6052

Abstract

A fast and efficient method based on a polyethylene glycol (PEG) 600/(NH₄)₂SO₄ aqueous two-phase system for extracting lectin from Zihua snap-bean (Phaseolus vulgaris) seeds was established. According to a Box–Behnken design (BBD), involving four factors at [...] Read more.

A fast and efficient method based on a polyethylene glycol (PEG) 600/(NH₄)₂SO₄ aqueous two-phase system for extracting lectin from Zihua snap-bean (Phaseolus vulgaris) seeds was established. According to a Box–Behnken design (BBD), involving four factors at three levels each subjected to analysis of variance (ANOVA) and response surface analysis, the protein recovery and the purification factor of lectin in the top phase were used as the response values of the variance analysis to acquire the multivariate quadratic regression model. SDS–PAGE electrophoresis and the hemagglutination test were used to detect the distribution of lectin in the aqueous two-phase system (ATPS). The obtained data indicated that lectin was preferentially partitioned into the PEG-rich phase, and the ATPS, composed of 15% (NH₄)₂SO₄ (w/w), 18% PEG 600 (w/w), 0.4 g/5 g NaCl and 1 mL crude extract, showed good selectivity for lectin when the pH value was 7.5. Under the optimal conditions, most of the lectin was assigned to the top phase in the ATPS, and the hemagglutination activity of the purified lectin in the top phase was 3.08 times that of the crude extract. Consequently, the PEG 600/(NH₄)₂SO₄ aqueous two-phase system was an effective method for separating and enriching lectin directly from the crude extract of Zihua snap-bean seeds. Full article

(This article belongs to the Special Issue New Methodologies in Natural Product Analytics and Structure Elucidation)

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12 pages, 2889 KiB

Open AccessArticle

Biomimetic-Functionalized, Tannic Acid-Templated Mesoporous Silica as a New Support for Immobilization of NHase

by Jun-kai Gao¹, Zi-jun Zhang¹, Yan-jun Jiang², Yan Chen^1,* and Shu-feng Gao³

¹ School of Port and Transportation Engineering, Zhejiang Ocean University, Zhoushan 316022, China

² School of Chemical Engineering and Technology, Hebei University of Technology, Tianjin 300130, China

³ YinzhouKefeng New Material of Polymer Co. Ltd., Ningbo 315100, China

Molecules 2017, 22(10), 1597; https://doi.org/10.3390/molecules22101597 - 25 Sep 2017

Cited by 17 | Viewed by 5642

Abstract

Tannic acid-templated mesoporous silica (TAMS) was synthesized using a simple nonsurfactant template method and dopamine-functionalized TAMS (Dop-TAMS), which was prepared via a biomimetic coating, was developed as a new support for immobilization of NHase (NHase@Dop-TAMS). The Dop-TAMS was thoroughly characterized by the transmission [...] Read more.

Tannic acid-templated mesoporous silica (TAMS) was synthesized using a simple nonsurfactant template method and dopamine-functionalized TAMS (Dop-TAMS), which was prepared via a biomimetic coating, was developed as a new support for immobilization of NHase (NHase@Dop-TAMS). The Dop-TAMS was thoroughly characterized by the transmission electron microscopy (TEM), scanning electron microscopy (SEM), Brunauer–Emmett–Teller (BET), and Fourier transform infrared (FT-IR) and the results showed that the Dop-TAMS possessed sufficiently large pore size and volume for the accommodation of NHase. Studying the thermal stability, storage, shaking stability, and pH stability of the free and immobilized NHase indicated that the catalytic properties of NHase@Dop-TAMS were significantly enhanced. Moreover, the NHase@Dop-TAMS exhibited good reusability. All the results demonstrated that Dop-TAMS could be used as an excellent matrix for the immobilization of NHase. Full article

(This article belongs to the Special Issue Mesoporous Silica in Biomedical Applications)

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20 pages, 3218 KiB

Open AccessArticle

Glycyrrhetinic Acid Liposomes Containing Mannose-Diester Lauric Diacid-Cholesterol Conjugate Synthesized by Lipase-Catalytic Acylation for Liver-Specific Delivery

by Jing Chen^1,†, Yuchao Chen^2,3,4,†, Yi Cheng^1,* and Youheng Gao^1,*

¹ Shool of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou 510006, China

² The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510115, China

³ Section of Immunology, Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou 510006, China

⁴ Postdoctoral Programme, Guangzhou University of Chinese Medicine, Guangzhou 510006, China

^† These authors contributed equally to this work.

Molecules 2017, 22(10), 1598; https://doi.org/10.3390/molecules22101598 - 24 Sep 2017

Cited by 18 | Viewed by 6354

Abstract

Mannose-diester lauric diacid-cholesterol (Man-DLD-Chol), as a liposomal target ligand, was synthesized by lipase catalyzed in a non-aqueous medium. Its chemical structure was confirmed by mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy. Glycyrrhetinic acid (GA) liposomes containing Man-DLD-Chol (Man-DLD-Chol-GA-Lp) were prepared by [...] Read more.

Mannose-diester lauric diacid-cholesterol (Man-DLD-Chol), as a liposomal target ligand, was synthesized by lipase catalyzed in a non-aqueous medium. Its chemical structure was confirmed by mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy. Glycyrrhetinic acid (GA) liposomes containing Man-DLD-Chol (Man-DLD-Chol-GA-Lp) were prepared by the film-dispersion method. We evaluated the characterizations of liposomes, drug-release in vitro, the hemolytic test, cellular uptake, pharmacokinetics, and the tissue distributions. The cellular uptake in vitro suggested that the uptake of Man-DLD-Chol-modified liposomes was significantly higher than that of unmodified liposomes in HepG2 cells. Pharmacokinetic parameters indicated that Man-DLD-Chol-GA-Lp was eliminated more rapidly than GA-Lp. In tissue distributions, the targeting efficiency (Te) of Man-DLD-Chol-GA-Lp on liver was 54.67%, relative targeting efficiency (R_Te) was 3.39, relative uptake rate (Re) was 4.78, and peak concentration ratio (Ce) was 3.46. All these results supported the hypothesis that Man-DLD-Chol would be an efficient liposomal carrier, and demonstrated that Man-DLD-Chol-GA-Lp has potential as a drug delivery for liver-targeting therapy. Full article

(This article belongs to the Special Issue Lipases and Lipases Modification)

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14 pages, 2928 KiB

Open AccessArticle

Integrative Pathway Analysis of Genes and Metabolites Reveals Metabolism Abnormal Subpathway Regions and Modules in Esophageal Squamous Cell Carcinoma

by Chunquan Li^1,2,*,†, Qiuyu Wang^1,*,†, Jiquan Ma^3,†, Shengshu Shi³, Xin Chen², Haixiu Yang² and Junwei Han^2,*

¹ Department of Medical Informatics, Daqing Campus, Harbin Medical University, Daqing 163319, China

² College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China

³ Department of Computer Science and Technology, Heilongjiang University, Harbin 150080, China

^† These authors contributed equally to this work.

Molecules 2017, 22(10), 1599; https://doi.org/10.3390/molecules22101599 - 22 Sep 2017

Cited by 14 | Viewed by 6224

Abstract

Aberrant metabolism is one of the main driving forces in the initiation and development of ESCC. Both genes and metabolites play important roles in metabolic pathways. Integrative pathway analysis of both genes and metabolites will thus help to interpret the underlying biological phenomena. [...] Read more.

Aberrant metabolism is one of the main driving forces in the initiation and development of ESCC. Both genes and metabolites play important roles in metabolic pathways. Integrative pathway analysis of both genes and metabolites will thus help to interpret the underlying biological phenomena. Here, we performed integrative pathway analysis of gene and metabolite profiles by analyzing six gene expression profiles and seven metabolite profiles of ESCC. Multiple known and novel subpathways associated with ESCC, such as ‘beta-Alanine metabolism’, were identified via the cooperative use of differential genes, differential metabolites, and their positional importance information in pathways. Furthermore, a global ESCC-Related Metabolic (ERM) network was constructed and 31 modules were identified on the basis of clustering analysis in the ERM network. We found that the three modules located just to the center regions of the ERM network—especially the core region of Module_1—primarily consisted of aldehyde dehydrogenase (ALDH) superfamily members, which contributes to the development of ESCC. For Module_4, pyruvate and the genes and metabolites in its adjacent region were clustered together, and formed a core region within the module. Several prognostic genes, including GPT, ALDH1B1, ABAT, WBSCR22 and MDH1, appeared in the three center modules of the network, suggesting that they can become potentially prognostic markers in ESCC. Full article

(This article belongs to the Special Issue Computational Analysis for Protein Structure and Interaction)

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10 pages, 3524 KiB

Open AccessArticle

Hydrogen-Bonding Interactions in Luminescent Quinoline-Triazoles with Dominant 1D Crystals

by Shi-Qiang Bai^1,*

, David James Young^1,2

and T. S. Andy Hor³

¹ Institute of Materials Research and Engineering, ASTAR (Agency for Science, Technology and Research), 2 Fusionopolis Way, #08-03, Innovis, Singapore 138634, Singapore

² Faculty of Science, Health, Education and Engineering, University of the Sunshine Coast, Maroochydore DC, Queensland 4558, Australia

³ Department of Chemistry, The University of Hong Kong, Pokfulam, Hong Kong, China

Molecules 2017, 22(10), 1600; https://doi.org/10.3390/molecules22101600 - 22 Sep 2017

Cited by 2 | Viewed by 5476

Abstract

Quinoline-triazoles 2-((4-(diethoxymethyl)-1H-1,2,3-triazol-1-yl)methyl)quinoline (1), 2-((4-(m-tolyl)-1H-1,2,3-triazol-1-yl)methyl)quinoline (2) and 2-((4-(p-tolyl)-1H-1,2,3-triazol-1-yl)methyl)quinoline (3) have been prepared with CuAAC click reactions and used as a model series to probe the relationship between lattice H-bonding interaction and crystal [...] Read more.

Quinoline-triazoles 2-((4-(diethoxymethyl)-1H-1,2,3-triazol-1-yl)methyl)quinoline (1), 2-((4-(m-tolyl)-1H-1,2,3-triazol-1-yl)methyl)quinoline (2) and 2-((4-(p-tolyl)-1H-1,2,3-triazol-1-yl)methyl)quinoline (3) have been prepared with CuAAC click reactions and used as a model series to probe the relationship between lattice H-bonding interaction and crystal direction of growth. Crystals of 1–3 are 1D tape and prism shapes that correlate with their intermolecular and solvent 1D lattice H-bonding interactions. All compounds were thermally stable up to about 200 C and blue-green emissive in solution. Full article

(This article belongs to the Collection Heterocyclic Compounds)

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10 pages, 3177 KiB

Open AccessArticle

Solvent-Free Synthesis and Safener Activity of Sulfonylurea Benzothiazolines

by Ying Fu

, Jing-Yi Wang, Dong Zhang, Yu-Feng Chen, Shuang Gao, Li-Xia Zhao and Fei Ye^*

Department of Applied Chemistry, College of Science, Northeast Agricultural University, Harbin 150030, China

Molecules 2017, 22(10), 1601; https://doi.org/10.3390/molecules22101601 - 22 Sep 2017

Cited by 11 | Viewed by 5828

Abstract

A series of novel sulfonylurea benzothiazolines was designed by splicing active groups and bioisosterism. A solvent-free synthetic route was developed for the sulfonylurea benzothiazoline derivatives via the cyclization and carbamylation. All compounds were characterized by IR, ¹H-NMR, ¹³C-NMR, HRMS. The biological [...] Read more.

A series of novel sulfonylurea benzothiazolines was designed by splicing active groups and bioisosterism. A solvent-free synthetic route was developed for the sulfonylurea benzothiazoline derivatives via the cyclization and carbamylation. All compounds were characterized by IR, ¹H-NMR, ¹³C-NMR, HRMS. The biological activity tests indicated the compounds could protect maize against the injury caused by chlorsulfuron to some extent. The molecular docking result showed that the new compound competed with chlorsulfuron to bind with the herbicide target enzyme active site to attain detoxification. Full article

(This article belongs to the Section Organic Chemistry)

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12 pages, 807 KiB

Open AccessArticle

Identification of DNA-Binding Proteins Using Mixed Feature Representation Methods

by Kaiyang Qu¹, Ke Han²

, Song Wu³, Guohua Wang⁴ and Leyi Wei^1,5,*

¹ School of Computer Science and Technology, Tianjin University, Tianjin 300350, China

² School of Computer and Information Engineering, Harbin University of Commerce, Harbin 150028, China

³ Center of Potential Illness, Qinhuangdao Hospital of Traditional Chinese Medicine, Qinhuangdao 066001, China

⁴ School of Computer Science and Technology, Harbin Institute of China, Harbin 150001, China

⁵ State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin 300074, China

Molecules 2017, 22(10), 1602; https://doi.org/10.3390/molecules22101602 - 22 Sep 2017

Cited by 33 | Viewed by 4843

Abstract

DNA-binding proteins play vital roles in cellular processes, such as DNA packaging, replication, transcription, regulation, and other DNA-associated activities. The current main prediction method is based on machine learning, and its accuracy mainly depends on the features extraction method. Therefore, using an efficient [...] Read more.

DNA-binding proteins play vital roles in cellular processes, such as DNA packaging, replication, transcription, regulation, and other DNA-associated activities. The current main prediction method is based on machine learning, and its accuracy mainly depends on the features extraction method. Therefore, using an efficient feature representation method is important to enhance the classification accuracy. However, existing feature representation methods cannot efficiently distinguish DNA-binding proteins from non-DNA-binding proteins. In this paper, a multi-feature representation method, which combines three feature representation methods, namely, K-Skip-N-Grams, Information theory, and Sequential and structural features (SSF), is used to represent the protein sequences and improve feature representation ability. In addition, the classifier is a support vector machine. The mixed-feature representation method is evaluated using 10-fold cross-validation and a test set. Feature vectors, which are obtained from a combination of three feature extractions, show the best performance in 10-fold cross-validation both under non-dimensional reduction and dimensional reduction by max-relevance-max-distance. Moreover, the reduced mixed feature method performs better than the non-reduced mixed feature technique. The feature vectors, which are a combination of SSF and K-Skip-N-Grams, show the best performance in the test set. Among these methods, mixed features exhibit superiority over the single features. Full article

(This article belongs to the Special Issue Computational Analysis for Protein Structure and Interaction)

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11 pages, 695 KiB

Open AccessArticle

Influence of Harvest Season and Cultivar on the Variation of Phenolic Compounds Composition and Antioxidant Properties in Vaccinium ashei Leaves

by Verciane Schneider Cezarotto^1,2, Sandro Rogério Giacomelli³, Maria Helena Vendruscolo², Angélica Signor Vestena², Caroll Schneider Cezarotto², Ritiel Corrêa Da Cruz¹, Luana Haselein Maurer⁴, Luana Mota Ferreira¹

, Tatiana Emanuelli⁴ and Letícia Cruz^1,*

¹ Departamento de Farmácia Industrial, Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal de Santa Maria, Santa Maria RS 97105-900, Brazil

² Departamento de Ciências da Saúde, Curso de Farmácia, Universidade Regional Integrada do Alto Uruguai e das Missões, Frederico Westphalen RS 98400-000, Brazil

³ Departamento de Ciências Exatas e da Terra, Curso de Química, Universidade Regional Integrada do Alto Uruguai e das Missões, Frederico Westphalen, RS 98400-000, Brazil

⁴ Departamento de Tecnologia e Ciência dos Alimentos, Programa de Pós-Graduação em Ciência e Tecnologia dos Alimentos, Centro de Ciências Rurais, Universidade Federal de Santa Maria, Santa Maria RS 97105-900, Brazil

Molecules 2017, 22(10), 1603; https://doi.org/10.3390/molecules22101603 - 30 Sep 2017

Cited by 38 | Viewed by 5672

Abstract

The effect of variation of harvest season and cultivar on the total phenolic content (TPC), total flavonoid content (TFC), HPLC-UV/DAD profile and antioxidant properties in Vaccinium ashei (Rabbiteye blueberry) leaves grown in Brazil was evaluated. The cultivars collected in December and March were [...] Read more.

The effect of variation of harvest season and cultivar on the total phenolic content (TPC), total flavonoid content (TFC), HPLC-UV/DAD profile and antioxidant properties in Vaccinium ashei (Rabbiteye blueberry) leaves grown in Brazil was evaluated. The cultivars collected in December and March were Aliceblue, Powderblue, Climax, Bluegem and FloridaM. It was observed that leaves from March had the highest TPC values (222 ± 1 mg gallic acid equivalents/g to Aliceblue cultivar) and highest TFC values (49.8 ± 0.8 and 48.7 ± 0.7 µg rutin/g to Clímax and Powderblue cultivars, respectively). The chromatographic profile was quantitatively similar, however, the proportions of each compound were influenced by cultivar and harvest season. Chlorogenic acid and rutin were the main identified phenolic compounds, but chlorogenic acid was the most abundant in both harvest seasons. Antioxidant capacities values ranged from 5.80 ± 0.04 to 105 ± 2 µg/mL (DPPH) and 178 ± 5 to 431 ± 8 mmol Trolox/100 g (ORAC). The cultivar Bluegem by March had the highest values in both assays. The results indicate that the blueberry leaves from different cultivars and harvest seasons have different phenolic compounds content and different antioxidant capacities. In addition, the antioxidant properties demonstrated a high correlation with rutin content. Full article

(This article belongs to the Section Natural Products Chemistry)

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13 pages, 2215 KiB

Open AccessArticle

Kinetics and Molecular Docking Studies of 6-Formyl Umbelliferone Isolated from Angelica decursiva as an Inhibitor of Cholinesterase and BACE1

by Md Yousof Ali^1,†

, Su Hui Seong^1,†, Machireddy Rajeshkumar Reddy², Sung Yong Seo², Jae Sue Choi^1,*

and Hyun Ah Jung^3,*

¹ Department of Food and Life Science, Pukyong National University, Busan 48513, Korea

² Department of Chemistry, Pukyong National University, Busan 48513, Korea

³ Department of Food Science and Human Nutrition, Chonbuk National University, Jeonju 54896, Korea

^† These two authors contributed equally to this work.

Molecules 2017, 22(10), 1604; https://doi.org/10.3390/molecules22101604 - 24 Sep 2017

Cited by 33 | Viewed by 7429

Abstract

Coumarins, which have low toxicity, are present in some natural foods, and are used in various herbal remedies, have attracted interest in recent years because of their potential medicinal properties. In this study, we report the isolation of two natural coumarins, namely umbelliferone [...] Read more.

Coumarins, which have low toxicity, are present in some natural foods, and are used in various herbal remedies, have attracted interest in recent years because of their potential medicinal properties. In this study, we report the isolation of two natural coumarins, namely umbelliferone (1) and 6-formyl umbelliferone (2), from Angelica decursiva, and the synthesis of 8-formyl umbelliferone (3) from 1. We investigated the anti-Alzheimer disease (anti-AD) potential of these coumarins by assessing their ability to inhibit acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and β-site amyloid precursor protein (APP) cleaving enzyme 1 (BACE1). Among these coumarins, 2 exhibited poor inhibitory activity against AChE and BChE, and modest activity against BACE1. Structure–activity relationship analysis showed that 2 has an aldehyde group at the C-6 position, and exhibited strong anti-AD activity, whereas the presence or absence of an aldehyde group at the C-8 position reduced the anti-AD activity of 3 and 1, respectively. In addition, 2 exhibited concentration-dependent inhibition of peroxynitrite-mediated protein tyrosine nitration. A kinetic study revealed that 2 and 3 non-competitively inhibited BACE1. To confirm enzyme inhibition, we predicted the 3D structures of AChE and BACE1, and used AutoDock 4.2 to simulate binding of coumarins to these enzymes. The blind docking studies demonstrated that these molecules could interact with both the catalytic active sites and peripheral anionic sites of AChE and BACE1. Together, our results indicate that 2 has an interesting inhibitory activity in vitro, and can be used in further studies to develop therapeutic modalities for the treatment of AD. Full article

(This article belongs to the Special Issue Versatile Coumarins)

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16 pages, 2754 KiB

Open AccessArticle

Evaluation of LPS-Induced Acute Lung Injury Attenuation in Rats by Aminothiazole-Paeonol Derivatives

by Pin-Kuei Fu^1,2,3

, Chi-Yu Yang⁴, Su-Chin Huang⁵, Yu-Wen Hung⁴, Kee-Ching Jeng⁶, Ying-Pei Huang⁷, Hong Chuang⁷, Nai-Chun Huang⁵, Jui-Ping Li⁵, Ming-Hua Hsu⁸ and Jen-Kun Chen^5,9,10,*

¹ Department of Critical Care Medicine, Taichung Veterans General Hospital, Taichung 40705, Taiwan

² Department of Biotechnology, Hungkuang University, Taichung 43302, Taiwan

³ School of Chinese Medicine, China Medical University, Taichung 40447, Taiwan

⁴ Animal Technology Laboratory, Agriculture Technology Research Institute, Miaoli 35053, Taiwan

⁵ Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, Miaoli 35053, Taiwan

⁶ Department of Medical Research, Tungs’ Taichung MetroHarbor Hospital, Taichung 43503, Taiwan

⁷ Department of Chemistry, National Tsing Hua University, Hsinchu 30013, Taiwan

⁸ Department of Chemistry, National Changhua University of Education, Changhua County 50007, Taiwan

⁹ Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 11490, Taiwan

¹⁰ School of Dentistry, National Defense Medical Center, Taipei 11490, Taiwan

Molecules 2017, 22(10), 1605; https://doi.org/10.3390/molecules22101605 - 25 Sep 2017

Cited by 18 | Viewed by 7530

Abstract

Paeonol is a key phenolic compound in the root bark of Moutan Cortex Radicis that has been used in traditional Chinese Medicine to ameliorate inflammation. A series of aminothiazole-paeonol derivatives (APDs) were synthesized in this work and subjected to preliminary evaluation in cells [...] Read more.

Paeonol is a key phenolic compound in the root bark of Moutan Cortex Radicis that has been used in traditional Chinese Medicine to ameliorate inflammation. A series of aminothiazole-paeonol derivatives (APDs) were synthesized in this work and subjected to preliminary evaluation in cells followed by verification in animals. Quantification of monocyte chemotactic protein-1 (MCP-1) and interleukin-6 (IL-6) in culture media of LPS-activated A549 cells, a lung epithelial adenocarcinoma cell line, were used to investigate the anti-inflammatory capability of APDs. ALI-bearing rats were employed to verify therapeutic efficacy of APDs according to observations of total cells, protein amounts, MCP-1 and IL-6 in bronchoalveolar lavage fluid (BALF). Histopathological examinations of lung tissues were consequently applied for validation of APDs. Among these compounds, 2-(2-aminothiazol-4-yl)-5-methoxyphenol (4) had the most potent activity, showing comparable inhibition of MCP-1/IL-6 and superior elimination of neutrophil infiltration and protein exudation in lungs compared to others as well as dexamethasone. This study demonstrated a comprehensive strategy to evaluate APDs through integration of cell-based screening and animal-based verification. In order to fulfill unmet needs of treating acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), APDs introduced in this work could be promising lead compounds to develop high potent anti-inflammation agents. Full article

(This article belongs to the Special Issue Focusing on Sulfur in Medicinal Chemistry)

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17 pages, 504 KiB

Open AccessReview

Diverse Phytochemicals and Bioactivities in the Ancient Fruit and Modern Functional Food Pomegranate (Punica granatum)

by Sheng Wu^1,2 and Li Tian^1,2,3,*

¹ Shanghai Key Laboratory of Plant Functional Genomics and Resources, Shanghai Chenshan Botanical Garden, Shanghai 201602, China

² Shanghai Chenshan Plant Science Research Center, Chinese Academy of Sciences, Shanghai 201602, China

³ Department of Plant Sciences, University of California, Davis, CA 95616, USA

Molecules 2017, 22(10), 1606; https://doi.org/10.3390/molecules22101606 - 25 Sep 2017

Cited by 171 | Viewed by 14710

Abstract

Having served as a symbolic fruit since ancient times, pomegranate (Punica granatum) has also gained considerable recognition as a functional food in the modern era. A large body of literature has linked pomegranate polyphenols, particularly anthocyanins (ATs) and hydrolyzable tannins (HTs), [...] Read more.

Having served as a symbolic fruit since ancient times, pomegranate (Punica granatum) has also gained considerable recognition as a functional food in the modern era. A large body of literature has linked pomegranate polyphenols, particularly anthocyanins (ATs) and hydrolyzable tannins (HTs), to the health-promoting activities of pomegranate juice and fruit extracts. However, it remains unclear as to how, and to what extent, the numerous phytochemicals in pomegranate may interact and exert cooperative activities in humans. In this review, we examine the structural and analytical information of the diverse phytochemicals that have been identified in different pomegranate tissues, to establish a knowledge base for characterization of metabolite profiles, discovery of novel phytochemicals, and investigation of phytochemical interactions in pomegranate. We also assess recent findings on the function and molecular mechanism of ATs as well as urolithins, the intestinal microbial derivatives of pomegranate HTs, on human nutrition and health. A better understanding of the structural diversity of pomegranate phytochemicals as well as their bioconversions and bioactivities in humans will facilitate the interrogation of their synergistic/antagonistic interactions and accelerate their applications in dietary-based cancer chemoprevention and treatment in the future. Full article

(This article belongs to the Collection Phytochemicals: Biosynthesis, Metabolism and Biological Activities)

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15 pages, 2779 KiB

Open AccessArticle

Small Molecules Derived from Thieno[3,4-c]pyrrole-4,6-dione (TPD) and Their Use in Solution Processed Organic Solar Cells

by Cesar Garcias-Morales^1,*,†

, Daniel Romero-Borja^1,‡, José-Luis Maldonado^1,*

, Arián E. Roa^1,§

, Mario Rodríguez¹, J. Pablo García-Merinos² and Armando Ariza-Castolo³

¹ Research Group of Optical Properties of Materials (GPOM), Centro de Investigaciones en Óptica, A.P. 1-948, 37000 León, Guanajuato, Mexico

² Instituto de Investigaciones Químico Biológicas Universidad Michoacana de San Nicolás de Hidalgo Edificio B-1. Ciudad Universitaria, 58030 Morelia, Michoacán, Mexico

³ Departamento de Química, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Avenida Instituto Politécnico Nacional 2508 Colonia San Pedro Zacatenco, 07360 Mexico, D.F., Mexico

^† Departamento de Química Orgánica, Facultad de Ciencias Químicas, Universidad Autónoma de Coahuila, Ing. José Cárdenas Valdez, República, 25280 Saltillo, Coahuila, México. Current address

^‡ Centro de Investigación en Química Aplicada, Boulevard E. Reyna 140, 25100 Saltillo, Mexico. Current address

^§ Instituto de Investigaciones en Materiales, Universidad Nacional Autónoma de México, Del. Coyoacán, 04510 Ciudad de Mexico, Mexico. Current address

Molecules 2017, 22(10), 1607; https://doi.org/10.3390/molecules22101607 - 30 Sep 2017

Cited by 35 | Viewed by 8749

Abstract

In this work, microwave synthesis, chemical, optical and electrochemical characterization of three small organic molecules, TPA-TPD, TPA-PT-TPD and TPA-TT-TPD with donor-acceptor structure and their use in organic photovoltaic cells are reported. For the synthesis, 5-(2-ethylhexyl)-4H-thieno[3,4-c]pyrrole-4,6(5H)-dione was [...] Read more.

In this work, microwave synthesis, chemical, optical and electrochemical characterization of three small organic molecules, TPA-TPD, TPA-PT-TPD and TPA-TT-TPD with donor-acceptor structure and their use in organic photovoltaic cells are reported. For the synthesis, 5-(2-ethylhexyl)-4H-thieno[3,4-c]pyrrole-4,6(5H)-dione was used as electron withdrawing fragment while the triphenylamine was used as electron donating fragment. Molecular electronic geometry and electronic distribution density were established by density functional theory (DFT) calculations and confirmed by optical and chemical characterization. These molecules were employed as electron-donors in the active layer for manufacturing bulk heterojunction organic solar cells, where [6,6]-phenyl C71 butyric acid methyl ester (PC71BM) was used as electron-acceptor. As cathode, Field′s metal (FM), an eutectic alloy (Bi/In/Sn: 32.5%, 51%, and 16.5%, respectively) with a melting point above 62 °C, was easily deposited by drop casting under vacuum-free process and at air atmosphere. Prepared devices based on TPA-TPD:PC71BM (1:4 w/w ratio) presented a large V_OC = 0.97 V, with J_SC = 7.9 mA/cm², a FF = 0.34, then, a power conversion efficiency (PCE) of 2.6%. Full article

(This article belongs to the Special Issue Direct (Hetero)Arylation: A New Tool for Organic Electronics)

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17 pages, 4901 KiB

Open AccessArticle

Identification of Carotenoids and Isoprenoid Quinones from Asaia lannensis and Asaia bogorensis

by Hubert Antolak^1,*, Joanna Oracz²

, Anna Otlewska¹, Dorota Żyżelewicz² and Dorota Kręgiel¹

¹ Institute of Fermentation Technology and Microbiology, Faculty of Biotechnology and Food Science, Lodz University of Technology, 171/173 Wólczańska, 90-924 Lodz, Poland

² Institute of Food Technology and Analysis, Faculty of Biotechnology and Food Science, Lodz University of Technology, 4/10 Stefanowskiego, 90-924 Lodz, Poland

Molecules 2017, 22(10), 1608; https://doi.org/10.3390/molecules22101608 - 25 Sep 2017

Cited by 6 | Viewed by 7377

Abstract

The aim of the study was to identify and quantitatively assess of carotenoids and isoprenoid quinones biosynthesized by six different strains of acetic acid bacteria, belonging to genus Asaia, that are common beverage-spoiling bacteria in Europe. Bacterial cultures were conducted in a [...] Read more.

The aim of the study was to identify and quantitatively assess of carotenoids and isoprenoid quinones biosynthesized by six different strains of acetic acid bacteria, belonging to genus Asaia, that are common beverage-spoiling bacteria in Europe. Bacterial cultures were conducted in a laboratory liquid culture minimal medium with 2% sucrose. Carotenoids and isoprenoid quinones were investigated using UHPLC-DAD-ESI-MS analysis. In general, tested strains of Asaia spp. were able to produce 10 carotenoids and 3 isoprenoid quinones: menaquinone-7, menaquinone-8, and ubiquinone-10. The main identified carotenoids in Asaia lannensis strains were phytofluene, neurosporene, α-carotene, while for Asaia bogorensis, neurosporene, canthaxanthin, and zeaxanthin were noted. What is more, tested Asaia spp. were able to produce myxoxanthophyll, which has so far been identified primarily in cyanobacteria. The results show that A. lannensis are characterized by statistically higher concentrations of produced carotenoids, as well as a greater variety of these compounds. We have noted that carotenoids were not only accumulated by bacterial cells, but also some strains of A. lannensis produced extracellular carotenoids. Full article

(This article belongs to the Section Metabolites)

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15 pages, 1551 KiB

Open AccessFeature PaperArticle

Comparison of Dilution, Filtration, and Microwave Digestion Sample Pretreatments in Elemental Profiling of Wine by ICP-MS

by Joshua Godshaw^1,2, Helene Hopfer³

, Jenny Nelson^1,2,4 and Susan E. Ebeler^1,2,*

¹ Department of Viticulture & Enology, University of California, One Shields Ave, Davis, CA 95616, USA

² Food Safety & Measurement Facility, University of California, One Shields Ave, Davis, CA 95616, USA

³ Department of Food Science, The Pennsylvania State University, 202 Food Science Building, University Park, PA 16802, USA

⁴ Agilent Technologies, 5301 Stevens Creek Blvd, Santa Clara, CA 95051, USA

Molecules 2017, 22(10), 1609; https://doi.org/10.3390/molecules22101609 - 25 Sep 2017

Cited by 21 | Viewed by 9331

Abstract

Wine elemental composition varies by cultivar, geographic origin, viticultural and enological practices, and is often used for authenticity validation. Elemental analysis of wine by Inductively Coupled Plasma Mass Spectrometry (ICP-MS) is challenging due to the potential for non-spectral interferences and plasma instability arising [...] Read more.

Wine elemental composition varies by cultivar, geographic origin, viticultural and enological practices, and is often used for authenticity validation. Elemental analysis of wine by Inductively Coupled Plasma Mass Spectrometry (ICP-MS) is challenging due to the potential for non-spectral interferences and plasma instability arising from organic matrix components. Sample preparation mitigates these interferences, however, conflicting recommendations of best practices in ICP-MS analysis of wine have been reported. This study compared direct dilution, microwave-assisted acid digestion, and two filtration sample pretreatments, acidification prior to filtration and filtration followed by acidification, in elemental profiling of one white and three red table wines by ICP-MS. Of 43 monitored isotopes, 37 varied by sample preparation method, with significantly higher results of 17 isotopes in the microwave-digested samples. Both filtration treatments resulted in lower results for 11 isotopes compared to the other methods. Finally, isotope dilution determination of copper based on natural abundances and the ⁶³Cu:⁶⁵Cu instrument response ratio agreed with external calibration and confirmed a significant sample preparation effect. Overall, microwave digestion did not compare favorably, and direct dilution was found to provide the best compromise between ease of use and result accuracy and precision, although all preparation strategies were able to differentiate the wines. Full article

(This article belongs to the Collection Wine Chemistry)

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15 pages, 14941 KiB

Open AccessArticle

Astragalus Polysaccharide Protect against Cadmium-Induced Cytotoxicity through the MDA5/NF-κB Pathway in Chicken Peripheral Blood Lymphocytes

by Wanqiu Xie^1,2,†

, Ming Ge^1,2,†, Guangxing Li^1,2, Linan Zhang^1,2, Zequn Tang^1,2, Ruyue Li^1,2 and Ruili Zhang^1,2,*

¹ College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China

² Heilongjiang Key Laboratory for Laboratory Animals and Comparative Medicine, Northeast Agricultural University, Harbin 150030, China

^† These authors contributed equally to this work and should be considered co-first authors.

Molecules 2017, 22(10), 1610; https://doi.org/10.3390/molecules22101610 - 25 Sep 2017

Cited by 22 | Viewed by 5419

Abstract

Cadmium (Cd) is a known environmental pollutant that is associated with inflammation, oxidative stress, and cell apoptosis. Astragalus polysaccharide (APS) is a major component of Astragalus membranaceus, a vital qi-reinforcing herb medicine with favorable immuneregulation properties. To study the effect of APS [...] Read more.

Cadmium (Cd) is a known environmental pollutant that is associated with inflammation, oxidative stress, and cell apoptosis. Astragalus polysaccharide (APS) is a major component of Astragalus membranaceus, a vital qi-reinforcing herb medicine with favorable immuneregulation properties. To study the effect of APS on the inhibition of the cadmium-induced injury of peripheral blood lymphocytes (PBLs) in chickens through the MDA5/NF-κB signaling pathway, PLBs acquired from 15-day-old chickens were divided into control group, Cd group, APS + Cd group, anti-MDA5 mAb + Cd group, BAY 11-7082 (a nuclear factor kappa-light chain-enhancer of activated B cells [NF-κB] inhibitor) +Cd group, APS group, anti-MDA5 mAb group, and BAY 11-7082 group. The transcription levels of melanoma differentiation-associated gene 5 (MDA5), interferon promoter-stimulating factor 1 (IPS-1), NF-κB, and inflammatory factors tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 were measured by quantitative real-time PCR. MDA5 protein expression was measured by western blotting. Levels of malondialdehyde (MDA), glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD) were measured by corresponding antioxidant kit. The morphological change of PBLs was measured by transmission electron microscopy. The results showed that Cd significantly increased the expression of MDA5, IPS-1, NF-κB, and their downstream cytokines, IL-1β and TNF-α, IL-6 in PLBs. In addition, a high level of MDA was observed in the Cd treatment group; the activities of GSH-Px and SOD were significantly lower in the Cd treatment group than those in controls (p < 0.05). Ultrastructural changes of PBLs showed that Cd promoted autophagy, apoptosis, and necrosis in PBLs. However, APS can efficiently improve Cd-induced cell damage by decreasing the activation of the MDA5 signaling pathway. The effect is consistent with that of anti-MDA5 mAb or/and BAY. The results indicated that APS inhibited Cd-induced cytotoxicity through the regulation of MDA5/NF-κB signaling. Full article

(This article belongs to the Special Issue Advances in Natural Polysaccharides Research)

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12 pages, 1461 KiB

Open AccessArticle

Acyclic Triterpenoids from Alpinia katsumadai Inhibit IL-6-Induced STAT3 Activation

by Hyun-Jae Jang

, Seung-Jae Lee, Soyoung Lee

, Kyungsook Jung, Seung Woong Lee^*

and Mun-Chual Rho^*

Immunoregulatory Material Research Center, Korea Research Institute of Bioscience and Biotechnology, 181 Ipsin-gil, Jeongeup-si, Jeonbuk 56212, Korea

Molecules 2017, 22(10), 1611; https://doi.org/10.3390/molecules22101611 - 25 Sep 2017

Cited by 13 | Viewed by 4619

Abstract

The seeds of Alpinia katsumadai yielded two new acyclic triterpenoids, 2,3,6,22,23-pentahydroxy-2,6,11,15,19,23-hexamethyl-tetracosa-7,10,14,18-tetraene (3) and 2,3,6,22,23-pentahydroxy-2,10,15,19,23-hexamethyl-7-methylenetetracosa-10,14,18-triene (4), as well as two known compounds, 2,3,22,23-tertrahydroxy-2,6,10,15,19,23-hexamethyl-tetracosa-6,10,14,18-tetraene (1) and 2,3,5,22,23-pentahydroxy-2,6,10,15,19,23-hexamethyl-tetracosa-6,10,14,18-tetraene (2). The absolute configurations of 2 and 3, which [...] Read more.

The seeds of Alpinia katsumadai yielded two new acyclic triterpenoids, 2,3,6,22,23-pentahydroxy-2,6,11,15,19,23-hexamethyl-tetracosa-7,10,14,18-tetraene (3) and 2,3,6,22,23-pentahydroxy-2,10,15,19,23-hexamethyl-7-methylenetetracosa-10,14,18-triene (4), as well as two known compounds, 2,3,22,23-tertrahydroxy-2,6,10,15,19,23-hexamethyl-tetracosa-6,10,14,18-tetraene (1) and 2,3,5,22,23-pentahydroxy-2,6,10,15,19,23-hexamethyl-tetracosa-6,10,14,18-tetraene (2). The absolute configurations of 2 and 3, which were determined by means of a modified Mosher’s method, are suggested as (3R; 5S; 22R) and (3R; 22R), respectively. Compounds 1–4 inhibited IL-6-induced JAK2/STAT3 activity in a dose-dependent fashion, with IC₅₀ values of 0.67, 0.71, 2.18, and 2.99 μM. Moreover, IL-6-stimulated phosphorylation of STAT3 was significantly suppressed in U266 cells by the administration of A. katsumadai EtOH extract and Compounds 1 and 2. These results suggest that major phytochemicals, Compounds 1 and 2, obtained from A. katsumadai may be useful candidates for designing new IL-6 inhibitors as anti-inflammatory agents. Full article

(This article belongs to the Special Issue Anti-inflammatory Agents)

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13 pages, 4714 KiB

Open AccessArticle

Discriminative Analysis of Different Grades of Gaharu (Aquilaria malaccensis Lamk.) via ¹H-NMR-Based Metabolomics Using PLS-DA and Random Forests Classification Models

by Siti Nazirah Ismail¹, M. Maulidiani¹, Muhammad Tayyab Akhtar¹, Faridah Abas^1,2, Intan Safinar Ismail^1,3

, Alfi Khatib⁴, Nor Azah Mohamad Ali⁵ and Khozirah Shaari^1,3,*

¹ Laboratory of Natural Products, Institute of Bioscience, Universiti Putra Malaysia, 43400 Serdang, Malaysia

² Department of Food Science, Faculty of Food Science and Technology, Universiti Putra Malaysia, 43400 Serdang, Malaysia

³ Department of Chemistry, Faculty of Science, Universiti Putra Malaysia, 43400 Serdang, Malaysia

⁴ Department of Pharmaceutical Chemistry, Kuliyyah of Pharmacy, International Islamic University Malaysia (Kuantan Campus), Bandar Indera Mahkota, 25200 Kuantan, Malaysia

⁵ Forest Research Institute Malaysia, 52109 Kepong, Malaysia

Molecules 2017, 22(10), 1612; https://doi.org/10.3390/molecules22101612 - 25 Sep 2017

Cited by 25 | Viewed by 8589

Abstract

Gaharu (agarwood, Aquilaria malaccensis Lamk.) is a valuable tropical rainforest product traded internationally for its distinctive fragrance. It is not only popular as incense and in perfumery, but also favored in traditional medicine due to its sedative, carminative, cardioprotective and analgesic effects. The [...] Read more.

Gaharu (agarwood, Aquilaria malaccensis Lamk.) is a valuable tropical rainforest product traded internationally for its distinctive fragrance. It is not only popular as incense and in perfumery, but also favored in traditional medicine due to its sedative, carminative, cardioprotective and analgesic effects. The current study addresses the chemical differences and similarities between gaharu samples of different grades, obtained commercially, using ¹H-NMR-based metabolomics. Two classification models: partial least squares-discriminant analysis (PLS-DA) and Random Forests were developed to classify the gaharu samples on the basis of their chemical constituents. The gaharu samples could be reclassified into a ‘high grade’ group (samples A, B and D), characterized by high contents of kusunol, jinkohol, and 10-epi-γ-eudesmol; an ‘intermediate grade’ group (samples C, F and G), dominated by fatty acid and vanillic acid; and a ‘low grade’ group (sample E and H), which had higher contents of aquilarone derivatives and phenylethyl chromones. The results showed that ¹H- NMR-based metabolomics can be a potential method to grade the quality of gaharu samples on the basis of their chemical constituents. Full article

(This article belongs to the Collection Recent Advances in Flavors and Fragrances)

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18 pages, 6912 KiB

Open AccessArticle

Efficacy of Bioactive Cyclic Peptides in Rheumatoid Arthritis: Translation from In Vitro to In Vivo Models

by Roger New^1,*, Michal Bogus¹, Gurpal S. Bansal^1,2, Malgorzata Dryjska¹, Katarzyna Zajkowska^1,3 and Michael Burnet⁴

¹ Proxima Concepts Limited, c/o London Bioscience Innovation Centre, 2 Royal College Street, London NW1 0NH, UK

² Adaptimmune Ltd., 60 Jubilee Ave., Milton Park, Abingdon OX14 4RX, UK

³ Cambridge Blue Ventures Ltd., 21 Arlington St, London SW1A 1RN, UK

⁴ Synovo GmbH, Paul Ehrlich Str. 15, 72076 Tübingen, Germany

Molecules 2017, 22(10), 1613; https://doi.org/10.3390/molecules22101613 - 25 Sep 2017

Cited by 7 | Viewed by 5726

Abstract

Using a novel drug discovery technology reported in previous issues of this journal cyclic peptides have been created which are able to down-regulate secretion of inflammatory cytokines, in vitro, by stimulated cells of the macrophage cell line J774. The cytokines in question, [...] Read more.

Using a novel drug discovery technology reported in previous issues of this journal cyclic peptides have been created which are able to down-regulate secretion of inflammatory cytokines, in vitro, by stimulated cells of the macrophage cell line J774. The cytokines in question, TNF-alpha and IL-6, are strongly implicated in etiology of diseases such as rheumatoid arthritis. Studies are reported here using the CAIA animal model for rheumatoid arthritis, which show that the peptides identified are indeed able to impact on inflammation of joints, induced in vivo. The results suggest that these peptides are effective at a dose which could be viable in man, and at which no adverse side effects are evident in the short term. Full article

(This article belongs to the Special Issue Peptide-Based Drugs and Drug Delivery Systems)

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16 pages, 11398 KiB

Open AccessArticle

In Silico Prediction of the Anti-Depression Mechanism of a Herbal Formula (Tiansi Liquid) Containing Morinda officinalis and Cuscuta chinensis

by Dan Cheng¹

, Ghualm Murtaza^1,2,3,*, Suya Ma¹, Lingling Li¹, Xinjie Li¹, Fangze Tian¹, Junchao Zheng¹ and Yi Lu^1,*

¹ School of Preclinical Medicine, Beijing University of Chinese Medicines, Beisanhuan East Road, Beijing 100029, China

² Department of Pharmacy, COMSATS Institute of Information Technology Abbottabad, Abbottabad 22060, Pakistan

³ Institute of Automation, Chinese Academy of Sciences, Beijing 100029, China

Molecules 2017, 22(10), 1614; https://doi.org/10.3390/molecules22101614 - 26 Sep 2017

Cited by 24 | Viewed by 8627

Abstract

Purpose: Depression is a sickening psychiatric condition that is prevalent worldwide. To manage depression, the underlying modes of antidepressant effect of herbals are important to be explored for the development of natural drugs. Tiansi Liquid is a traditional Chinese medicine (TCM) that [...] Read more.

Purpose: Depression is a sickening psychiatric condition that is prevalent worldwide. To manage depression, the underlying modes of antidepressant effect of herbals are important to be explored for the development of natural drugs. Tiansi Liquid is a traditional Chinese medicine (TCM) that is prescribed for the management of depression, however its underlying mechanism of action is still uncertain. The purpose of this study was to systematically investigate the pharmacological mode of action of a herbal formula used in TCM for the treatment of depression. Methods: Based on literature search, an ingredients-targets database was developed for Tiansi Liquid, followed by the identification of targets related to depression. The interaction between these targets was evaluated on the basis of protein-protein interaction network constructed by STITCH and gene ontology (GO) enrichment analysis using ClueGO plugin. Results: As a result of literature search, 57 components in Tiansi Liquid formula and 106 potential targets of these ingredients were retrieved. A careful screening of these targets led to the identification of 42 potential targets associated with depression. Ultimately, 327 GO terms were found by analysis of gene functional annotation clusters and abundance value of these targets. Most of these terms were found to be closely related to depression. A significant number of protein targets such as IL10, MAPK1, PTGS2, AKT1, APOE, PPARA, MAPK1, MIF, NOS3 and TNF-α were found to be involved in the functioning of Tiansi Liquid against depression. Conclusions: The findings elaborate that Tiansi Liquid can be utilized to manage depression, however, multiple molecular mechanisms of action could be proposed for this effect. The observed core mechanisms could be the sensory perception of pain, regulation of lipid transport and lipopolysaccharide-mediated signaling pathway. Full article

(This article belongs to the Collection Bioactive Compounds)

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13 pages, 5747 KiB

Open AccessArticle

Solid-State Form Characterization of Riparin I

by Elisana Afonso De Moura^1,*, Márcio Vinícius Cahino Terto¹, Elisângela Afonso De Moura Mendonça², José Valdilânio Virgulino Procópio¹, Vicente Carlos De O. Costa¹, José Maria Barbosa Filho¹, Stanley Juan Chavez Gutierrez³, Josean Fechine Tavares¹, Rui Oliveira Macedo¹ and Marcelo Sobral Da Silva¹

¹ Pharmaceutical Sciences Departament, Federal University of Paraíba, University City, João Pessoa PB 58059-970, Brazil

² Biotechnology Departament, Federal University of Paraíba, University City, João Pessoa PB 58059-970, Brazil

³ Pharmaceutical Sciences Departament, Federal University of Piauí, Teresina PI 64600-000, Brazil

Molecules 2017, 22(10), 1615; https://doi.org/10.3390/molecules22101615 - 9 Oct 2017

Cited by 2 | Viewed by 3618

Abstract

Riparin I is an alkamide with potential anxiolytic activity in preclinical studies. The characterization and understanding of solid-state properties play an importance role in drug development. For this work, the solid state of five riparin I batches (RIP-1, RIP-2, RIP-3, RIP-4, and RIP-5), [...] Read more.

Riparin I is an alkamide with potential anxiolytic activity in preclinical studies. The characterization and understanding of solid-state properties play an importance role in drug development. For this work, the solid state of five riparin I batches (RIP-1, RIP-2, RIP-3, RIP-4, and RIP-5), obtained by the same synthesis process, were characterized by Scanning Electron Microscopy (SEM), Differential Scanning Calorimetry (DSC), DSC-photovisual, Thermogravimetry (TG), Fourier Transform Infrared (FTIR), Pyrolysis (Pyr-GC/MS), X-ray Powder Diffraction (PXRD), and Solid-State Nuclear Magnetic Resonance (ssNMR) techniques. Batches of riparin I with different crystal habits resulting in crystallization impurities were observed, which can be attributed to the presence of triethylamine. The main differences were observed by DSC, PXRD, and ssNMR analysis. DSC curves of RIP-2 and RIP-3 presented endothermic peaks at different temperatures of fusion, which can be attributed to the mixture of different crystalline forms. PXRD and ssNMR results confirmed crystallinity differences. The results offer evidence of the importance of controlling the reproducibility of the synthesis in order to obtain the adequate morphology for therapeutic efficacy and avoiding future problems in quality control of riparin I products. Full article

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13 pages, 1470 KiB

Open AccessArticle

Pharmacokinetics, Tissue Distribution, and Elimination of Three Active Alkaloids in Rats after Oral Administration of the Effective Fraction of Alkaloids from Ramulus Mori, an Innovative Hypoglycemic Agent

by Shuang Yang^1,2,†, Jiaqi Mi^1,†

, Zhihao Liu¹, Baolian Wang^1,*, Xuejun Xia³, Renyun Wang³, Yuling Liu³ and Yan Li¹

¹ State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Beijing Key Laboratory of Non-Clinical Drug Metabolism and PK/PD Study, Department of Drug Metabolism, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China

² Department of Pharmaceutical Analysis, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China

³ Department of Pharmaceutics, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China

^† These authors contributed equally to this work.

Molecules 2017, 22(10), 1616; https://doi.org/10.3390/molecules22101616 - 26 Sep 2017

Cited by 20 | Viewed by 5774

Abstract

In this study, we systematically investigated the plasma pharmacokinetics, tissue distribution, and elimination of three active alkaloids after oral administration of the effective fraction of alkaloids from Ramulus Mori (SZ–A)—an innovative hypoglycemic agent—in rats. Moreover, the influences of other components in SZ–A on [...] Read more.

In this study, we systematically investigated the plasma pharmacokinetics, tissue distribution, and elimination of three active alkaloids after oral administration of the effective fraction of alkaloids from Ramulus Mori (SZ–A)—an innovative hypoglycemic agent—in rats. Moreover, the influences of other components in SZ–A on dynamic process of alkaloids were explored for the first time. The results showed that 1-deoxynojirimycin (DNJ), fagomine (FGM) and 1,4-dideoxy-1,4-imino-d-arabinitol (DAB) exhibited nonlinear pharmacokinetics following oral administration of SZ–A (40–1000 mg/kg). The prolonged t_1/2 and greater area under concentration-time curve (AUC) versus time (AUC_0–t) of DNJ for SZ–A than for purified DNJ has been observed after both oral and intravenous administration. It was found that other components in SZ–A could enhance the absorption of DNJ through the intestinal barrier. The major distribution tissues of DNJ, FGM, and DAB were the gastrointestinal tract, liver, and kidney. Three alkaloids were mainly excreted into urine and feces, but less into bile. Interestingly, the excess excretion of FGM was revealed to be partly due to the biotransformation of other components in SZ–A via gut microbiota. These information provide a rational basis for the use of SZ–A in clinical practice. Full article

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11 pages, 814 KiB

Open AccessArticle

A Network Pharmacology-Based Study on the Hepatoprotective Effect of Fructus Schisandrae

by Ming Hong^1,2,†, Yongsheng Zhang^1,3,†, Sha Li¹, Hor Yue Tan¹, Ning Wang¹, Shuzhen Mu⁴, Xiaojiang Hao^4,5 and Yibin Feng^1,*

¹ School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 10 Sassoon Road, Pokfulam, Hong Kong, China

² Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, 12 Jichang Road, Guangzhou 510405, China

³ Zhejiang Chinese Medical University, 548 Binwen Road, Hangzhou 310053, China

⁴ The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences, Guiyang 55500, China

⁵ State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650000, China

^† These authors contribute equally to this work.

Molecules 2017, 22(10), 1617; https://doi.org/10.3390/molecules22101617 - 28 Sep 2017

Cited by 59 | Viewed by 10221

Abstract

Fructus schisandrae (Wuweizi in Chinese), a common traditional Chinese herbal medicine, has been used for centuries to treat chronic liver disease. The therapeutic efficacy of Wuweizi has also been validated in clinical practice. In this study, molecular docking and network analysis were carried [...] Read more.

Fructus schisandrae (Wuweizi in Chinese), a common traditional Chinese herbal medicine, has been used for centuries to treat chronic liver disease. The therapeutic efficacy of Wuweizi has also been validated in clinical practice. In this study, molecular docking and network analysis were carried out to explore the hepatoprotective mechanism of Wuweizi as an effective therapeutic approach to treat liver disease. Multiple active compounds of Wuweizi were docked with 44 protein targets related with viral hepatitis, fatty liver, liver fibrosis, cirrhosis, and liver cancer. A compound–target network was constructed through network pharmacology analysis, predicting the relationships of active ingredients to the targets. Our results demonstrated that schisantherin, schisandrin B, schisandrol B, kadsurin, Wuweizisu C, Gomisin A, Gomisin G, and angeloylgomisin may target with 21 intracellular proteins associated with liver diseases, especially with fatty liver disease. The CYP2E1, PPARα, and AMPK genes and their related pathway may play a pivotal role in the hepatoprotective effects of Wuweizi. The network pharmacology strategy used provides a forceful tool for searching the action mechanism of traditional herbal medicines and novel bioactive ingredients. Full article

(This article belongs to the Collection Phytochemicals: Biosynthesis, Metabolism and Biological Activities)

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12 pages, 3405 KiB

Open AccessArticle

A Fluorescent Coumarin-Based Probe for the Fast Detection of Cysteine with Live Cell Application

by Rui-Feng Zeng^1,†, Jin-Shuai Lan^2,†, Xiao-Die Li¹, Hui-Fen Liang¹, Yan Liao¹, Ying-Jie Lu¹, Tong Zhang^1,* and Yue Ding^2,*

¹ School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China

² Experiment Center of Teaching & Learning, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China

^† These authors contributed equally to this work.

Molecules 2017, 22(10), 1618; https://doi.org/10.3390/molecules22101618 - 26 Sep 2017

Cited by 18 | Viewed by 8170

Abstract

A new coumarin-based fluorescent probe, containing an allylic esters group, has been designed and synthesized for sensing cysteine in physiological pH. In this fluorescent probe, the coumarin was applied as the fluorophore and an allylic esters group was combined as both a fluorescence [...] Read more.

A new coumarin-based fluorescent probe, containing an allylic esters group, has been designed and synthesized for sensing cysteine in physiological pH. In this fluorescent probe, the coumarin was applied as the fluorophore and an allylic esters group was combined as both a fluorescence quencher and a recognition unit. The probe can selectively and sensitively detect cysteine (Cys) over homocysteine, glutathione, and other amino acids, and has a rapid response time of 30 min and a low detection limit of 47.7 nM. In addition, the probe could be applied for cell imaging with low cytotoxicity. Full article

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8 pages, 2284 KiB

Open AccessArticle

NMR Detection of Semi-Specific Antibody Interactions in Serum Environments

by Saeko Yanaka^1,2, Toshio Yamazaki³, Rina Yogo^1,2, Masanori Noda^4,5, Susumu Uchiyama⁴, Hirokazu Yagi² and Koichi Kato^1,2,*

¹ Institute for Molecular Science and Okazaki Institute for Integrative Bioscience, National Institutes of Natural Sciences, 5-1 Higashiyama, Myodaiji, Okazaki 444-8787, Japan

² Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya 467-8603, Japan

³ NMR Facility, Division of Structural and Synthetic Biology, Center for Life Science Technologies, RIKEN, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama City, Kanagawa 230-0045, Japan

⁴ Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka, 565-0871 Japan

⁵ U-Medico Inc., 2-1 Yamadaoka, Suita, Osaka 565-0871, Japan

Molecules 2017, 22(10), 1619; https://doi.org/10.3390/molecules22101619 - 27 Sep 2017

Cited by 13 | Viewed by 6312

Abstract

Although antibody functions are executed in heterogeneous blood streams characterized by molecular crowding and promiscuous intermolecular interaction, detailed structural characterizations of antibody interactions have thus far been performed under homogeneous in vitro conditions. NMR spectroscopy potentially has the ability to study protein structures [...] Read more.

Although antibody functions are executed in heterogeneous blood streams characterized by molecular crowding and promiscuous intermolecular interaction, detailed structural characterizations of antibody interactions have thus far been performed under homogeneous in vitro conditions. NMR spectroscopy potentially has the ability to study protein structures in heterogeneous environments, assuming that the target protein can be labeled with NMR-active isotopes. Based on our successful development of isotope labeling of antibody glycoproteins, here we apply NMR spectroscopy to characterize antibody interactions in heterogeneous extracellular environments using mouse IgG-Fc as a test molecule. In human serum, many of the HSQC peaks originating from the Fc backbone exhibited attenuation in intensity of various magnitudes. Similar spectral changes were induced by the Fab fragment of polyclonal IgG isolated from the serum, but not by serum albumin, indicating that a subset of antibodies reactive with mouse IgG-Fc exists in human serum without preimmunization. The metaepitopes recognized by serum polyclonal IgG cover the entire molecular surface of Fc, including the binding sites to Fc receptors and C1q. In-serum NMR observation will offer useful tools for the detailed characterization of biopharamaceuticals, including therapeutic antibodies in physiologically relevant heterogeneous environments, also giving deeper insight into molecular recognition by polyclonal antibodies in the immune system. Full article

(This article belongs to the Special Issue Recent Advances in Biomolecular NMR Spectroscopy)

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13 pages, 1438 KiB

Open AccessArticle

Time-Dependent Antimicrobial Activity of Filtering Nonwovens with Gemini Surfactant-Based Biocides

by Katarzyna Majchrzycka¹, Małgorzata Okrasa^1,*

, Justyna Szulc², Bogumił Brycki³ and Beata Gutarowska²

¹ Department of Personal Protective Equipment, Central Institute for Labour Protection—National Research Institute, Łódź 90-133, Poland

² Institute of Fermentation Technology and Microbiology, Lodz University of Technology, Łódź 90-924, Poland

³ Faculty of Chemistry, Adam Mickiewicz University in Poznań, Poznań 61-614, Poland

Molecules 2017, 22(10), 1620; https://doi.org/10.3390/molecules22101620 - 27 Sep 2017

Cited by 18 | Viewed by 5025

Abstract

Previous studies on nonwovens used for respiratory protective devices (RPDs) were related to equipment intended for short-term use. There is only limited research on the development of biocidal nonwoven fabrics for reusable RPDs that could be used safely in an industrial work environment [...] Read more.

Previous studies on nonwovens used for respiratory protective devices (RPDs) were related to equipment intended for short-term use. There is only limited research on the development of biocidal nonwoven fabrics for reusable RPDs that could be used safely in an industrial work environment where there is a risk of microbial growth. Moreover, a new group of biocides with high antimicrobial activity—gemini surfactants, has never been explored for textile’s application in previous studies. The aim of this study was to develop high-efficiency melt-blown nonwovens containing gemini surfactants with time-dependent biocidal activity, and to validate their antimicrobial properties under conditions simulating their use at a plant biomass-processing unit. A set of porous biocidal structures (SPBS) was prepared and applied to the melt-blown polypropylene (PP) nonwovens. The biocidal properties of the structures were triggered by humidity and had different activation rates. Scanning electron microscopy was used to undertake structural studies of the modified PP/SPBS nonwovens. In addition, simulation of plant biomass dust deposition on the nonwovens was performed. The biocidal activity of PP/SPBS nonwovens was evaluated following incubation with Escherichia coli and Aspergillus niger from the American Type Culture Collection, and with Pseudomonas fluorescens and Penicillium chrysogenum isolated from the biomass. PP/SPBS nonwovens exhibited antimicrobial activity to varying levels. Higher antimicrobial activity was noted for bacteria (R = 87.85–97.46%) and lower for moulds (R = 80.11–94.53%). Full article

(This article belongs to the Special Issue Antibacterial Materials and Coatings)

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23 pages, 3559 KiB

Open AccessReview

A Phytochemical-Sensing Strategy Based on Mass Spectrometry Imaging and Metabolic Profiling for Understanding the Functionality of the Medicinal Herb Green Tea

by Yoshinori Fujimura^*, Daisuke Miura^* and Hirofumi Tachibana

Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka 812-8581, Japan

Molecules 2017, 22(10), 1621; https://doi.org/10.3390/molecules22101621 - 27 Sep 2017

Cited by 13 | Viewed by 10082

Abstract

Low-molecular-weight phytochemicals have health benefits and reduce the risk of diseases, but the mechanisms underlying their activities have remained elusive because of the lack of a methodology that can easily visualize the exact behavior of such small molecules. Recently, we developed an in [...] Read more.

Low-molecular-weight phytochemicals have health benefits and reduce the risk of diseases, but the mechanisms underlying their activities have remained elusive because of the lack of a methodology that can easily visualize the exact behavior of such small molecules. Recently, we developed an in situ label-free imaging technique, called mass spectrometry imaging, for visualizing spatially-resolved biotransformations based on simultaneous mapping of the major bioactive green tea polyphenol and its phase II metabolites. In addition, we established a mass spectrometry-based metabolic profiling technique capable of evaluating the bioactivities of diverse green tea extracts, which contain multiple phytochemicals, by focusing on their compositional balances. This methodology allowed us to simultaneously evaluate the relative contributions of the multiple compounds present in a multicomponent system to its bioactivity. This review highlights small molecule-sensing techniques for visualizing the complex behaviors of herbal components and linking such information to an enhanced understanding of the functionalities of multicomponent medicinal herbs. Full article

(This article belongs to the Collection Phytochemicals: Biosynthesis, Metabolism and Biological Activities)

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18 pages, 1746 KiB

Open AccessArticle

DPPH Radical Scavenging and Postprandial Hyperglycemia Inhibition Activities and Flavonoid Composition Analysis of Hawk Tea by UPLC-DAD and UPLC-Q/TOF MS^E

by Xuan Xiao¹

, Lijia Xu¹, Huagang Hu², Yinjun Yang¹, Xinyao Zhang¹, Yong Peng^1,* and Peigen Xiao^1,*

¹ Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China

² Beijing Xiaotangshan Hospital, Xiaotangshan town, Beijing 102211, China

Molecules 2017, 22(10), 1622; https://doi.org/10.3390/molecules22101622 - 13 Oct 2017

Cited by 26 | Viewed by 5851

Abstract

Hawk tea (Litsea coreana Lévl. var. Lanuginosa (Migo) Yen C. Yang & P.H. Huang), a very popular herbal tea material, has attracted more and more attention due to its high antioxidant properties and possible therapeutic effect on type II diabetes mellitus. The [...] Read more.

Hawk tea (Litsea coreana Lévl. var. Lanuginosa (Migo) Yen C. Yang & P.H. Huang), a very popular herbal tea material, has attracted more and more attention due to its high antioxidant properties and possible therapeutic effect on type II diabetes mellitus. The raw materials of Hawk tea are usually divided into three kinds: bud tea (BT), primary leaf tea (PLT) and mature leaf tea (MLT). In this study, the DPPH radical scavenging activity and the antimicrobial properties of these three kinds of Hawk tea from different regions were comparatively investigated, and a ultra-high performance liquid chromatographic coupled with a photodiode array detector (UPLC-DAD) method was employed for comparison of the three major flavonoid constituents, including hyperoside, isoquercitrin and astragalin, in different samples of Hawk tea. At the same time, the effect of methanol extract (ME) of PLT on the mouse postprandial blood glucose and the effect of ME and its different fractions (petroleum ether fraction (PE), ethyl acetate fraction (EA), n-butanol fraction (n-BuOH), and water fraction (WF)) on the activity of α-glucosidase were studied. The results showed that Hawk BT and Hawk PLT possessed the higher radicals scavenging activity than Hawk MLT, while the antibacterial activity against P. vulgaris of PLT and MLT was higher than Hawk BT. The contents of the three major flavonoid constituents in samples of Hawk PLT are higher than Hawk BT and Hawk MLT. The mouse postprandial blood glucose levels of the middle dose (0.5 g/kg) group and the high dose (1 g/kg) group with oral administration of the ME of PLT were significantly lower than the control group. What’s more, the inhibitory effect of ME of PLT and its EA and n-BuOH fractions on α-glucosidase was significantly higher than that of acarbose. Rapid ultra-high performance liquid chromatography/quadrupole time-of-flight-mass spectrometry (UPLC-ESI-QTOF-MS) was used to identify the flavonoids in Hawk PLT, and a total of 20 flavonoids were identified or tentatively identified by comparing their retention times and accurate mass measurements with reference compounds or literature data. The bioactive flavonoid composition and DPPH radical scavenging activities present in different Hawk tea raw materials are quite different due to the different ontogenesis of these raw materials. Further studies on PLT showed that the substances in PLT ME could reduce the level of mouse postprandial blood glucose through inhibiting the activity of α-glucosidase. Full article

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16 pages, 774 KiB

Open AccessArticle

Effect of Cadmium and Copper Exposure on Growth, Secondary Metabolites and Antioxidant Activity in the Medicinal Plant Sambung Nyawa (Gynura procumbens (Lour.) Merr)

by Mohd Hafiz Ibrahim^1,*, Yap Chee Kong¹

and Nurul Amalina Mohd Zain^2,*

¹ Department of Biology, Faculty of Science, Universiti Putra Malaysia, UPM Serdang, Selangor Darul Ehsan 43400, Malaysia

² Department of Biology, Institute of Biological Science, Faculty of Science, University Malaya, Kuala Lumpur 50603, Malaysia

Molecules 2017, 22(10), 1623; https://doi.org/10.3390/molecules22101623 - 12 Oct 2017

Cited by 122 | Viewed by 9363

Abstract

A randomized complete block (RCBD) study was designed to investigate the effects of cadmium (Cd) and copper (Cu) on the growth, bioaccumulation of the two heavy metals, metabolite content and antibacterial activities in Gyanura procumbens (Lour.) Merr. Nine treatments including (1) control (no [...] Read more.

A randomized complete block (RCBD) study was designed to investigate the effects of cadmium (Cd) and copper (Cu) on the growth, bioaccumulation of the two heavy metals, metabolite content and antibacterial activities in Gyanura procumbens (Lour.) Merr. Nine treatments including (1) control (no Cd and Cu); (2) Cd 2 = cadmium 2 mg/L; (3) Cd 4 = cadmium 4 mg/L; (4) Cu 70 = copper 70 mg/L; (5) Cu 140 = copper 140 mg/L); (6) Cd 2 + Cu 70 = cadmium 2 mg/L + copper 70 mg/L); (7) Cd 2 + Cu 140 = cadmium 2 mg/L + copper 70 mg/L); (8) Cd 4 + Cu 70 = cadmium 4 mg/L+ copper 70 mg/L and (9) Cd 4 + Cu 140 = cadmium 4 mg/L + copper 140 mg/L) were evaluated in this experiment. It was found that the growth parameters (plant dry weight, total leaf area and basal diameter) were reduced with the exposure to increased concentrations of Cd and Cu and further decreased under interaction between Cd and Cu. Production of total phenolics, flavonoids and saponin was observed to be reduced under combined Cd and Cu treatment. The reduction in the production of plant secondary metabolites might be due to lower phenyl alanine lyase (PAL) activity under these conditions. Due to that, the 1,1-diphenyl-2-picrylhydrazyl (DPPH), ferric reducing antioxidant potential (FRAP) and antibacterial activities was also found to be reduced by the combined treatments. The current experiments show that the medicinal properties of G. procumbens are reduced by cadmium and copper contamination. The accumulation of heavy metal also was found to be higher than the safety level recommended by the WHO in the single and combined treatments of Cd and Cu. These results indicate that exposure of G. procumbens to Cd and Cu contaminated soil may potentially harm consumers due to bioaccumulation of metals and reduced efficacy of the herbal product. Full article

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11 pages, 1230 KiB

Open AccessArticle

Design, Synthesis, and Antitumor Activity of Novel Quinazoline Derivatives

by Liuchang Wang¹

, Pengna Li^1,*, Baolin Li², Yawen Wang³, Jiangtao Li¹ and Limei Song¹

¹ School of Chemical Engineering, The Key Laboratory for Surface Engineering and Remanufacturing in Shaanxi Province, Xi’an University, Xi’an 710065, China

² School of Chemistry and Chemical Engineering, Shaanxi Normal University, Xi’an 710062, China

³ College of Chemistry and Chemical Engineering, Taiyuan University of Technology, Taiyuan 030024, China

Molecules 2017, 22(10), 1624; https://doi.org/10.3390/molecules22101624 - 28 Sep 2017

Cited by 8 | Viewed by 5288

Abstract

In an attempt to explore a new class of epidermal growth factor receptor (EGFR) inhibitors, novel 4-stilbenylamino quinazoline derivatives were synthesized through a Dimorth rearrangement reaction and characterized via IR, ¹H-NMR, ¹³C-NMR, and HRMS. Methoxyl, methyl, halogen, and trifluoromethyl groups on [...] Read more.

In an attempt to explore a new class of epidermal growth factor receptor (EGFR) inhibitors, novel 4-stilbenylamino quinazoline derivatives were synthesized through a Dimorth rearrangement reaction and characterized via IR, ¹H-NMR, ¹³C-NMR, and HRMS. Methoxyl, methyl, halogen, and trifluoromethyl groups on stilbeneamino were detected. These synthesized compounds were evaluated for antitumor activity in vitro against eight human tumor cell lines with an MTS assay. Most synthesized compounds exhibited more potent activity (IC₅₀ = ~2.0 μM) than gefitinib (IC₅₀ > 10.0 μM) against the A431, A549, and BGC-823 cell lines. Docking methodology of compound 6c and 6i binding into the ATP site of EGFR was carried out. The results showed that fluorine and trifluoromethyl played an important role in efficient cell activity. Full article

(This article belongs to the Section Bioorganic Chemistry)

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11 pages, 3263 KiB

Open AccessArticle

Valorization of Lignin by Partial Wet Oxidation Using Sustainable Heteropoly Acid Catalysts

by Abayneh Getachew Demesa^1,*

, Arto Laari¹, Mika Sillanpää² and Tuomas Koiranen¹

¹ Laboratory of Process and Product Development, LUT School of Engineering Science, Lappeenranta University of Technology, Skinnarilankatu 34, FI-53850 Lappeenranta, Finland

² Laboratory of Green Chemistry, LUT School of Engineering Science, Lappeenranta University of Technology, Sammonkatu 12, FI-50130 Mikkeli, Finland

Molecules 2017, 22(10), 1625; https://doi.org/10.3390/molecules22101625 - 28 Sep 2017

Cited by 30 | Viewed by 6378

Abstract

The production of carboxylic acids by partial wet oxidation of alkali lignin at elevated temperatures and pressures was studied experimentally. Two different heteropoly acids, phosphotungstic acid (H₃PW₁₂O₄₀) and phosphomolybdic acid (H₃PMo₁₂O₄₀), [...] Read more.

The production of carboxylic acids by partial wet oxidation of alkali lignin at elevated temperatures and pressures was studied experimentally. Two different heteropoly acids, phosphotungstic acid (H₃PW₁₂O₄₀) and phosphomolybdic acid (H₃PMo₁₂O₄₀), were used to catalyze the oxidation of lignin under hydrothermal conditions. Factors influencing the total yield of carboxylic acids formed during the partial oxidation of lignin were investigated. Formic, acetic and succinic acids were the major products identified. Of the two catalysts used, phosphomolybdic acid gave the most promising results, with carboxylic acid yields and lignin conversions of up to 45% and 95%, respectively. Full article

(This article belongs to the Special Issue Lignin for Energy, Chemicals and Materials)

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13 pages, 2938 KiB

Open AccessArticle

Anticarcinogenic Effect of Spices Due to Phenolic and Flavonoid Compounds—In Vitro Evaluation on Prostate Cells

by Zuzana Lackova^1,2, Hana Buchtelova^1,2, Zaneta Buchtova¹, Borivoj Klejdus¹, Zbynek Heger^1,2, Martin Brtnicky^2,3

, Jindrich Kynicky^2,3, Ondrej Zitka^1,2 and Vojtech Adam^1,2,*

¹ Department of Chemistry and Biochemistry, Mendel University in Brno, Zemedelska 1, Brno CZ-613 00, Czech Republic

² Central European Institute of Technology, Brno University of Technology, Technicka 3058/10, Brno CZ-616 00, Czech Republic

³ Department of Geology and Pedology, Mendel University in Brno, Zemedelska 1, Brno CZ-613 00, Czech Republic

Molecules 2017, 22(10), 1626; https://doi.org/10.3390/molecules22101626 - 28 Sep 2017

Cited by 12 | Viewed by 7250

Abstract

This study shows the effects of spices, and their phenolic and flavonoid compounds, on prostate cell lines (PNT1A, 22RV1 and PC3). The results of an MTT assay on extracts from eight spices revealed the strongest inhibitory effects were from black pepper and caraway [...] Read more.

This study shows the effects of spices, and their phenolic and flavonoid compounds, on prostate cell lines (PNT1A, 22RV1 and PC3). The results of an MTT assay on extracts from eight spices revealed the strongest inhibitory effects were from black pepper and caraway seed extracts. The strongest inhibitory effect on prostatic cells was observed after the application of extracts of spices in concentration of 12.5 mg·mL⁻¹. An LC/MS analysis identified that the most abundant phenolic and flavonoid compounds in black pepper are 3,4-dihydroxybenzaldehyde and naringenin chalcone, while the most abundant phenolic and flavonoid compounds in caraway seeds are neochlorogenic acid and apigenin. Using an MTT assay for the phenolic and flavonoid compounds from spices, we identified the IC₅₀ value of ~1 mmol·L⁻¹ PNT1A. The scratch test demonstrated that the most potent inhibitory effect on PNT1A, 22RV1 and PC3 cells is from the naringenin chalcone contained in black pepper. From the spectrum of compounds assessed, the naringenin chalcone contained in black pepper was identified as the most potent inhibitor of the growth of prostate cells. Full article

(This article belongs to the Collection Efficient Pharmaceutical and Chemical Approaches for Anticancer Therapy: Design, Preliminary Evaluations, and Further Developments)

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12 pages, 2387 KiB

Open AccessArticle

Intestinal Absorption of Triterpenoids and Flavonoids from Glycyrrhizae radix et rhizoma in the Human Caco-2 Monolayer Cell Model

by Xiao-Xue Wang^1,2, Gui-Yan Liu^1,*, Yan-Fang Yang², Xiu-Wen Wu², Wei Xu² and Xiu-Wei Yang^2,*

¹ School of Life Science and Technology, Beijing Institute of Technology, No. 5, Zhongguancun South Street, Haidian District, Beijing 100081, China

² State Key Laboratory of Natural and Biomimetic Drugs, Department of Natural Medicines, School of Pharmaceutical Sciences, Peking University Health Science Center, Peking University, No. 38, Xueyuan Road, Haidian District, Beijing 100191, China

Molecules 2017, 22(10), 1627; https://doi.org/10.3390/molecules22101627 - 29 Sep 2017

Cited by 38 | Viewed by 6045

Abstract

Glycyrrhizae radix et rhizoma has been used as a traditional Chinese medicine for the treatment of various diseases. Triterpenoids and flavonoids from the plant have many beneficial effects and their chemical structures are modified in the gastrointestinal tract after oral administration. However, absorption [...] Read more.

Glycyrrhizae radix et rhizoma has been used as a traditional Chinese medicine for the treatment of various diseases. Triterpenoids and flavonoids from the plant have many beneficial effects and their chemical structures are modified in the gastrointestinal tract after oral administration. However, absorption of these triterpenoids and flavonoids still needs to be defined. Here, the uptake and transepithelial transport of the selected major triterpenoids, glycyrrhizin (1), glycyrrhetic acid-3-O-mono-β-d-glucuronide (2), and glycyrrhetinic acid (3); and the selected major flavonoids, licochalcone A (4), licochalcone B (5), licochalcone C (6), echinatin (7), isoliquiritin apioside (8), liquiritigenin (9), liquiritin apioside (10) isolated from Glycyrrhizae radix et rhizoma, were investigated in the human intestinal epithelium-like Caco-2 cell monolayer model. Compounds 3, 5–7, and 9 were designated as well-absorbed compounds, 2 and 4 were designated as moderately absorbed ones, and 1, 8, and 10 were assigned for the poorly absorbed ones. The absorption mechanism of well and moderately absorbed compound was mainly passive diffusion to pass through the human intestinal Caco-2 cell monolayer. These findings provided useful information for predicting their oral bioavailability and the clinical application. Full article

(This article belongs to the Collection Herbal Medicine Research)

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17 pages, 1070 KiB

Open AccessArticle

Ionic Liquid-Catalyzed Green Protocol for Multi-Component Synthesis of Dihydropyrano[2,3-c]pyrazoles as Potential Anticancer Scaffolds

by Urja D. Nimbalkar¹, Julio A. Seijas²

, Maria Pilar Vazquez-Tato², Manoj G. Damale³, Jaiprakash N. Sangshetti⁴ and Anna Pratima G. Nikalje^4,*

¹ Maulana Azad Post Graduate and Research Centre, Dr. Rafiq Zakaria Campus, Rauza Baug, Aurangabad 431001, India

² Departamento de Química Orgánica, Facultad de Ciencias, Universidad of Santiago de Compostela, Alfonso X el Sabio, 27002 Lugo, Spain

³ Shreeyash Institute of Pharmaceutical Education and Research, Aurangabad 431010, India

⁴ Y.B. Chavan College of Pharmacy, Dr. Rafiq Zakaria Campus, Rauza Baug, Aurangabad 431001, India

Molecules 2017, 22(10), 1628; https://doi.org/10.3390/molecules22101628 - 28 Sep 2017

Cited by 40 | Viewed by 7288

Abstract

A series of 6-amino-4-substituted-3-methyl-2,4-dihydropyrano[2,3-c]pyrazole-5-carbonitriles 5a–j were synthesized via one-pot, four-component condensation reactions of aryl aldehydes 1a–j, propanedinitrile (2), hydrazine hydrate (3) and ethyl acetoacetate (4) under solvent-free conditions. We report [...] Read more.

A series of 6-amino-4-substituted-3-methyl-2,4-dihydropyrano[2,3-c]pyrazole-5-carbonitriles 5a–j were synthesized via one-pot, four-component condensation reactions of aryl aldehydes 1a–j, propanedinitrile (2), hydrazine hydrate (3) and ethyl acetoacetate (4) under solvent-free conditions. We report herein the use of the Brønsted acid ionic liquid (BAIL) triethylammonium hydrogen sulphate [Et₃NH][HSO₄] as catalyst for this multi-component synthesis. Compared with the available reaction methodology, this new method has consistent advantages, including excellent yields, a short reaction time, mild reaction conditions and catalyst reusability. Selected synthesized derivatives were evaluated for in vitro anticancer activity against four human cancer cell lines viz. melanoma cancer cell line (SK-MEL-2), breast cancer cell line(MDA-MB-231), leukemia cancer cell line (K-562) and cervical cancer cell line (HeLa). Compounds 5b, 5d, 5g, 5h and 5j exhibited promising anticancer activity against all selected human cancer cell lines, except HeLa. Molecular docking studies also confirmed 5b and 5d as good lead molecules. An in silico ADMET study of the synthesized anticancer agents indicated good oral drug-like behavior and non-toxic nature. Full article

(This article belongs to the Special Issue ECSOC-20)

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14 pages, 9875 KiB

Open AccessArticle

Predicting the Global Potential Distribution of Four Endangered Panax Species in Middle-and Low-Latitude Regions of China by the Geographic Information System for Global Medicinal Plants (GMPGIS)

by Zhixia Du¹, Jie Wu², Xiangxiao Meng², Jinhua Li¹ and Linfang Huang^1,*

¹ Institute of Medicinal Plant Development (IMPLAD), Chinese Academy of Medical Sciences (CAMS), Peking Union Medical College (PUMC), Beijing 100193, China

² Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China

Molecules 2017, 22(10), 1630; https://doi.org/10.3390/molecules22101630 - 28 Sep 2017

Cited by 18 | Viewed by 6886

Abstract

Global biodiversity is strongly influenced by the decrease in endangered biological species. Predicting the distribution of endangered medicinal plants is necessary for resource conservation. A spatial distribution model—geographic information system for global medicinal plants (GMPGIS)—is used to predict the global potential suitable distribution [...] Read more.

Global biodiversity is strongly influenced by the decrease in endangered biological species. Predicting the distribution of endangered medicinal plants is necessary for resource conservation. A spatial distribution model—geographic information system for global medicinal plants (GMPGIS)—is used to predict the global potential suitable distribution of four endangered Panax species, including Panax japonicas (T. Nees) C. A. Meyer and Panax japonicas var. major (Burkill) C. Y. Wu & K. M. Feng distributed in low- and middle-latitude, Panax zingiberensis C. Y. Wu & K. M. Feng and Panax stipuleanatus C. T. Tsai & K. M. Feng in low-latitude regions of China based on seven bioclimatic variables and 600 occurrence points. Results indicate that areas of P. japonicus and P. japonicus var. major are 266.29 × 10⁵ and 77.5 × 10⁵ km², respectively, which are mainly distributed in China and America. By contrast, the areas of P. zingiberensis and P. stipuleanatus are 5.09 × 10⁵ and 2.05 × 10⁵ km², respectively, which are mainly distributed in Brazil and China. P. japonicus has the widest distribution among the four species. The data also indicate that the mean temperature of coldest quarter is the most critical factor. This scientific prediction can be used as reference for resource conservation of endangered plants and as a guide to search for endangered species in previously unknown areas. Full article

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12 pages, 1893 KiB

Open AccessArticle

Characterization and Trypanocidal Activity of a Novel Pyranaphthoquinone

by Elen Diana Dantas¹, Fabia Julliana Jorge De Souza¹, William Nascimento Litaiff Nogueira¹, Cláudia Cândida Silva², Pedro Henrique Antunes De Azevedo¹, Cícero Flávio Soares Aragão¹

, Patricia Danielle Oliveira de Almeida³, Mariana Filomena do Carmo Cardoso⁴

, Fernando De Carvalho Da Silva⁴

, Eduardo Pereira De Azevedo⁵, Euzébio Guimarães Barbosa¹, Emerson Silva Lima³

, Vitor Francisco Ferreira⁴ and Ádley Antonini Neves de Lima^1,*

¹ Pharmacy Department, Health Sciences Center, Universidade Federal do Rio Grande do Norte (UFRN), Natal RN 59012-570, Brazil

² Crowfoot Group of X-ray Techniques, Universidade Estadual do Amazonas (UEA), Manaus AM 69065-020, Brazil

³ Biological Activities Laboratory, Universidade Federal do Amazonas (UFAM), Pharmaceutical Sciences, Manaus AM 69080-900, Brazil

⁴ Laboratory of Synthesis of Bioactive Molecules, Organic Chemistry Department, Universidade Federal Fluminense (UFF), Niterói RJ 24020-141, Brazil

⁵ Graduate Program in Biotechnology, Laureate International Universities—Universidade Potiguar (UnP), Natal RN 59056-000, Brazil

Molecules 2017, 22(10), 1631; https://doi.org/10.3390/molecules22101631 - 30 Sep 2017

Cited by 12 | Viewed by 4838

Abstract

Chagas disease is an endemic parasitic infection that occurs in 21 Latin American countries. New therapies for this disease are urgently needed, as the only two drugs available (nifurtimox and benznidazol) have high toxicity and variable efficacy in the disease’s chronic phase. Recently, [...] Read more.

Chagas disease is an endemic parasitic infection that occurs in 21 Latin American countries. New therapies for this disease are urgently needed, as the only two drugs available (nifurtimox and benznidazol) have high toxicity and variable efficacy in the disease’s chronic phase. Recently, a new chemical entity (NCE) named Pyranaphthoquinone (IVS320) was synthesized from lawsone. We report herein, a detailed study of the physicochemical properties and in vitro trypanocidal activity of IVS320. A series of assays were performed for characterization, where thermal, diffractometric, and morphological analysis were performed. In addition, the solubility, permeability, and hygroscopicity of IVS320 were determined. The results show that its poor solubility and low permeability may be due to its high degree of crystallinity (99.19%), which might require the use of proper techniques to increase the IVS320’s aqueous solubility and permeability. The trypanocidal activity study demonstrated that IVS320 is more potent than the reference drug benznidazole, with IC50/24 h of 1.49 ± 0.1 μM, which indicates that IVS320 has potential as a new drug candidate for the treatment of Chagas disease. Full article

(This article belongs to the Special Issue From Bioactive Compounds to New Drugs: Commemorative Issue Dedicated to Professor Ernesto Fattorusso (1937-2012))

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9 pages, 712 KiB

Open AccessCommunication

Investigation of the N-Terminus Amino Function of Arg₁₀-Teixobactin

by Shimaa A. H. Abdel Monaim¹, Sikabwe Noki¹, Estelle J. Ramchuran¹, Ayman El-Faham^2,3

, Fernando Albericio^1,2,4,5,6,*

and Beatriz G. de la Torre^1,7,*

¹ Catalysis and Peptide Research Unit, School of Health Sciences, University of KwaZulu-Natal, Durban 4001, South Africa

² Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia

³ Chemistry Department, Faculty of Science, Alexandria University, P.O. Box 426, Ibrahimia, Alexandria 12321, Egypt

⁴ School of Chemistry and Physics, University of KwaZulu-Natal, Durban 4001, South Africa

⁵ Department of Organic Chemistry, University of Barcelona, Barcelona 08028, Spain

⁶ CIBER-BBN, Networking Centre on Bioengineering, Biomaterials and Nanomedicine, Barcelona Science Park, Barcelona 08028, Spain

⁷ KRISP, College of Health Sciences, University of KwaZulu-Natal, Durban 4001, South Africa

Molecules 2017, 22(10), 1632; https://doi.org/10.3390/molecules22101632 - 28 Sep 2017

Cited by 22 | Viewed by 6029

Abstract

Teixobactin is a recently described antimicrobial peptide that shows high activity against gram-positive bacteria as well as mycobacterium tuberculosis. Due to both its structure as a head-to-side chain cyclodepsipeptide and its activity, it has attracted the attention of several research groups. In [...] Read more.

Teixobactin is a recently described antimicrobial peptide that shows high activity against gram-positive bacteria as well as mycobacterium tuberculosis. Due to both its structure as a head-to-side chain cyclodepsipeptide and its activity, it has attracted the attention of several research groups. In this regard, a large number of analogs with substitutions in both the cycle and the tail has been described. Here, we report the contribution of the N-terminus residue, N-Me-d-Phe, to the activity of Arg₁₀-teixobactin. On the basis of our findings, we conclude that the N-terminus accepts minimum changes but not the presence of long alkyl chains. The presence of a positive charge is a requirement for the activity of the peptide. Furthermore, acylation of the N-terminus leads to total loss of activity. Full article

(This article belongs to the Special Issue Peptide Therapeutics)

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14 pages, 805 KiB

Open AccessArticle

Profiles of Volatile Flavor Compounds in Milk Fermented with Different Proportional Combinations of Lactobacillus delbrueckii subsp. bulgaricus and Streptococcus thermophilus

by Tong Dan, Dan Wang

, Shimei Wu, Rulin Jin, Weiyi Ren and Tiansong Sun^*

Key Laboratory of Dairy Biotechnology and Engineering, Ministry of Education, Inner Mongolia Agricultural University, Hohhot 010018, China

Molecules 2017, 22(10), 1633; https://doi.org/10.3390/molecules22101633 - 29 Sep 2017

Cited by 98 | Viewed by 8157

Abstract

Lactobacillus delbrueckii subsp. bulgaricus and Streptococcus thermophilus are key factors in the fermentation process and the final quality of dairy products worldwide. This study was performed to investigate the effects of the proportions of Lactobacillus delbrueckii subsp. bulgaricus and Streptococcus thermophilus isolated from [...] Read more.

Lactobacillus delbrueckii subsp. bulgaricus and Streptococcus thermophilus are key factors in the fermentation process and the final quality of dairy products worldwide. This study was performed to investigate the effects of the proportions of Lactobacillus delbrueckii subsp. bulgaricus and Streptococcus thermophilus isolated from traditionally fermented dairy products in China and Mongolia on the profile of volatile compounds produced in samples. Six proportional combinations (1:1, 1:10, 1:50, 1:100, 1:1000, and 1:10,000) of L. delbrueckii subsp. bulgaricus IMAU20401 to S. thermophilus ND03 were considered, and the volatiles were identified and quantified by solid-phase microextraction and gas chromatography–mass spectrometry (SPME-GC-MS) against an internal standard. In total, 89 volatile flavor compounds, consisting of aldehydes, ketones, acids, alcohols, esters, and aromatic hydrocarbons, were identified. Among these, some key flavor volatile compounds were identified, including acetaldehyde, 3-methylbutanal, acetoin, 2-heptanone, acetic acid, butanoic acid, and 3-methyl-1-butanol. The of L. delbrueckii subsp. bulgaricus IMAU20401 to S. thermophilus ND03 influenced the type and concentration of volatiles produced. In particular, aldehydes and ketones were present at higher concentrations in the 1:1000 treatment combination than in the other combinations. Our findings emphasize the importance of selecting the appropriate proportions of L. delbrueckii subsp. bulgaricus and S. thermophilus for the starter culture in determining the final profile of volatiles and the overall flavor of dairy products. Full article

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14 pages, 789 KiB

Open AccessFeature PaperArticle

Halogen Bonds Formed between Substituted Imidazoliums and N Bases of Varying N-Hybridization

by Steve Scheiner

Department of Chemistry and Biochemistry, Utah State University, Logan, UT 84322-0300, USA

Molecules 2017, 22(10), 1634; https://doi.org/10.3390/molecules22101634 - 29 Sep 2017

Cited by 23 | Viewed by 5969

Abstract

Heterodimers are constructed containing imidazolium and its halogen-substituted derivatives as Lewis acid. N in its sp³, sp² and sp hybridizations is taken as the electron-donating base. The halogen bond is strengthened in the Cl < Br < I order, with [...] Read more.

Heterodimers are constructed containing imidazolium and its halogen-substituted derivatives as Lewis acid. N in its sp³, sp² and sp hybridizations is taken as the electron-donating base. The halogen bond is strengthened in the Cl < Br < I order, with the H-bond generally similar in magnitude to the Br-bond. Methyl substitution on the N electron donor enhances the binding energy. Very little perturbation arises if the imidazolium is attached to a phenyl ring. The energetics are not sensitive to the hybridization of the N atom. More regular patterns appear in the individual phenomena. Charge transfer diminishes uniformly on going from amine to imine to nitrile, a pattern that is echoed by the elongation of the C-Z (Z=H, Cl, Br, I) bond in the Lewis acid. These trends are also evident in the Atoms in Molecules topography of the electron density. Molecular electrostatic potentials are not entirely consistent with energetics. Although I of the Lewis acid engages in a stronger bond than does H, it is the potential of the latter which is much more positive. The minimum on the potential of the base is most negative for the nitrile even though acetonitrile does not form the strongest bonds. Placing the systems in dichloromethane solvent reduces the binding energies but leaves intact most of the trends observed in vacuo; the same can be said of ∆G in solution. Full article

(This article belongs to the Special Issue Halogen Bonds and Beyond)

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14 pages, 2562 KiB

Open AccessArticle

A New Series of Cytotoxic Pyrazoline Derivatives as Potential Anticancer Agents that Induce Cell Cycle Arrest and Apoptosis

by Hong Wang^1,†

, Jinhong Zheng^1,†, Weijie Xu¹

, Cheng Chen¹, Duncan Wei², Wenxiu Ni^1,* and Ying Pan^1,*

¹ Department of Chemistry, Shantou University Medical College, Shantou 515041, Guangdong, China

² Department of Pharmacy, The First Affiliated Hospital of Shantou University Medical College, Shantou 515041, Guangdong, China

^† These authors contributed equally to this work.

Molecules 2017, 22(10), 1635; https://doi.org/10.3390/molecules22101635 - 29 Sep 2017

Cited by 33 | Viewed by 5148

Abstract

A new series of pyrazoline derivatives 1b–12b was designed, synthesized and evaluated for antiproliferative activity against three cancer cell lines (HepG-2, Hela and A549). Additionally, NIH/3T3 cell cytotoxicity were tested and the structure activity relationships (SARs) were also determined. Among these [...] Read more.

A new series of pyrazoline derivatives 1b–12b was designed, synthesized and evaluated for antiproliferative activity against three cancer cell lines (HepG-2, Hela and A549). Additionally, NIH/3T3 cell cytotoxicity were tested and the structure activity relationships (SARs) were also determined. Among these new derivatives, the compounds 3-(4-fluorophenyl)-5-(3,4,5-trimethoxythiophenyl)-4,5-dihydro-1H-pyrazole-1-carbothioamide (1b) and 3-(4-chlorophenyl)-5-(3,4,5-trimethoxythiphenyl)-4,5-dihydro-1H-pyrazole-1-carbothioamide (2b) showed the best activity against HepG-2 cells, with IC₅₀ values of 6.78 μM and 16.02 μM, respectively. They also displayed potent activity against Hela cells; meanwhile, 3-(4-chlorophenyl)-5-(3-bromo-4-hydroxy-5-methoxythiophenyl)-4,5-dihydro-1H-pyrazole-1-carbothioamide (5b) and 3-(4-bromo-phenyl)-5-(3-bromo-4-hydroxy-5-methoxythiophenyl)-4,5-dihydro-1H-pyrazole-1-carbothioamide (6b) were also identified as promising anticancer agents against A549 cells owing to their notable inhibitory effect, compared with cisplatin (IC₅₀ = 29.48 μM). Furthermore, it was also found that compounds 1b and 2b had low cytotoxicity against NIH/3T3 cells and further mechanistic studies revealed that 1b arrested HepG-2 cells cycle at the G2/M phase at high concentrations and induced apoptosis in HepG-2 cells. Moreover, 1b upregulated protein expression level of cleaved caspase-3, cleaved PARP, Bax and p53 and downregulated protein expression level of Bcl-2 in dose-dependent way in HepG-2 cells. Thus, this study indicates that compound 1b might be a promising antitumor drug candidate. Full article

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30 pages, 7199 KiB

Open AccessFeature PaperReview

Non-Covalent Organocatalyzed Domino Reactions Involving Oxindoles: Recent Advances

by Tecla Gasperi^1,*

, Martina Miceli¹

, Jean-Marc Campagne²

and Renata Marcia de Figueiredo^2,*

¹ Dipartimento di Scienze, Sezione di Nanoscienze e Nanotecnologie, Università degli Studi Roma Tre, via della Vasca Navale 79, I-00146 Roma, Italy

² ICGM-Institut Charles Gerhardt Montpellier, UMR 5253 CNRS-UM-ENSCM, Ecole Nationale Supérieure de Chimie, 8, Rue de l’Ecole Normale, 34296 Montpellier CEDEX 5, France

Molecules 2017, 22(10), 1636; https://doi.org/10.3390/molecules22101636 - 29 Sep 2017

Cited by 25 | Viewed by 7233

Abstract

The ubiquitous presence of spirooxindole architectures with several functionalities and stereogenic centers in bioactive molecules has been appealing for the development of novel methodologies seeking their preparation in high yields and selectivities. Expansion and refinement in the field of asymmetric organocatalysis have made [...] Read more.

The ubiquitous presence of spirooxindole architectures with several functionalities and stereogenic centers in bioactive molecules has been appealing for the development of novel methodologies seeking their preparation in high yields and selectivities. Expansion and refinement in the field of asymmetric organocatalysis have made possible the development of straightforward strategies that address these two requisites. In this review, we illustrate the current state-of-the-art in the field of spirooxindole synthesis through the use of non-covalent organocatalysis. We aim to provide a concise overview of very recent methods that allow to the isolation of unique, densely and diversified spirocyclic oxindole derivatives with high structural diversity via the use of cascade, tandem and domino processes. Full article

(This article belongs to the Collection Recent Advances in Organocatalysis)

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12 pages, 4693 KiB

Open AccessArticle

Fabrication of Antimicrobial Peptide-Loaded PLGA/Chitosan Composite Microspheres for Long-Acting Bacterial Resistance

by Yuanyuan Li^1,2,3, Rongwei Na^1,2, Xiumei Wang^1,*

, Huiying Liu^2,*, Lingyun Zhao¹, Xiaodan Sun¹, Guowu Ma² and Fuzhai Cui¹

¹ State Key Laboratory of New Ceramic & Fine Processing, School of Materials Science and Engineering, Tsinghua University, Beijing 100084, China

² Department of Prosthodontics, School of Stomatology, Dalian Medical University, Dalian 116044, China

³ Department of Stomatology, Shengli Oil Field Central Hospital, Dongying 257034, China

Molecules 2017, 22(10), 1637; https://doi.org/10.3390/molecules22101637 - 29 Sep 2017

Cited by 54 | Viewed by 7511

Abstract

An antimicrobial decapeptide, KSL-W (KKVVFWVKFK-CONH₂), which could maintain stable antimicrobial activity in saliva, has therefore been widely used to inhibit biofilm formation on teeth and prevent the growth of oral microorganisms for related infectious diseases treatment. In order to control the [...] Read more.

An antimicrobial decapeptide, KSL-W (KKVVFWVKFK-CONH₂), which could maintain stable antimicrobial activity in saliva, has therefore been widely used to inhibit biofilm formation on teeth and prevent the growth of oral microorganisms for related infectious diseases treatment. In order to control the release of KSL-W for long-term bacterial resistance, KSL-W-loaded PLGA/chitosan composite microspheres (KSL/PLGA/CS MSs) were prepared by electrospraying and combined crosslinking-emulsion methods. Different formulations of microspheres were characterized as to surface morphology, size distribution, encapsulation efficiency, in vitro drug release, and antimicrobial activity. Antibacterial experiment demonstrated the prolonged antimicrobial and inhibitory effects of KSL/PLGA/CS MSs on oral bacteria. Moreover, the cell proliferation assay proved that the released KSL-W antibacterial dosage had no cytotoxicity to the growth of osteoblast MC3T3-E1. Thus, our study suggested that the KSL-W-loaded PLGA/CS composite microspheres may have potentially therapeutic applications as an effective drug delivery system in the treatment of oral infectious diseases such as periodontitis and periodontitis, and also within bone graft substitutes for alveolar bone augmentation. Full article

(This article belongs to the Special Issue Biomedical Applications of Polylactide (PLA) and its Copolymers)

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12 pages, 963 KiB

Open AccessArticle

Bioassay-Guided Isolated Compounds from Morinda officinalis Inhibit Alzheimer’s Disease Pathologies

by Yoon Kyoung Lee

, Hyo Jeong Bang, Jeong Bin Oh and Wan Kyunn Whang^*

Pharmaceutical Botany Laboratory, College of Pharmacy, Chung-Ang University, Heukseok-dong, Dongjak-gu, Seoul 151-756, Korea

Molecules 2017, 22(10), 1638; https://doi.org/10.3390/molecules22101638 - 29 Sep 2017

Cited by 37 | Viewed by 7084

Abstract

Due to the side effects of synthetic drugs, the therapeutic potential of natural products for Alzheimer’s disease (AD) has gained interest. Morinda officinalis has demonstrated inhibitory effects on geriatric diseases, such as bone loss and osteoporosis. However, although AD is a geriatric disease, [...] Read more.

Due to the side effects of synthetic drugs, the therapeutic potential of natural products for Alzheimer’s disease (AD) has gained interest. Morinda officinalis has demonstrated inhibitory effects on geriatric diseases, such as bone loss and osteoporosis. However, although AD is a geriatric disease, M. officinalis has not been evaluated in an AD bioassay. Therefore, M. officinalis extracts and fractions were tested for AD-related activity, including inhibition of acetylcholinesterase (AChE), butyrylcholinesterase (BChE), β-site amyloid precursor protein cleaving enzyme 1 (BACE1), and advanced glycation end-product (AGE) formation. A bioassay-guided approach led to isolation of 10 active compounds, eight anthraquinones (1–8), one coumarin (9), and one phytosterol (10), from n-hexane and ethyl acetate fractions of M. officinalis. The five anthraquinones (4–8) were stronger inhibitors of AChE than were other compounds. Compounds 3 and 9 were good inhibitors of BChE, and compounds 3 and 8 were good inhibitors of BACE1. Compounds 1–5 and 7–9 were more active than the positive control in inhibiting AGE formation. In addition, we first suggested a structure-activity relationship by which anthraquinones inhibit AChE and BACE1. Our findings demonstrate the preventive and therapeutic efficacy of M. officinalis for AD and its potential use as a natural alternative medicine. Full article

(This article belongs to the Collection Bioactive Compounds)

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14 pages, 5665 KiB

Open AccessArticle

N-(4-bromophenethyl) Caffeamide Protects Skin from UVB-Induced Inflammation Through MAPK/IL-6/NF-κB-Dependent Signaling in Human Skin Fibroblasts and Hairless Mouse Skin

by Yueh-Hsiung Kuo^1,2,†

, Po-Yuan Wu^3,4,†, Chien-Wen Chen⁵, Ping Lin⁵, Kuo-Ching Wen⁵, Chien-Yih Lin² and Hsiu-Mei Chiang^5,*

¹ Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, China Medical University, Taichung 404, Taiwan

² Department of Biotechnology, Asia University, Taichung 413, Taiwan

³ Department of Dermatology, China Medical University Hospital, Taichung 404, Taiwan

⁴ School of Medicine, China Medical University, Taichung 404, Taiwan

⁵ Department of Cosmeceutics, China Medical University, Taichung 404, Taiwan

^† These two authors contribute equally to this work.

Molecules 2017, 22(10), 1639; https://doi.org/10.3390/molecules22101639 - 29 Sep 2017

Cited by 10 | Viewed by 5628

Abstract

Long-term exposure to ultraviolet (UV) irradiation causes skin inflammation and aging. N-(4-bromophenethyl) caffeamide (K36H) possesses antioxidant and antimelanogenic properties. The present study investigated the effects of K36H on UVB-induced skin inflammation in human skin fibroblasts and hairless mice and evaluated the underlying [...] Read more.

Long-term exposure to ultraviolet (UV) irradiation causes skin inflammation and aging. N-(4-bromophenethyl) caffeamide (K36H) possesses antioxidant and antimelanogenic properties. The present study investigated the effects of K36H on UVB-induced skin inflammation in human skin fibroblasts and hairless mice and evaluated the underlying mechanisms. The in vitro results indicated that K36H reduced UVB-induced mitogen-activated protein kinase (MAP kinase) expression. Furthermore, K36H treatment reduced cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) protein expression in UVB-irradiated fibroblasts by regulating IκB and nuclear factor-kappa B (NF-κB) expression. In the animal study, topically applied K36H markedly reduced inflammation and skin thickness and prevented photodamage to the skin of hairless mice. In addition, K36H inhibited the levels of UV-upregulated inflammation-related proteins levels such as IL-1, iNOS, and NF-κB in the dermis of hairless mice. Our findings demonstrated the antioxidant and anti-inflammatory properties of K36H in human skin fibroblasts and hairless mice. Therefore, K36H can be developed as an antiphotodamage and antiphotoinflammation agent. Full article

(This article belongs to the Special Issue Anti-inflammatory Agents)

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16 pages, 2594 KiB

Open AccessFeature PaperReview

Fluorescence Resonance Energy Transfer Systems in Supramolecular Macrocyclic Chemistry

by Xin-Yue Lou, Nan Song and Ying-Wei Yang^*

International Joint Research Laboratory of Nano-Micro Architecture Chemistry (NMAC), College of Chemistry, Jilin University, 2699 Qianjin Street, Changchun 130012, China

Molecules 2017, 22(10), 1640; https://doi.org/10.3390/molecules22101640 - 29 Sep 2017

Cited by 46 | Viewed by 11538

Abstract

The fabrication of smart materials is gradually becoming a research focus in nanotechnology and materials science. An important criterion of smart materials is the capacity of stimuli-responsiveness, while another lies in selective recognition. Accordingly, supramolecular host-guest chemistry has proven a promising support for [...] Read more.

The fabrication of smart materials is gradually becoming a research focus in nanotechnology and materials science. An important criterion of smart materials is the capacity of stimuli-responsiveness, while another lies in selective recognition. Accordingly, supramolecular host-guest chemistry has proven a promising support for building intelligent, responsive systems; hence, synthetic macrocyclic hosts, such as calixarenes, cucurbiturils, cyclodextrins, and pillararenes, have been used as ideal building blocks. Meanwhile, manipulating and harnessing light artificially is always an intensive attempt for scientists in order to meet the urgent demands of technological developments. Fluorescence resonance energy transfer (FRET), known as a well-studied luminescent activity and also a powerful tool in spectroscopic area, has been investigated from various facets, of which the application range has been broadly expanded. In this review, the innovative collaboration between FRET and supramolecular macrocyclic chemistry will be presented and depicted with typical examples. Facilitated by the dynamic features of supramolecular macrocyclic motifs, a large variety of FRET systems have been designed and organized, resulting in promising optical materials with potential for applications in protein assembly, enzyme assays, diagnosis, drug delivery monitoring, sensing, photosynthesis mimicking and chemical encryption. Full article

(This article belongs to the Special Issue Calixarenes, Pillararenes, and Cucurbiturils)

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11 pages, 1049 KiB

Open AccessArticle

Antibacterial Synthetic Peptides Derived from Bovine Lactoferricin Exhibit Cytotoxic Effect against MDA-MB-468 and MDA-MB-231 Breast Cancer Cell Lines

by Yerly Vargas Casanova^1,†, Jorge Antonio Rodríguez Guerra^2,†, Yadi Adriana Umaña Pérez³, Aura Lucía Leal Castro⁴, Giovanni Almanzar Reina⁵, Javier Eduardo García Castañeda² and Zuly Jenny Rivera Monroy^3,*

¹ Biotechnology Institute, Universidad Nacional de Colombia, Carrera 45 No 26-85, 11321 Bogotá, Colombia

² Pharmacy Department, Universidad Nacional de Colombia, Carrera 45 No 26-85, Building 450, Office 213, 11321 Bogotá, Colombia

³ Chemistry Department, Universidad Nacional de Colombia, Carrera 45 No 26-85, Building 450, Office 213, 11321 Bogotá, Colombia

⁴ Medicine Faculty, Universidad Nacional de Colombia, Carrera 45 No 26-85, Building 450, Office 213, 11321 Bogotá, Colombia

⁵ University Children’s Hospital, University of Wurzburg, 97080 Wurzburg, Germany

^† These authors contributed equally to this work, they are considered as first author.

Molecules 2017, 22(10), 1641; https://doi.org/10.3390/molecules22101641 - 29 Sep 2017

Cited by 42 | Viewed by 6945

Abstract

Linear, dimeric, tetrameric, and cyclic peptides derived from lactoferricin B, containing the RRWQWR motif, were designed, synthesized, purified, and characterized using RP-HPLC chromatography and MALDI-TOF mass spectrometry. The antibacterial activity of the designed peptides against E. coli (ATCC 11775 and 25922) and their [...] Read more.

Linear, dimeric, tetrameric, and cyclic peptides derived from lactoferricin B, containing the RRWQWR motif, were designed, synthesized, purified, and characterized using RP-HPLC chromatography and MALDI-TOF mass spectrometry. The antibacterial activity of the designed peptides against E. coli (ATCC 11775 and 25922) and their cytotoxic effect against MDA-MB-468 and MDA-MB-231 breast cancer cell lines were evaluated. Dimeric and tetrameric peptides showed higher antibacterial activity in both bacteria strains than linear peptides. The dimeric peptide (RRWQWR)₂K-Ahx exhibited the highest antibacterial activity against the tested bacterial strains. Furthermore, the peptides with high antibacterial activity exhibited significant cytotoxic effect against the tested breast cancer cell lines. This cytotoxic effect was fast and dependent on the peptide concentration. The tetrameric molecule containing RRWQWR motif has an optimal cytotoxic effect at a concentration of 22 µM. The evaluated dimeric and tetrameric peptides could be considered as candidates for developing new therapeutic agents against breast cancer. Polyvalence of linear sequences could be considered as a novel and versatile strategy for obtaining molecules with high anticancer activity. Full article

(This article belongs to the Special Issue Peptide Therapeutics)

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5 pages, 170 KiB

Open AccessEditorial

Special Issue: Sulfonamides

by Claudiu T. Supuran

Dipartimento Neurofarba, Sezione di Scienze Farmaceutiche e Nutraceutiche, Università degli Studi di Firenze, Via Ugo Schiff 6, I-50019 Sesto Fiorentino (Florence), Italy

Molecules 2017, 22(10), 1642; https://doi.org/10.3390/molecules22101642 - 29 Sep 2017

Cited by 91 | Viewed by 11006

Abstract

The sulfonamides and their structurally related derivatives, such as the sulfamates and sulfamides, possess the general formula A-SO2NHR, in which the functional group is either directly bound to an aromatic, heterocyclic, aliphatic, or sugar scaffold (of type A), or appended to such a [...] Read more.

The sulfonamides and their structurally related derivatives, such as the sulfamates and sulfamides, possess the general formula A-SO2NHR, in which the functional group is either directly bound to an aromatic, heterocyclic, aliphatic, or sugar scaffold (of type A), or appended to such a scaffold via a heteroatom, most frequently oxygen or nitrogen (leading thus to sulfamates and sulfamides, respectively) [...] Full article

(This article belongs to the Special Issue Sulfonamides)

18 pages, 1405 KiB

Open AccessArticle

Nonempirical Simulations of Inhomogeneous Broadening of Electronic Transitions in Solution: Predicting Band Shapes in One- and Two-Photon Absorption Spectra of Chalcones

by Joanna Bednarska^1,*, Robert Zaleśny^1,*

, Guangjun Tian², Natarajan Arul Murugan³, Hans Ågren³

and Wojciech Bartkowiak^1,*

¹ Department of Physical and Quantum Chemistry, Faculty of Chemistry, Wrocław University of Science and Technology, Wyb. Wyspiańskiego 27, PL-50370 Wrocław, Poland

² Hebei Key Laboratory of Microstructural Material Physics, School of Science, Yanshan University, Qinhuangdao 066004, China

³ Division of Theoretical Chemistry and Biology, School of Biotechnology, Royal Institute of Technology, SE–10691 Stockholm, Sweden

Molecules 2017, 22(10), 1643; https://doi.org/10.3390/molecules22101643 - 30 Sep 2017

Cited by 18 | Viewed by 5343

Abstract

We have examined several approaches relying on the Polarizable Embedding (PE) scheme to predict optical band shapes for two chalcone molecules in methanol solution. The PE-TDDFT and PERI-CC2 methods were combined with molecular dynamics simulations, where the solute geometry was kept either as [...] Read more.

We have examined several approaches relying on the Polarizable Embedding (PE) scheme to predict optical band shapes for two chalcone molecules in methanol solution. The PE-TDDFT and PERI-CC2 methods were combined with molecular dynamics simulations, where the solute geometry was kept either as rigid, flexible or partly-flexible (restrained) body. The first approach, termed RBMD-PE-TDDFT, was employed to estimate the inhomogeneous broadening for subsequent convolution with the vibrationally-resolved spectra of the molecule in solution determined quantum-mechanically (QM). As demonstrated, the RBMD-PE-TDDFT/QM-PCM approach delivers accurate band widths, also reproducing their correct asymmetric shapes. Further refinement can be obtained by the estimation of the inhomogeneous broadening using the RBMD-PERI-CC2 method. On the other hand, the remaining two approaches (FBMD-PE-TDDFT and ResBMD-PE-TDDFT), which lack quantum-mechanical treatment of molecular vibrations, lead to underestimated band widths. In this study, we also proposed a simple strategy regarding the rapid selection of the exchange-correlation functional for the simulations of vibrationally-resolved one- and two-photon absorption spectra based on two easy-to-compute metrics. Full article

(This article belongs to the Special Issue Theoretical Excited-State Chemistry: New Developments and Cutting-Edge Applications)

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21 pages, 2736 KiB

Open AccessArticle

Versatility of 7-Substituted Coumarin Molecules as Antimycobacterial Agents, Neuronal Enzyme Inhibitors and Neuroprotective Agents

by Erika Kapp¹, Hanri Visser², Samantha L. Sampson², Sarel F. Malan¹

, Elizabeth M. Streicher², Germaine B. Foka¹, Digby F. Warner³, Sylvester I. Omoruyi⁴, Adaze B. Enogieru⁴, Okobi E. Ekpo⁴, Frank T. Zindo¹ and Jacques Joubert^1,*

¹ School of Pharmacy, Faculty of Natural Sciences, University of the Western Cape, Cape Town, Bellville 7550, South Africa

² DST/NRF Centre of Excellence in Biomedical Tuberculosis Research, SA MRC Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, University of Stellenbosch, Cape Town, Tygerberg 7505, South Africa

³ Medical Research Council/National Health Laboratory Service/University of Cape Town Molecular Mycobacteriology Research Unit, Department of Science and Technology/National Research Foundation Centre of Excellence for Biomedical Tuberculosis Research, Institute of Infectious Disease and Molecular Medicine and Department of Clinical Laboratory Sciences, University of Cape Town, Cape Town, Rondebosch 7700, South Africa

⁴ Department of Medical Biosciences, University of the Western Cape, Cape Town, Bellville 7550, South Africa

Molecules 2017, 22(10), 1644; https://doi.org/10.3390/molecules22101644 - 30 Sep 2017

Cited by 26 | Viewed by 6881

Abstract

A medium-throughput screen using Mycobacterium tuberculosis H37Rv was employed to screen an in-house library of structurally diverse compounds for antimycobacterial activity. In this initial screen, eleven 7-substituted coumarin derivatives with confirmed monoamine oxidase-B and cholinesterase inhibitory activities, demonstrated growth inhibition of more than [...] Read more.

A medium-throughput screen using Mycobacterium tuberculosis H37Rv was employed to screen an in-house library of structurally diverse compounds for antimycobacterial activity. In this initial screen, eleven 7-substituted coumarin derivatives with confirmed monoamine oxidase-B and cholinesterase inhibitory activities, demonstrated growth inhibition of more than 50% at 50 µM. This prompted further exploration of all the 7-substituted coumarins in our library. Four compounds showed promising MIC₉₉ values of 8.31–29.70 µM and 44.15–57.17 µM on M. tuberculosis H37Rv in independent assays using GAST-Fe and 7H9+OADC media, respectively. These compounds were found to bind to albumin, which may explain the variations in MIC between the two assays. Preliminary data showed that they were able to maintain their activity in fluoroquinolone resistant mycobacteria. Structure-activity relationships indicated that structural modification on position 4 and/or 7 of the coumarin scaffold could direct the selectivity towards either the inhibition of neuronal enzymes or the antimycobacterial effect. Moderate cytotoxicities were observed for these compounds and slight selectivity towards mycobacteria was indicated. Further neuroprotective assays showed significant neuroprotection for selected compounds irrespective of their neuronal enzyme inhibitory properties. These coumarin molecules are thus interesting lead compounds that may provide insight into the design of new antimicrobacterial and neuroprotective agents. Full article

(This article belongs to the Special Issue Versatile Coumarins)

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24 pages, 7591 KiB

Open AccessReview

A Review of the Biomedical Applications of Zerumbone and the Techniques for Its Extraction from Ginger Rhizomes

by Katayoon Kalantari^1,2,*, Mona Moniri³, Amin Boroumand Moghaddam³, Raha Abdul Rahim⁴, Arbakariya Bin Ariff^3,5, Zahra Izadiyan⁶ and Rosfarizan Mohamad^3,7,*

¹ Department of Mechanical Engineering, Faculty of Engineering, University of Malaya, Kuala Lumpur 50603, Malaysia

² Centre of Advanced Materials (CAM), Faculty of Engineering, University of Malaya, Kuala Lumpur 50603, Malaysia

³ Department of Bioprocess Technology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, UPM Serdang, Selangor 43400, Malaysia

⁴ Department of Cell and Molecular Biology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, UPM Serdang, Selangor 43400, Malaysia

⁵ Bioprocessing and Biomanufacturing Research Center, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, UPM Serdang, Selangor 43400, Malaysia

⁶ Malaysia-Japan International Institute of Technology (MJIIT), Universiti Teknologi Malaysia, Kuala Lumpur 54100, Malaysia

⁷ Institute of Tropical Forestry and Forest Products, Univerciti Putra Malaysia, UPM Serdang, Selangor 43400, Malaysia

Molecules 2017, 22(10), 1645; https://doi.org/10.3390/molecules22101645 - 30 Sep 2017

Cited by 73 | Viewed by 11913

Abstract

Zerumbone (ZER) is a phytochemical isolated from the subtropical Zingiberaceae family and as a natural compound it has different biomedical properties such as antioxidant, anti-inflammatory anti-proliferative activity. ZER also has effects on angiogenesis and acts as an antitumor drug in the treatment of [...] Read more.

Zerumbone (ZER) is a phytochemical isolated from the subtropical Zingiberaceae family and as a natural compound it has different biomedical properties such as antioxidant, anti-inflammatory anti-proliferative activity. ZER also has effects on angiogenesis and acts as an antitumor drug in the treatment of cancer, showing selective toxicity toward various cancer cell lines. Several techniques also have been established for extraction of ZER from the rhizomes of ginger. This review paper is an overview of recent research about different extraction methods and their efficiencies, in vivo and vitro investigations of ZER and also its prominent chemopreventive properties and treatment mechanisms. Most of the studies mentioned in this review paper may be useful use as a knowledge summary to explain ZER extraction and anticancer activities, which will show a way for the development of strategies in the treatment of malignancies using ZER. Full article

(This article belongs to the Section Medicinal Chemistry)

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10 pages, 5103 KiB

Open AccessArticle

Melandrii Herba Extract Attenuates H₂O₂-Induced Neurotoxicity in Human Neuroblastoma SH-SY5Y Cells and Scopolamine-Induced Memory Impairment in Mice

by Kwang Min Lee^†, Ae Sin Lee^†

and Inwook Choi^*

¹ Korea Food Research Institute, Seongnam-si, Gyeonggi-do 13539, Korea

^† These authors equally contributed to this work.

Molecules 2017, 22(10), 1646; https://doi.org/10.3390/molecules22101646 - 30 Sep 2017

Cited by 12 | Viewed by 6361

Abstract

Oxidative stress plays a significant role in the etiology of a variety of neurodegenerative diseases. In this study, we found that Melandrii Herba extract (ME) attenuated oxidative-induced damage in cells. Mechanistically, ME exhibited protection from H₂O₂-induced neurotoxicity via caspase-3 [...] Read more.

Oxidative stress plays a significant role in the etiology of a variety of neurodegenerative diseases. In this study, we found that Melandrii Herba extract (ME) attenuated oxidative-induced damage in cells. Mechanistically, ME exhibited protection from H₂O₂-induced neurotoxicity via caspase-3 inactivation, Bcl-2 downregulation, Bax upregulation, and MAPK activation (ERK 1/2, JNK 1/2, and p38 MAPK) in vitro. Moreover, our in vivo data showed that ME was able to attenuate scopolamine-induced cognitive impairment. These results provide in vitro and in vivo evidence that ME exhibits neuroprotective properties against oxidative stress, which suggests that ME is worthy of further investigation as a complementary, or even as an alternative, product for preventing and treating neurodegenerative disorders. Full article

(This article belongs to the Section Natural Products Chemistry)

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20 pages, 286 KiB

Open AccessArticle

The Effect of Different Starch Liberation and Saccharification Methods on the Microbial Contaminations of Distillery Mashes, Fermentation Efficiency, and Spirits Quality

by Katarzyna Pielech-Przybylska^1,*

, Maria Balcerek¹

, Agnieszka Nowak², Maciej Wojtczak³, Agata Czyżowska², Urszula Dziekońska-Kubczak¹ and Piotr Patelski¹

¹ Department of Spirit and Yeast Technology, Institute of Fermentation Technology and Microbiology, Faculty of Biotechnology and Food Sciences, Lodz University of Technology, Wolczanska 171/173, 90-924 Lodz, Poland

² Department of Technical Microbiology, Institute of Fermentation Technology and Microbiology, Faculty of Biotechnology and Food Sciences, Lodz University of Technology, Wolczanska 171/173, 90-924 Lodz, Poland

³ Institute of Food Technology and Analysis, Faculty of Biotechnology and Food Sciences, Lodz University of Technology, Wolczanska 171/173, 90-924 Lodz, Poland

Molecules 2017, 22(10), 1647; https://doi.org/10.3390/molecules22101647 - 30 Sep 2017

Cited by 16 | Viewed by 6356

Abstract

The aim of this study was to evaluate the influence of different starch liberation and saccharification methods on microbiological contamination of distillery mashes. Moreover, the effect of hop α-acid preparation for protection against microbial infections was assessed. The quality of agricultural distillates was [...] Read more.

The aim of this study was to evaluate the influence of different starch liberation and saccharification methods on microbiological contamination of distillery mashes. Moreover, the effect of hop α-acid preparation for protection against microbial infections was assessed. The quality of agricultural distillates was also evaluated. When applying the pressureless liberation of starch (PLS) and malt as a source of amylolytic enzymes, the lactic acid bacteria count in the mashes increased several times during fermentation. The mashes obtained using the pressure-thermal method and malt enzymes revealed a similar pattern. Samples prepared using cereal malt exhibited higher concentrations of lactic and acetic acids, as compared to mashes prepared using enzymes of microbial origin. The use of hop α-acids led to the reduction of bacterial contamination in all tested mashes. As a result, fermentation of both mashes prepared with microbial origin enzyme preparations and with barley malt resulted in satisfactory efficiency and distillates with low concentrations of aldehydes. Full article

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15 pages, 1456 KiB

Open AccessArticle

Complex Enzyme-Assisted Extraction Releases Antioxidative Phenolic Compositions from Guava Leaves

by Lu Wang, Yanan Wu, Yan Liu and Zhenqiang Wu^*

School of Biology and Biological Engineering, South China University of Technology, Guangzhou 510006, China

Molecules 2017, 22(10), 1648; https://doi.org/10.3390/molecules22101648 - 30 Sep 2017

Cited by 69 | Viewed by 8356

Abstract

Phenolics in food and fruit tree leaves exist in free, soluble-conjugate, and insoluble-bound forms. In this study, in order to enhance the bioavailability of insoluble-bound phenolics from guava leaves (GL), the ability of enzyme-assisted extraction in improving the release of insoluble-bound phenolics was [...] Read more.

Phenolics in food and fruit tree leaves exist in free, soluble-conjugate, and insoluble-bound forms. In this study, in order to enhance the bioavailability of insoluble-bound phenolics from guava leaves (GL), the ability of enzyme-assisted extraction in improving the release of insoluble-bound phenolics was investigated. Compared to untreated GL, single xylanase-assisted extraction did not change the composition and yield of soluble phenolics, whereas single cellulase or β-glucosidase-assisted extraction significantly enhanced the soluble phenolics content of PGL. However, complex enzyme-assisted extraction (CEAE) greatly improved the soluble phenolics content, flavonoids content, ABTS, DPPH, and FRAP by 103.2%, 81.6%, 104.4%, 126.5%, and 90.3%, respectively. Interestingly, after CEAE, a major proportion of phenolics existed in the soluble form, and rarely in the insoluble-bound form. Especially, the contents of quercetin and kaempferol with higher bio-activity were enhanced by 3.5- and 2.2-fold, respectively. More importantly, total soluble phenolics extracts of GL following CEAE exhibited the highest antioxidant activity and protective effect against supercoiled DNA damage. This enzyme-assisted extraction technology can be useful for extracting biochemical components from plant matrix, and has good potential for use in the food and pharmaceutical industries. Full article

(This article belongs to the Special Issue Green Extraction of Natural Product: Innovative Techniques, Alternative Solvents and Original Procedures)

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16 pages, 5304 KiB

Open AccessArticle

Inhibitory Effects of Total Triterpenoid Saponins Isolated from the Seeds of the Tea Plant (Camellia sinensis) on Human Ovarian Cancer Cells

by Ling-Yan Jia^1,2, Xue-Jin Wu¹, Ying Gao³, Gary O. Rankin⁴, Alexa Pigliacampi², Heather Bucur², Bo Li¹, You-Ying Tu^1,* and Yi Charlie Chen^2,*

¹ Department of Tea Science, Zhejiang University, Hangzhou 310058, China

² College of Science, Technology and Mathematics, Alderson Broaddus University, Philippi, WV 26416, USA

³ Tea Research Institute, Chinese Academy of Agricultural Sciences, Hangzhou 310008, China

⁴ Department of Pharmacology, Physiology and Toxicology, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25755, USA

Molecules 2017, 22(10), 1649; https://doi.org/10.3390/molecules22101649 - 30 Sep 2017

Cited by 34 | Viewed by 7335

Abstract

Ovarian cancer is regarded as one of the most severe malignancies for women in the world. Death rates have remained steady over the past five decades, due to the undeniable inefficiency of the current treatment in preventing its recurrence and death. The development [...] Read more.

Ovarian cancer is regarded as one of the most severe malignancies for women in the world. Death rates have remained steady over the past five decades, due to the undeniable inefficiency of the current treatment in preventing its recurrence and death. The development of new effective alternative agents for ovarian cancer treatment is becoming increasingly critical. Tea saponins (TS) are triterpenoidsaponins composed of sapogenins, glycosides, and organic acids, which possess a variety of pharmacological activities, and have shown promise in the anti-cancer field. Through cell CellTiter 96^® Aqueous One Solution Cell Proliferation assay (MTS) assay, colony formation, Hoechst 33342 staining assay, caspase-3/7 activities, flow cytometry for apoptosis analysis, and Western blot, we observed that TS isolated from the seeds of tea plants, Camellia sinensis, exhibited strong anti-proliferation inhibitory effects on OVCAR-3 and A2780/CP70 ovarian cancer cell lines. Our results indicate that TS may selectivity inhibit human ovarian cancer cells by mediating apoptosis through the extrinsic pathway, and initiating anti-angiogenesis via decreased VEGF protein levels in a HIF-1α-dependent pathway. Our data suggests that, in the future, TS could be incorporated into a potential therapeutic agent against human ovarian cancer. Full article

(This article belongs to the Collection Efficient Pharmaceutical and Chemical Approaches for Anticancer Therapy: Design, Preliminary Evaluations, and Further Developments)

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21 pages, 2227 KiB

Open AccessArticle

Synthesis of Disaccharide Nucleosides Utilizing the Temporary Protection of the 2′,3′-cis-Diol of Ribonucleosides by a Boronic Ester

by Hidehisa Someya¹, Taiki Itoh¹ and Shin Aoki^1,2,*

¹ Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan

² Imaging Frontier Center, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan

Molecules 2017, 22(10), 1650; https://doi.org/10.3390/molecules22101650 - 1 Oct 2017

Cited by 10 | Viewed by 8343

Abstract

Disaccharide nucleosides are an important class of natural compounds that have a variety of biological activities. In this study, we report on the synthesis of disaccharide nucleosides utilizing the temporary protection of the 2′,3′-cis-diol of ribonucleosides, such as adenosine, guanosine, uridine, [...] Read more.

Disaccharide nucleosides are an important class of natural compounds that have a variety of biological activities. In this study, we report on the synthesis of disaccharide nucleosides utilizing the temporary protection of the 2′,3′-cis-diol of ribonucleosides, such as adenosine, guanosine, uridine, 5-metyluridine, 5-fluorouridine and cytidine, by a boronic ester. The temporary protection of the above ribonucleosides permits the regioselective O-glycosylation of the 5’-hydroxyl group with thioglycosides using a p-toluenesulfenyl chloride (p-TolSCl)/silver triflate (AgOTf) promoter system to afford the corresponding disaccharide nucleosides in fairly good chemical yields. The formation of a boronic ester prepared from uridine and 4-(trifluoromethyl)phenylboronic acid was examined by ¹H, ¹¹B and ¹⁹F NMR spectroscopy. Full article

(This article belongs to the Special Issue Nucleoside and Nucleotide Analogues)

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13 pages, 2141 KiB

Open AccessArticle

5-Hydroxycyclopenicillone Inhibits β-Amyloid Oligomerization and Produces Anti-β-Amyloid Neuroprotective Effects In Vitro

by Jiaying Zhao^1,2, Fufeng Liu³, Chunhui Huang^1,2, Jieyi Shentu^1,2, Minjun Wang^1,2, Chenkai Sun^1,2, Liping Chen², Sicheng Yan², Fang Fang¹, Yuanyuan Wang², Shujun Xu², C. Benjamin Naman^1,4, Qinwen Wang², Shan He^1,*

and Wei Cui^2,*

¹ Li Dak Sum Yip Yio Chin Kenneth Li Marine Biopharmaceutical Research Center, Ningbo University, Ningbo 315211, China

² Ningbo Key Laboratory of Behavioral Neuroscience, Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo 315211, China

³ Key Laboratory of Industrial Fermentation Microbiology of Education, College of Biotechnology, Tianjin University of Science & Technology, Tianjin 300457, China

⁴ Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California, San Diego, La Jolla, CA 92093, USA

Molecules 2017, 22(10), 1651; https://doi.org/10.3390/molecules22101651 - 1 Oct 2017

Cited by 11 | Viewed by 5982

Abstract

The oligomer of β-amyloid (Aβ) is considered the main neurotoxin in Alzheimer’s disease (AD). Therefore, the inhibition of the formation of Aβ oligomer could be a target for AD therapy. In this study, with the help of the dot blotting assay and transmission [...] Read more.

The oligomer of β-amyloid (Aβ) is considered the main neurotoxin in Alzheimer’s disease (AD). Therefore, the inhibition of the formation of Aβ oligomer could be a target for AD therapy. In this study, with the help of the dot blotting assay and transmission electronic microscopy, it was have discovered that 5-hydroxycyclopenicillone, a cyclopentenone recently isolated from a sponge-associated fungus, effectively reduced the formation of Aβ oligomer from Aβ peptide in vitro. Molecular dynamics simulations suggested hydrophobic interactions between 5-hydroxycyclopenicillone and Aβ peptide, which might prevent the conformational transition and oligomerization of Aβ peptide. Moreover, Aβ oligomer pre-incubated with 5-hydroxycyclopenicillone was less toxic when added to neuronal SH-SY5Y cells compared to the normal Aβ oligomer. Although 5-hydroxycyclopenicillone is not bioavailable in the brain in its current form, further modification or encapsulation of this chemical might improve the penetration of 5-hydroxycyclopenicillone into the brain. Based on the current findings and the anti-oxidative stress properties of 5-hydroxycyclopenicillone, it is suggested that 5-hydroxycyclopenicillone may have potential therapeutic efficacy in treating AD. Full article

(This article belongs to the Special Issue 25th Anniversary of the Amyloid Hypothesis and Alzheimer Disease)

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9 pages, 1739 KiB

Open AccessArticle

Characterization of the Ornithine Hydroxylation Step in Albachelin Biosynthesis

by Kendra Bufkin¹ and Pablo Sobrado^1,2,*

¹ Department of Biochemistry, Virginia Tech, Blacksburg, VA 24061, USA

² Center for Drug Discovery, Virginia Tech, Blacksburg, VA 24061, USA

Molecules 2017, 22(10), 1652; https://doi.org/10.3390/molecules22101652 - 1 Oct 2017

Cited by 7 | Viewed by 5793

Abstract

N-Hydroxylating monooxygenases (NMOs) are involved in siderophore biosynthesis. Siderophores are high affinity iron chelators composed of catechol and hydroxamate functional groups that are synthesized and secreted by microorganisms and plants. Recently, a new siderophore named albachelin was isolated from a culture of [...] Read more.

N-Hydroxylating monooxygenases (NMOs) are involved in siderophore biosynthesis. Siderophores are high affinity iron chelators composed of catechol and hydroxamate functional groups that are synthesized and secreted by microorganisms and plants. Recently, a new siderophore named albachelin was isolated from a culture of Amycolatopsis alba growing under iron-limiting conditions. This work focuses on the expression, purification, and characterization of the NMO, abachelin monooxygenase (AMO) from A. alba. This enzyme was purified and characterized in its holo (FAD-bound) and apo (FAD-free) forms. The apo-AMO could be reconstituted by addition of free FAD. The two forms of AMO hydroxylate ornithine, while lysine increases oxidase activity but is not hydroxylated and display low affinity for NADPH. Full article

(This article belongs to the Special Issue Flavoenzymes)

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15 pages, 5217 KiB

Open AccessArticle

A Comparative Genomic and Transcriptomic Survey Provides Novel Insights into N-Acetylserotonin Methyltransferase (ASMT) in Fish

by Kai Zhang^1,2

, Zhiqiang Ruan², Jia Li², Chao Bian^2,3, Xinxin You², Steven L. Coon^4,5,* and Qiong Shi^1,2,3,*

¹ BGI Education Center, University of Chinese Academy of Sciences, Shenzhen 518083, China

² Shenzhen Key Lab of Marine Genomics, Guangdong Provincial Key Lab of Molecular Breeding in Marine Economic Animals, BGI Academy of Marine Sciences, BGI Marine, BGI, Shenzhen 518083, China

³ BGI-Zhenjiang Institute of Hydrobiology, BGI Marine, Zhenjiang 212000, China

⁴ Molecular Genomics Core, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA

⁵ Molecular Genomics Laboratory, National Institutes of Health, Bethesda, MD 20892, USA

Molecules 2017, 22(10), 1653; https://doi.org/10.3390/molecules22101653 - 2 Oct 2017

Cited by 17 | Viewed by 5699

Abstract

Melatonin is a multifunctional bioactive molecule that plays comprehensive physiological roles in all living organisms. N-acetylserotonin methyltransferase (ASMT, also known as hydroxyindole O-methyltransferase or HIOMT) is the final enzyme for biosynthesis of melatonin. Here, we performed a comparative genomic and transcriptomic [...] Read more.

Melatonin is a multifunctional bioactive molecule that plays comprehensive physiological roles in all living organisms. N-acetylserotonin methyltransferase (ASMT, also known as hydroxyindole O-methyltransferase or HIOMT) is the final enzyme for biosynthesis of melatonin. Here, we performed a comparative genomic and transcriptomic survey to explore the ASMT family in fish. Two ASMT isotypes (ASMT1 and ASMT2) and a new ASMT-like (ASMTL) are all extracted from teleost genomes on the basis of phylogenetic and synteny analyses. We confirmed that C-terminal of the ASMTL proteins (ASMTL-ASMT) is homology to the full length of ASMT1 and ASMT2. Our results also demonstrate that the two ASMT isotypes and their distribution in teleosts seem to be the result of combinations of whole-genome duplication (WGD) and gene loss. Differences were also observed in tissue distribution and relative transcript abundances of ASMT1, ASMT2 and ASMTL through transcriptomic analysis. Protein sequence alignment and 3D structure prediction of ASMTs and ASMTL suggest differential roles for these ASMT genes. In summary, our current work provides novel insights into the ASMT genes in fish by combination of genomic and transcriptomic data. Full article

(This article belongs to the Special Issue Melatonin as an Antioxidant and a Functionally Pleiotropic Molecule: Synthesis, Metabolism and Activities in Organisms)

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11 pages, 2269 KiB

Open AccessArticle

Protective Effects of Parkia biglobosa Protein Isolate on Streptozotocin-Induced Hepatic Damage and Oxidative Stress in Diabetic Male Rats

by Bolajoko Idiat Ogunyinka¹, Babatunji Emmanuel Oyinloye^1,2

, Foluso Oluwagbemiga Osunsanmi¹, Andrew Rowland Opoku¹ and Abidemi Paul Kappo^1,*

¹ Biotechnology and Structural Biology (BSB) Group, Department of Biochemistry and Microbiology, University of Zululand, KwaDlangezwa 3886, South Africa

² Department of Biochemistry, College of Sciences, Afe Babalola University, PMB 5454, Ado-Ekiti 360001, Nigeria

Molecules 2017, 22(10), 1654; https://doi.org/10.3390/molecules22101654 - 2 Oct 2017

Cited by 17 | Viewed by 5692

Abstract

This study sought to investigate the possible protective role of Parkia biglobosa seed protein isolate (PBPi) against streptozotocin-induced hepatic damage and oxidative stress in diabetic male rats. Prior to animal experiments, a HPLC fingerprint of PBPi was recorded. Diabetes was induced in rats [...] Read more.

This study sought to investigate the possible protective role of Parkia biglobosa seed protein isolate (PBPi) against streptozotocin-induced hepatic damage and oxidative stress in diabetic male rats. Prior to animal experiments, a HPLC fingerprint of PBPi was recorded. Diabetes was induced in rats by a single intraperitoneal injection of streptozotocin (STZ; 60 mg/kg body weight). Diabetic rats were orally treated daily with PBPi (200 or 400 mg/kg body weight) or insulin (5 U/kg, i.p.) for 28 days. The degree of protection was evaluated using biochemical parameters such as malondialdehyde (MDA) levels, serum transaminases (ALT and AST), total protein, total glutathione (Total GSH), glutathione-S-transferase (GST), superoxide dismutase (SOD), catalase (CAT), and interleukin-6 (IL-6) activities. Histology of liver sections was also performed. The HPLC fingerprint of PBPi revealed eleven distinct peaks; PBPi at tested doses significantly attenuates STZ-induced elevated levels of serum IL-6, ALT and AST; and hepatic TBARS levels. Hepatic antioxidants (Total GSH, GST, SOD, CAT) as well as total protein were markedly restored in a dose-dependent manner. Histopathological results strongly support the protective role of PBPi. These results suggest PBPi could confer protection by ameliorating hepatic damage and oxidative stress caused by STZ in animal model possibly via its anti-inflammatory and antioxidant properties. Full article

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11 pages, 1081 KiB

Open AccessArticle

Influence of Plant Growth Retardants on Quality of Codonopsis Radix

by Yinyin Liao^1,2,†, Lanting Zeng^1,2,†, Pan Li³, Tian Sun⁴, Chao Wang⁵, Fangwen Li³, Yiyong Chen^1,2, Bing Du^3,* and Ziyin Yang^1,2,*

¹ Key Laboratory of South China Agricultural Plant Molecular Analysis and Genetic Improvement & Guangdong Provincial Key Laboratory of Applied Botany, South China Botanical Garden, Chinese Academy of Sciences, Xingke Road 723, Tianhe District, Guangzhou 510650, China

² University of Chinese Academy of Sciences, No.19A Yuquan Road, Beijing 100049, China

³ College of Food, South China Agricultural University, Wushan Road, Tianhe District, Guangzhou 510642, China

⁴ Tianfangjian (China) Pharmacy Company Ltd, 11 Xiancun Road, Tianhe District, Guangzhou 510623, China

⁵ Infinitus (China) Company Ltd, 11 Xiancun Road, Tianhe District, Guangzhou 510623, China

^† These authors contributed equally to this work.

Molecules 2017, 22(10), 1655; https://doi.org/10.3390/molecules22101655 - 9 Oct 2017

Cited by 21 | Viewed by 6597

Abstract

Plant growth retardant (PGR) refers to organics that can inhibit the cell division of plant stem tip sub-apical meristem cells or primordial meristem cell. They are widely used in the cultivation of rhizomatous functional plants; such as Codonopsis Radix, that is a famous [...] Read more.

Plant growth retardant (PGR) refers to organics that can inhibit the cell division of plant stem tip sub-apical meristem cells or primordial meristem cell. They are widely used in the cultivation of rhizomatous functional plants; such as Codonopsis Radix, that is a famous Chinese traditional herb. However, it is still unclear whether PGR affects the medicinal quality of C. Radix. In the present study, amino acid analyses, targeted and non-targeted analyses by ultra-performance liquid chromatography combined with time-of-flight mass spectrometry (UPLC-TOF-MS) and gas chromatography-MS were used to analyze and compare the composition of untreated C. Radix and C. Radix treated with PGR. The contents of two key bioactive compounds, lobetyolin and atractylenolide III, were not affected by PGR treatment. The amounts of polysaccharides and some internal volatiles were significantly decreased by PGR treatment; while the free amino acids content was generally increased. Fifteen metabolites whose abundance were affected by PGR treatment were identified by UPLC-TOF-MS. Five of the up-regulated compounds have been reported to show immune activity, which might contribute to the healing efficacy (“buqi”) of C. Radix. The results of this study showed that treatment of C. Radix with PGR during cultivation has economic benefits and affected some main bioactive compounds in C. Radix. Full article

(This article belongs to the Collection Herbal Medicine Research)

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12 pages, 870 KiB

Open AccessArticle

Comparison of the Effectiveness of Water-Based Extraction of Substances from Dry Tea Leaves with the Use of Magnetic Field Assisted Extraction Techniques

by Grzegorz Zaguła^1,*

, Marcin Bajcar¹, Bogdan Saletnik¹, Maria Czernicka¹

, Czesław Puchalski¹, Ireneusz Kapusta²

and Jan Oszmiański^2,3

¹ Department of Bioenergetics and Food Analysis, Faculty of Biology and Agriculture, University of Rzeszów, 35-601 Rzeszów, Poland

² Department of Food Technology and Human Nutrition, Faculty of Biology and Agriculture, University of Rzeszów, 35-601 Rzeszów, Poland

³ Wrocław University of Environmental and Life Sciences, Faculty of Biotechnology and Food Science, Department of Fruit, Vegetable and Plant Nutraceutical Technology, 37 Chełmonskiego Street, 51-630 Wrocław, Poland

Molecules 2017, 22(10), 1656; https://doi.org/10.3390/molecules22101656 - 3 Oct 2017

Cited by 19 | Viewed by 4523

Abstract

This article presents the findings of a study investigating the feasibility of using a magnetic field assisted technique for the water-based extraction of mineral components, polyphenols, and caffeine from dry black and green tea leaves. The authors present a concept of applying constant [...] Read more.

This article presents the findings of a study investigating the feasibility of using a magnetic field assisted technique for the water-based extraction of mineral components, polyphenols, and caffeine from dry black and green tea leaves. The authors present a concept of applying constant and variable magnetic fields in the process of producing water-based infusions from selected types of tea. Analyses investigating the effectiveness of the proposed technique in comparison with conventional infusion methods assessed the contents of selected mineral components—i.e., Al, Ca, Cu, K, Mg, P, S, and Zn—which were examined with the use of ICP-OES. The contents of caffeine and polyphenolic compounds were assessed using the HPLC. A changing magnetic field permitted an increased effectiveness of extraction of the mineral components, caffeine, and polyphenols. The findings support the conclusion that a changing magnetic field assisted extraction method is useful for obtaining biologically valuable components from tea infusions. Full article

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17 pages, 4420 KiB

Open AccessArticle

Inositol Hexaphosphate Inhibits Proliferation and Induces Apoptosis of Colon Cancer Cells by Suppressing the AKT/mTOR Signaling Pathway

by Małgorzata Kapral^1,*

, Joanna Wawszczyk¹

, Katarzyna Jesse¹, Monika Paul-Samojedny², Dariusz Kuśmierz³ and Ludmiła Węglarz¹

¹ Department of Biochemistry, School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia in Katowice, Jedności 8, 41-200 Sosnowiec, Poland

² Department of Medical Genetics, School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia in Katowice, Jedności 8, 41-200 Sosnowiec, Poland

³ Department of Cell Biology, School of Pharmacy with Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia in Katowice, Jedności 8, 41-200 Sosnowiec, Poland

Molecules 2017, 22(10), 1657; https://doi.org/10.3390/molecules22101657 - 3 Oct 2017

Cited by 39 | Viewed by 7265

Abstract

Abstract: AKT, a serine/threonine protein kinase and mammalian target of rapamycin (mTOR) plays a critical role in the proliferation and resistance to apoptosis that are essential to the development and progression of colon cancer. Therefore, AKT/mTOR signaling pathway has been recognized as [...] Read more.

Abstract: AKT, a serine/threonine protein kinase and mammalian target of rapamycin (mTOR) plays a critical role in the proliferation and resistance to apoptosis that are essential to the development and progression of colon cancer. Therefore, AKT/mTOR signaling pathway has been recognized as an attractive target for anticancer therapy. Inositol hexaphosphate (InsP6), a natural occurring phytochemical, has been shown to have both preventive and therapeutic effects against various cancers, however, its exact molecular mechanisms of action are not fully understood. The aim of the in vitro study was to investigate the anticancer activity of InsP6 on colon cancer with the focus on inhibiting the AKT1 kinase and p70S6K1 as mTOR effector, in relation to proliferation and apoptosis of cells. The colon cancer Caco-2 cells were cultured using standard techniques and exposed to InsP6 at different concentrations (1 mM, 2.5 mM and 5 mM). Cellular proliferative activity was monitored by 5-bromo-2′-deoxyuridine (BrdU) incorporation into cellular DNA. Flow cytometric analysis was performed for cell cycle progression and apoptosis studies. Real-time RT-qPCR was used to validate mRNA levels of CDNK1A, CDNK1B, CASP3, CASP9, AKT1 and S6K1 genes. The concentration of p21 protein as well as the activities of caspase 3, AKT1 and p70S6K1 were determined by the ELISA method. The results revealed that IP6 inhibited proliferation and stimulated apoptosis of colon cancer cells. This effect was mediated by an increase in the expression of genes encoding p21, p27, caspase 3, caspase 9 as well a decrease in transcription of AKT1 and S6K1. InsP6 suppressed phosphorylation of AKT1 and p70S6K1, downstream effector of mTOR. Based on these studies it may be concluded that InsP6 can reduce proliferation and induce apoptosis through inhibition of the AKT/mTOR pathway and mTOR effector followed by modulation of the expression and activity of several key components of these pathways in colon cancer cells. Full article

(This article belongs to the Collection Phytochemicals: Biosynthesis, Metabolism and Biological Activities)

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15 pages, 14022 KiB

Open AccessArticle

Design, Synthesis and Biological Evaluation of N,N-Substituted Amine Derivatives as Cholesteryl Ester Transfer Protein Inhibitors

by Xinran Wang¹, Lijuan Hao¹, Xuanqi Xu², Wei Li¹, Chunchi Liu¹, Dongmei Zhao^1,*

and Maosheng Cheng¹

¹ Key Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, China

² Department of Chemistry, University of Wisconsin-Madison, Madison, WI, 53715, USA

Molecules 2017, 22(10), 1658; https://doi.org/10.3390/molecules22101658 - 3 Oct 2017

Viewed by 5236

Abstract

N,N-Substituted amine derivatives were designed by utilizing a bioisosterism strategy. Consequently, twenty-two compounds were synthesized and evaluated for their inhibitory activity against CETP. Structure-activity relationship (SAR) studies indicate that hydrophilic groups at the 2-position of the tetrazole and 3,5-bistrifluoromethyl groups on the benzene [...] Read more.

N,N-Substituted amine derivatives were designed by utilizing a bioisosterism strategy. Consequently, twenty-two compounds were synthesized and evaluated for their inhibitory activity against CETP. Structure-activity relationship (SAR) studies indicate that hydrophilic groups at the 2-position of the tetrazole and 3,5-bistrifluoromethyl groups on the benzene ring provide important contributions to the potency. Among these compounds, compound 17 exhibited excellent CETP inhibitory activity (IC₅₀ = 0.38 ± 0.08 μM) in vitro. Furthermore, compound 17 was selected for an in vitro metabolic stability study. Full article

(This article belongs to the Section Medicinal Chemistry)

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9 pages, 2075 KiB

Open AccessArticle

Effect of High-Pressure Treatment on Catalytic and Physicochemical Properties of Pepsin

by Jianan Wang, Tenghui Bai, Yaping Ma and Hanjun Ma^*

School of Food Science, Henan Institute of Science and Technology, Xinxiang 453003, China

Molecules 2017, 22(10), 1659; https://doi.org/10.3390/molecules22101659 - 11 Oct 2017

Cited by 6 | Viewed by 4021

Abstract

For a long time, high-pressure treatment has been used to destroy the compact structures of natural proteins in order to promote subsequent enzymatic hydrolysis. However, there are few reports evaluating the feasibility of directly improving the catalytic capability of proteases by using high-pressure [...] Read more.

For a long time, high-pressure treatment has been used to destroy the compact structures of natural proteins in order to promote subsequent enzymatic hydrolysis. However, there are few reports evaluating the feasibility of directly improving the catalytic capability of proteases by using high-pressure treatments. In this study, the effects of high-pressure treatment on the catalytic capacity and structure of pepsin were investigated, and the relationship between its catalytic properties and changes in its physicochemical properties was explored. It was found that high-pressure treatment could lead to changes of the sulfhydryl group/disulfide bond content, hydrophobicity, hydrodynamic radius, intrinsic viscosity, and subunit composition of pepsin, and the conformational change of pepsin resulted in improvement to its enzymatic activity and hydrolysis efficiency, which had an obvious relationship with the high-pressure treatment conditions. Full article

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11 pages, 1524 KiB

Open AccessArticle

Selective O-Alkylation of the Crown Conformer of Tetra(4-hydroxyphenyl)calix[4]resorcinarene to the Corresponding Tetraalkyl Ether

by Alver Castillo-Aguirre, Zuly Rivera-Monroy and Mauricio Maldonado^*

Departamento de Química, Facultad de Ciencias, Universidad Nacional de Colombia-Sede Bogotá, Carrera 30 No. 45-03, Bogotá 111321

Molecules 2017, 22(10), 1660; https://doi.org/10.3390/molecules22101660 - 4 Oct 2017

Cited by 23 | Viewed by 5592

Abstract

Reactions of glycidyl methacrylate with the crown and chair conformers of tetra(4-hydroxyphenyl)calix[4]resorcinarene were studied. The reactions were done over epoxide groups present in the ester, which can easily undergo an opening reaction with hydroxyl groups in the macrocyclic system. Initially, epoxidation reactions were [...] Read more.

Reactions of glycidyl methacrylate with the crown and chair conformers of tetra(4-hydroxyphenyl)calix[4]resorcinarene were studied. The reactions were done over epoxide groups present in the ester, which can easily undergo an opening reaction with hydroxyl groups in the macrocyclic system. Initially, epoxidation reactions were carried out with pure conformers, and it was observed that the reaction between tetra(4-hydroxyphenyl)calix[4]resorcinarene fixed in the chair conformation does not occur, while for the molecule fixed in the crown conformation only one tetraalkylated derivative was obtained. The obtained product was characterized using IR, ¹H-NMR, ¹³C-NMR, COSY, HMQC and HMBC techniques. An exhaustive NMR study showed that the reaction is selective at the hydroxyl groups in the lower rim, without affecting the hydroxyl groups in the upper rim. In addition, the RP–HPLC analysis of the epoxidation reaction mixture, using both crown and chair conformers, showed that only the crown conformer reacted under tested conditions. Finally, a comparative study of the reactivity of tetranonylcalix[4]resorcinarene with glycidyl methacrylate showed that the reaction does not take place. Instead, the formation of the tetranonylcalix[4]resorcinarene tetrasodium salt was observed, which confirms that the hydroxyl groups in the upper rim are unreactive under these conditions. Full article

(This article belongs to the Section Organic Chemistry)

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12 pages, 3202 KiB

Open AccessArticle

In Vitro Evaluation of Third Generation PAMAM Dendrimer Conjugates

by Mohammad Najlah^1,*

, Sally Freeman²

, Mouhamad Khoder³, David Attwood² and Antony D’Emanuele⁴

¹ Faculty of Medical Science, Anglia Ruskin University, Bishops Hall Lane, Chelmsford CM1 1SQ, UK

² Division of Pharmacy and Optometry, School of Health Sciences, Manchester Academic Health Sciences Centre, University of Manchester, Manchester M13 9PL, UK

³ School of Life Sciences, Pharmacy and Chemistry, Kingston University London, Kingston upon Thames KT1 2EE, UK

⁴ Leicester School of Pharmacy, De Montfort University, Leicester LE1 9BH, UK

Molecules 2017, 22(10), 1661; https://doi.org/10.3390/molecules22101661 - 4 Oct 2017

Cited by 25 | Viewed by 7398

Abstract

The present study compares the use of high generation G3 and low generation G0 Polyamidoamine (PAMAM) dendrimers as drug carriers of naproxen (NAP), a poorly water soluble drug. Naproxen was conjugated to G3 in different ratios and to G0 in a 1:1 ratio [...] Read more.

The present study compares the use of high generation G3 and low generation G0 Polyamidoamine (PAMAM) dendrimers as drug carriers of naproxen (NAP), a poorly water soluble drug. Naproxen was conjugated to G3 in different ratios and to G0 in a 1:1 ratio via a diethylene glycol linker. A lauroyl chain (L), a lipophilic permeability enhancer, was attached to G3 and G0 prodrugs. The G3 and G0 conjugates were more hydrophilic than naproxen as evaluated by the measurement of partitioning between 1-octanol and a phosphate buffer at pH 7.4 and pH 1.2. The unmodified surface PAMAM-NAP conjugates showed significant solubility enhancements of NAP at pH 1.2; however, with the number of NAP conjugated to G3, this was limited to 10 molecules. The lactate dehydrogenase (LDH) assay indicated that the G3 dendrimer conjugates had a concentration dependent toxicity towards Caco-2 cells. Attaching naproxen to the surface of the dendrimer increased the IC₅₀ of the resulting prodrugs towards Caco-2 cells. The lauroyl G3 conjugates showed the highest toxicity amongst the PAMAM dendrimer conjugates investigated and were significantly more toxic than the lauroyl-G0-naproxen conjugates. The permeability of naproxen across monolayers of Caco-2 cells was significantly increased by its conjugation to either G3 or G0 PAMAM dendrimers. Lauroyl-G0 conjugates displayed considerably lower cytotoxicity than G3 conjugates and may be preferable for use as a drug carrier for low soluble drugs such as naproxen. Full article

(This article belongs to the Special Issue Dendrimers in Medicine)

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17 pages, 1620 KiB

Open AccessReview

Versatile Chemical Derivatizations to Design Glycol Chitosan-Based Drug Carriers

by Sung Eun Kim¹, Hak-Jun Kim¹, Jin-Kyu Rhee^2,* and Kyeongsoon Park^3,*

¹ Department of Orthopedic Surgery and Rare Diseases Institute, Korea University Medical College, Guro Hospital, Seoul 08308, Korea

² Department of Food Science and Engineering, Ewha Womans University, Seoul 03760, Korea

³ Department of Systems Biotechnology, College of Biotechnology and Natural Resources, Chung-Ang University, Gyeonggi-do 17546, Korea

Molecules 2017, 22(10), 1662; https://doi.org/10.3390/molecules22101662 - 5 Oct 2017

Cited by 13 | Viewed by 8578

Abstract

Glycol chitosan (GC) and its derivatives have been extensively investigated as safe and effective drug delivery carriers because of their unique physiochemical and biological properties. The reactive functional groups such as the amine and hydroxyl groups on the GC backbone allow for easy [...] Read more.

Glycol chitosan (GC) and its derivatives have been extensively investigated as safe and effective drug delivery carriers because of their unique physiochemical and biological properties. The reactive functional groups such as the amine and hydroxyl groups on the GC backbone allow for easy chemical modification with various chemical compounds (e.g., hydrophobic molecules, crosslinkers, and acid-sensitive and labile molecules), and the versatility in chemical modifications enables production of a wide range of GC-based drug carriers. This review summarizes the versatile chemical modification methods that can be used to design GC-based drug carriers and describes their recent applications in disease therapy. Full article

(This article belongs to the Special Issue Chitin and Chitosan Derivatives: Biological Activities and Application)

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72 pages, 34169 KiB

Open AccessReview

High Resolution NMR Spectroscopy as a Structural and Analytical Tool for Unsaturated Lipids in Solution

by Eleni Alexandri¹, Raheel Ahmed², Hina Siddiqui², Muhammad I. Choudhary³, Constantinos G. Tsiafoulis⁴ and Ioannis P. Gerothanassis^1,2,*

¹ Section of Organic Chemistry and Biochemistry, Department of Chemistry, University of Ioannina, GR-45110 Ioannina, Greece

² H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan

³ Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah 214412, Saudi Arabia

⁴ NMR Center, University of Ioannina, GR-45110 Ioannina, Greece

Molecules 2017, 22(10), 1663; https://doi.org/10.3390/molecules22101663 - 5 Oct 2017

Cited by 206 | Viewed by 28134

Abstract

Abstract: Mono- and polyunsaturated lipids are widely distributed in Nature, and are structurally and functionally a diverse class of molecules with a variety of physicochemical, biological, medicinal and nutritional properties. High resolution NMR spectroscopic techniques including 1H-, 13C- and 31P-NMR have been successfully [...] Read more.

Abstract: Mono- and polyunsaturated lipids are widely distributed in Nature, and are structurally and functionally a diverse class of molecules with a variety of physicochemical, biological, medicinal and nutritional properties. High resolution NMR spectroscopic techniques including 1H-, 13C- and 31P-NMR have been successfully employed as a structural and analytical tool for unsaturated lipids. The objective of this review article is to provide: (i) an overview of the critical 1H-, 13C- and 31P-NMR parameters for structural and analytical investigations; (ii) an overview of various 1D and 2D NMR techniques that have been used for resonance assignments; (iii) selected analytical and structural studies with emphasis in the identification of major and minor unsaturated fatty acids in complex lipid extracts without the need for the isolation of the individual components; (iv) selected investigations of oxidation products of lipids; (v) applications in the emerging field of lipidomics; (vi) studies of protein-lipid interactions at a molecular level; (vii) practical considerations and (viii) an overview of future developments in the field. Full article

(This article belongs to the Special Issue New Methodologies in Natural Product Analytics and Structure Elucidation)

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14 pages, 234 KiB

Open AccessArticle

Associations of Dietary Antioxidants and Risk of Type 2 Diabetes: Data from the 2007–2012 Korea National Health and Nutrition Examination Survey

by Dan Yedu Quansah^1,†

, Kyungho Ha^1,†

, Shinyoung Jun²

, Seong-Ah Kim¹, Sangah Shin³, Gyung-Ah Wie⁴

and Hyojee Joung^1,5,*

¹ Graduate School of Public Health, Seoul National University, Seoul 08826, Korea

² Department of Nutrition Science, Purdue University, West Lafayette, IN 47907, USA

³ Department of Food and Nutrition, Chung-Ang University, Gyeonggi-do 17546, Korea

⁴ Department of Clinical Nutrition, Research Institute & Hospital, National Cancer Center, Goyang 10408, Korea

⁵ Institute of Health and Environment, Seoul National University, Seoul 08826, Korea

^† These authors contributed equally to this work.

Molecules 2017, 22(10), 1664; https://doi.org/10.3390/molecules22101664 - 5 Oct 2017

Cited by 18 | Viewed by 4962

Abstract

Antioxidants are suggested to decrease risk of type 2 diabetes (T2D) by preventing progressive impairment of pancreatic β-cell and endothelial function. This study was aimed to investigate the association between dietary antioxidants and risk of T2D in Korean adults based on a national [...] Read more.

Antioxidants are suggested to decrease risk of type 2 diabetes (T2D) by preventing progressive impairment of pancreatic β-cell and endothelial function. This study was aimed to investigate the association between dietary antioxidants and risk of T2D in Korean adults based on a national representative data. A total of 24,377 adults (19–74 years) who completed one-day 24 h dietary recall and health examination were included. Dietary antioxidant intakes including α-carotene (p < 0.0001), lycopene (p = 0.0107), flavan-3-ols (p < 0.0001), and proanthocyanidins (p = 0.0075) were significantly higher in non-diabetic subjects than in diabetic subjects. After adjusting for confounding variables, the highest quartile group of α-carotene intake was associated with a 48% reduced risk of T2D in men (OR: 0.52, 95% CI: 0.34–0.80, p for trend = 0.0037) and a 39% reduced risk in women (OR: 0.61, 95% CI: 0.38–0.996, p for trend = 0.0377) compared to the lowest quartile group. Men in the highest quartile of β-carotene intake showed lower risk of T2D (OR: 0.64, 95% CI: 0.42–0.97), but no significant decreasing trend. However, the intakes of total carotenoids and other antioxidants showed no significant association with the risk of T2D. These findings suggest that a further comprehensive approach which considers overall dietary pattern is required. Full article

(This article belongs to the Special Issue Bioactive Compounds for Metabolic Syndrome and Type 2 Diabetes)

47 pages, 25027 KiB

Open AccessReview

Synthesis of Chromone-Related Pyrazole Compounds

by Clementina M. M. Santos^1,2

, Vera L. M. Silva²

and Artur M. S. Silva^2,*

¹ School of Agriculture, Polytechnic Institute of Bragança, 5300-253 Bragança, Portugal

² Department of Chemistry & QOPNA, University of Aveiro, Campus Universitário de Santiago, 3810-193 Aveiro, Portugal

Molecules 2017, 22(10), 1665; https://doi.org/10.3390/molecules22101665 - 5 Oct 2017

Cited by 44 | Viewed by 14074

Abstract

Chromones, six-membered oxygen heterocycles, and pyrazoles, five-membered two-adjacentnitrogen- containing heterocycles, represent two important classes of biologically active compounds. Certain derivatives of these scaffolds play an important role in medicinal chemistry and have been extensively used as versatile building blocks in organic synthesis. In [...] Read more.

Chromones, six-membered oxygen heterocycles, and pyrazoles, five-membered two-adjacentnitrogen- containing heterocycles, represent two important classes of biologically active compounds. Certain derivatives of these scaffolds play an important role in medicinal chemistry and have been extensively used as versatile building blocks in organic synthesis. In this context, we will discuss the most relevant advances on the chemistry that involves both chromone and pyrazole rings. The methods reviewed include the synthesis of chromone-pyrazole dyads, synthesis of chromone-pyrazole-fused compounds, and chromones as starting materials in the synthesis of 3(5)-(2-hydroxyaryl)pyrazoles, among others. This review will cover the literature on the chromone and pyrazole dual chemistry and their outcomes in the 21st century. Full article

(This article belongs to the Special Issue Pyrazole Derivatives)

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15 pages, 1195 KiB

Open AccessArticle

Synthesis of Novel Glycerol-Derived 1,2,3-Triazoles and Evaluation of Their Fungicide, Phytotoxic and Cytotoxic Activities

by Adilson Vidal Costa^1,*

, Marcos Vinicius Lacerda de Oliveira¹, Roberta Tristão Pinto¹, Luiza Carvalheira Moreira¹, Ediellen Mayara Corrêa Gomes², Thammyres de Assis Alves³

, Patrícia Fontes Pinheiro¹

, Vagner Tebaldi de Queiroz¹

, Larissa Fonseca Andrade Vieira⁴

, Robson Ricardo Teixeira⁵

and Waldir Cintra de Jesus Júnior⁶

¹ Graduate Program in Agrochemistry, Universidade Federal do Espírito Santo, Alto Universitário, S/N, Guararema, Alegre ES 29500-000, Brazil

² Graduate Program in Plant Production, Universidade Federal do Espírito Santo, Alto Universitário, S/N, Guararema, Alegre ES 29500-000, Brazil

³ Graduate Program in Biotechnology, Universidade Federal do Espírito Santo, Alto Universitário, S/N, Guararema, Alegre ES 29500-000, Brazil

⁴ Department of Biology, Universidade Federal de Lavras, Lavras MG 37200-000, Brazil

⁵ Departament of Chemistry, Universidade Federal de Viçosa, Av. P.H. Rolfs, S/N, Viçosa MG 36570-900, Brazil

⁶ ersidade Federal de São Carlos, Campus Lagoa do Sino, Buri SP 18290-000, Brazil

Molecules 2017, 22(10), 1666; https://doi.org/10.3390/molecules22101666 - 7 Oct 2017

Cited by 37 | Viewed by 6855

Abstract

The synthesis of a series of 1,2,3-triazoles using glycerol as starting material is described. The key step in the preparation of these triazolic derivatives is the copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC), also known as click reaction, between 4-(azidomethyl)-2,2-dimethyl-1,3-dioxolane (3) and different terminal [...] Read more.

The synthesis of a series of 1,2,3-triazoles using glycerol as starting material is described. The key step in the preparation of these triazolic derivatives is the copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC), also known as click reaction, between 4-(azidomethyl)-2,2-dimethyl-1,3-dioxolane (3) and different terminal alkynes. The eight prepared derivatives were evaluated with regard to their fungicide, phytotoxic and cytotoxic activities. The fungicidal activity was assessed in vitro against Colletotrichum gloeosporioides, the causative agent of papaya anthracnose. It was found that the compounds 1-(1-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-1H-1,2,3-triazol-4-yl)-cyclo-hexanol (4g) and 2-(1-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-1H-1,2,3-triazol-4-yl)propan-2-ol (4h) demonstrated high efficiency in controlling C. gloeosporioides when compared to the commercial fungicide tebuconazole. The triazoles did not present any phytotoxic effect when evaluated against Lactuca sativa. However, five derivatives were mitodepressive, inducing cell death detected by the presence of condensed nuclei and acted as aneugenic agents in the cell cycle of L. sativa. It is believed that glycerol derivatives bearing 1,2,3-triazole functionalities may represent a promising scaffold to be explored for the development of new agents to control C. gloeosporioides. Full article

(This article belongs to the Collection Heterocyclic Compounds)

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12 pages, 2272 KiB

Open AccessArticle

A Theoretical Study of the N to O Linkage Photoisomerization Efficiency in a Series of Ruthenium Mononitrosyl Complexes

by Juan Sanz García^1,2,*

, Francesco Talotta¹, Fabienne Alary¹, Isabelle M. Dixon¹, Jean-Louis Heully¹ and Martial Boggio-Pasqua^1,*

¹ Laboratoire de Chimie et Physique Quantiques, IRSAMC, CNRS et Université Toulouse 3, 118 route de Narbonne, 31062 Toulouse, France

² Present address: Institut de Recherche de Chimie Paris, PSL Research University, CNRS, Chimie ParisTech, 11 Rue Pierre et Marie Curie, F-75005 Paris, France

Molecules 2017, 22(10), 1667; https://doi.org/10.3390/molecules22101667 - 6 Oct 2017

Cited by 9 | Viewed by 5779

Abstract

Ruthenium nitrosyl complexes are fascinating versatile photoactive molecules that can either undergo NO linkage photoisomerization or NO photorelease. The photochromic response of three ruthenium mononitrosyl complexes, trans-[RuCl(NO)(py)₄]²⁺, trans-[RuBr(NO)(py)₄]²⁺, and trans-(Cl,Cl)[RuCl₂(NO)(tpy)] [...] Read more.

Ruthenium nitrosyl complexes are fascinating versatile photoactive molecules that can either undergo NO linkage photoisomerization or NO photorelease. The photochromic response of three ruthenium mononitrosyl complexes, trans-[RuCl(NO)(py)₄]²⁺, trans-[RuBr(NO)(py)₄]²⁺, and trans-(Cl,Cl)[RuCl₂(NO)(tpy)]⁺, has been investigated using density functional theory and time-dependent density functional theory. The N to O photoisomerization pathways and absorption properties of the various stable and metastable species have been computed, providing a simple rationalization of the photoconversion trend in this series of complexes. The dramatic decrease of the N to O photoisomerization efficiency going from the first to the last complex is mainly attributed to an increase of the photoproduct absorption at the irradiation wavelength, rather than a change in the photoisomerization pathways. Full article

(This article belongs to the Special Issue Theoretical Excited-State Chemistry: New Developments and Cutting-Edge Applications)

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12 pages, 1407 KiB

Open AccessArticle

Two-Dimensional Capillary Electrophoresis with On-Line Sample Preparation and Cyclodextrin Separation Environment for Direct Determination of Serotonin in Human Urine

by Juraj Piešťanský^1,2, Katarína Maráková^1,2 and Peter Mikuš^1,2,*

¹ Department of Pharmaceutical Analysis and Nuclear Pharmacy, Faculty of Pharmacy, Comenius University in Bratislava, Odbojárov 10, SK-832 32 Bratislava, Slovak

² Toxicological and Antidoping center, Faculty of Pharmacy, Comenius University in Bratislava, Odbojárov 10, SK-832 32 Bratislava, Slovak

Molecules 2017, 22(10), 1668; https://doi.org/10.3390/molecules22101668 - 7 Oct 2017

Cited by 15 | Viewed by 5228

Abstract

An advanced two-dimensional capillary electrophoresis method, based on on-line combination of capillary isotachophoresis and capillary zone electrophoresis with cyclodextrin additive in background electrolyte, was developed for effective determination of serotonin in human urine. Hydrodynamically closed separation system and large bore capillaries (300–800 µm) [...] Read more.

An advanced two-dimensional capillary electrophoresis method, based on on-line combination of capillary isotachophoresis and capillary zone electrophoresis with cyclodextrin additive in background electrolyte, was developed for effective determination of serotonin in human urine. Hydrodynamically closed separation system and large bore capillaries (300–800 µm) were chosen for the possibility to enhance the sample load capacity, and, by that, to decrease limit of detection. Isotachophoresis served for the sample preseparation, defined elimination of sample matrix constituents (sample clean up), and preconcentration of the analyte. Cyclodextrin separation environment enhanced separation selectivity of capillary zone electrophoresis. In this way, serotonin could be successfully separated from the rest of the sample matrix constituents migrating in capillary zone electrophoresis step so that human urine could be directly (i.e., without any external sample preparation) injected into the analyzer. The proposed method was successfully validated, showing favorable parameters of sensitivity (limit of detection for serotonin was 2.32 ng·mL⁻¹), linearity (regression coefficient higher than 0.99), precision (repeatability of the migration time and peak area were in the range of 0.02–1.17% and 5.25–7.88%, respectively), and recovery (ranging in the interval of 90.0–93.6%). The developed method was applied for the assay of the human urine samples obtained from healthy volunteers. The determined concentrations of serotonin in such samples were in the range of 12.4–491.2 ng·mL⁻¹ that was in good agreement with literature data. This advanced method represents a highly effective, reliable, and low-cost alternative for the routine determination of serotonin as a biomarker in human urine. Full article

(This article belongs to the Special Issue Selected Papers from the 46th EuroCongress on Drug Synthesis and Analysis (ECDSA-2017))

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16 pages, 3806 KiB

Open AccessArticle

Rosmarinic Acid, a Rosemary Extract Polyphenol, Increases Skeletal Muscle Cell Glucose Uptake and Activates AMPK

by Filip Vlavcheski¹, Madina Naimi¹, Brennan Murphy², Tomas Hudlicky²

and Evangelia Tsiani^1,3,*

¹ Department of Health Sciences, Brock University, St. Catharines, ON L2S 3A1, Canada

² Department of Chemistry, Brock University, St. Catharines, ON L2S 3A1, Canada

³ Centre for Bone and Muscle Health, Brock University, St. Catharines, ON L2S 3A1, Canada

Molecules 2017, 22(10), 1669; https://doi.org/10.3390/molecules22101669 - 7 Oct 2017

Cited by 64 | Viewed by 13897

Abstract

Skeletal muscle is a major insulin-target tissue and plays an important role in glucose homeostasis. Impaired insulin action in muscles leads to insulin resistance and type 2 diabetes mellitus. 5′ AMP-activated kinase (AMPK) is an energy sensor, its activation increases glucose uptake in [...] Read more.

Skeletal muscle is a major insulin-target tissue and plays an important role in glucose homeostasis. Impaired insulin action in muscles leads to insulin resistance and type 2 diabetes mellitus. 5′ AMP-activated kinase (AMPK) is an energy sensor, its activation increases glucose uptake in skeletal muscle and AMPK activators have been viewed as a targeted approach in combating insulin resistance. We previously reported AMPK activation and increased muscle glucose uptake by rosemary extract (RE). In the present study, we examined the effects and the mechanism of action of rosmarinic acid (RA), a major RE constituent, in L6 rat muscle cells. RA (5.0 µM) increased glucose uptake (186 ± 4.17% of control, p < 0.001) to levels comparable to maximum insulin (204 ± 10.73% of control, p < 0.001) and metformin (202 ± 14.37% of control, p < 0.001). Akt phosphorylation was not affected by RA, while AMPK phosphorylation was increased. The RA-stimulated glucose uptake was inhibited by the AMPK inhibitor compound C and was not affected by wortmannin, an inhibitor of phosphoinositide 3-kinase (PI3K). The current study shows an effect of RA to increase muscle glucose uptake and AMPK phosphorylation. RA deserves further study as it shows potential to be used as an agent to regulate glucose homeostasis. Full article

(This article belongs to the Section Natural Products Chemistry)

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17 pages, 6778 KiB

Open AccessArticle

Phaseolus acutifolius Lectin Fractions Exhibit Apoptotic Effects on Colon Cancer: Preclinical Studies Using Dimethilhydrazine or Azoxi-Methane as Cancer Induction Agents

by Ulisses Moreno-Celis^1,†

, Josué López-Martínez^1,†, Alejandro Blanco-Labra², Ricardo Cervantes-Jiménez¹, Laura Elena Estrada-Martínez¹, Alejandro Eduardo García-Pascalin¹, María De Jesús Guerrero-Carrillo¹

, Adriana Jheny Rodríguez-Méndez³, Carmen Mejía¹, Roberto Augusto Ferríz-Martínez^1,* and Teresa García-Gasca^1,*

¹ Facultad de Ciencias Naturales, Universidad Autónoma de Querétaro, Av. de las Ciencias s/n. Juriquilla, CP 76230 Querétaro, Mexico

² Depto de Biotecnología y Bioquímica, CINVESTAV-Unidad Irapuato, Guanajuato CP 36821, Mexico

³ Universidad Autónoma de Querétaro, Querétaro CP 76176, Mexico

^† Ulisses Moreno-Celis and Josué López-Martínez share the first authorship.

Molecules 2017, 22(10), 1670; https://doi.org/10.3390/molecules22101670 - 8 Oct 2017

Cited by 25 | Viewed by 6234

Abstract

Phaseolus acutifolius (Tepary bean) lectins have been studied as cytotoxic molecules on colon cancer cells. The toxicological profile of a Tepary bean lectin fraction (TBLF) has shown low toxicity in experimental animals; exhibiting anti-nutritional effects such as a reduction in body weight gain [...] Read more.

Phaseolus acutifolius (Tepary bean) lectins have been studied as cytotoxic molecules on colon cancer cells. The toxicological profile of a Tepary bean lectin fraction (TBLF) has shown low toxicity in experimental animals; exhibiting anti-nutritional effects such as a reduction in body weight gain and a decrease in food intake when using a dose of 50 mg/kg on alternate days for six weeks. Taking this information into account, the focus of this work was to evaluate the effect of the TBLF on colon cancer using 1,2-dimethylhydrazine (DMH) or azoxy-methane/dextran sodium sulfate (AOM/DSS) as colon cancer inductors. Rats were treated with DMH or AOM/DSS and then administered with TBFL (50 mg/kg) for six weeks. TBLF significantly decreased early tumorigenesis triggered by DMH by 70%, but without any evidence of an apoptotic effect. In an independent experiment, AOM/DSS was used to generate aberrant cryptic foci, which decreased by 50% after TBLF treatment. TBLF exhibited antiproliferative and proapoptotic effects related to a decrease of the signal transduction pathway protein Akt in its activated form and an increase of caspase 3 activity, but not to p53 activation. Further studies will deepen our knowledge of specific apoptosis pathways and cellular stress processes such as oxidative damage. Full article

(This article belongs to the Collection Natural Products: Anticancer Potential and Beyond)

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11 pages, 875 KiB

Open AccessArticle

Predictive QSAR Models for the Toxicity of Disinfection Byproducts

by Litang Qin^1,2,3, Xin Zhang¹, Yuhan Chen¹, Lingyun Mo^2,3,*

, Honghu Zeng^1,2,3 and Yanpeng Liang^1,2,3

¹ College of Environmental Science and Engineering, Guilin University of Technology, Guilin 541004, China

² Guangxi Key Laboratory of Environmental Pollution Control Theory and Technology, Guilin University of Technology, Guilin 541004, China

³ Collaborative Innovation Center for Water Pollution Control and Water Safety in Karst Area, Guilin University of Technology, Guilin 541004, China

Molecules 2017, 22(10), 1671; https://doi.org/10.3390/molecules22101671 - 9 Oct 2017

Cited by 19 | Viewed by 6301

Abstract

Several hundred disinfection byproducts (DBPs) in drinking water have been identified, and are known to have potentially adverse health effects. There are toxicological data gaps for most DBPs, and the predictive method may provide an effective way to address this. The development of [...] Read more.

Several hundred disinfection byproducts (DBPs) in drinking water have been identified, and are known to have potentially adverse health effects. There are toxicological data gaps for most DBPs, and the predictive method may provide an effective way to address this. The development of an in-silico model of toxicology endpoints of DBPs is rarely studied. The main aim of the present study is to develop predictive quantitative structure–activity relationship (QSAR) models for the reactive toxicities of 50 DBPs in the five bioassays of X-Microtox, GSH+, GSH−, DNA+ and DNA−. All-subset regression was used to select the optimal descriptors, and multiple linear-regression models were built. The developed QSAR models for five endpoints satisfied the internal and external validation criteria: coefficient of determination (R²) > 0.7, explained variance in leave-one-out prediction (Q²_LOO) and in leave-many-out prediction (Q²_LMO) > 0.6, variance explained in external prediction (Q²_F1, Q²_F2, and Q²_F3) > 0.7, and concordance correlation coefficient (CCC) > 0.85. The application domains and the meaning of the selective descriptors for the QSAR models were discussed. The obtained QSAR models can be used in predicting the toxicities of the 50 DBPs. Full article

(This article belongs to the Section Molecular Diversity)

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11 pages, 1341 KiB

Open AccessArticle

Design, Synthesis and Antifungal Activity of Psoralen Derivatives

by Xiang Yu, Ya Wen, Chao-Gen Liang, Jia Liu, Yu-Bin Ding and Wei-Hua Zhang^*

Jiangsu Key Laboratory of Pesticide Science, Department of Chemistry, College of Sciences, Nanjing Agricultural University, Nanjing 210095, China

Molecules 2017, 22(10), 1672; https://doi.org/10.3390/molecules22101672 - 9 Oct 2017

Cited by 29 | Viewed by 6261

Abstract

A series of linear furanocoumarins with different substituents have been designed and synthesized. Their structures were confirmed by ¹H-NMR spectroscopy, high resolution mass spectra (EI-MS), IR, and X-ray single-crystal diffraction. All of the target compounds were evaluated in vitro for their antifungal [...] Read more.

A series of linear furanocoumarins with different substituents have been designed and synthesized. Their structures were confirmed by ¹H-NMR spectroscopy, high resolution mass spectra (EI-MS), IR, and X-ray single-crystal diffraction. All of the target compounds were evaluated in vitro for their antifungal activity against Rhizoctorzia solani, Botrytis cinerea, Alternaria solani, Gibberella zeae, Cucumber anthrax, and Alternaria leaf spot at 100 μg/mL, and some of the designed compounds exhibited potential antifungal activities. Compound 3a (67.9%) exhibited higher activity than the control Osthole (66.1%) against Botrytis cinerea. Furthermore, compound 4b (62.4%) represented equivalent antifungal activity as Osthole (69.5%) against Rhizoctonia solani. The structure-activity relationship (SAR) study demonstrates that linear furanocoumarin moiety has an important effect on the antifungal activity, promoting the idea of the coumarin ring as a framework that might be exploited in the future. Full article

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17 pages, 824 KiB

Open AccessArticle

Systematic Identification of Machine-Learning Models Aimed to Classify Critical Residues for Protein Function from Protein Structure

by Ricardo Corral-Corral¹, Jesús A. Beltrán², Carlos A. Brizuela² and Gabriel Del Rio^1,*

¹ Department of Biochemistry and Structural Biology, Instituto de Fisiologa Celular, Universidad Nacional Autónoma de México, México D.F. 04510, Mexico

² Computer Science Department, CICESE Research Center, Ensenada, Baja California 22860, Mexico

Molecules 2017, 22(10), 1673; https://doi.org/10.3390/molecules22101673 - 9 Oct 2017

Cited by 11 | Viewed by 5090

Abstract

Protein structure and protein function should be related, yet the nature of this relationship remains unsolved. Mapping the critical residues for protein function with protein structure features represents an opportunity to explore this relationship, yet two important limitations have precluded a proper analysis [...] Read more.

Protein structure and protein function should be related, yet the nature of this relationship remains unsolved. Mapping the critical residues for protein function with protein structure features represents an opportunity to explore this relationship, yet two important limitations have precluded a proper analysis of the structure-function relationship of proteins: (i) the lack of a formal definition of what critical residues are and (ii) the lack of a systematic evaluation of methods and protein structure features. To address this problem, here we introduce an index to quantify the protein-function criticality of a residue based on experimental data and a strategy aimed to optimize both, descriptors of protein structure (physicochemical and centrality descriptors) and machine learning algorithms, to minimize the error in the classification of critical residues. We observed that both physicochemical and centrality descriptors of residues effectively relate protein structure and protein function, and that physicochemical descriptors better describe critical residues. We also show that critical residues are better classified when residue criticality is considered as a binary attribute (i.e., residues are considered critical or not critical). Using this binary annotation for critical residues 8 models rendered accurate and non-overlapping classification of critical residues, confirming the multi-factorial character of the structure-function relationship of proteins. Full article

(This article belongs to the Special Issue Computational Analysis for Protein Structure and Interaction)

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12 pages, 1240 KiB

Open AccessArticle

Furanones and Anthranilic Acid Derivatives from the Endophytic Fungus Dendrothyrium variisporum

by Rémy B. Teponno^1,2,†, Sara R. Noumeur^1,3,4,†, Soleiman E. Helaly^1,5, Stephan Hüttel¹, Daoud Harzallah³ and Marc Stadler^1,*

¹ Department of Microbial Drugs, Helmholtz Centre for Infection Research and German Centre for Infection Research (DZIF), partner site Hannover/Braunschweig, Inhoffenstrasse 7, 38124 Braunschweig, Germany

² Department of Chemistry, Faculty of Science, University of Dschang, P.O. Box 67, Dschang, Cameroon

³ Laboratory of Applied Microbiology, Department of Microbiology, Faculty of Natural and Life Sciences, University Sétif 1 Ferhat Abbas, 19000 Sétif, Algeria

⁴ Department of Microbiology-Biochemistry, Faculty of Natural and Life Sciences, University of Batna 2, 05000 Batna, Algeria

⁵ Department of Chemistry, Faculty of Science, Aswan University, 81528 Aswan, Egypt

^† These authors contributed equally to this work.

Molecules 2017, 22(10), 1674; https://doi.org/10.3390/molecules22101674 - 9 Oct 2017

Cited by 22 | Viewed by 6016

Abstract

Extracts from an endophytic fungus isolated from the roots of the Algerian plant Globularia alypum showed prominent antimicrobial activity in a screening for novel antibiotics. The producer organism was identified as Dendrothyrium variisporum by means of morphological studies and molecular phylogenetic methods. Studies [...] Read more.

Extracts from an endophytic fungus isolated from the roots of the Algerian plant Globularia alypum showed prominent antimicrobial activity in a screening for novel antibiotics. The producer organism was identified as Dendrothyrium variisporum by means of morphological studies and molecular phylogenetic methods. Studies on the secondary metabolite production of this strain in various culture media revealed that the major components from shake flasks were massarilactones D (1) and H (2) as well as two new furanone derivatives for which we propose the trivial names (5S)-cis-gregatin B (3) and graminin D (4). Scale-up of the fermentation in a 10 L bioreactor yielded massarilactone D and several further metabolites. Among those were three new anthranilic acid derivatives (5–7), two known anthranilic acid analogues (8 and 9) and three cyclopeptides (10–12). Their structures were elucidated on the basis of extensive spectroscopic analysis (1D- and 2D-NMR), high-resolution mass spectrometry (HRESIMS), and the application of the modified Mosher’s method. The isolated metabolites were tested for antimicrobial and cytotoxic activities against various bacteria, fungi, and two mammalian cell lines. The new Metabolite 5 and Compound 9 exhibited antimicrobial activity while Compound 9 showed cytotoxicity activity against KB3.1 cells. Full article

(This article belongs to the Section Natural Products Chemistry)

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9 pages, 1228 KiB

Open AccessArticle

Gypmacrophin A, a Rare Pentacyclic Sesterterpenoid, Together with Three Depsides, Functioned as New Chemical Evidence for Gypsoplaca macrophylla (Zahlbr.) Timdal Identification

by Yuan-Fei Zhou^1,2, Hai-Xia Shi³, Kun Hu^1,2, Jian-Wei Tang^1,2, Xing-Ren Li^1,2, Xue Du¹, Han-Dong Sun¹

, Li-Song Wang^3,* and Jian-Xin Pu^1,*

¹ State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China

² Kunming College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100039, China

³ Key Laboratory for Plant Biodiversity and Biogeography of East Asia, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China

Molecules 2017, 22(10), 1675; https://doi.org/10.3390/molecules22101675 - 9 Oct 2017

Cited by 6 | Viewed by 11301

Abstract

The phytochemical investigation on 1 g of materials from Gypsoplaca macrophylla (Zahlbr.) Timdal resulted in the discovery of gypmacrophin A, a rare pentacyclic sesterterpenoid; brialmontin III, a new polysubstituted depside and two known ones, brialmontins I and II. The structure and absolute configurations [...] Read more.

The phytochemical investigation on 1 g of materials from Gypsoplaca macrophylla (Zahlbr.) Timdal resulted in the discovery of gypmacrophin A, a rare pentacyclic sesterterpenoid; brialmontin III, a new polysubstituted depside and two known ones, brialmontins I and II. The structure and absolute configurations of gypmacrophin A were elucidated by spectroscopic analyses and computational methods. Gypmacrophin A showed weak inhibition of AchE with an IC₅₀ value of 32.03 μM. The four compounds provided new chemical evidence for G. macrophylla identification. Full article

(This article belongs to the Special Issue Diversity of Terpenoids)

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17 pages, 2728 KiB

Open AccessFeature PaperArticle

Exploring the Degradation of Ibuprofen by Bacillus thuringiensis B1(2015b): The New Pathway and Factors Affecting Degradation

by Ariel Marchlewicz¹, Urszula Guzik¹

, Wojciech Smułek² and Danuta Wojcieszyńska^1,*

¹ Department of Biochemistry, Faculty of Biology and Environmental Protection, University of Silesia in Katowice, Jagiellońska 28, 40-032 Katowice, Poland

² Institute of Chemical Technology and Engineering, Poznan University of Technology, Berdychowo 4, 60-965 Poznan, Poland

Molecules 2017, 22(10), 1676; https://doi.org/10.3390/molecules22101676 - 9 Oct 2017

Cited by 64 | Viewed by 9802

Abstract

Ibuprofen is one of the most often detected pollutants in the environment, particularly at landfill sites and in wastewaters. Contamination with pharmaceuticals is often accompanied by the presence of other compounds which may influence their degradation. This work describes the new degradation pathway [...] Read more.

Ibuprofen is one of the most often detected pollutants in the environment, particularly at landfill sites and in wastewaters. Contamination with pharmaceuticals is often accompanied by the presence of other compounds which may influence their degradation. This work describes the new degradation pathway of ibuprofen by Bacillus thuringiensis B1(2015b), focusing on enzymes engaged in this process. It is known that the key intermediate which transformation limits the velocity of the degradation process is hydroxyibuprofen. As the degradation rate also depends on various factors, the influence of selected heavy metals and aromatic compounds on ibuprofen degradation by the B1(2015b) strain was examined. Based on the values of non-observed effect concentration (NOEC) it was found that the toxicity of tested metals increases from Hg(II) < Cu(II) < Cd(II) < Co(II) < Cr(VI). Despite the toxic effect of metals, the biodegradation of ibuprofen was observed. The addition of Co²⁺ ions into the medium significantly extended the time necessary for the complete removal of ibuprofen. It was shown that Bacillus thuringiensis B1(2015b) was able to degrade ibuprofen in the presence of phenol, benzoate, and 2-chlorophenol. Moreover, along with the removal of ibuprofen, degradation of phenol and benzoate was observed. Introduction of 4-chlorophenol into the culture completely inhibits degradation of ibuprofen. Full article

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12 pages, 896 KiB

Open AccessArticle

Molecular Affinity of Mabolo Extracts to an Octopamine Receptor of a Fruit Fly

by Francoise Neil D. Dacanay, Ma. Carmina Joyce A. Ladra, Hiyas A. Junio and Ricky B. Nellas^*

Institute of Chemistry, University of the Philippines Diliman, Quezon City 1101, Philippines

Molecules 2017, 22(10), 1677; https://doi.org/10.3390/molecules22101677 - 24 Oct 2017

Cited by 12 | Viewed by 10221

Abstract

Essential oils extracted from plants are composed of volatile organic compounds that can affect insect behavior. Identifying the active components of the essential oils to their biochemical target is necessary to design novel biopesticides. In this study, essential oils extracted from Diospyros discolor [...] Read more.

Essential oils extracted from plants are composed of volatile organic compounds that can affect insect behavior. Identifying the active components of the essential oils to their biochemical target is necessary to design novel biopesticides. In this study, essential oils extracted from Diospyros discolor (Willd.) were analyzed using gas chromatography mass spectroscopy (GC-MS) to create an untargeted metabolite profile. Subsequently, a conformational ensemble of the Drosophila melanogaster octopamine receptor in mushroom bodies (OAMB) was created from a molecular dynamics simulation to resemble a flexible receptor for docking studies. GC-MS analysis revealed the presence of several metabolites, i.e. mostly aromatic esters. Interestingly, these aromatic esters were found to exhibit relatively higher binding affinities to OAMB than the receptor’s natural agonist, octopamine. The molecular origin of this observed enhanced affinity is the

π

-stacking interaction between the aromatic moieties of the residues and ligands. This strategy, computational inspection in tandem with untargeted metabolomics, may provide insights in screening the essential oils as potential OAMB inhibitors. Full article

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16 pages, 669 KiB

Open AccessArticle

Synthesis and Biological Activity of Novel (Z)- and (E)-Verbenone Oxime Esters

by Qiong Hu¹, Gui-Shan Lin^1,*, Wen-Gui Duan^1,*, Min Huang¹ and Fu-Hou Lei²

¹ School of Chemistry and Chemical Engineering, Guangxi University, Nanning 530004, Guangxi, China

² Guangxi Key Laboratory of Chemistry and Engineering of Forest Products, Nanning 530008, Guangxi, China

Molecules 2017, 22(10), 1678; https://doi.org/10.3390/molecules22101678 - 12 Oct 2017

Cited by 35 | Viewed by 6329

Abstract

Twenty-seven (Z)- and (E)-verbenone derivatives bearing an oxime ester moiety were designed and synthesized in search of novel bioactive molecules. Their structures were confirmed by UV-Vis, FTIR, NMR, ESI-MS, and elemental analysis. The antifungal and herbicidal activities of the [...] Read more.

Twenty-seven (Z)- and (E)-verbenone derivatives bearing an oxime ester moiety were designed and synthesized in search of novel bioactive molecules. Their structures were confirmed by UV-Vis, FTIR, NMR, ESI-MS, and elemental analysis. The antifungal and herbicidal activities of the target compounds were preliminarily evaluated. As a result, compound (E)-4n (R = β-pyridyl) exhibited excellent antifungal activity with growth inhibition percentages of 92.2%, 80.0% and 76.3% against Alternaria solani, Physalospora piricola, and Cercospora arachidicola at 50 µg/mL, showing comparable or better antifungal activity than the commercial fungicide chlorothalonil with growth inhibition of 96.1%, 75.0% and 73.3%, respectively, and 1.7−5.5-fold more growth inhibition than its stereoisomer (Z)-4n (R = β-pyridyl) with inhibition rates of 22.6%, 28.6% and 43.7%, respectively. In addition, seven compounds displayed significant growth inhibition activity of over 90% against the root of rape (Brassica campestris) at 100 µg/mL, exhibiting much better herbicidal activity than the commercial herbicide flumioxazin with a 63.0% growth inhibition. Among these seven compounds, compound (E)-4n (R = β-pyridyl) inhibited growth by 92.1%, which was 1.7-fold more than its stereoisomer (Z)-4n (R = β-pyridyl) which inhibited growth by 54.0%. Full article

(This article belongs to the Section Organic Chemistry)

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13 pages, 5038 KiB

Open AccessFeature PaperArticle

Tetraphenylpyrimidine-Based AIEgens: Facile Preparation, Theoretical Investigation and Practical Application

by Junkai Liu^1,2, Lingxiang Pan¹, Qian Peng^2,* and Anjun Qin^1,*

¹ State Key Laboratory of Luminescent Materials and Devices, South China University of Technology, Guangzhou 510640, China

² Key Laboratory of Organic Solids, Beijing National Laboratory for Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China

Molecules 2017, 22(10), 1679; https://doi.org/10.3390/molecules22101679 - 10 Oct 2017

Cited by 9 | Viewed by 4884

Abstract

Aggregation-induced emission (AIE) has become a hot research area and tremendous amounts of AIE-active luminogens (AIEgens) have been generated. To further promote the development of AIE, new AIEgens are highly desirable. Herein, new AIEgens based on tetraphenylpyrimidine (TPPM) are rationally designed according to [...] Read more.

Aggregation-induced emission (AIE) has become a hot research area and tremendous amounts of AIE-active luminogens (AIEgens) have been generated. To further promote the development of AIE, new AIEgens are highly desirable. Herein, new AIEgens based on tetraphenylpyrimidine (TPPM) are rationally designed according to the AIE mechanism of restriction of intramolecular motion, and facilely prepared under mild reaction conditions. The photophysical property of the generated TPPM, TPPM-4M and TPPM-4P are systematically investigated and the results show that they feature the aggregation-enhanced emission (AEE) characteristics. Theoretical study shows the high-frequency bending vibrations in the central pyrimidine ring of TPPM derivatives dominate the nonradiative decay channels. Thanks to the AEE feature, their aggregates can be used to detect explosives with super-amplification quenching effects, and the sensing ability is higher than typical AIE-active tetraphenylethene. It is anticipated that TPPM derivatives could serve as a new type of widely used AIEgen based on their facile preparation and good thermo-, photo- and chemostabilities. Full article

(This article belongs to the Special Issue Aggregation-Induced Emission: Commemorative Issue in Honor of Professor Ben Zhong Tang’s Research Achievements on the Occasion of His 60th Birthday)

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13 pages, 1132 KiB

Open AccessReview

Natriuretic Peptides: The Case of Prostate Cancer

by Letizia Mezzasoma, Matthew J. Peirce, Alba Minelli and Ilaria Bellezza^*

Dipartimento di Medicina Sperimentale, Università di Perugia, 06123 Perugia, Italy

Molecules 2017, 22(10), 1680; https://doi.org/10.3390/molecules22101680 - 10 Oct 2017

Cited by 11 | Viewed by 6930

Abstract

Cardiac natriuretic peptides have long been known to act as main players in the homeostatic control of blood pressure, salt and water balance. However, in the last few decades, new properties have been ascribed to these hormones. A systematic review of English articles [...] Read more.

Cardiac natriuretic peptides have long been known to act as main players in the homeostatic control of blood pressure, salt and water balance. However, in the last few decades, new properties have been ascribed to these hormones. A systematic review of English articles using MEDLINE Search terms included prostate cancer, inflammation, cardiac hormones, atrial natriuretic peptide, and brain natriuretic peptide. Most recent publications were selected. Natriuretic peptides are strongly connected to the immune system, whose two branches, innate and adaptive, are finely tuned and organized to kill invaders and repair injured tissues. These peptides control the immune response and act as anti-inflammatory and immune-modulatory agents. In addition, in cancers, natriuretic peptides have anti-proliferative effects by molecular mechanisms based on the inhibition/regulation of several pathways promoting cell proliferation and survival. Nowadays, it is accepted that chronic inflammation is a crucial player in prostate cancer development and progression. In this review, we summarize the current knowledge on the link between prostate cancer and inflammation and the potential use of natriuretic peptides as anti-inflammatory and anticancer agents. Full article

(This article belongs to the Section Medicinal Chemistry)

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14 pages, 5853 KiB

Open AccessArticle

Middle Ear Prosthesis with Bactericidal Efficacy—In Vitro Investigation

by Magdalena Ziąbka^1,*, Michał Dziadek²

, Elżbieta Menaszek³

, Rafał Banasiuk⁴ and Aleksandra Królicka⁴

¹ AGH University of Science and Technology, Faculty of Materials Science and Ceramics, Department of Ceramics and Refractories, Krakow 30-059, Poland

² AGH University of Science and Technology, Faculty of Materials Science and Ceramics, Department of Glass Technology and Amorphous Coatings, Krakow 30-059, Poland

³ UJ-Jagiellonian University, Medical College, Faculty of Pharmacy, Department of Cytobiology, Krakow 30-001, Poland

⁴ University of Gdansk, Intercollegiate Faculty of Biotechnology UG-GUMed, Department of Biotechnology, Laboratory of Biologically Active Compounds, Gdansk 80-307, Poland

Molecules 2017, 22(10), 1681; https://doi.org/10.3390/molecules22101681 - 10 Oct 2017

Cited by 25 | Viewed by 5743

Abstract

Materials used in ossicular replacement prostheses must possess appropriate biological properties, such as biocompatibility, stability, no cytotoxicity. Due to the risk of infection (otitis media and chronic otitis media), it is desirable to use an antibacterial agent for illness prevention during the ossicular [...] Read more.

Materials used in ossicular replacement prostheses must possess appropriate biological properties, such as biocompatibility, stability, no cytotoxicity. Due to the risk of infection (otitis media and chronic otitis media), it is desirable to use an antibacterial agent for illness prevention during the ossicular reconstruction. The goal of this work was to observe biological properties of a new composite prosthesis made of ABS containing silver nanoparticles (AgNPs 45T). Samples for biological tests and then a prototype of middle ear prosthesis were prepared using injection moulding and extrusion techniques. In vitro experiments were carried out to assess bactericidal efficacy against Staphylococcus aureus and Pseudomona aeruginosa standard strains, cell proliferation, viability and cytotoxicity, using Hs680.Tr. fibroblast cells. Surface parameters of the samples were evaluated, including roughness and wettability. The silver ions were continually released from the polymer in aqueous solution. The silver ions release was measured as increasing with time and concentration of the silver nanoparticles in the polymer matrix. No cytotoxicity effect was observed, while bactericidal efficacy was noticed for silver nanoparticles. The roughness studies showed an increase in roughness for the samples with silver nanoparticles. All polymer and composite materials containing silver nanoparticles showed hydrophilic properties. The composites were found to release silver ions at a concentration level capable of rendering the antimicrobial efficacy even with the lowest concentration of silver nanoparticles in the material. Our results demonstrate that middle ear prosthesis made of polymer and silver nanoparticles may eliminate bacteria during inflammation in the middle ear. Full article

(This article belongs to the Special Issue Antibacterial Materials and Coatings)

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14 pages, 2300 KiB

Open AccessCommunication

Design, Modeling and Synthesis of 1,2,3-Triazole-Linked Nucleoside-Amino Acid Conjugates as Potential Antibacterial Agents

by Sarah N. Malkowski

, Carolyn F. Dishuck

, Gene G. Lamanilao

, Carter P. Embry, Christopher S. Grubb, Mauricio Cafiero and Larryn W. Peterson^*

Department of Chemistry, Rhodes College, 2000 North Parkway, Memphis, TN 38112, USA

Molecules 2017, 22(10), 1682; https://doi.org/10.3390/molecules22101682 - 10 Oct 2017

Cited by 12 | Viewed by 8594

Abstract

Copper-catalyzed azide-alkyne cycloadditions (CuAAC or click chemistry) are convenient methods to easily couple various pharmacophores or bioactive molecules. A new series of 1,2,3-triazole-linked nucleoside-amino acid conjugates have been designed and synthesized in 57–76% yields using CuAAC. The azido group was introduced on the [...] Read more.

Copper-catalyzed azide-alkyne cycloadditions (CuAAC or click chemistry) are convenient methods to easily couple various pharmacophores or bioactive molecules. A new series of 1,2,3-triazole-linked nucleoside-amino acid conjugates have been designed and synthesized in 57–76% yields using CuAAC. The azido group was introduced on the 5′-position of uridine or the acyclic analogue using the tosyl-azide exchange method and alkylated serine or proparylglycine was the alkyne. Modeling studies of the conjugates in the active site of LpxC indicate they have promise as antibacterial agents. Full article

(This article belongs to the Section Bioorganic Chemistry)

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10 pages, 4871 KiB

Open AccessArticle

Anti-Inflammatory Pyranochalcone Derivative Attenuates LPS-Induced Acute Kidney Injury via Inhibiting TLR4/NF-κB Pathway

by Min Shi^†, Xiaoxi Zeng^†, Fan Guo, Rongshuang Huang, Yanhuan Feng, Liang Ma^*

, Li Zhou

and Ping Fu^*

¹ Kidney Research Institute, Division of Nephrology, West China Hospital of Sichuan University, Chengdu 610041, Sichuan, China

^† These authors contributed equally to this article.

Molecules 2017, 22(10), 1683; https://doi.org/10.3390/molecules22101683 - 10 Oct 2017

Cited by 55 | Viewed by 8385

Abstract

Treatment of septic acute kidney injury (AKI) has still been beyond satisfaction, although anti-inflammatory therapy is beneficial for sepsis-induced AKI. Compound 5b was derived from natural pyranochalcones and exhibited potent anti-inflammatory activity in adjuvant-induced arthritis. In this study, we aimed to investigate the [...] Read more.

Treatment of septic acute kidney injury (AKI) has still been beyond satisfaction, although anti-inflammatory therapy is beneficial for sepsis-induced AKI. Compound 5b was derived from natural pyranochalcones and exhibited potent anti-inflammatory activity in adjuvant-induced arthritis. In this study, we aimed to investigate the renoprotective effects and potential mechanism of 5b against lipopolysaccharide (LPS)-induced AKI. C57BL/6 mice and human renal proximal tubule cell line (HK-2 cell) were treated with LPS, respectively. Compound 5b was orally administrated at a dose of 25 mg/kg/day for 5 days before LPS (10 mg/kg) intraperitoneal injection. Cells were pretreated with 25 μg/mL 5b for 30 min before LPS (1 μg/mL) treatment. Pretreatment with 5b markedly alleviated tubular injury and renal dysfunction in LPS-induced AKI. The expression of IL-1β, IL-6, and TNF-α both in renal tissue of AKI mice and in the LPS-stimulated HK-2 cell culture medium were reduced by 5b treatment (p < 0.05). The results of immunohistochemistry staining showed that 5b reduced the expression of NF-κB p65 in kidneys. Similarly, 5b decreased the LPS-induced levels of NF-κB p65 and TLR4 proteins in kidneys and HK-2 cells. These data demonstrated that a potent pyranochalcone derivative, 5b, exhibited renoprotective effect against LPS-induced AKI, which was associated with anti-inflammatory activity by inhibiting the TLR4/NF-κB pathway. Full article

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24 pages, 2905 KiB

Open AccessReview

Participation of the Halogens in Photochemical Reactions in Natural and Treated Waters

by Yi Yang and Joseph J. Pignatello^*

Department of Environmental Sciences, The Connecticut Agricultural Experiment Station, 123 Huntington St., P.O. Box 1106, New Haven, CT 06504-1106, USA

Molecules 2017, 22(10), 1684; https://doi.org/10.3390/molecules22101684 - 13 Oct 2017

Cited by 69 | Viewed by 12301

Abstract

Halide ions are ubiquitous in natural waters and wastewaters. Halogens play an important and complex role in environmental photochemical processes and in reactions taking place during photochemical water treatment. While inert to solar wavelengths, halides can be converted into radical and non-radical reactive [...] Read more.

Halide ions are ubiquitous in natural waters and wastewaters. Halogens play an important and complex role in environmental photochemical processes and in reactions taking place during photochemical water treatment. While inert to solar wavelengths, halides can be converted into radical and non-radical reactive halogen species (RHS) by sensitized photolysis and by reactions with secondary reactive oxygen species (ROS) produced through sunlight-initiated reactions in water and atmospheric aerosols, such as hydroxyl radical, ozone, and nitrate radical. In photochemical advanced oxidation processes for water treatment, RHS can be generated by UV photolysis and by reactions of halides with hydroxyl radicals, sulfate radicals, ozone, and other ROS. RHS are reactive toward organic compounds, and some reactions lead to incorporation of halogen into byproducts. Recent studies indicate that halides, or the RHS derived from them, affect the concentrations of photogenerated reactive oxygen species (ROS) and other reactive species; influence the photobleaching of dissolved natural organic matter (DOM); alter the rates and products of pollutant transformations; lead to covalent incorporation of halogen into small natural molecules, DOM, and pollutants; and give rise to certain halogen oxides of concern as water contaminants. The complex and colorful chemistry of halogen in waters will be summarized in detail and the implications of this chemistry for global biogeochemical cycling of halogen, contaminant fate in natural waters, and water purification technologies will be discussed. Full article

(This article belongs to the Special Issue Photon-involving Purification of Water and Air)

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12 pages, 944 KiB

Open AccessArticle

Antibacterial and Antitubercular Activities of Cinnamylideneacetophenones

by Carlos R. Polaquini^1,†

, Guilherme S. Torrezan^1,†, Vanessa R. Santos², Ana C. Nazaré¹, Débora L. Campos³, Laíza A. Almeida¹

, Isabel C. Silva³

, Henrique Ferreira⁴

, Fernando R. Pavan³

, Cristiane Duque²

and Luis O. Regasini^1,*

¹ Laboratory of Green and Medicinal Chemistry, Department of Chemistry and Environmental Sciences, Institute of Biosciences, Humanities and Exact Sciences, São Paulo State University (Unesp), São José do Rio Preto, SP 15054-000, Brazil

² Department of Pediatric Dentistry and Public Health, School of Dentistry, São Paulo State University (Unesp), Araçatuba, SP 16015-050, Brazil

³ Department of Biological Sciences, School of Pharmaceutical Sciences, São Paulo State University (Unesp), Araraquara, SP 14800-903, Brazil

⁴ Department of Biochemistry and Microbiology, Institute of Biosciences, São Paulo State University (Unesp), Rio Claro, SP 13506-900, Brazil

^† These two authors contributed equally to this work.

Molecules 2017, 22(10), 1685; https://doi.org/10.3390/molecules22101685 - 10 Oct 2017

Cited by 25 | Viewed by 7350

Abstract

Cinnamaldehyde is a natural product with broad spectrum of antibacterial activity. In this work, it was used as a template for design and synthesis of a series of 17 cinnamylideneacetophenones. Phenolic compounds 3 and 4 exhibited MIC (minimum inhibitory concentration) and MBC (minimum [...] Read more.

Cinnamaldehyde is a natural product with broad spectrum of antibacterial activity. In this work, it was used as a template for design and synthesis of a series of 17 cinnamylideneacetophenones. Phenolic compounds 3 and 4 exhibited MIC (minimum inhibitory concentration) and MBC (minimum bactericidal concentration) values of 77.9 to 312 µM against Staphylococcus aureus, Streptococcus mutans, and Streptococcus sanguinis. Compounds 2, 7, 10, and 18 presented potent effects against Mycobacterium tuberculosis (57.2 µM ≤ MIC ≤ 70.9 µM). Hydrophilic effects caused by substituents on ring B increased antibacterial activity against Gram-positive species. Thus, log P_o/w were calculated by using high-performance liquid chromatography-photodiode array detection (HPLC-PDA) analyses, and cinnamylideneacetophenones presented values ranging from 2.5 to 4.1. In addition, the effects of 3 and 4 were evaluated on pulmonary cells, indicating their moderate toxicity (46.3 µM ≤ IC₅₀ ≤ 96.7 µM) when compared with doxorubicin. Bioactive compounds were subjected to in silico prediction of pharmacokinetic properties, and did not violate Lipinski’s and Veber’s rules, corroborating their potential bioavailability by an oral route. Full article

(This article belongs to the Special Issue Emerging Drug Discovery Approaches against Infectious Diseases)

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12 pages, 4409 KiB

Open AccessArticle

Identification of Metabolites of the Cardioprotective Alkaloid Dehydrocorydaline in Rat Plasma and Bile by Liquid Chromatography Coupled with Triple Quadrupole Linear Ion Trap Mass Spectrometry

by Huanyu Guan^1,2

, Kaitong Li¹, Xiaoming Wang¹, Xiaomei Luo¹, Meifeng Su¹, Wenting Tan¹, Xiaoyan Chang¹ and Yue Shi^1,*

¹ Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, China

² School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang 550004, China

Molecules 2017, 22(10), 1686; https://doi.org/10.3390/molecules22101686 - 10 Oct 2017

Cited by 14 | Viewed by 5561

Abstract

Dehydrocorydaline (DHC), a quaternary alkaloid from Corydalis yanhusuo, has been demonstrated to be the active constituent in the treatment of coronary heart disease. In this study, a high-performance liquid chromatography–electrospray ionization–triple quadrupole linear ion trap mass spectrometry (HPLC–ESI–QTRAP MS) technique was used [...] Read more.

Dehydrocorydaline (DHC), a quaternary alkaloid from Corydalis yanhusuo, has been demonstrated to be the active constituent in the treatment of coronary heart disease. In this study, a high-performance liquid chromatography–electrospray ionization–triple quadrupole linear ion trap mass spectrometry (HPLC–ESI–QTRAP MS) technique was used to identify DHC metabolites in plasma and bile after oral administration of DHC to rats. A total of 18 metabolites (M1 to M18) were identified and characterized by LC–MS/MS in the positive ion mode. These 18 metabolites were all present in rat bile, while only 9 were detected in plasma. O-demethylation, hydroxylation, di-hydroxylation, glucuronidation of O-demethyl DHC, sulfation of O-demethyl DHC and di-hydroxylation of dehydro-DHC were the major metabolic pathways of DHC. This is the first time that these metabolites of DHC have been identified in rat plasma and bile, which provides useful information for further analysis of the biotransformation of DHC and other quaternary protoberberine-type alkaloids. Full article

(This article belongs to the Collection Phytochemicals: Biosynthesis, Metabolism and Biological Activities)

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14 pages, 3211 KiB

Open AccessFeature PaperArticle

Phosphorus-Sulfur Heterocycles Incorporating an O-P(S)-O or O-P(S)-S-S-P(S)-O Scaffold: One-Pot Synthesis and Crystal Structure Study

by Guoxiong Hua, Kate Davidson, David B. Cordes, Junyi Du, Alexandra M. Z. Slawin

and J. Derek Woollins^*

EaStCHEM School of Chemistry, University of St Andrews, Fife KY16 9ST, UK

Molecules 2017, 22(10), 1687; https://doi.org/10.3390/molecules22101687 - 10 Oct 2017

Cited by 2 | Viewed by 5508

Abstract

A new one-pot preparative route was developed to synthesize novel organophosphorus-sulfur heterocycles via the reaction of the four-membered ring thionation reagent [2,4-diferrocenyl-1,3,2,4-diathiadiphosphetane 2,4-disulfide (FcLR, a ferrocene analogue of Lawesson’s reagent)] and alkenyl/aryl-diols and I₂ (or SOCl₂) in the presence of [...] Read more.

A new one-pot preparative route was developed to synthesize novel organophosphorus-sulfur heterocycles via the reaction of the four-membered ring thionation reagent [2,4-diferrocenyl-1,3,2,4-diathiadiphosphetane 2,4-disulfide (FcLR, a ferrocene analogue of Lawesson’s reagent)] and alkenyl/aryl-diols and I₂ (or SOCl₂) in the presence of triethylamine. Therefore, a series of five- to ten-membered heterocycles bearing an O-P(S)-O or an O-P(S)-S-S-P(S)-O linkage were synthesized. The synthesis features a novel application of the multicomponent reaction, providing an efficient and environmentally benign method for the preparation of the unusual phosphorus-sulfur heterocycles. Seven representative X-ray structures confirm the formation of these heterocycles. Full article

(This article belongs to the Special Issue Main Group Elements in Synthesis)

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21 pages, 3761 KiB

Open AccessArticle

Synthesis of ¹¹C-Labelled Ureas by Palladium(II)-Mediated Oxidative Carbonylation

by Sara Roslin^1,*

, Peter Brandt¹

, Patrik Nordeman¹, Mats Larhed²

, Luke R. Odell¹ and Jonas Eriksson¹

¹ Organic Pharmaceutical Chemistry, Department of Medicinal Chemistry, BMC, Uppsala University, Box 574, SE-751 23 Uppsala, Sweden

² Science for Life Laboratory, Department of Medicinal Chemistry, BMC, Uppsala University, Box 574, SE-751 23 Uppsala, Sweden

Molecules 2017, 22(10), 1688; https://doi.org/10.3390/molecules22101688 - 10 Oct 2017

Cited by 14 | Viewed by 6418

Abstract

Positron emission tomography is an imaging technique with applications in clinical settings as well as in basic research for the study of biological processes. A PET tracer, a biologically active molecule where a positron-emitting radioisotope such as carbon-11 has been incorporated, is used [...] Read more.

Positron emission tomography is an imaging technique with applications in clinical settings as well as in basic research for the study of biological processes. A PET tracer, a biologically active molecule where a positron-emitting radioisotope such as carbon-11 has been incorporated, is used for the studies. Development of robust methods for incorporation of the radioisotope is therefore of the utmost importance. The urea functional group is present in many biologically active compounds and is thus an attractive target for incorporation of carbon-11 in the form of [¹¹C]carbon monoxide. Starting with amines and [¹¹C]carbon monoxide, both symmetrical and unsymmetrical ¹¹C-labelled ureas were synthesised via a palladium(II)-mediated oxidative carbonylation and obtained in decay-corrected radiochemical yields up to 65%. The added advantage of using [¹¹C]carbon monoxide was shown by the molar activity obtained for an inhibitor of soluble epoxide hydrolase (247 GBq/μmol–319 GBq/μmol). DFT calculations were found to support a reaction mechanism proceeding through an ¹¹C-labelled isocyanate intermediate. Full article

(This article belongs to the Special Issue Current Aspects of Radiopharmaceutical Chemistry)

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29 pages, 864 KiB

Open AccessReview

A Review on the Phytochemistry, Pharmacology, Pharmacokinetics and Toxicology of Geniposide, a Natural Product

by Mingqiu Shan^1,*

, Sheng Yu¹, Hui Yan¹, Sheng Guo¹, Wei Xiao², Zhenzhong Wang², Li Zhang¹, Anwei Ding¹, Qinan Wu¹ and Sam Fong Yau Li³

¹ Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing 210023, China

² National Key Laboratory of Pharmaceutical New Technology for Chinese Medicine, Jiangsu Kanion Pharmaceutical Co. Ltd., Lianyungang 222001, China

³ Department of Chemistry, National University of Singapore, Singapore 117543, Singapore

Molecules 2017, 22(10), 1689; https://doi.org/10.3390/molecules22101689 - 10 Oct 2017

Cited by 106 | Viewed by 12058

Abstract

Iridoid glycosides are natural products occurring widely in many herbal plants. Geniposide (C₁₇H₂₄O₁₀) is a well-known one, present in nearly 40 species belonging to various families, especially the Rubiaceae. Along with this herbal component, dozens of its [...] Read more.

Iridoid glycosides are natural products occurring widely in many herbal plants. Geniposide (C₁₇H₂₄O₁₀) is a well-known one, present in nearly 40 species belonging to various families, especially the Rubiaceae. Along with this herbal component, dozens of its natural derivatives have also been isolated and characterized by researchers. Furthermore, a large body of pharmacological evidence has proved the various biological activities of geniposide, such as anti-inflammatory, anti-oxidative, anti-diabetic, neuroprotective, hepatoprotective, cholagogic effects and so on. However, there have been some research articles on its toxicity in recent years. Therefore, this review paper aims to provide the researchers with a comprehensive profile of geniposide on its phytochemistry, pharmacology, pharmacokinetics and toxicology in order to highlight some present issues and future perspectives as well as to help us develop and utilize this iridoid glycoside more efficiently and safely. Full article

(This article belongs to the Collection Bioactive Compounds)

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22 pages, 2278 KiB

Open AccessArticle

Structure, Absolute Configuration, and Antiproliferative Activity of Abietane and Icetexane Diterpenoids from Salvia ballotiflora

by Baldomero Esquivel^1,*, Celia Bustos-Brito¹

, Mariano Sánchez-Castellanos², Antonio Nieto-Camacho¹, Teresa Ramírez-Apan¹, Pedro Joseph-Nathan³

and Leovigildo Quijano^1,*

¹ Instituto de Química, Universidad Nacional Autónoma de México (UNAM), Circuito Exterior, Ciudad Universitaria, Mexico City 04510, Mexico

² Facultad de Química, Universidad Nacional Autónoma de México, Circuito Exterior, Ciudad Universitaria, Mexico City 04510, Mexico

³ Departamento de Química, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Apartado 14-740, Mexico City 07000, Mexico

Molecules 2017, 22(10), 1690; https://doi.org/10.3390/molecules22101690 - 18 Oct 2017

Cited by 29 | Viewed by 7214

Abstract

From the aerial parts of Salvia ballotiflora, eleven diterpenoids were isolated; among them, four icetexanes and one abietane (1–5) are reported for the first time. Their structures were established by spectroscopic means, mainly ¹H- and ¹³C-NMR, [...] Read more.

From the aerial parts of Salvia ballotiflora, eleven diterpenoids were isolated; among them, four icetexanes and one abietane (1–5) are reported for the first time. Their structures were established by spectroscopic means, mainly ¹H- and ¹³C-NMR, including 1D and 2D homo- and hetero-nuclear experiments. Most of the isolated diterpenoids were tested for their antiproliferative, anti-inflammatory, and radical scavenging activities using the sulforhodamine B assay on six cancer cell lines, the TPA-induced ear edema test in mice, and the reduction of the DPPH assay, respectively. Some diterpenoids showed anti-proliferative activity, these being icetexanes 6 and 3, which were the most active with IC₅₀ (μM) = 0.27 ± 0.08 and 1.40 ± 0.03, respectively, for U251 (human glioblastoma) and IC₅₀ (μM) = 0.0.46 ± 0.05 and 0.82 ± 0.06 for SKLU-1 (human lung adenocarcinoma), when compared with adriamycin (IC₅₀ (μM) = 0.08 ± 0.003 and 0.05 ± 0.003, as the positive control), respectively. Compounds 3 and 10 showed significant reduction of the induced ear edema of 37.4 ± 2.8 and 25.4 ± 3.0% (at 1.0 μmol/ear), respectively. Compound 4 was the sole active diterpenoid in the antioxidant assay (IC₅₀ = 98. 4 ± 3.3), using α-tocopherol as the positive control (IC₅₀ (μM) = 31.7 ± 1.04). The diterpenoid profile found is of chemotaxonomic relevance and reinforces the evolutionary link of S. ballotiflora with other members of the section Tomentellae. Full article

(This article belongs to the Collection Bioactive Compounds)

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22 pages, 9772 KiB

Open AccessReview

Facile and Green Synthesis of Saturated Cyclic Amines

by Arruje Hameed¹, Sadia Javed¹, Razia Noreen¹, Tayyaba Huma², Sarosh Iqbal³, Huma Umbreen⁴, Tahsin Gulzar³ and Tahir Farooq^3,*

¹ Department of Biochemistry, Government College University, Faisalabad 38900, Pakistan

² Department of Bioinformatics and Biotechnology, Government College University, Faisalabad 38900, Pakistan

³ Department of Applied Chemistry, Government College University, Faisalabad 38900, Pakistan

⁴ Department of Home Economics, Government College Women University, Faisalabad 38900, Pakistan

Molecules 2017, 22(10), 1691; https://doi.org/10.3390/molecules22101691 - 12 Oct 2017

Cited by 22 | Viewed by 14165

Abstract

Single-nitrogen containing saturated cyclic amines are an important part of both natural and synthetic bioactive compounds. A number of methodologies have been developed for the synthesis of aziridines, azetidines, pyrrolidines, piperidines, azepanes and azocanes. This review highlights some facile and green synthetic routes [...] Read more.

Single-nitrogen containing saturated cyclic amines are an important part of both natural and synthetic bioactive compounds. A number of methodologies have been developed for the synthesis of aziridines, azetidines, pyrrolidines, piperidines, azepanes and azocanes. This review highlights some facile and green synthetic routes for the synthesis of unsubstituted, multisubstituted and highly functionalized saturated cyclic amines including one-pot, microwave assisted, metal-free, solvent-free and in aqueous media. Full article

(This article belongs to the Section Bioorganic Chemistry)

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32 pages, 2028 KiB

Open AccessReview

β-Amyloid and the Pathomechanisms of Alzheimer’s Disease: A Comprehensive View

by Botond Penke^1,*, Ferenc Bogár²

and Lívia Fülöp¹

¹ Department of Medical Chemistry, University of Szeged, H-6720 Szeged, Dóm Square 8, Hungary

² MTA-SZTE Biomimetic Systems Research Group and Department of Medical Chemistry, University of Szeged, H-6720 Szeged, Dóm Square 8, Hungary

Molecules 2017, 22(10), 1692; https://doi.org/10.3390/molecules22101692 - 10 Oct 2017

Cited by 108 | Viewed by 16966

Abstract

Protein dyshomeostasis is the common mechanism of neurodegenerative diseases such as Alzheimer’s disease (AD). Aging is the key risk factor, as the capacity of the proteostasis network declines during aging. Different cellular stress conditions result in the up-regulation of the neurotrophic, neuroprotective amyloid [...] Read more.

Protein dyshomeostasis is the common mechanism of neurodegenerative diseases such as Alzheimer’s disease (AD). Aging is the key risk factor, as the capacity of the proteostasis network declines during aging. Different cellular stress conditions result in the up-regulation of the neurotrophic, neuroprotective amyloid precursor protein (APP). Enzymatic processing of APP may result in formation of toxic Aβ aggregates (β-amyloids). Protein folding is the basis of life and death. Intracellular Aβ affects the function of subcellular organelles by disturbing the endoplasmic reticulum-mitochondria cross-talk and causing severe Ca²⁺-dysregulation and lipid dyshomeostasis. The extensive and complex network of proteostasis declines during aging and is not able to maintain the balance between production and disposal of proteins. The effectivity of cellular pathways that safeguard cells against proteotoxic stress (molecular chaperones, aggresomes, the ubiquitin-proteasome system, autophagy) declines with age. Chronic cerebral hypoperfusion causes dysfunction of the blood-brain barrier (BBB), and thus the Aβ-clearance from brain-to-blood decreases. Microglia-mediated clearance of Aβ also declines, Aβ accumulates in the brain and causes neuroinflammation. Recognition of the above mentioned complex pathogenesis pathway resulted in novel drug targets in AD research. Full article

(This article belongs to the Special Issue 25th Anniversary of the Amyloid Hypothesis and Alzheimer Disease)

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11 pages, 1014 KiB

Open AccessFeature PaperArticle

Large-Scale Oral Treatment Study with the Four Most Promising D3-Derivatives for the Treatment of Alzheimer’s Disease

by Janine Kutzsche^1,†, Sarah Schemmert^1,†, Markus Tusche¹, Jörg Neddens², Roland Rabl², Dagmar Jürgens¹, Oleksandr Brener³, Antje Willuweit⁴

, Birgit Hutter-Paier² and Dieter Willbold^1,3,*

¹ Institute of Complex Systems, Structural Biochemistry (ICS-6), Forschungszentrum Jülich, Jülich 52425, Germany

² QPS Austria GmbH, Grambach A-8074, Austria

³ Institut für Physikalische Biologie, Heinrich-Heine-Universität Düsseldorf, Düsseldorf 40225, Germany

⁴ Institute of Neuroscience and Medicine, Medical Imaging Physics (INM-4), Forschungszentrum Jülich, Jülich 52425, Germany

^† These authors contributed equally to this work.

Molecules 2017, 22(10), 1693; https://doi.org/10.3390/molecules22101693 - 10 Oct 2017

Cited by 30 | Viewed by 5481

Abstract

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that is associated with the aggregation of the amyloid β protein (Aβ). Aβ oligomers are currently thought to be the major neurotoxic agent responsible for disease development and progression. Thus, their elimination is highly desirable [...] Read more.

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that is associated with the aggregation of the amyloid β protein (Aβ). Aβ oligomers are currently thought to be the major neurotoxic agent responsible for disease development and progression. Thus, their elimination is highly desirable for therapy development. Our therapeutic approach aims at specific and direct elimination of toxic Aβ oligomers by stabilizing Aβ monomers in an aggregation-incompetent conformation. We have proven that our lead compound “D3”, an all d-enantiomeric-peptide, specifically eliminates Aβ oligomers in vitro. In vivo, D3 enhances cognition and reduces plaque load in several transgenic AD mouse models. Here, we performed a large-scale oral proof of concept efficacy study, in which we directly compared four of the most promising D3-derivatives in transgenic mice expressing human amyloid precursor protein with Swedish and London mutations (APP_SL), transgenic mice, to identify the most effective compound. RD2 and D3D3, both derived from D3 by rational design, were discovered to be the most effective derivatives in improving cognition in the Morris water maze. The performance of RD2- and D3D3-treated mice within the Morris water maze was significantly better than placebo-treated mice and, importantly, nearly as good as those of non-transgenic littermates, suggesting a complete reversal of the cognitive deficit of APP_SL mice. Full article

(This article belongs to the Special Issue 25th Anniversary of the Amyloid Hypothesis and Alzheimer Disease)

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14 pages, 3447 KiB

Open AccessArticle

PrLPAAT4, a Putative Lysophosphatidic Acid Acyltransferase from Paeonia rockii, Plays an Important Role in Seed Fatty Acid Biosynthesis

by Qingyu Zhang^1,†, Rui Yu^1,†

, Daoyang Sun¹, Zhangzhen Bai¹, Hong Li², Liang Xue², Yanlong Zhang^1,* and Lixin Niu^1,*

¹ College of Landscape Architecture and Arts, Northwest A&F University, Yangling, Shaanxi 712100, China

² Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China

^† These authors contributed equally to this work.

Molecules 2017, 22(10), 1694; https://doi.org/10.3390/molecules22101694 - 10 Oct 2017

Cited by 13 | Viewed by 4895

Abstract

Lysophosphatidic acid acyltransferases (LPAATs) are essential for the acylation of lysophosphatidic acid (LPA) and the synthesis of phosphatidic acid (PA), a key intermediate in the synthesis of membrane phospholipids and storage lipids. Here, a putative lysophosphatidic acid acyltransferase gene, designated PrLPAAT4, was [...] Read more.

Lysophosphatidic acid acyltransferases (LPAATs) are essential for the acylation of lysophosphatidic acid (LPA) and the synthesis of phosphatidic acid (PA), a key intermediate in the synthesis of membrane phospholipids and storage lipids. Here, a putative lysophosphatidic acid acyltransferase gene, designated PrLPAAT4, was isolated from seed unsaturated fatty acid (UFA)-rich P. rockii. The complete PrLPAAT4 cDNA contained a 1116-bp open reading frame (ORF), encoding a 42.9 kDa protein with 371 amino acid residues. Bioinformatic analysis indicates that PrLPAAT4 is a plasma membrane protein belonging to acyl-CoA:1-acylglycerol-sn-3-phosphate acyltranferases (AGPAT) family. PrLPAAT4 shared high sequence similarity with its homologs from Citrus clementina, Populus trichocarpa, Manihot esculenta, and Ricinus communis. In Arabidopsis, overexpression of PrLPAAT4 resulted in a significant increase in the content of oleic acid (OA) and total fatty acids (FAs) in seeds. AtDGAT1, AtGPAT9, and AtOleosin, involved in TAG assembly, were upregulated in PrLPAAT4-overexpressing lines. These results indicated that PrLPAAT4 functions may be as a positive regulator in seed FA biosynthesis. Full article

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16 pages, 3860 KiB

Open AccessFeature PaperArticle

Production of Single-Chain Fv Antibodies Specific for GA-Pyridine, an Advanced Glycation End-Product (AGE), with Reduced Inter-Domain Motion

by Natsuki Fukuda¹, Kentaro Noi^2,3,†, Lidong Weng¹, Yoshihiro Kobashigawa¹, Hiromi Miyazaki¹, Yukari Wakeyama¹, Michiyo Takaki¹, Yusuke Nakahara¹, Yuka Tatsuno¹, Makiyo Uchida-Kamekura^1,4, Yoshiaki Suwa¹, Takashi Sato¹, Naoki Ichikawa-Tomikawa^4,‡, Motoyoshi Nomizu^4,§, Yukio Fujiwara⁵, Fumina Ohsaka⁶, Takashi Saitoh^6,‖, Katsumi Maenaka⁶, Hiroyuki Kumeta⁷, Shoko Shinya⁸, Chojiro Kojima^8,9

, Teru Ogura^2,3 and Hiroshi Morioka^1,*

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¹ Department of Analytical and Biophysical Chemistry, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan

² Department of Molecular Cell Biology, Institute of Molecular Embryology and Genetics, Kumamoto University, 2-2-1 Honjo, Chuo-ku, Kumamoto 860-0811, Japan

³ CREST, JST, 4-1-8, Honcho, Kawaguchi, Saitama 332-0012, Japan

⁴ Graduate School of Environmental Earth Science, Hokkaido University, Kita-10 Nishi-5, Kita-ku, Sapporo 060-0810, Japan

⁵ Department of Cell Pathology, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-8556, Japan

⁶ Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita-12 Nishi-6, Kita-ku, Sapporo 060-0812, Japan

⁷ Global Station of Soft Matter, Global Institution for Collaborative Research and Education, Hokkaido University, Kita-15 Nishi-8, Kita-ku, Sapporo 060-0815, Japan

⁸ Laboratory of Molecular Biophysics, Institute for Protein Research, Osaka University, 3-2 Yamadaoka, Suita, Osaka 565-0871, Japan

⁹ Division of Materials Science and Chemical Engineering, Graduate School of Engineering, Yokohama National University, 79-5 Tokiwadai, Hodogaya-ku, Yokohama 240-8501, Japan

^† Present address: Kentaro Noi, Department of Mechanical Science and Bioengineering, Graduate School of Engineering Science, Osaka University, 1-3 Machikaneyama, Toyonaka 560-8531, Japan

^‡ Present address: Naoki Ichikawa-Tomikawa, Department of Basic Pathology, Fukushima Medical University School of Medicine, 1 Hikariga-oka, Fukushima 960-1295, Japan

^§ Present address: Motoyoshi Nomizu, Department of Clinical Biochemistry, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan

^‖ Present address: Takashi Saito, Division of Pharmaceutics, Hokkaido Pharmaceutical University School of Pharmacy, 7-15-4-1 Maeda, Teine, Sapporo 006-8590, Japan

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Molecules 2017, 22(10), 1695; https://doi.org/10.3390/molecules22101695 - 10 Oct 2017

Cited by 10 | Viewed by 6806

Abstract

Due to their lower production cost compared with monoclonal antibodies, single-chain variable fragments (scFvs) have potential for use in several applications, such as for diagnosis and treatment of a range of diseases, and as sensor elements. However, the usefulness of scFvs is limited [...] Read more.

Due to their lower production cost compared with monoclonal antibodies, single-chain variable fragments (scFvs) have potential for use in several applications, such as for diagnosis and treatment of a range of diseases, and as sensor elements. However, the usefulness of scFvs is limited by inhomogeneity through the formation of dimers, trimers, and larger oligomers. The scFv protein is assumed to be in equilibrium between the closed and open states formed by assembly or disassembly of VH and VL domains. Therefore, the production of an scFv with equilibrium biased to the closed state would be critical to overcome the problem in inhomogeneity of scFv for industrial or therapeutic applications. In this study, we obtained scFv clones stable against GA-pyridine, an advanced glycation end-product (AGE), by using a combination of a phage display system and random mutagenesis. Executing the bio-panning at 37 °C markedly improved the stability of scFvs. We further evaluated the radius of gyration by small-angle X-ray scattering (SAXS), obtained compact clones, and also visualized open Full article

(This article belongs to the Special Issue Recent Advances in Biomolecular NMR Spectroscopy)

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11 pages, 5074 KiB

Open AccessArticle

Biological Evaluation and Molecular Docking of Protocatechuic Acid from Hibiscus sabdariffa L. as a Potent Urease Inhibitor by an ESI-MS Based Method

by Sherif T. S. Hassan^1,2,*

and Emil Švajdlenka¹

¹ Department of Natural Drugs, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences Brno, Palackého tř. 1946/1, 612 42 Brno, Czech Republic

² Department of Applied Ecology, Faculty of Environmental Sciences, Czech University of Life Sciences Prague, Kamýcká 129, 165 21 Praha 6-Suchdol, Czech Republic

Molecules 2017, 22(10), 1696; https://doi.org/10.3390/molecules22101696 - 11 Oct 2017

Cited by 36 | Viewed by 6411

Abstract

Studies on enzyme inhibition remain a crucial area in drug discovery since these studies have led to the discoveries of new lead compounds useful in the treatment of several diseases. In this study, protocatechuic acid (PCA), an active compound from Hibiscus sabdariffa L. [...] Read more.

Studies on enzyme inhibition remain a crucial area in drug discovery since these studies have led to the discoveries of new lead compounds useful in the treatment of several diseases. In this study, protocatechuic acid (PCA), an active compound from Hibiscus sabdariffa L. has been evaluated for its inhibitory properties against jack bean urease (JBU) as well as its possible toxic effect on human gastric epithelial cells (GES-1). Anti-urease activity was evaluated by an Electrospray Ionization-Mass Spectrometry (ESI-MS) based method, while cytotoxicity was assayed by the MTT method. PCA exerted notable anti-JBU activity compared with that of acetohydroxamic acid (AHA), with IC₅₀ values of 1.7 and 3.2 µM, respectively. PCA did not show any significant cytotoxic effect on (GES-1) cells at concentrations ranging from 1.12 to 3.12 µM. Molecular docking study revealed high spontaneous binding ability of PCA to the active site of urease. Additionally, the anti-urease activity was found to be related to the presence of hydroxyl moieties of PCA. This study presents PCA as a natural urease inhibitor, which could be used safely in the treatment of diseases caused by urease-producing bacteria. Full article

(This article belongs to the Section Natural Products Chemistry)

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13 pages, 2150 KiB

Open AccessArticle

Nano-Formulation of Ethambutol with Multifunctional Graphene Oxide and Magnetic Nanoparticles Retains Its Anti-Tubercular Activity with Prospects of Improving Chemotherapeutic Efficacy

by Bullo Saifullah^1,2,3

, Arundhati Maitra^1,†, Alina Chrzastek^1,†, Bullo Naeemullah⁴, Sharida Fakurazi^3,5, Sanjib Bhakta¹

and Mohd Zobir Hussein^2,*

¹ Mycobacteria Research Laboratory, Department of Biological Sciences, Institute of Structural and Molecular Biology (ISMB), Birkbeck, University of London, Malet Street, London WC1E 7HX, UK

² Material Synthesis and Characterization Laboratory, Institute of Advanced Technology (ITMA), Universiti Putra Malaysia (UPM), Serdang 43400, Selangor, Malaysia

³ Laboratory for Vaccine and Immunotherapeutics, Institute of Biosciences, Universiti Putra Malaysia (UPM), Serdang 43400, Selangor, Malaysia

⁴ Department of Neurology (Ward No. 18), Jinnah Postgraduate Medical Center/Jinnah Sindh Medical, University Karachi, Karachi 75510, Pakistan

⁵ Department of Human Anatomy, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia (UPM), Serdang 43400, Selangor, Malaysia

^† These authors contributed equally to this work.

Molecules 2017, 22(10), 1697; https://doi.org/10.3390/molecules22101697 - 12 Oct 2017

Cited by 23 | Viewed by 6873

Abstract

Tuberculosis (TB) is a dreadful bacterial disease, infecting millions of human and cattle every year worldwide. More than 50 years after its discovery, ethambutol continues to be an effective part of the World Health Organization’s recommended frontline chemotherapy against TB. However, the lengthy [...] Read more.

Tuberculosis (TB) is a dreadful bacterial disease, infecting millions of human and cattle every year worldwide. More than 50 years after its discovery, ethambutol continues to be an effective part of the World Health Organization’s recommended frontline chemotherapy against TB. However, the lengthy treatment regimens consisting of a cocktail of antibiotics affect patient compliance. There is an urgent need to improve the current therapy so as to reduce treatment duration and dosing frequency. In this study, we have designed a novel anti-TB multifunctional formulation by fabricating graphene oxide with iron oxide magnetite nanoparticles serving as a nano-carrier on to which ethambutol was successfully loaded. The designed nanoformulation was characterised using various analytical techniques. The release of ethambutol from anti-TB multifunctional nanoparticles formulation was found to be sustained over a significantly longer period of time in phosphate buffer saline solution at two physiological pH (7.4 and 4.8). Furthermore, the nano-formulation showed potent anti-tubercular activity while remaining non-toxic to the eukaryotic cells tested. The results of this in vitro evaluation of the newly designed nano-formulation endorse its further development in vivo. Full article

(This article belongs to the Special Issue Emerging Drug Discovery Approaches against Infectious Diseases)

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19 pages, 2004 KiB

Open AccessReview

Chemical and Biological Research on Herbal Medicines Rich in Xanthones

by Jingya Ruan¹, Chang Zheng¹, Yanxia Liu¹, Lu Qu², Haiyang Yu², Lifeng Han², Yi Zhang^1,2,* and Tao Wang^1,2,*

¹ Tianjin State Key Laboratory of Modern Chinese Medicine, 312 Anshanxi Road, Nankai District, Tianjin 300193, China

² Tianjin Key Laboratory of TCM Chemistry and Analysis, Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, 312 Anshan Road, Nankai District, Tianjin 300193, China

Molecules 2017, 22(10), 1698; https://doi.org/10.3390/molecules22101698 - 11 Oct 2017

Cited by 49 | Viewed by 9279

Abstract

Xanthones, as some of the most active components and widely distributed in various herb medicines, have drawn more and more attention in recent years. So far, 168 species of herbal plants belong to 58 genera, 24 families have been reported to contain xanthones. [...] Read more.

Xanthones, as some of the most active components and widely distributed in various herb medicines, have drawn more and more attention in recent years. So far, 168 species of herbal plants belong to 58 genera, 24 families have been reported to contain xanthones. Among them, Calophyllum, Cratoxylum, Cudrania, Garcinia, Gentiana, Hypericum and Swertia genera are plant resources with great development prospect. This paper summarizes the plant resources, bioactivity and the structure-activity relationships (SARs) of xanthones from references published over the last few decades, which may be useful for new drug research and development on xanthones. Full article

(This article belongs to the Collection Herbal Medicine Research)

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20 pages, 858 KiB

Open AccessReview

Phytotherapeutics: The Emerging Role of Intestinal and Hepatocellular Transporters in Drug Interactions with Botanical Supplements

by Ghulam Murtaza¹, Naveed Ullah², Farah Mukhtar³, Shamyla Nawazish⁴, Saiqa Muneer⁵ and Mariam^6,*

¹ Department of Pharmacy, COMSATS Institute of Information Technology, Abbottabad 22060, Pakistan

² Department of Pharmacy, University of Swabi, Swabi 23340, Pakistan

³ Department of Microbiology, Sardar Bahdur Khan Women University, Quetta 87300, Pakistan

⁴ Department of Environmental Sciences, COMSATS Institute of Information Technology, Abbottabad 22060, Pakistan

⁵ Department of Pharmacy, University of Lahore, Lahore 54000, Pakistan

⁶ Department of Biotechnology, COMSATS Institute of Information Technology, Abbottabad 22060, Pakistan

Molecules 2017, 22(10), 1699; https://doi.org/10.3390/molecules22101699 - 21 Oct 2017

Cited by 16 | Viewed by 8919

Abstract

In herbalism, botanical supplements are commonly believed to be safe remedies, however, botanical supplements and dietary ingredients interact with transport and metabolic processes, affecting drug disposition. Although a large number of studies have described that botanical supplements interfere with drug metabolism, the mode [...] Read more.

In herbalism, botanical supplements are commonly believed to be safe remedies, however, botanical supplements and dietary ingredients interact with transport and metabolic processes, affecting drug disposition. Although a large number of studies have described that botanical supplements interfere with drug metabolism, the mode of their interaction with drug transport processes is not well described. Such interactions may result in serious undesired effects and changed drug efficacy, therefore, some studies on interaction between botanical supplement ingredients and drug transporters such as P-gp and OATPs are described here, suggesting that the interaction between botanical supplements and the drug transporters is clinically significant. Full article

(This article belongs to the Section Natural Products Chemistry)

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3 pages, 150 KiB

Open AccessEditorial

Special Issue “Synthesis and Applications of Oligonucleotide Conjugates”

by Harri Lönnberg

Department of Chemistry, University of Turku, FIN-20014 Turku, Finland

Molecules 2017, 22(10), 1700; https://doi.org/10.3390/molecules22101700 - 13 Oct 2017

Viewed by 3388

Abstract

The underlying idea of oligonucleotide conjugates is to provide oligonucleotide with some novel property [...] Full article

(This article belongs to the Special Issue Synthesis and Applications of Oligonucleotide Conjugates)

12 pages, 5107 KiB

Open AccessArticle

Molecular Insights into the Potential Insecticidal Interaction of β-Dihydroagarofuran Derivatives with the H Subunit of V-ATPase

by Jielu Wei^1,†, Ding Li^1,†, Xin Xi¹, Lulu Liu¹, Ximei Zhao¹, Wenjun Wu² and Jiwen Zhang^1,2,*

¹ College of Chemistry & Pharmacy, Northwest A&F University, Yangling 712100, Shaanxi, China

² Key Laboratory of Botanical Pesticide R&D in Shaanxi Province, Yangling 712100, Shaanxi, China

^† These authors contributed equally to this work.

Molecules 2017, 22(10), 1701; https://doi.org/10.3390/molecules22101701 - 11 Oct 2017

Cited by 15 | Viewed by 4641

Abstract

Celangulin V (CV), one of dihydroagarofuran sesquiterpene polyesters isolated from Chinese bittersweet (Celastrus angulatus Maxim), is famous natural botanical insecticide. Decades of research suggests that is displays excellent insecticidal activity against some insects, such as Mythimna separata Walker. Recently, it has been [...] Read more.

Celangulin V (CV), one of dihydroagarofuran sesquiterpene polyesters isolated from Chinese bittersweet (Celastrus angulatus Maxim), is famous natural botanical insecticide. Decades of research suggests that is displays excellent insecticidal activity against some insects, such as Mythimna separata Walker. Recently, it has been validated that the H subunit of V-ATPase is one of the target proteins of the insecticidal dihydroagarofuran sesquiterpene polyesters. As a continuation of the development of new pesticides from these natural products, a series of β-dihydroagarofuran derivatives have been designed and synthesized. The compound JW-3, an insecticidal derivative of CV with a p-fluorobenzyl group, exhibits higher insecticidal activity than CV. In this study, the potential inhibitory effect aused by the interaction of JW-3 with the H subunit of V-ATPase c was verified by confirmatory experiments at the molecular level. Both spectroscopic techniques and isothermal titration calorimetry measurements showed the binding of JW-3 to the subunit H of V-ATPase was specific and spontaneous. In addition, the possible mechanism of action of the compound was discussed. Docking results indicated compound JW-3 could bind well in ‘the interdomain cleft’ of the V-ATPase subunit H by the hydrogen bonding and make conformation of the ligand–protein complex become more stable. All results are the further validations of the hypothesis, that the target protein of insecticidal dihydroagarofuran sesquiterpene polyesters and their β-dihydroagarofuran derivatives is the subunit H of V-ATPase. The results also provide new ideas for developing pesticides acting on V-ATPase of insects. Full article

(This article belongs to the Section Bioorganic Chemistry)

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18 pages, 1439 KiB

Open AccessArticle

Long Term Osmotic Mini Pump Treatment with Alpha-MSH Improves Myocardial Function in Zucker Diabetic Fatty Rats

by Miklos Szokol¹, Daniel Priksz², Mariann Bombicz², Balazs Varga², Arpad Kovacs³, Gabor Aron Fulop³, Tamas Csipo³, Aniko Posa⁴, Attila Toth³, Zoltan Papp³, Zoltan Szilvassy² and Bela Juhasz^2,*

¹ Department of Cardiology, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary

² Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary

³ Division of Clinical Physiology, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary

⁴ Department of Physiology, Anatomy and Neuroscience, Faculty of Science and Informatics, University of Szeged, H-6720 Szeged, Hungary

Molecules 2017, 22(10), 1702; https://doi.org/10.3390/molecules22101702 - 12 Oct 2017

Cited by 2 | Viewed by 6311

Abstract

The present investigation evaluates the cardiovascular effects of the anorexigenic mediator alpha-melanocyte stimulating hormone (MSH), in a rat model of type 2 diabetes. Osmotic mini pumps delivering MSH or vehicle, for 6 weeks, were surgically implanted in Zucker Diabetic Fatty (ZDF) rats. Serum [...] Read more.

The present investigation evaluates the cardiovascular effects of the anorexigenic mediator alpha-melanocyte stimulating hormone (MSH), in a rat model of type 2 diabetes. Osmotic mini pumps delivering MSH or vehicle, for 6 weeks, were surgically implanted in Zucker Diabetic Fatty (ZDF) rats. Serum parameters, blood pressure, and weight gain were monitored along with oral glucose tolerance (OGTT). Echocardiography was conducted and, following sacrifice, the effects of treatment on ischemia/reperfusion cardiac injury were assessed using the isolated working heart method. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity was measured to evaluate levels of oxidative stress, and force measurements were performed on isolated cardiomyocytes to determine calcium sensitivity, active tension and myofilament co-operation. Vascular status was also evaluated on isolated arterioles using a contractile force measurement setup. The echocardiographic parameters ejection fraction (EF), fractional shortening (FS), isovolumetric relaxation time (IVRT), mitral annular plane systolic excursion (MAPSE), and Tei-index were significantly better in the MSH-treated group compared to ZDF controls. Isolated working heart aortic and coronary flow was increased in treated rats, and higher Hill coefficient indicated better myofilament co-operation in the MSH-treated group. We conclude that MSH improves global heart functions in ZDF rats, but these effects are not related to the vascular status. Full article

(This article belongs to the Special Issue Bioactive Compounds for Metabolic Syndrome and Type 2 Diabetes)

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14 pages, 925 KiB

Open AccessArticle

Triterpenoids from Ocimum labiatum Activates Latent HIV-1 Expression In Vitro: Potential for Use in Adjuvant Therapy

by Petrina Kapewangolo^1,2

, Justin J. Omolo³, Pascaline Fonteh^1,4, Martha Kandawa-Schulz² and Debra Meyer^1,5,*

¹ Department of Biochemistry, Faculty of Natural and Agricultural Sciences, University of Pretoria, Hatfield Campus, Pretoria 0002, South Africa

² Department of Chemistry and Biochemistry, Faculty of Science, University of Namibia, P/Bag 13301, Windhoek 9000, Namibia

³ Department of Traditional Medicine, National Institute for Medical Research, P.O. Box 9653, Dar es Salaam 2448, Tanzania

⁴ Department of Surgery, Faculty of Health Sciences, University of Witwatersrand, 7 York Road, Parktown, Johannesburg 2193, South Africa

⁵ Department of Biochemistry, Faculty of Science, University of Johannesburg, Auckland Park, Johannesburg 2006, South Africa

Molecules 2017, 22(10), 1703; https://doi.org/10.3390/molecules22101703 - 13 Oct 2017

Cited by 9 | Viewed by 5480

Abstract

Latent HIV reservoirs in infected individuals prevent current treatment from eradicating infection. Treatment strategies against latency involve adjuvants for viral reactivation which exposes viral particles to antiretroviral drugs. In this study, the effect of novel triterpenoids isolated from Ocimum labiatum on HIV-1 expression [...] Read more.

Latent HIV reservoirs in infected individuals prevent current treatment from eradicating infection. Treatment strategies against latency involve adjuvants for viral reactivation which exposes viral particles to antiretroviral drugs. In this study, the effect of novel triterpenoids isolated from Ocimum labiatum on HIV-1 expression was measured through HIV-1 p24 antigen capture in the U1 latency model of HIV-1 infection and in peripheral blood mononuclear cells (PBMCs) of infected patients on combination antiretroviral therapy (cART). The mechanism of viral reactivation was determined through the compound’s effect on cytokine production, histone deacetylase (HDAC) inhibition, and protein kinase C (PKC) activation. Cytotoxicity of the triterpenoids was determined using a tetrazolium dye and flow cytometry. The isolated triterpene isomers, 3-hydroxy-4,6a,6b,11,12,14b-hexamethyl-1,2,3,4,6,6a,6b,7,8,8a,9,10,11,12,12a,14,14a,14b-octadecahydropicene-4,8a-dicarboxylic acid (HHODC), significantly (p < 0.05) induced HIV-1 expression in a dose-dependent manner in U1 cells at non-cytotoxic concentrations. HHODC also induced viral expression in PBMCs of HIV-1 infected patients on cART. In addition, the compound up-regulated the production of interleukin (IL)-2, IL-6, tumour necrosis factor (TNF)-α, and interferon (IFN)-γ but had no effect on HDAC and PKC activity, suggesting cytokine upregulation as being involved in latency activation. The observed in vitro reactivation of HIV-1 introduces the adjuvant potential of HHODC for the first time here. Full article

(This article belongs to the Collection Herbal Medicine Research)

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11 pages, 2651 KiB

Open AccessArticle

Pratol, an O-Methylated Flavone, Induces Melanogenesis in B16F10 Melanoma Cells via p-p38 and p-JNK Upregulation

by You Chul Chung¹

, Seoyeon Kim¹, Jin Hwa Kim², Geun Soo Lee², Jung No Lee³, Nam Ho Lee¹ and Chang-Gu Hyun^1,*

¹ Department of Chemistry and Cosmetics, Jeju National University, Jeju 63243, Korea

² Skin Science Research Institute, Itshanbul Cosmetics Co., Chungbuk 27651, Korea

³ R&D Center, CoSeedBioPham Co., Chungbuk 28161, Korea

Molecules 2017, 22(10), 1704; https://doi.org/10.3390/molecules22101704 - 11 Oct 2017

Cited by 35 | Viewed by 8492

Abstract

Tyrosinase is the rate-limiting enzyme critical for melanin synthesis. It controls pigmentation in the skin. Activation of tyrosinase is currently the most common approach in the development of tanning and haircare products. Pratol is a 7-hydroxy-4-methoxyflavone found in Trifolium pratense. In this [...] Read more.

Tyrosinase is the rate-limiting enzyme critical for melanin synthesis. It controls pigmentation in the skin. Activation of tyrosinase is currently the most common approach in the development of tanning and haircare products. Pratol is a 7-hydroxy-4-methoxyflavone found in Trifolium pratense. In this study, we investigated the effects of pratol on melanogenesis. We also studied the mechanism of action of pratol in B16F10 mouse melanoma cells. The cells were treated with various concentrations (6.25, 12.5, 25, and 50 μM) of pratol to observe its effects. The results showed that pratol significantly increased melanin content and tyrosinase activity in the cells without being cytotoxic. In addition, pratol strongly increased the expression of tyrosinase and tyrosinase-related protein-1 and 2 by enhancing the expression of microphthalmia-associated transcription factor. Furthermore, pratol stimulated melanogenesis via the phosphorylation of p38, c-Jun N-terminal kinases (JNK), and extracellular signal–regulated kinase (ERK). The findings from an assay searching for the inhibitor revealed that SB203580 (a specific p38 inhibitor) or SP600125 (a p-JNK inhibitor) attenuated pratol-induced cellular tyrosinase activity whereas PD98059 (an ERK inhibitor) did not. Additionally, pratol interfered with the phosphorylation of p-AKT. We also found that pratol-induced melanogenesis was reversed by H89, which is a specific protein kinase A inhibitor. The results suggest that, owing to its multi-functional properties, pratol may be a potential tanning agent or a therapeutic agent for hair depigmentation in the cosmetic industry. Full article

(This article belongs to the Collection Efficient Pharmaceutical and Chemical Approaches for Anticancer Therapy: Design, Preliminary Evaluations, and Further Developments)

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11 pages, 8107 KiB

Open AccessArticle

Crosstalk Influence between P38MAPK and Autophagy on Mitochondria-Mediated Apoptosis Induced by Anti-Fas Antibody/Actinomycin D in Human Hepatoma Bel-7402 Cells

by Yu Wang¹, Chunhui Xia^2,*, Yanxin Lv¹, Chengjun Li¹, Qingbu Mei¹, Hongmei Li², Haijun Wang² and Shuang Li²

¹ Basic Medicine Department, Qiqihar Medical University, Qiqihar 161006, China

² Pharmacy Department, Qiqihar Medical University, Qiqihar 161006, China

Molecules 2017, 22(10), 1705; https://doi.org/10.3390/molecules22101705 - 17 Oct 2017

Cited by 13 | Viewed by 4349

Abstract

Our previous study indicated that anti-Fas antibody/actinomycin D (AF/AD) induced apoptosis of human hepatocellular carcinoma Bel-7402 cells; however, crosstalk influence between P38MAPK and autophagy on mitochondria-mediated apoptosis induced by AF/AD in Bel-7402 cells remains unclear. Therefore, effect of AF/AD on apoptosis, autophagy, phosphorylated-P38MAPK [...] Read more.

Our previous study indicated that anti-Fas antibody/actinomycin D (AF/AD) induced apoptosis of human hepatocellular carcinoma Bel-7402 cells; however, crosstalk influence between P38MAPK and autophagy on mitochondria-mediated apoptosis induced by AF/AD in Bel-7402 cells remains unclear. Therefore, effect of AF/AD on apoptosis, autophagy, phosphorylated-P38MAPK (p-P38MAPK), and membrane potential (ΔΨm) with or without the P38MAPK inhibitor SB203580 or the autophagy inhibitor 3-methyladenine (3-MA) in Bel-7402 cells was investigated in the present study. The results showed that AF/AD resulted in induction of apoptosis concomitant with autophagy, upregulation of p-P38MAPK and autophagy-associated gene proteins (Atg5-Atg12 protein complex, Atg7, Atg10, Beclin-1, LC3 I, and LC3 II), and downregulation of ΔΨm in Bel-7402 cells. In contrast, SB203580 attenuated the effects of AF/AD in Bel-7402 cells. Furthermore, the findings also demonstrated that 3-MA inhibited the impact of AF/AD on autophagy, Atg5-Atg12 protein complex, Atg7, Atg10, Beclin-1, LC3 I, LC3 II, and ΔΨm, and promoted the influence of AF/AD on apoptosis and p-P38MAPK in Bel-7402 cells. Taken together, we conclude that crosstalk between P38MAPK and autophagy regulates mitochondria-mediated apoptosis induced by AF/AD in Bel-7402 cells. Full article

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19 pages, 3496 KiB

Open AccessArticle

Characterization, Function, and Transcriptional Profiling Analysis of 3-Hydroxy-3-methylglutaryl-CoA Synthase Gene (GbHMGS1) towards Stresses and Exogenous Hormone Treatments in Ginkgo biloba

by Xiangxiang Meng, Qiling Song, Jiabao Ye, Lanlan Wang and Feng Xu^*

College of Horticulture and Gardening, Yangtze University, Jingzhou 434025, Hubei, China

Molecules 2017, 22(10), 1706; https://doi.org/10.3390/molecules22101706 - 12 Oct 2017

Cited by 30 | Viewed by 6146

Abstract

3-Hydroxy-3-methylglutaryl-CoA synthase (HMGS) is one of the rate-limiting enzymes in the mevalonate pathway as it catalyzes the condensation of acetoacetyl-CoA to form 3-hydroxy-3-methylglutaryl-CoA. In this study, A HMGS gene (designated as GbHMGS1) was cloned from Ginkgo biloba for the first time. GbHMGS1 [...] Read more.

3-Hydroxy-3-methylglutaryl-CoA synthase (HMGS) is one of the rate-limiting enzymes in the mevalonate pathway as it catalyzes the condensation of acetoacetyl-CoA to form 3-hydroxy-3-methylglutaryl-CoA. In this study, A HMGS gene (designated as GbHMGS1) was cloned from Ginkgo biloba for the first time. GbHMGS1 contained a 1422-bp open-reading frame encoding 474 amino acids. Comparative and bioinformatics analysis revealed that GbHMGS1 was extensively homologous to HMGSs from other plant species. Phylogenetic analysis indicated that the GbHMGS1 belonged to the plant HMGS superfamily, sharing a common evolutionary ancestor with other HMGSs, and had a further relationship with other gymnosperm species. The yeast complement assay of GbHMGS1 in HMGS-deficient Saccharomyces cerevisiae strain YSC6274 demonstrated that GbHMGS1 gene encodes a functional HMGS enzyme. The recombinant protein of GbHMGS1 was successfully expressed in E. coli. The in vitro enzyme activity assay showed that the k_cat and K_m values of GbHMGS1 were 195.4 min⁻¹ and 689 μM, respectively. GbHMGS1 was constitutively expressed in all tested tissues, including the roots, stems, leaves, female flowers, male flowers and fruits. The transcript accumulation for GbHMGS1 was highest in the leaves. Expression profiling analyses revealed that GbHMGS1 expression was induced by abiotic stresses (ultraviolet B and cold) and hormone treatments (salicylic acid, methyl jasmonate, and ethephon) in G. biloba, indicating that GbHMGS1 gene was involved in the response to environmental stresses and plant hormones. Full article

(This article belongs to the Special Issue Diversity of Terpenoids)

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21 pages, 2723 KiB

Open AccessArticle

Electrostatic Self-Assembled Chitosan-Pectin Nano- and Microparticles for Insulin Delivery

by Vinicius B. V. Maciel^1,5, Cristiana M. P. Yoshida^2,*, Susana M. S. S. Pereira³, Francisco M. Goycoolea^3,4,*

and Telma T. Franco⁵

¹ Faculty of Animal Science and Food Engineering, USP—University of São Paulo, Av. Duque de Caxias Norte, 225, Pirassununga CEP 13635-900, São Paulo, Brazil

² Department of Exact and Earth Science, UNIFESP—Federal University of São Paulo, Rua São Nicolau, 210, Diadema CEP 09913-030, São Paulo, Brazil

³ Institut für Biologie und Biotechnologie der Pflanzen, Westfälische Wilhelms—Universität Münster, Schlossgarten 3, 48149 Münster, Germany

⁴ School of Food Science and Nutrition, University of Leeds, Leeds LS2 9JT, UK

⁵ School of Chemical Engineering, UNICAMP—State University of Campinas, Av. Albert Einstein, 500, Campinas CEP 13083-852, São Paulo, Brazil

Molecules 2017, 22(10), 1707; https://doi.org/10.3390/molecules22101707 - 12 Oct 2017

Cited by 98 | Viewed by 8394

Abstract

A polyelectrolyte complex system of chitosan-pectin nano- and microparticles was developed to encapsulate the hormone insulin. The aim of this work was to obtain small particles for oral insulin delivery without chemical crosslinkers based on natural and biodegradable polysaccharides. The nano- and microparticles [...] Read more.

A polyelectrolyte complex system of chitosan-pectin nano- and microparticles was developed to encapsulate the hormone insulin. The aim of this work was to obtain small particles for oral insulin delivery without chemical crosslinkers based on natural and biodegradable polysaccharides. The nano- and microparticles were developed using chitosans (with different degrees of acetylation: 15.0% and 28.8%) and pectin solutions at various charge ratios (n⁺/n⁻ given by the chitosan/pectin mass ratio) and total charge. Nano- and microparticles were characterized regarding particle size, zeta potential, production yield, encapsulation efficiency, stability in different media, transmission electron microscopy and cytotoxicity assays using Caco-2 cells. The insulin release was evaluated in vitro in simulated gastric and intestinal media. Small-sized particles (~240–~1900 nm) with a maximum production yield of ~34.0% were obtained. The highest encapsulation efficiency (~62.0%) of the system was observed at a charge ratio (n⁺/n⁻) 5.00. The system was stable in various media, particularly in simulated gastric fluid (pH 1.2). Transmission electron microscopy (TEM) analysis showed spherical shape particles when insulin was added to the system. In simulated intestinal fluid (pH 6.8), controlled insulin release occurred over 2 h. In vitro tests indicated that the proposed system presents potential as a drug delivery for oral administration of bioactive peptides. Full article

(This article belongs to the Special Issue Selected Papers from the 13th International Conference of the European Chitin Society – 8th Simposio de la Sociedad Iberoamericana de Quitina (EUCHIS-SIAQ 2017))

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16 pages, 2441 KiB

Open AccessArticle

Electrospun Phospholipid Fibers as Micro-Encapsulation and Antioxidant Matrices

by Elhamalsadat Shekarforoush¹, Ana C. Mendes^1,*

, Vanessa Baj², Sophie R. Beeren²

and Ioannis S. Chronakis¹

¹ Nano-Bio Science Research Group, DTU-Food, Technical University of Denmark, Kemitorvet 202, 2800 Kongens Lyngby, Denmark

² DTU-Chemistry, Technical University of Denmark, Kemitorvet 207, 2800 Kongens Lyngby, Denmark

Molecules 2017, 22(10), 1708; https://doi.org/10.3390/molecules22101708 - 17 Oct 2017

Cited by 37 | Viewed by 6651

Abstract

Electrospun phospholipid (asolectin) microfibers were investigated as antioxidants and encapsulation matrices for curcumin and vanillin. These phospholipid microfibers exhibited antioxidant properties which increased after the encapsulation of both curcumin and vanillin. The total antioxidant capacity (TAC) and the total phenolic content (TPC) of [...] Read more.

Electrospun phospholipid (asolectin) microfibers were investigated as antioxidants and encapsulation matrices for curcumin and vanillin. These phospholipid microfibers exhibited antioxidant properties which increased after the encapsulation of both curcumin and vanillin. The total antioxidant capacity (TAC) and the total phenolic content (TPC) of curcumin/phospholipid and vanillin/phospholipid microfibers remained stable over time at different temperatures (refrigerated, ambient) and pressures (vacuum, ambient). ¹H-NMR confirmed the chemical stability of both encapsulated curcumin and vanillin within phospholipid fibers. Release studies in aqueous media revealed that the phenolic bioactives were released mainly due to swelling of the phospholipid fiber matrix over time. The above studies confirm the efficacy of electrospun phospholipid microfibers as encapsulation and antioxidant systems. Full article

(This article belongs to the Collection Bioactive Compounds)

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12 pages, 977 KiB

Open AccessArticle

Halogenated 1-Hydroxynaphthalene-2-Carboxanilides Affecting Photosynthetic Electron Transport in Photosystem II

by Tomas Gonec^1,*

, Jiri Kos^1,2, Matus Pesko³, Jana Dohanosova⁴, Michal Oravec⁵, Tibor Liptaj⁴, Katarina Kralova⁶ and Josef Jampilek^2,*

¹ Department of Chemical Drugs, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences, Palackeho 1, Brno 61242, Czech Republic

² Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Comenius University, Odbojarov 10, Bratislava 83232, Slovakia

³ Department of Environmental Ecology, Faculty of Natural Sciences, Comenius University, Ilkovicova 6, Bratislava 84215, Slovakia

⁴ Central Laboratories, Faculty of Chemical and Food Technology, Slovak University of Technology in Bratislava, Radlinskeho 9, Bratislava 81237, Slovakia

⁵ Global Change Research Institute CAS, Belidla 986/4a, 60300 Brno, Czech Republic

⁶ Institute of Chemistry, Faculty of Natural Sciences, Comenius University, Ilkovicova 6, Bratislava 84215, Slovakia

Molecules 2017, 22(10), 1709; https://doi.org/10.3390/molecules22101709 - 12 Oct 2017

Cited by 21 | Viewed by 4368

Abstract

Series of seventeen new multihalogenated 1-hydroxynaphthalene-2-carboxanilides was prepared and characterized. All the compounds were tested for their activity related to the inhibition of photosynthetic electron transport (PET) in spinach (Spinacia oleracea L.) chloroplasts. 1-Hydroxy-N-phenylnaphthalene-2-carboxamides substituted in the anilide part by [...] Read more.

Series of seventeen new multihalogenated 1-hydroxynaphthalene-2-carboxanilides was prepared and characterized. All the compounds were tested for their activity related to the inhibition of photosynthetic electron transport (PET) in spinach (Spinacia oleracea L.) chloroplasts. 1-Hydroxy-N-phenylnaphthalene-2-carboxamides substituted in the anilide part by 3,5-dichloro-, 4-bromo-3-chloro-, 2,5-dibromo- and 3,4,5-trichloro atoms were the most potent PET inhibitors (IC₅₀ = 5.2, 6.7, 7.6 and 8.0 µM, respectively). The inhibitory activity of these compounds depends on the position and the type of halogen substituents, i.e., on lipophilicity and electronic properties of individual substituents of the anilide part of the molecule. Interactions of the studied compounds with chlorophyll a and aromatic amino acids present in pigment-protein complexes mainly in PS II were documented by fluorescence spectroscopy. The section between P₆₈₀ and plastoquinone Q_B in the PET chain occurring on the acceptor side of PS II can be suggested as the site of action of the compounds. The structure-activity relationships are discussed. Full article

(This article belongs to the Special Issue Selected Papers from the 46th EuroCongress on Drug Synthesis and Analysis (ECDSA-2017))

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18 pages, 3500 KiB

Open AccessArticle

Rational Design of Nucleoside–Bile Acid Conjugates Incorporating a Triazole Moiety for Anticancer Evaluation and SAR Exploration

by Maria Luisa Navacchia^1,*

, Elena Marchesi²

, Lara Mari², Nicola Chinaglia², Eleonora Gallerani³, Riccardo Gavioli³, Massimo Luigi Capobianco¹ and Daniela Perrone²

¹ Consiglio Nazionale delle Ricerche, Istituto per la Sintesi Organica e la Fotoreattività (CNR-ISOF), via P. Gobetti 101, 40129 Bologna, Italy

² Dipartimento di Scienze Chimiche e Farmaceutiche, Università degli studi di Ferrara, via L. Borsari 46, 44121 Ferrara, Italy

³ Dipartimento di Scienze della Vita e Biotecnologie, Università degli studi di Ferrara, via L. Borsari 46, 44121 Ferrara, Italy

Molecules 2017, 22(10), 1710; https://doi.org/10.3390/molecules22101710 - 12 Oct 2017

Cited by 26 | Viewed by 5473

Abstract

Herein we report a study on the synthesis and biological evaluation of a library of nucleoside-bile acid conjugates prepared by combining 2′-deoxyadenosine, 2′-deoxyguanosine, 2′-deoxyuridine as well as adenosine and guanosine derivatives with cheno-, urso-, nor-cheno-, nor-urso- and taurourso-desoxycholic acid derivatives by [...] Read more.

Herein we report a study on the synthesis and biological evaluation of a library of nucleoside-bile acid conjugates prepared by combining 2′-deoxyadenosine, 2′-deoxyguanosine, 2′-deoxyuridine as well as adenosine and guanosine derivatives with cheno-, urso-, nor-cheno-, nor-urso- and taurourso-desoxycholic acid derivatives by means of the click reaction. The new nucleoside-bile acid conjugates incorporating a triazole moiety were tested in vitro against leukemic K562 and HCT116 colon carcinoma, as well as on normal fibroblast cells. Six compounds displayed interesting anti-proliferative activity against the selected cancer lines and no cytotoxic effects against normal fibroblasts. A possible structure activity relationship was also investigated. Full article

(This article belongs to the Special Issue Medicinal Chemistry in Europe)

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14 pages, 3668 KiB

Open AccessFeature PaperArticle

Diallylthiosulfinate (Allicin), a Volatile Antimicrobial from Garlic (Allium sativum), Kills Human Lung Pathogenic Bacteria, Including MDR Strains, as a Vapor

by Jana Reiter¹, Natalja Levina², Mark Van der Linden²

, Martin Gruhlke¹, Christian Martin³ and Alan J. Slusarenko^1,*

¹ Department of Plant Physiology, RWTH Aachen University, 52056 Aachen, Germany

² German National Reference Centre of Streptococci (GNRCS), University Hospital RWTH Aachen, 52074 Aachen, Germany

³ Institute of Pharmacology and Toxicology, Medical Faculty of RWTH Aachen University, 52074 Aachen, Germany

Molecules 2017, 22(10), 1711; https://doi.org/10.3390/molecules22101711 - 12 Oct 2017

Cited by 131 | Viewed by 19123

Abstract

Garlic (Allium sativum) has potent antimicrobial activity due to allicin (diallylthiosulfinate) synthesized by enzyme catalysis in damaged garlic tissues. Allicin gives crushed garlic its characteristic odor and its volatility makes it potentially useful for combating lung infections. Allicin was synthesized (>98% [...] Read more.

Garlic (Allium sativum) has potent antimicrobial activity due to allicin (diallylthiosulfinate) synthesized by enzyme catalysis in damaged garlic tissues. Allicin gives crushed garlic its characteristic odor and its volatility makes it potentially useful for combating lung infections. Allicin was synthesized (>98% pure) by oxidation of diallyl disulfide by H₂O₂ using formic acid as a catalyst and the growth inhibitory effect of allicin vapor and allicin in solution to clinical isolates of lung pathogenic bacteria from the genera Pseudomonas, Streptococcus, and Staphylococcus, including multi-drug resistant (MDR) strains, was demonstrated. Minimal inhibitory (MIC) and minimal bactericidal concentrations (MBC) were determined and compared to clinical antibiotics using standard European Committee on Antimicrobial Susceptibility Testing (EUCAST) procedures. The cytotoxicity of allicin to human lung and colon epithelial and murine fibroblast cells was tested in vitro and shown to be ameliorated by glutathione (GSH). Similarly, the sensitivity of rat precision-cut lung slices (PCLS) to allicin was decreased by raising the [GSH] to the approximate blood plasma level of 1 mM. Because allicin inhibited bacterial growth as a vapor, it could be used to combat bacterial lung infections via direct inhalation. Since there are no volatile antibiotics available to treat pulmonary infections, allicin, particularly at sublethal doses in combination with oral antibiotics, could make a valuable addition to currently available treatments. Full article

(This article belongs to the Special Issue Small Molecule Catalysts with Therapeutic Potential)

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12 pages, 3823 KiB

Open AccessArticle

Novel Synthesis of Core-Shell Silica Nanoparticles for the Capture of Low Molecular Weight Proteins and Peptides

by Sergio G. Hernandez-Leon¹

, Jose Andre-i Sarabia-Sainz², Gabriela Ramos-Clamont Montfort¹

, Ana M. Guzman-Partida¹, Maria Del Refugio Robles-Burgueño¹ and Luz Vazquez-Moreno^1,*

¹ Centro de Investigación en Alimentación y Desarrollo A.C. Carretera a la Victoria km 0.6 C.P. 83304, Hermosillo 83304, Sonora, Mexico

² Universidad de Sonora. Blvd. Luis Encinas y Rosales S/N, Col. Centro, Hermosillo 83000, Sonora, Mexico

Molecules 2017, 22(10), 1712; https://doi.org/10.3390/molecules22101712 - 12 Oct 2017

Cited by 11 | Viewed by 8944

Abstract

Silica nanoparticles were functionalized with immobilized molecular bait, Cibacron Blue, and a porous polymeric bis-acrylamide shell. These nanoparticles represent a new alternative to capture low molecular weight (LMW) proteins/peptides, that might be potential biomarkers. Functionalized core-shell silica nanoparticles (FCSNP) presented a size distribution [...] Read more.

Silica nanoparticles were functionalized with immobilized molecular bait, Cibacron Blue, and a porous polymeric bis-acrylamide shell. These nanoparticles represent a new alternative to capture low molecular weight (LMW) proteins/peptides, that might be potential biomarkers. Functionalized core-shell silica nanoparticles (FCSNP) presented a size distribution of 243.9 ± 11.6 nm and an estimated surface charge of −38.1 ± 0.9 mV. The successful attachment of compounds at every stage of synthesis was evidenced by ATR-FTIR. The capture of model peptides was determined by mass spectrometry, indicating that only the peptide with a long sequence of hydrophobic amino acids (alpha zein 34-mer) interacted with the molecular bait. FCSNP excluded the high molecular weight protein (HMW), BSA, and captured LMW proteins (myoglobin and aprotinin), as evidenced by SDS-PAGE. Functionalization of nanoparticles with Cibacron Blue was crucial to capture these molecules. FCSNP were stable after twelve months of storage and maintained a capacity of 3.1–3.4 µg/mg. Full article

(This article belongs to the Special Issue Mesoporous Silica in Biomedical Applications)

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17 pages, 271 KiB

Open AccessArticle

Effects of Sorghum Malting on Colour, Major Classes of Phenolics and Individual Anthocyanins

by Ali Khoddami^1,*

, Mohammad Mohammadrezaei²

and Thomas H. Roberts¹

¹ Plant Breeding Institute, Sydney Institute of Agriculture, University of Sydney, Sydney, NSW 2006, Australia

² Young Researchers and Elite Club, Isfahan (Khorasgan) Branch, Islamic Azad University, Isfahan 81595-158, Iran

Molecules 2017, 22(10), 1713; https://doi.org/10.3390/molecules22101713 - 12 Oct 2017

Cited by 35 | Viewed by 5679

Abstract

Sorghum (Sorghum bicolor) grain contains many health-promoting phytochemicals, including a broad range of phenolic compounds. Malting of cereal grains is known to increase the bioavailability of macro- and micronutrients. However, the detailed effects of malting on sorghum grain anthocyanins, a major [...] Read more.

Sorghum (Sorghum bicolor) grain contains many health-promoting phytochemicals, including a broad range of phenolic compounds. Malting of cereal grains is known to increase the bioavailability of macro- and micronutrients. However, the detailed effects of malting on sorghum grain anthocyanins, a major class of phenolics that influence the taste and colour of sorghum-based foods, requires further investigation. Eight commercial sorghum hybrids harvested from three regions in eastern Australia were malted and analysed for colour, tannin content, total phenolic content (TPC), flavan-4-ols, total flavonoids, total anthocyanins and 3-deoxyanthocyanins. Grains of all the sorghums were found to be tannin-free. Malting decreased the TPC of all samples. For TPC, the grand means among all the sorghum cultivars for raw and malted grain were 2.77 and 2.48 mg gallic acid equivalents (GAE)/g, respectively. For flavan-4-ols, the grand means for raw and malted sorghum grains were 2.98 and 2.23 abs/mL/g, respectively. Remarkably, total anthocyanin levels more than doubled upon malting whereas total flavonoid levels decreased by 12%. The average abundance of 3-deoxyanthocyanins in raw sorghum grains increased for about 8-fold upon malting. Our results will be valuable for sorghum breeders in the selection of lines for specific end uses and for food scientists developing sorghum-based products. Full article

(This article belongs to the Section Natural Products Chemistry)

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12 pages, 9064 KiB

Open AccessArticle

Rapid Identification of Dipeptidyl Peptidase-IV (DPP-IV) Inhibitory Peptides from Ruditapes philippinarum Hydrolysate

by Rui Liu^1,2,3,*,†

, Lei Zhou^4,†, Yan Zhang⁵, Nai-Juan Sheng^1,2, Zhi-Kang Wang^1,2, Ti-Zhi Wu^1,2, Xin-Zhi Wang^1,2 and Hao Wu^1,2,*

¹ Jiangsu Key Laboratory of Research and Development in Marine Bio-Resource Pharmaceutics, Nanjing University of Chinese Medicine, Nanjing 210023, China

² College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China

³ Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing 210023, China

⁴ The Affiliated Huai’an of Xuzhou Medical College and The Second People’s Hospital of Huai’an, Huai’an 223002, China

⁵ Nanjing Normal University, School of Public Administration, Nanjing 210023, China

^† These authors contributed equally to this work.

Molecules 2017, 22(10), 1714; https://doi.org/10.3390/molecules22101714 - 13 Oct 2017

Cited by 62 | Viewed by 5590

Abstract

Dipeptidyl peptidase-IV (DPP-IV) inhibitory peptides were rapidly identified from Ruditapes philippinarum hydrolysate. The hydrolysate was fractionated by ethanol precipitation and preparative reverse phase high-performance liquid chromatography (RP-HPLC). The fraction which showed the highest DPP-IV inhibitory activity was then analyzed by a high-throughput nano-liquid [...] Read more.

Dipeptidyl peptidase-IV (DPP-IV) inhibitory peptides were rapidly identified from Ruditapes philippinarum hydrolysate. The hydrolysate was fractionated by ethanol precipitation and preparative reverse phase high-performance liquid chromatography (RP-HPLC). The fraction which showed the highest DPP-IV inhibitory activity was then analyzed by a high-throughput nano-liquid chromatography electrospray ionization tandem mass spectrometry (nano-LC ESI-MS/MS) method, and the sequences of peptides were identified based on the MS/MS spectra against the Mollusca protein data from the UniProt database. In total, 50 peptides were identified. Furthermore, molecular docking was used to identify potential DPP-IV inhibitors from the identified peptides. Docking results suggested that four peptides: FAGDDAPR, LAPSTM, FAGDDAPRA, and FLMESH, could bind pockets of DPP-IV through hydrogen bonds, π-π bonds, and charge interactions. The four peptides were chemically synthesized and tested for DPP-IV inhibitory activity. The results showed that they possessed DPP-IV inhibitory activity with IC₅₀ values of 168.72 μM, 140.82 μM, 393.30 μM, and >500 μM, respectively. These results indicate that R. philippinarum-derived peptides may have potential as functional food ingredients for the prevention of diabetes. Full article

(This article belongs to the Special Issue New Methodologies in Natural Product Analytics and Structure Elucidation)

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19 pages, 1923 KiB

Open AccessArticle

Screening a Natural Product-Based Library against Kinetoplastid Parasites

by Bilal Zulfiqar¹, Amy J. Jones¹, Melissa L. Sykes¹, Todd B. Shelper¹, Rohan A. Davis²

and Vicky M. Avery^1,*

¹ Discovery Biology, Griffith Institute for Drug Discovery, Griffith University, Nathan, Queensland 4111, Australia

² Natural Product Chemistry, Griffith Institute for Drug Discovery, Griffith University, Nathan, Queensland 4111, Australia

Molecules 2017, 22(10), 1715; https://doi.org/10.3390/molecules22101715 - 12 Oct 2017

Cited by 53 | Viewed by 8753

Abstract

Kinetoplastid parasites cause vector-borne parasitic diseases including leishmaniasis, human African trypanosomiasis (HAT) and Chagas disease. These Neglected Tropical Diseases (NTDs) impact on some of the world’s lowest socioeconomic communities. Current treatments for these diseases cause severe toxicity and have limited efficacy, highlighting the [...] Read more.

Kinetoplastid parasites cause vector-borne parasitic diseases including leishmaniasis, human African trypanosomiasis (HAT) and Chagas disease. These Neglected Tropical Diseases (NTDs) impact on some of the world’s lowest socioeconomic communities. Current treatments for these diseases cause severe toxicity and have limited efficacy, highlighting the need to identify new treatments. In this study, the Davis open access natural product-based library was screened against kinetoplastids (Leishmania donovani DD8, Trypanosoma brucei brucei and Trypanosoma cruzi) using phenotypic assays. The aim of this study was to identify hit compounds, with a focus on improved efficacy, selectivity and potential to target several kinetoplastid parasites. The IC₅₀ values of the natural products were obtained for L. donovani DD8, T. b. brucei and T. cruzi in addition to cytotoxicity against the mammalian cell lines, HEK-293, 3T3 and THP-1 cell lines were determined to ascertain parasite selectivity. Thirty-one compounds were identified with IC₅₀ values of ≤ 10 µM against the kinetoplastid parasites tested. Lissoclinotoxin E (1) was the only compound identified with activity across all three investigated parasites, exhibiting IC₅₀ values < 5 µM. In this study, natural products with the potential to be new chemical starting points for drug discovery efforts for kinetoplastid diseases were identified. Full article

(This article belongs to the Special Issue Emerging Drug Discovery Approaches against Infectious Diseases)

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15 pages, 4890 KiB

Open AccessArticle

Validation of Molecular Dynamics Simulations for Prediction of Three-Dimensional Structures of Small Proteins

by Koichi Kato^1,2

, Tomoki Nakayoshi^1,3

, Shuichi Fukuyoshi³, Eiji Kurimoto¹ and Akifumi Oda^1,3,4,*

¹ Graduate School of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku-ku, Nagoya, Aichi 468-8503, Јapan

² Department of Pharmacy, Kinjo Gakuin University, 2-1723 Omori, Moriyama-ku, Nagoya, Aichi 463-8521, Japan

³ Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kakuma-machi, Kanazawa, Ishikawa 920-1192, Japan

⁴ Institute for Protein Research, Osaka University, 3-2 Yamadaoka, Suita, Osaka 565-0871, Japan

Molecules 2017, 22(10), 1716; https://doi.org/10.3390/molecules22101716 - 12 Oct 2017

Cited by 24 | Viewed by 6965

Abstract

Although various higher-order protein structure prediction methods have been developed, almost all of them were developed based on the three-dimensional (3D) structure information of known proteins. Here we predicted the short protein structures by molecular dynamics (MD) simulations in which only Newton’s equations [...] Read more.

Although various higher-order protein structure prediction methods have been developed, almost all of them were developed based on the three-dimensional (3D) structure information of known proteins. Here we predicted the short protein structures by molecular dynamics (MD) simulations in which only Newton’s equations of motion were used and 3D structural information of known proteins was not required. To evaluate the ability of MD simulationto predict protein structures, we calculated seven short test protein (10–46 residues) in the denatured state and compared their predicted and experimental structures. The predicted structure for Trp-cage (20 residues) was close to the experimental structure by 200-ns MD simulation. For proteins shorter or longer than Trp-cage, root-mean square deviation values were larger than those for Trp-cage. However, secondary structures could be reproduced by MD simulations for proteins with 10–34 residues. Simulations by replica exchange MD were performed, but the results were similar to those from normal MD simulations. These results suggest that normal MD simulations can roughly predict short protein structures and 200-ns simulations are frequently sufficient for estimating the secondary structures of protein (approximately 20 residues). Structural prediction method using only fundamental physical laws are useful for investigating non-natural proteins, such as primitive proteins and artificial proteins for peptide-based drug delivery systems. Full article

(This article belongs to the Section Green Chemistry)

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15 pages, 3059 KiB

Open AccessArticle

New and Old Genes Associated with Primary and Established Responses to Cisplatin and Topotecan Treatment in Ovarian Cancer Cell Lines

by Monika Świerczewska^1,†

, Andrzej Klejewski^2,3,*,†, Karolina Wojtowicz¹, Maciej Brązert⁴, Dariusz Iżycki⁵, Michał Nowicki¹, Maciej Zabel^1,6

and Radosław Januchowski¹

¹ Department of Histology and Embryology, Poznan University of Medical Sciences, Święcickiego 6 St., 61-781 Poznań, Poland

² Department of Nursing, Poznan University of Medical Sciences, Smoluchowskiego 11 St., 60-179 Poznan, Poland

³ Department of Obstetrics and Womens Diseases, Poznan University of Medical Sciences, Smoluchowskiego 11 St., 60-179 Poznan, Poland

⁴ Division of Infertility and Reproductive Endocrinology, Department of Gynecology, Obstetrics and Gynecological Oncology, Poznan University of Medical Sciences, Polna 33 St., 60-535 Poznań, Poland

⁵ Department of Cancer Immunology, Poznan University of Medical Sciences, Poland, Garbary 15 St., 61-866 Poznań, Poland

⁶ Division of Histology and Embryology, Wrocław Medical University, Chałubińskiego 6a, 50-368 Wrocław, Poland

^† These authors have contributed equally.

Molecules 2017, 22(10), 1717; https://doi.org/10.3390/molecules22101717 - 13 Oct 2017

Cited by 23 | Viewed by 4943

Abstract

Low efficiency of chemotherapy in ovarian cancer results from the development of drug resistance. Cisplatin (CIS) and topotecan (TOP) are drugs used in chemotherapy of this cancer. We analyzed the development of CIS and TOP resistance in ovarian cancer cell lines. Incubation of [...] Read more.

Low efficiency of chemotherapy in ovarian cancer results from the development of drug resistance. Cisplatin (CIS) and topotecan (TOP) are drugs used in chemotherapy of this cancer. We analyzed the development of CIS and TOP resistance in ovarian cancer cell lines. Incubation of drug sensitive cell lines (W1 and A2780) with cytostatic drugs was used to determine the primary response to CIS and TOP. Quantitative polymerase chain reaction (Q-PCR) was performed to measure the expression levels of the genes. We observed decreased expression of the MCTP1 gene in all resistant cell lines. We observed overexpression of the S100A3 and HERC5 genes in TOP-resistant cell lines. Increased expression of the S100A3 gene was also observed in CIS-resistant A2780 sublines. Overexpression of the C4orf18 gene was observed in CIS- and TOP-resistant A2780 sublines. A short time of exposure to CIS led to increased expression of the ABCC2 gene in the W1 and A2780 cell lines and increased expression of the C4orf18 gene in the A2780 cell line. A short time of exposure to TOP led to increased expression of the S100A3 and HERC5 genes in both sensitive cell lines, increased expression of the C4orf18 gene in the A2780 cell line and downregulation of the MCTP1 gene in the W1 cell line. Our results suggest that changes in expression of the MCTP1, S100A3 and C4orf18 genes may be related to both CIS and TOP resistance. Increased expression of the HERC5 gene seems to be important only in TOP resistance. Full article

(This article belongs to the Special Issue Counteracting Drug Resistant Mechanisms in Cancer)

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6 pages, 206 KiB

Open AccessFeature PaperArticle

Peroxisomal 2-Hydroxyacyl-CoA Lyase Is Involved in Endogenous Biosynthesis of Heptadecanoic Acid

by Benjamin Jenkins^1,2, Evelyn De Schryver³, Paul P. Van Veldhoven³ and Albert Koulman^1,2,*

¹ NIHR BRC Core Metabolomics and Lipidomics Laboratory, University of Cambridge, Pathology building Level 4, Addenbrooke’s Hospital, Cambridge CB2 0QQ, UK

² Medical Research Council Elsie Widdowson Laboratory, Fulbourn Road, Cambridge CB1 9NL, UK

³ Laboratory of Lipid Biochemistry and Protein Interactions (LIPIT), Campus Gasthuisberg—KU Leuven, Herestraat Box 601, B-3000 Leuven, Belgium

Molecules 2017, 22(10), 1718; https://doi.org/10.3390/molecules22101718 - 13 Oct 2017

Cited by 20 | Viewed by 5247

Abstract

Circulating heptadecanoic acid (C17:0) is reported to be a pathology risk/prognosis biomarker and a dietary biomarker. This pathology relationship has been shown to be reliably predictive even when independent of dietary contributions, suggesting that the endogenous biosynthesis of C17:0 is related to the [...] Read more.

Circulating heptadecanoic acid (C17:0) is reported to be a pathology risk/prognosis biomarker and a dietary biomarker. This pathology relationship has been shown to be reliably predictive even when independent of dietary contributions, suggesting that the endogenous biosynthesis of C17:0 is related to the pathological aetiology. Little is known about C17:0 biosynthesis, which tissues contribute to the circulating levels, and how C17:0 is related to pathology. Hacl1+/− mice were mated to obtain Hacl1−/− and Hacl1+/+ control mice. At 14 weeks, they were anesthetized for tissue collection and fatty acid analysis. Compared to Hacl1+/+, C15:0 was not significantly affected in any Hacl1−/− tissues. However, the Hacl1−/− plasma and liver C17:0 levels were significantly lower: ~26% and ~22%, respectively. No significant differences were seen in the different adipose tissues. To conclude, Hacl1 plays a significant role in the liver and plasma levels of C17:0, providing evidence it can be endogenously biosynthesized via alpha-oxidation. The strong inverse association of C17:0 with pathology raises the question whether there is a direct link between α-oxidation and these diseases. Currently, there is no clear evidence, warranting further research into the role of α-oxidation in relation to metabolic diseases. Full article

(This article belongs to the Section Metabolites)

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18 pages, 2177 KiB

Open AccessArticle

Stereopermutation on the Putative Structure of the Marine Natural Product Mucosin

by Simen G. Antonsen¹

, Harrison Gallantree-Smith¹, Carl Henrik Görbitz²

, Trond Vidar Hansen^1,3, Yngve H. Stenstrøm¹

and Jens M. J. Nolsøe^1,*,†

¹ Faculty of Chemistry, Biotechnology and Food Science, Norwegian University of Life Sciences, P.O. Box 5003, 1433 Ås, Norway

² Department of Chemistry, University of Oslo, P.O. Box 1033, 0315 Oslo, Norway

³ Department of Pharmaceutical Chemistry, University of Oslo, P.O. Box 1068, 0316 Oslo, Norway

^† Dedication: Dedicated to Lars Skattebøl on the occasion of his 90th birthday.

Molecules 2017, 22(10), 1720; https://doi.org/10.3390/molecules22101720 - 13 Oct 2017

Cited by 6 | Viewed by 5592

Abstract

A stereodivergent total synthesis has been executed based on the plausibly misassigned structure of the unusual marine hydrindane mucosin (1). The topological connectivity of the four contiguous all-carbon stereocenters has been examined by selective permutation on the highlighted core. Thus, [...] Read more.

A stereodivergent total synthesis has been executed based on the plausibly misassigned structure of the unusual marine hydrindane mucosin (1). The topological connectivity of the four contiguous all-carbon stereocenters has been examined by selective permutation on the highlighted core. Thus, capitalizing on an unprecedented stereofacial preference of the cis-fused bicycle[4.3.0]non-3-ene system when a Michael acceptor motif is incorporated, copper-mediated conjugate addition furnished a single diastereomer. Cued by the relative relationship reported for the appendices in the natural product, the resulting anti-adduct was elaborated into a probative target structure 1*. Full article

(This article belongs to the Section Natural Products Chemistry)

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27 pages, 3294 KiB

Open AccessArticle

Chemotaxonomic Classification Applied to the Identification of Two Closely-Related Citrus TCMs Using UPLC-Q-TOF-MS-Based Metabolomics

by Si-Yu Zhao^1,2, Zhen-Li Liu^3,*, Yi-Song Shu^1,2, Meng-Lei Wang^1,2, Dan He^1,2, Zhi-Qian Song³, Hong-Lian Zeng^1,2, Zhang-Chi Ning³, Cheng Lu^4,*

, Ai-Ping Lu^4,5,* and Yuan-Yan Liu^1,*

¹ School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, China

² State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100700, China

³ Institution of Basic Theory, China Academy of Chinese Medical Sciences, Beijing 100700, China

⁴ Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, China

⁵ School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China

Molecules 2017, 22(10), 1721; https://doi.org/10.3390/molecules22101721 - 13 Oct 2017

Cited by 60 | Viewed by 7394

Abstract

This manuscript elaborates on the establishment of a chemotaxonomic classification strategy for closely-related Citrus fruits in Traditional Chinese Medicines (TCMs). UPLC-Q-TOF-MS-based metabolomics was applied to depict the variable chemotaxonomic markers and elucidate the metabolic mechanism of Citrus TCMs from different species and at [...] Read more.

This manuscript elaborates on the establishment of a chemotaxonomic classification strategy for closely-related Citrus fruits in Traditional Chinese Medicines (TCMs). UPLC-Q-TOF-MS-based metabolomics was applied to depict the variable chemotaxonomic markers and elucidate the metabolic mechanism of Citrus TCMs from different species and at different ripening stages. Metabolomics can capture a comprehensive analysis of small molecule metabolites and can provide a powerful approach to establish metabolic profiling, creating a bridge between genotype and phenotype. To further investigate the different metabolites in four closely-related Citrus TCMs, non-targeted metabolite profiling analysis was employed as an efficient technique to profile the primary and secondary metabolites. The results presented in this manuscript indicate that primary metabolites enable the discrimination of species, whereas secondary metabolites are associated with species and the ripening process. In addition, analysis of the biosynthetic pathway highlighted that the syntheses of flavone and flavone glycosides are deeply affected in Citrus ripening stages. Ultimately, this work might provide a feasible strategy for the authentication of Citrus fruits from different species and ripening stages and facilitate a better understanding of their different medicinal uses. Full article

(This article belongs to the Section Natural Products Chemistry)

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15 pages, 1253 KiB

Open AccessArticle

Binding Direction-Based Two-Dimensional Flattened Contact Area Computing Algorithm for Protein–Protein Interactions

by Beom Sik Kang¹

, GaneshKumar Pugalendhi² and Ku-Jin Kim^3,*

¹ School of Life Sciences and Biotechnology, Kyungpook National University, 80 Daehakro, Bukgu, Daegu 41566, Korea

² Department of Information Technology, Anna University Regional Campus, Coimbatore 641046, Tamil Nadu, India

³ School of Computer Science and Engineering, Kyungpook National University, 80 Daehakro, Bukgu, Daegu 41566, Korea

Molecules 2017, 22(10), 1722; https://doi.org/10.3390/molecules22101722 - 13 Oct 2017

Cited by 2 | Viewed by 4339

Abstract

Interactions between protein molecules are essential for the assembly, function, and regulation of proteins. The contact region between two protein molecules in a protein complex is usually complementary in shape for both molecules and the area of the contact region can be used [...] Read more.

Interactions between protein molecules are essential for the assembly, function, and regulation of proteins. The contact region between two protein molecules in a protein complex is usually complementary in shape for both molecules and the area of the contact region can be used to estimate the binding strength between two molecules. Although the area is a value calculated from the three-dimensional surface, it cannot represent the three-dimensional shape of the surface. Therefore, we propose an original concept of two-dimensional contact area which provides further information such as the ruggedness of the contact region. We present a novel algorithm for calculating the binding direction between two molecules in a protein complex, and then suggest a method to compute the two-dimensional flattened area of the contact region between two molecules based on the binding direction. Full article

(This article belongs to the Special Issue Protein-Protein Interactions)

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20 pages, 947 KiB

Open AccessReview

BACE1 Function and Inhibition: Implications of Intervention in the Amyloid Pathway of Alzheimer’s Disease Pathology

by Gerald Koelsch

CoMentis, Inc., South San Francisco, CA 94080, USA

Molecules 2017, 22(10), 1723; https://doi.org/10.3390/molecules22101723 - 13 Oct 2017

Cited by 105 | Viewed by 14221

Abstract

Alzheimer’s disease (AD) is a fatal progressive neurodegenerative disorder characterized by increasing loss in memory, cognition, and function of daily living. Among the many pathologic events observed in the progression of AD, changes in amyloid β peptide (Aβ) metabolism proceed fastest, and precede [...] Read more.

Alzheimer’s disease (AD) is a fatal progressive neurodegenerative disorder characterized by increasing loss in memory, cognition, and function of daily living. Among the many pathologic events observed in the progression of AD, changes in amyloid β peptide (Aβ) metabolism proceed fastest, and precede clinical symptoms. BACE1 (β-secretase 1) catalyzes the initial cleavage of the amyloid precursor protein to generate Aβ. Therefore inhibition of BACE1 activity could block one of the earliest pathologic events in AD. However, therapeutic BACE1 inhibition to block Aβ production may need to be balanced with possible effects that might result from diminished physiologic functions BACE1, in particular processing of substrates involved in neuronal function of the brain and periphery. Potentials for beneficial or consequential effects resulting from pharmacologic inhibition of BACE1 are reviewed in context of ongoing clinical trials testing the effect of BACE1 candidate inhibitor drugs in AD populations. Full article

(This article belongs to the Special Issue 25th Anniversary of the Amyloid Hypothesis and Alzheimer Disease)

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20 pages, 1590 KiB

Open AccessReview

Enhancing the Therapeutic Delivery of Oligonucleotides by Chemical Modification and Nanoparticle Encapsulation

by Yating Sun¹, Yarong Zhao¹, Xiuting Zhao¹, Robert J. Lee^1,2

, Lesheng Teng^1,*

and Chenguang Zhou^3,*

¹ School of Life Sciences, Jilin University, Changchun 130012, China

² College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA

³ Tavistock Life Sciences, San Diego, CA 92130, USA

Molecules 2017, 22(10), 1724; https://doi.org/10.3390/molecules22101724 - 13 Oct 2017

Cited by 45 | Viewed by 8648

Abstract

Oligonucleotide (ON) drugs, including small interfering RNA (siRNA), microRNA (miRNA) and antisense oligonucleotides, are promising therapeutic agents. However, their low membrane permeability and sensitivity to nucleases present challenges to in vivo delivery. Chemical modifications of the ON offer a potential solution to improve [...] Read more.

Oligonucleotide (ON) drugs, including small interfering RNA (siRNA), microRNA (miRNA) and antisense oligonucleotides, are promising therapeutic agents. However, their low membrane permeability and sensitivity to nucleases present challenges to in vivo delivery. Chemical modifications of the ON offer a potential solution to improve the stability and efficacy of ON drugs. Combined with nanoparticle encapsulation, delivery at the site of action and gene silencing activity of chemically modified ON drugs can be further enhanced. In the present review, several types of ON drugs, selection of chemical modification, and nanoparticle-based delivery systems to deliver these ON drugs are discussed. Full article

(This article belongs to the Special Issue Nucleic Acid Chemistry and Nucleic Acid Drugs: A Themed Issue in Honor of Professor Lihe Zhang on the Occasion of His 80th Birthday)

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12 pages, 1733 KiB

Open AccessArticle

Alpha-Galacto-Oligosaccharides at Low Dose Improve Liver Steatosis in a High-Fat Diet Mouse Model

by Eric Chappuis^1,*, Fanny Morel-Depeisse¹, Bruno Bariohay² and Julien Roux²

¹ Olygose, Rue les Rives de l’Oise, Venette 60200, France

² Biomeostasis, ActiParc I - Bat.6 Traverse de la Penne, La Penne-sur-Huveaune 13821, France

Molecules 2017, 22(10), 1725; https://doi.org/10.3390/molecules22101725 - 14 Oct 2017

Cited by 28 | Viewed by 6799

Abstract

Non-Alcoholic Fatty Liver Disease (NAFLD) is the major liver disease worldwide and is linked to the development of metabolic syndrome and obesity. As alpha-galacto-oligosaccharides (α-GOS) from legumes have been shown to reduce body weight and hyperphagia in overweight adults, it was hypothesized that [...] Read more.

Non-Alcoholic Fatty Liver Disease (NAFLD) is the major liver disease worldwide and is linked to the development of metabolic syndrome and obesity. As alpha-galacto-oligosaccharides (α-GOS) from legumes have been shown to reduce body weight and hyperphagia in overweight adults, it was hypothesized that they would exert benefits on the development of metabolic syndrome and associated NAFLD in a rodent model. C57Bl/6J mice were fed a high-fat diet until they developed metabolic syndrome and were then orally treated either with α-GOS at a physiological dose (2.2 g/kg BW/d) or the vehicle over 7 weeks. α-GOS induced a reduction in food intake, but without affecting body weight during the first week of treatment, when compared to the vehicle. Fasting glycaemia was improved after 4 weeks of treatment with α-GOS, whereas insulin sensitivity (assessed with HOMA-IR) was unaffected at the end of the experiment. Plasma non-esterified fatty acids, low-density lipoprotein (LDL) and total cholesterol were lowered by α-GOS while high-density lipoprotein (HDL) and triglycerides levels remained unaffected. α-GOS markedly improved liver steatosis as well as free fatty acid and triglyceride accumulation in the liver. α-GOS improved plasma lipids and prevented NAFLD development through mechanisms which are independent of body weight management and glycemic control. Full article

(This article belongs to the Special Issue Bioactive Compounds for Metabolic Syndrome and Type 2 Diabetes)

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11 pages, 401 KiB

Open AccessArticle

Caustic Ingestion in the Elderly: Influence of Age on Clinical Outcome

by Blazena Caganova¹, Tatiana Foltanova^2,*, Erik Puchon², Elena Ondriasova², Silvia Plackova¹, Tomas Fazekas³

and Magdalena Kuzelova²

¹ Department of Occupational Medicine and Toxicology, National Toxicological Information Centre, University Hospital Bratislava, Bratislava 83305, Slovak

² Department of Pharmacology and Toxicology, Faculty of Pharmacy, Comenius University in Bratislava, Bratislava 81499, Slovak

³ Department of Physical Chemistry of Drugs, Faculty of Pharmacy, Comenius University in Bratislava, Bratislava 81499, Slovak

Molecules 2017, 22(10), 1726; https://doi.org/10.3390/molecules22101726 - 14 Oct 2017

Cited by 7 | Viewed by 6509

Abstract

Caustic poisonings are still associated with many fatalities. Studies focusing on the elderly are rare. The purpose of the present study was to compare the clinical outcomes of caustic ingestion injury in elderly and non-elderly adults with regard to gender, intent of exposure, [...] Read more.

Caustic poisonings are still associated with many fatalities. Studies focusing on the elderly are rare. The purpose of the present study was to compare the clinical outcomes of caustic ingestion injury in elderly and non-elderly adults with regard to gender, intent of exposure, substance ingested, severity of mucosal injury, complications, and mortality. Caustic substance exposures reported to the National Toxicological Information Centre in Slovakia during 1998–2015 were reviewed retrospectively. The patients were divided into two groups: the non-elderly (<60 years) and elderly adults (≥60 years). The mortality rate in the elderly was significantly higher (elderly 23.0% vs. non-elderly 11.3%; p = 0.041). The risk of fatal outcome in the elderly was increased by acid ingestion (OR = 7.822; p = 0.002), particularly hydrochloric acid (OR = 5.714, p = 0.006). The incidence of respiratory complications was almost two times higher in the elderly was 31.1% vs. 17.4% for the non-elderly (p = 0.037). Respiratory complications significantly correlated with an increased mortality rate (p = 0.001) in the elderly whereas there was no association between GI complications and mortality in the elderly (p = 0.480). Elderly patients with respiratory complications had the poorest clinical outcomes. The highest risk of complications and fatalities was observed in patients after hydrochloric acid ingestion. Full article

(This article belongs to the Special Issue Selected Papers from the 46th EuroCongress on Drug Synthesis and Analysis (ECDSA-2017))

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12 pages, 2837 KiB

Open AccessArticle

Melatonin Improves the Photosynthetic Carbon Assimilation and Antioxidant Capacity in Wheat Exposed to Nano-ZnO Stress

by Zhiyu Zuo¹

, Luying Sun², Tianyu Wang¹, Peng Miao¹, Xiancan Zhu², Shengqun Liu², Fengbin Song², Hanping Mao¹ and Xiangnan Li^2,*

¹ Key Laboratory of Modern Agricultural Equipment and Technology, Ministry of Education/High-tech Key Laboratory of Agricultural Equipment and Intelligence of Jiangsu Province, School of Agricultural Equipment and Engineering, Jiangsu University, Zhenjiang 212013, China

² Northeast Institute of Geography and Agroecology, Chinese Academy of Sciences, Changchun 130102, China

Molecules 2017, 22(10), 1727; https://doi.org/10.3390/molecules22101727 - 18 Oct 2017

Cited by 74 | Viewed by 7003

Abstract

The release of nanoparticles into the environment is inevitable, which has raised global environmental concern. Melatonin is involved in various stress responses in plants. The present study investigated the effects of melatonin on photosynthetic carbon (C) assimilation and plant growth in nano-ZnO stressed [...] Read more.

The release of nanoparticles into the environment is inevitable, which has raised global environmental concern. Melatonin is involved in various stress responses in plants. The present study investigated the effects of melatonin on photosynthetic carbon (C) assimilation and plant growth in nano-ZnO stressed plants. It was found that melatonin improved the photosynthetic C assimilation in nano-ZnO stressed wheat plants, mainly due to the enhanced photosynthetic energy transport efficiency, higher chlorophyll concentration and higher activities of Rubisco and ATPases. In addition, melatonin enhanced the activities of antioxidant enzymes to protect the photosynthetic electron transport system in wheat leaves against the oxidative burst caused by nano-ZnO stress. These results suggest that melatonin could improve the tolerance of wheat plants to nano-ZnO stress. Full article

(This article belongs to the Special Issue Melatonin as an Antioxidant and a Functionally Pleiotropic Molecule: Synthesis, Metabolism and Activities in Organisms)

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14 pages, 1293 KiB

Open AccessArticle

Melatonin Treatment Reduces Oxidative Damage and Normalizes Plasma Pro-Inflammatory Cytokines in Patients Suffering from Charcot-Marie-Tooth Neuropathy: A Pilot Study in Three Children

by Mariam Chahbouni¹, María Del Señor López², Antonio Molina-Carballo³, Tomás De Haro², Antonio Muñoz-Hoyos³, Marisol Fernández-Ortiz¹, Ana Guerra-Librero¹

and Darío Acuña-Castroviejo^1,2,*

¹ Departamento de Fisiología, Facultad de Medicina, Instituto de Biotecnología, Centro de Investigación Biomédica, Parque Tecnológico de Ciencias de la Salud, Universidad de Granada, 18016-Granada, Spain

² CIBERfes, Ibs.Granada, and UGC de Laboratorios Clínicos, Complejo Hospitalario de Granada, 18016-Granada, Spain

³ Unidad de Gestión Clínica de Pediatría, Hospital Universitario San Cecilio, 18012-Granada, Spain

Molecules 2017, 22(10), 1728; https://doi.org/10.3390/molecules22101728 - 14 Oct 2017

Cited by 29 | Viewed by 7754

Abstract

Charcot-Marie-Tooth neuropathy (CMT) is a motor and sensory neuropathy comprising a heterogeneous group of inherited diseases. The CMT1A phenotype is predominant in the 70% of CMT patients, with nerve conduction velocity reduction and hypertrophic demyelination. These patients have elevated oxidative stress and chronic [...] Read more.

Charcot-Marie-Tooth neuropathy (CMT) is a motor and sensory neuropathy comprising a heterogeneous group of inherited diseases. The CMT1A phenotype is predominant in the 70% of CMT patients, with nerve conduction velocity reduction and hypertrophic demyelination. These patients have elevated oxidative stress and chronic inflammation. Currently, there is no effective cure for CMT; herein, we investigated whether melatonin treatment may reduce the inflammatory and oxidative damage in CMT1A patients. Three patients, aged 8–10 years, were treated with melatonin (60 mg at 21:00 h plus 10 mg at 09:00 h), and plasma levels of lipid peroxidation (LPO), nitrites (NOx), IL-1β, IL-2, IL-6, TNF-α, INF-γ, oxidized to reduced glutathione (GSSG/GSH) ratio, and the activities of superoxide dismutase (SOD), glutathione-S transferase (GST), glutathione peroxidase (GPx), and reductase (GRd), were determined in erythrocytes at 3 and 6 months of treatment. Healthy age- and sex-matched subjects were used as controls. The results showed increased activities of SOD, GST, GPx, and GRd in CMT1A patients, which were reduced at 3 and 6 months of treatment. The GSSG/GSH ratio significantly increased in the patients, returning to control values after melatonin treatment. The inflammatory process was confirmed by the elevation of all proinflammatory cytokines measured, which were also normalized by melatonin. LPO and NOx, which also were elevated in the patients, were normalized by melatonin. The results document beneficial effects of the use of melatonin in CMT1A patients to reduce the hyperoxidative and inflammatory condition, which may correlate with a reduction of the degenerative process. Full article

(This article belongs to the Special Issue Melatonin as an Antioxidant and a Functionally Pleiotropic Molecule: Synthesis, Metabolism and Activities in Organisms)

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11 pages, 1554 KiB

Open AccessArticle

From 2-Alkylsulfanylimidazoles to 2-Alkylimidazoles: An Approach towards Metabolically More Stable p38α MAP Kinase Inhibitors

by Fabian Heider¹

, Urs Haun¹, Eva Döring¹, Mark Kudolo¹, Catharina Sessler¹, Wolfgang Albrecht², Stefan Laufer¹ and Pierre Koch^1,*

¹ Department of Pharmaceutical and Medicinal Chemistry, Institute of Pharmaceutical Sciences, Eberhard Karls Universität Tübingen, Auf der Morgenstelle 8, 72076 Tübingen, Germany

² Teva-ratiopharm, Graf-Arco-Str. 3, 89079 Ulm, Germany

Molecules 2017, 22(10), 1729; https://doi.org/10.3390/molecules22101729 - 14 Oct 2017

Cited by 11 | Viewed by 6408

Abstract

In vitro and in vivo metabolism studies revealed that 2-alkylsulfanylimidazole ML3403 (4-(5-(4-fluorophenyl)-2-(methylthio)-1H-imidazol-4-yl)-N-(1-phenylethyl)pyridin-2-amine) undergoes rapid oxidation to the sulfoxide. Replacing the sulfur atom present in the two potent p38α mitogen-activated protein (MAP) kinase inhibitors ML3403 and LN950 (2-((5-(4-fluorophenyl)-4-(2-((3-methylbutan-2-yl)amino)pyridin-4-yl)-1H-imidazol-2-yl)thio)ethan-1-ol) [...] Read more.

In vitro and in vivo metabolism studies revealed that 2-alkylsulfanylimidazole ML3403 (4-(5-(4-fluorophenyl)-2-(methylthio)-1H-imidazol-4-yl)-N-(1-phenylethyl)pyridin-2-amine) undergoes rapid oxidation to the sulfoxide. Replacing the sulfur atom present in the two potent p38α mitogen-activated protein (MAP) kinase inhibitors ML3403 and LN950 (2-((5-(4-fluorophenyl)-4-(2-((3-methylbutan-2-yl)amino)pyridin-4-yl)-1H-imidazol-2-yl)thio)ethan-1-ol) by a methylene group resulted in 2-alkylimidazole derivatives 1 and 2, respectively, having a remarkably improved metabolic stability. The 2-alkylimidazole analogs 1 and 2 showed 20% and 10% biotransformation after 4 h of incubation with human liver microsomes, respectively. They display a 4-fold increased binding affinity towards the target kinase as well as similar in vitro potency and ex vivo efficacy relative to their 2-alkylsulfanylimidazole counterparts ML3403 and LN950. For example, 2-alkylimidazole 2, the analog of LN950, inhibits both the p38α MAP kinase as well as the LPS-stimulated tumor necrosis factor-α release from human whole blood in the low double-digit nanomolar range. Full article

(This article belongs to the Special Issue Kinase Inhibitors)

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12 pages, 2992 KiB

Open AccessArticle

NIR Rapid Assessments of Blumea balsamifera (Ai-na-xiang) in China

by Fu-Lai Yu^1,†, Na Zhao^2,3,†, Zhi-Sheng Wu^4,*, Mei Huang¹, Dan Wang¹, Ying-Bo Zhang¹

, Xuan Hu¹, Xiao-Lu Chen¹

, Lu-Qi Huang⁵ and Yu-Xin Pang^1,5,6,*

¹ Tropical Crops Genetic Resources Institute, Chinese Academy of Tropical Agricultural Sciences, Danzhou 571737, China

² School of Pharmacy, Shihezi University, Shihezi 832002, China

³ Key Laboratory of Xinjiang Plant Resources and Utilization, Ministry of Education, Shihezi 832002, China

⁴ School of Chinese Material Medica, Beijing University of Chinese Medicine, Beijing 100029, China

⁵ National Resource Center for Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China

⁶ Center for Post-Doctoral Research, China Academy of Chinese Medical Sciences, Beijing 100700, China

^† These authors contribute equally to this work.

Molecules 2017, 22(10), 1730; https://doi.org/10.3390/molecules22101730 - 16 Oct 2017

Cited by 16 | Viewed by 4902

Abstract

Blumea balsamifera (Ai-na-xiang) is used as an important plant source of natural borneol, which is widely used in the pharmaceutical industry. The aim of this study was to establish the methods based on near infrared (NIR) spectroscopy for determining the geographical [...] Read more.

Blumea balsamifera (Ai-na-xiang) is used as an important plant source of natural borneol, which is widely used in the pharmaceutical industry. The aim of this study was to establish the methods based on near infrared (NIR) spectroscopy for determining the geographical origin of B. balsamifera, as well as developing a method for the quantitative rapid analysis of the active pharmaceutical ingredients (APIs). A total of 109 samples were collected from China in 2013 and arbitrarily divided into calibration and prediction sets using the Kennard–Stone algorithm. The l-borneol and total flavone contents of the samples were measured by gas chromatography and ultraviolet-visible spectroscopy, respectively. The NIR spectra were acquired using an integrating sphere and a partial least squares (PLS) model was built using the optimum wavelength regions, which were selected using a synergy interval partial least-squares (SiPLS) algorithm. The root mean square errors of prediction of the l-borneol and total flavone models were 0.0779 and 2.2694 mg/g, with R² of 0.9069 and 0.8013, respectively. A discriminant model to determine the geographical origin of B. balsamifera (Guizhou and Hainan) was also established using a partial least squares discriminant analysis method with an optimum pretreatment method. The prediction accuracy rate of the model was 100%. NIR spectroscopy can be used as a reliable and environmentally friendly method to determine the API and the origin of different B. balsamifera samples. Full article

(This article belongs to the Section Green Chemistry)

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9 pages, 423 KiB

Open AccessArticle

New Triterpenoid Saponins from the Herb Hylomecon japonica

by Yan-Fei Qu^1,2, Jing-Yu Gao^1,3, Jing Wang¹, Yan-Mei Geng¹, Yu Zhou¹, Cheng-Xin Sun¹, Fei Li¹, Lei Feng¹, Meng-Juan Yu¹ and Guang-Shu Wang^1,*

¹ School of Pharmaceutical Sciences, Jilin University, Changchun 130021, Jilin, China

² Logistics University of PAP, Tianjin 300162, China

³ Department of Pharmacy, Central Hospital of Yingkou Economic and Technological Development Zone, Yingkou 115007, Liaoning, China

Molecules 2017, 22(10), 1731; https://doi.org/10.3390/molecules22101731 - 23 Oct 2017

Cited by 15 | Viewed by 4790

Abstract

Background: Hylomecon japonica, a plant of the Papaveraceae family which is well-known for the alkaloids they produce, is a perennial plant widely distributed in the northeast, central and east regions of China. Although a variety of chemical constituents, including alkaloids, flavonoids, [...] Read more.

Background: Hylomecon japonica, a plant of the Papaveraceae family which is well-known for the alkaloids they produce, is a perennial plant widely distributed in the northeast, central and east regions of China. Although a variety of chemical constituents, including alkaloids, flavonoids, and megastigmoids, have been isolated from H. japonica, the investigation of saponins in H. japonica has not been reported until now. Methods: Various separation techniques, including polyporous resin column chromatography, silica gel column chromatography and hemi-preparative HPLC were applied to the isolation of triterpenoid saponins, and chemical methods such as acid hydrolysis and spectroscopic methods including HRESIMS and NMR were applied to their structure elucidation, and the XTT reduction method was used to assay cytotoxicity. Results: Two new triterpenoid saponins, named hylomeconoside A (1) and B (2) which were identified as 3-O-β-d-galactopyranosyl-(1→2)-β-d-glucuronopyranosyl-gypsogenin-28-O-β-d-xylopyranosyl-(1→3)-β-d-xylopyranosyl-(1→4)-α-l-rhamnopyranosyl-(1→2)-β-d-quinovopyranoside (1) and 3-O-β-d-galactopyranosyl-(1→2)-β-d-glucuronopyranosyl-gypsogenin-28-O-β-d-xylopyranosyl-(1→3)-β-d-xylopyranosyl-(1→4)-α-l-rhamnopyranosyl-(1→2)-α-l-arabinopyranoside (2), and two known triterpenoid saponins identified as dubioside C (3) and lucyoside P (4) on the basis of spectroscopic and chemical evidence, were isolated from H. japonica. Compound 1 exhibited moderate cytotoxicity on MGC-803 and HL-60 cells, with IC₅₀ values of 43.8 and 32.4 μg·mL⁻¹, respectively. Conclusions: Compounds 1 and 2 are new saponins, and 1 is considered to be one of the antitumor principles in this plant. This is the first time that triterpenoid saponins have been isolated from plants of the Papaveraceae family. Full article

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14 pages, 612 KiB

Open AccessArticle

ProLanGO: Protein Function Prediction Using Neural Machine Translation Based on a Recurrent Neural Network

by Renzhi Cao^1,*, Colton Freitas¹, Leong Chan², Miao Sun³, Haiqing Jiang⁴ and Zhangxin Chen^5,*

¹ Department of Computer Science, Pacific Lutheran University, Tacoma, WA 98447, USA

² School of Business, Pacific Lutheran University, Tacoma, WA 98447, USA

³ Baidu Inc. 1195 Bordeaux Dr, Sunnyvale, CA 94089, USA

⁴ Hiretual Inc., San Jose, CA 95131, USA

⁵ School of electronic engineering, University of Electronic Science and Technology of China, Chengdu 610051, China

Molecules 2017, 22(10), 1732; https://doi.org/10.3390/molecules22101732 - 17 Oct 2017

Cited by 159 | Viewed by 11008

Abstract

With the development of next generation sequencing techniques, it is fast and cheap to determine protein sequences but relatively slow and expensive to extract useful information from protein sequences because of limitations of traditional biological experimental techniques. Protein function prediction has been a [...] Read more.

With the development of next generation sequencing techniques, it is fast and cheap to determine protein sequences but relatively slow and expensive to extract useful information from protein sequences because of limitations of traditional biological experimental techniques. Protein function prediction has been a long standing challenge to fill the gap between the huge amount of protein sequences and the known function. In this paper, we propose a novel method to convert the protein function problem into a language translation problem by the new proposed protein sequence language “ProLan” to the protein function language “GOLan”, and build a neural machine translation model based on recurrent neural networks to translate “ProLan” language to “GOLan” language. We blindly tested our method by attending the latest third Critical Assessment of Function Annotation (CAFA 3) in 2016, and also evaluate the performance of our methods on selected proteins whose function was released after CAFA competition. The good performance on the training and testing datasets demonstrates that our new proposed method is a promising direction for protein function prediction. In summary, we first time propose a method which converts the protein function prediction problem to a language translation problem and applies a neural machine translation model for protein function prediction. Full article

(This article belongs to the Special Issue Computational Analysis for Protein Structure and Interaction)

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18 pages, 2507 KiB

Open AccessArticle

Analysis of Genetic Diversity and Structure Pattern of Indigofera Pseudotinctoria in Karst Habitats of the Wushan Mountains Using AFLP Markers

by Yan Fan^1,†, Chenglin Zhang^2,†

, Wendan Wu², Wei He¹, Li Zhang¹ and Xiao Ma^2,*

¹ Chongqing Academy of Animal Husbandry, Chongqing 400039, China

² Department of Grassland Science, Animal Science and Technology College, Sichuan Agricultural University, Chengdu 611130, China

^† These authors contributed equally to this work and should be considered co-first authors.

Molecules 2017, 22(10), 1734; https://doi.org/10.3390/molecules22101734 - 16 Oct 2017

Cited by 7 | Viewed by 5050

Abstract

Indigofera pseudotinctoria Mats is an agronomically and economically important perennial legume shrub with a high forage yield, protein content and strong adaptability, which is subject to natural habitat fragmentation and serious human disturbance. Until now, our knowledge of the genetic relationships and intraspecific [...] Read more.

Indigofera pseudotinctoria Mats is an agronomically and economically important perennial legume shrub with a high forage yield, protein content and strong adaptability, which is subject to natural habitat fragmentation and serious human disturbance. Until now, our knowledge of the genetic relationships and intraspecific genetic diversity for its wild collections is still poor, especially at small spatial scales. Here amplified fragment length polymorphism (AFLP) technology was employed for analysis of genetic diversity, differentiation, and structure of 364 genotypes of I. pseudotinctoria from 15 natural locations in Wushan Montain, a highly structured mountain with typical karst landforms in Southwest China. We also tested whether eco-climate factors has affected genetic structure by correlating genetic diversity with habitat features. A total of 515 distinctly scoreable bands were generated, and 324 of them were polymorphic. The polymorphic information content (PIC) ranged from 0.694 to 0.890 with an average of 0.789 per primer pair. On species level, Nei’s gene diversity (H_j), the Bayesian genetic diversity index (H_B) and the Shannon information index (I) were 0.2465, 0.2363 and 0.3772, respectively. The high differentiation among all sampling sites was detected (F_ST = 0.2217, G_ST = 0.1746, G’_ST = 0.2060, θ^B = 0.1844), and instead, gene flow among accessions (N_m = 1.1819) was restricted. The population genetic structure resolved by the UPGMA tree, principal coordinate analysis, and Bayesian-based cluster analyses irrefutably grouped all accessions into two distinct clusters, i.e., lowland and highland groups. The population genetic structure resolved by the UPGMA tree, principal coordinate analysis, and Bayesian-based cluster analyses irrefutably grouped all accessions into two distinct clusters, i.e., lowland and highland groups. This structure pattern may indicate joint effects by the neutral evolution and natural selection. Restricted N_m was observed across all accessions, and genetic barriers were detected between adjacent accessions due to specifically geographical landform. Full article

(This article belongs to the Section Molecular Diversity)

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12 pages, 2630 KiB

Open AccessArticle

Promoting Effect of Pinostrobin on the Proliferation, Differentiation, and Mineralization of Murine Pre-osteoblastic MC3T3-E1 Cells

by Chengbo Gu^1,*, Linan Fu¹, Xiaohan Yuan² and Zhiguo Liu^1,*

¹ Key Laboratory of Forest Plant Ecology, Ministry of Education, Northeast Forestry University, Harbin 150040, China

² Life Science and Biotechnique Research Center, Northeast Agricultural University, Harbin 150030, China

Molecules 2017, 22(10), 1735; https://doi.org/10.3390/molecules22101735 - 16 Oct 2017

Cited by 19 | Viewed by 6744

Abstract

Pinostrobin (PI), a natural flavonoid found in a variety of plants, is well known for its rich pharmacological activities. However, its osteogenic function remains unclear. The aim of this study is to evaluate the effect of PI on the proliferation, differentiation, and mineralization [...] Read more.

Pinostrobin (PI), a natural flavonoid found in a variety of plants, is well known for its rich pharmacological activities. However, its osteogenic function remains unclear. The aim of this study is to evaluate the effect of PI on the proliferation, differentiation, and mineralization of murine pre-osteoblastic MC3T3-E1 cells in vitro using MTT, alkaline phosphatase (ALP) activity, the synthesis of collagen I (Col I) assay, and Von-Kossa staining, respectively. The expression of osteocalcin (OCN) mRNA in cells was detected by real-time PCR. The effect of PI on the differentiation of dexamethasone (DEX)-suppressed cells was also investigated. The results showed that PI greatly promoted the proliferation of MC3T3-E1 cells at 5–80 μg/mL (p < 0.05 or p < 0.01), and caused a significant elevation of ALP activity, Col I content, and mineralization of osteoblasts at 10–40 μg/mL (p < 0.05 or p < 0.01), and the expression levels of OCN gene were greatly upregulated after PI treatment (p < 0.01). Furthermore, PI could rescue the inhibition effect of cell differentiation induced by DEX. Taken together, these results indicated that PI could directly promote proliferation, differentiation, and mineralization of MC3T3-E1 cells and has potential for use as a natural treatment for osteoporosis. Full article

(This article belongs to the Special Issue Herbal Remedies Meet Modern Day Medicine: Challenges and Opportunities)

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18 pages, 3413 KiB

Open AccessReview

Advanced Prodrug Strategies in Nucleoside and Non-Nucleoside Antiviral Agents: A Review of the Recent Five Years

by Hanadi Sinokrot, Tasneem Smerat, Anas Najjar and Rafik Karaman^*

Department of Bioorganic & Pharmaceutical Chemistry, Faculty of Pharmacy, Al-Quds University, Jerusalem P.O. Box 20002, Palestine

Molecules 2017, 22(10), 1736; https://doi.org/10.3390/molecules22101736 - 16 Oct 2017

Cited by 46 | Viewed by 10353

Abstract

Background: Poor pharmacokinetic profiles and resistance are the main two drawbacks from which currently used antiviral agents suffer, thus make them excellent targets for research, especially in the presence of viral pandemics such as HIV and hepatitis C. Methods: The strategies [...] Read more.

Background: Poor pharmacokinetic profiles and resistance are the main two drawbacks from which currently used antiviral agents suffer, thus make them excellent targets for research, especially in the presence of viral pandemics such as HIV and hepatitis C. Methods: The strategies employed in the studies covered in this review were sorted by the type of drug synthesized into ester prodrugs, targeted delivery prodrugs, macromolecular prodrugs, other nucleoside conjugates, and non-nucleoside drugs. Results: Utilizing the ester prodrug approach a novel isopropyl ester prodrug was found to be potent HIV integrase inhibitor. Further, employing the targeted delivery prodrug zanamivir and valine ester prodrug was made and shown a sole delivery of zanamivir. Additionally, VivaGel, a dendrimer macromolecular prodrug, was found to be very efficient and is now undergoing clinical trials. Conclusions: Of all the strategies employed (ester, targeted delivery, macromolecular, protides and nucleoside analogues, and non-nucleoside analogues prodrugs), the most promising are nucleoside analogues and macromolecular prodrugs. The macromolecular prodrug VivaGel works by two mechanisms: envelope mediated and receptor mediated disruption. Nucleotide analogues have witnessed productive era in the recent past few years. The era of non-interferon based treatment of hepatitis (through direct inhibitors of NS5A) has dawned. Full article

(This article belongs to the Section Medicinal Chemistry)

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3 pages, 169 KiB

Open AccessEditorial

Special Issue: Improvements for Resveratrol Efficacy

by Dominique Vervandier-Fasseur¹

, Ole Vang²

and Norbert Latruffe^3,*

¹ Institut de Chimie Moléculaire de l’Université de Bourgogne (ICMUB UMR 6302), Université of Bourgogne, 9 Av. Alain Savary, Dijon F-21000, France

² Department of Science and Environment, Roskilde University, DK-4000 Roskilde, Denmark

³ Laboratoire de Biochimie (Bio-peroxIL n°7270), 6 Boulevard Gabriel, Université de Bourgogne, Dijon F-21000, France

Molecules 2017, 22(10), 1737; https://doi.org/10.3390/molecules22101737 - 16 Oct 2017

Cited by 9 | Viewed by 3823

Abstract

Resveratrol is a well-known phenolic stilbene because of its presence in several edible plants and its proposed properties that are beneficial to human health [...]
Full article

(This article belongs to the Special Issue Improvements for Resveratrol Efficacy)

14 pages, 7961 KiB

Open AccessArticle

Pterodontic Acid Isolated from Laggera pterodonta Inhibits Viral Replication and Inflammation Induced by Influenza A Virus

by Wenda Guan^1,2,†, Jing Li^2,†, Qiaolian Chen², Zhihong Jiang³, Rongping Zhang⁴, Xinhua Wang^2,*, Zifeng Yang^2,3,* and Xiping Pan^5,*

¹ Tropical Medicine Institute, Guangzhou University of Chinese Medicine, Guangzhou 510405, China

² State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, First Affiliated Hospital of Guangzhou Medical University, (Guangzhou Medical University), Guangzhou 510120, China

³ State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau (SAR) 519020, China

⁴ School of Pharmaceutical Science & Biomedical Engineering Research Center, Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming 650500, China

⁵ Institute of Chinese Integrative Medicine, Guangzhou Medical University, Guangzhou 511436, China

^† These authors contributed equally to this work.

Molecules 2017, 22(10), 1738; https://doi.org/10.3390/molecules22101738 - 16 Oct 2017

Cited by 27 | Viewed by 5594

Abstract

Laggera pterodonta (DC.) Benth. is a traditional Chinese medicine. The previous study revealed that the crude extracts of this herb could inhibit influenza virus infection, but its anti-influenza components and underlying mechanism of action remain unknown. Column chromatography was performed to isolate components [...] Read more.

Laggera pterodonta (DC.) Benth. is a traditional Chinese medicine. The previous study revealed that the crude extracts of this herb could inhibit influenza virus infection, but its anti-influenza components and underlying mechanism of action remain unknown. Column chromatography was performed to isolate components from the plant. Activity against influenza virus of the compound was determined by CPE inhibition assay. Neuraminidase (NA) inhibition was measured by chemiluminescence assay. The anti-virus and anti-inflammation effects were determined using dual-luciferase reporter assay, immunofluorescence, quantitative real-time PCR and luminex assay. Pterodontic acid was isolated from L. pterodonta, which showed selective anti-viral activities to H1 subtype of human influenza A virus. Meanwhile, the NA activity was not obviously inhibited by the compound. Further experiments exhibited that the compound can suppress the activation of NF-κB signal pathway and export of viral RNP complexes from the nucleus. In addition, it can significantly attenuate expression of the pro-inflammatory molecules IL-6, MIP-1β, MCP-1, and IP-10 induced by human influenza A virus (H1N1) and similarly downregulate expression of cytokines and chemokines induced by avian influenza A virus (H9N2). This study showed that in vitro antiviral activity of pterodontic acid is most probably associated with inhibiting the replication of influenza A virus by blocking nuclear export of viral RNP complexes, and attenuating the inflammatory response by inhibiting activation of the NF-κB pathway. Pterodontic acid might be a potential antiviral agent against influenza A virus. Full article

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12 pages, 1748 KiB

Open AccessArticle

New Methods of Esterification of Nanodiamonds in Fighting Breast Cancer—A Density Functional Theory Approach

by Linda-Lucila Landeros-Martinez, Daniel Glossman-Mitnik

, Erasmo Orrantia-Borunda and Norma Flores-Holguín^*

Laboratorio Virtual Nanocosmos, Departamento de Medio Ambiente y Energia, Centro de Investigacion en Materiales Avanzados, Miguel de Cervantes 120, Complejo Industrial Chihuahua, Chihuahua, Chih 31136, Mexico

Molecules 2017, 22(10), 1740; https://doi.org/10.3390/molecules22101740 - 19 Oct 2017

Cited by 5 | Viewed by 5113

Abstract

The use of nanodiamonds as anticancer drug delivery vehicles has received much attention in recent years. In this theoretical paper, we propose using different esterification methods for nanodiamonds. The monomers proposed are 2-hydroxypropanal, polyethylene glycol, and polyglicolic acid. Specifically, the hydrogen bonds, infrared [...] Read more.

The use of nanodiamonds as anticancer drug delivery vehicles has received much attention in recent years. In this theoretical paper, we propose using different esterification methods for nanodiamonds. The monomers proposed are 2-hydroxypropanal, polyethylene glycol, and polyglicolic acid. Specifically, the hydrogen bonds, infrared (IR) spectra, molecular polar surface area, and reactivity parameters are analyzed. The monomers proposed for use in esterification follow Lipinski’s rule of five, meaning permeability is good, they have good permeation, and their bioactivity is high. The results show that the complex formed between tamoxifen and nanodiamond esterified with polyglicolic acid presents the greatest number of hydrogen bonds and a good amount of molecular polar surface area. Calculations concerning the esterified nanodiamond and reactivity parameters were performed using Density Functional Theory with the M06 functional and the basis set 6–31G (d); for the esterified nanodiamond–Tamoxifen complexes, the semi-empirical method PM6 was used. The solvent effect has been taken into account by using implicit modelling and the conductor-like polarizable continuum model. Full article

(This article belongs to the Section Computational and Theoretical Chemistry)

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14 pages, 5727 KiB

Open AccessArticle

A Highly Selective and Sensitive Fluorescent Turn-Off Probe for Cu²⁺ Based on a Guanidine Derivative

by Fei Ye, Qiong Chai, Xiao-Min Liang, Ming-Qiang Li, Zhi-Qiang Wang and Ying Fu^*

Department of Applied Chemistry, College of Science, Northeast Agricultural University, Harbin 150030, China

Molecules 2017, 22(10), 1741; https://doi.org/10.3390/molecules22101741 - 16 Oct 2017

Cited by 33 | Viewed by 5565

Abstract

A new highly selective and sensitive fluorescent probe for Cu²⁺, N-n-butyl-4-(1′-cyclooctene-1′,3′,6′-triazole)-1,8-naphthalimide (L), was synthesized and evaluated. The structure of compound L was characterized via IR, ¹H-NMR, ¹³C-NMR and HRMS. The fluorescent probe was quenched [...] Read more.

A new highly selective and sensitive fluorescent probe for Cu²⁺, N-n-butyl-4-(1′-cyclooctene-1′,3′,6′-triazole)-1,8-naphthalimide (L), was synthesized and evaluated. The structure of compound L was characterized via IR, ¹H-NMR, ¹³C-NMR and HRMS. The fluorescent probe was quenched by Cu²⁺ with a 1:1 binding ratio and behaved as a “turn-off” sensor. An efficient and sensitive spectrofluorometric method was developed for detecting and estimating trace levels of Cu²⁺ in EtOH/H₂O. The ligand exhibited excitation and emission maxima at 447 and 518 nm, respectively. The equilibrium binding constant of the ligand with Cu²⁺ was 1.57 × 10⁴ M⁻¹, as calculated using the Stern Full article

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12 pages, 2937 KiB

Open AccessArticle

The Application of Ultra-High-Performance Liquid Chromatography Coupled with a LTQ-Orbitrap Mass Technique to Reveal the Dynamic Accumulation of Secondary Metabolites in Licorice under ABA Stress

by Da Li

, Guojie Xu, Guangxi Ren, Yufeng Sun, Ying Huang and Chunsheng Liu^*

School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China

Molecules 2017, 22(10), 1742; https://doi.org/10.3390/molecules22101742 - 20 Oct 2017

Cited by 18 | Viewed by 5334

Abstract

The traditional medicine licorice is the most widely consumed herbal product in the world. Although much research work on studying the changes in the active compounds of licorice has been reported, there are still many areas, such as the dynamic accumulation of secondary [...] Read more.

The traditional medicine licorice is the most widely consumed herbal product in the world. Although much research work on studying the changes in the active compounds of licorice has been reported, there are still many areas, such as the dynamic accumulation of secondary metabolites in licorice, that need to be further studied. In this study, the secondary metabolites from licorice under two different methods of stress were investigated by ultra-high-performance liquid chromatography coupled with hybrid linear ion trap–Orbitrap mass spectrometry (UHPLC-LTQ-Orbitrap-MS). A complex continuous coordination of flavonoids and triterpenoids in a network was modulated by different methods of stress during growth. The results showed that a total of 51 secondary metabolites were identified in licorice under ABA stress. The partial least squares–discriminate analysis (PLS-DA) revealed the distinction of obvious compounds among stress-specific districts relative to ABA stress. The targeted results showed that there were significant differences in the accumulation patterns of the deeply targeted 41 flavonoids and 10 triterpenoids compounds by PCA and PLS-DA analyses. To survey the effects of flavonoid and triterpenoid metabolism under ABA stress, we inspected the stress-specific metabolic changes. Our study testified that the majority of flavonoids and triterpenoids were elevated in licorice under ABA stress, while the signature metabolite affecting the dynamic accumulation of secondary metabolites was detected. Taken together, our results suggest that ABA-specific metabolite profiling dynamically changed in terms of the biosynthesis of flavonoids and triterpenoids, which may offer new trains of thought on the regular pattern of dynamic accumulation of secondary metabolites in licorice at the metabolite level. Our results also provide a reference for clinical applications and directional planting and licorice breeding. Full article

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18 pages, 1549 KiB

Open AccessReview

Wound-Healing Peptides for Treatment of Chronic Diabetic Foot Ulcers and Other Infected Skin Injuries

by Ana Gomes¹, Cátia Teixeira^1,*

, Ricardo Ferraz^1,2

, Cristina Prudêncio^2,3 and Paula Gomes^1,*

¹ LAQV-REQUIMTE, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, Rua do Campo Alegre 687, P-4169-007 Porto, Portugal

² Ciências Químicas e das Biomoléculas, Escola Superior de Saúde–Instituto Politécnico do Porto, Rua Dr. António Bernardino de Almeida 400, P-4200-072 Porto, Portugal

³ i3S–Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen 208, P-4200-135 Porto, Portugal

Molecules 2017, 22(10), 1743; https://doi.org/10.3390/molecules22101743 - 18 Oct 2017

Cited by 115 | Viewed by 31764

Abstract

As the incidence of diabetes continues to increase in the western world, the prevalence of chronic wounds related to this condition continues to be a major focus of wound care research. Additionally, over 50% of chronic wounds exhibit signs and symptoms that are [...] Read more.

As the incidence of diabetes continues to increase in the western world, the prevalence of chronic wounds related to this condition continues to be a major focus of wound care research. Additionally, over 50% of chronic wounds exhibit signs and symptoms that are consistent with localized bacterial biofilms underlying severe infections that contribute to tissue destruction, delayed wound-healing and other serious complications. Most current biomedical approaches for advanced wound care aim at providing antimicrobial protection to the open wound together with a matrix scaffold (often collagen-based) to boost reestablishment of the skin tissue. Therefore, the present review is focused on the efforts that have been made over the past years to find peptides possessing wound-healing properties, towards the development of new and effective wound care treatments for diabetic foot ulcers and other skin and soft tissue infections. Full article

(This article belongs to the Special Issue Peptide-Based Drugs and Drug Delivery Systems)

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25 pages, 5749 KiB

Open AccessArticle

A DFT Study of the Geometrical, Spectroscopical and Reactivity Properties of Diindolylmethane-Phenylboronic Acid Hybrids

by Amira Jalil Fragoso-Medina, René Gerardo Escobedo-González

, María Inés Nicolás-Vázquez^*

, Gabriel Arturo Arroyo-Razo

, María Olivia Noguez-Córdova and René Miranda-Ruvalcaba

Departamento de Ciencias Químicas, Facultad de Estudios Superiores Cuautitlán, Campo 1, Universidad Nacional Autónoma de México, Cuautitlán Izcalli, Estado de Mexico C.P. 54740, Mexico

Molecules 2017, 22(10), 1744; https://doi.org/10.3390/molecules22101744 - 17 Oct 2017

Cited by 17 | Viewed by 5264

Abstract

The structure of the ortho-, meta- and para- hybrid diindolylmethane-phenylboronic acids and their interactions were optimized with by a quantum chemical method, using density functional theory at the (DFT) level. Thus, infrared bands were assigned based on the scaled theoretical [...] Read more.

The structure of the ortho-, meta- and para- hybrid diindolylmethane-phenylboronic acids and their interactions were optimized with by a quantum chemical method, using density functional theory at the (DFT) level. Thus, infrared bands were assigned based on the scaled theoretical wavenumbers by correlating the respective experimental data of the molecules. In addition, the corresponding ¹H-/¹³C-/¹¹B-NMR experimental and theoretical chemical shifts were correlated. The target molecules showed a poor treatment of the OH shifts in the GIAO method due to the absence of explicit solvent effects in these calculations; therefore, they were explicitly considered with acetone molecules. Moreover, the electron density at the hydrogen bond critical point increased, generating stabilization energy, from weak to moderate or weak to strong, serving as an indicator of the strength of the hydrogen bond between the different intermolecular interactions. Finally, some properties related to the reactive behavior of the target molecules associated with their cytotoxic effects and metabolic pathways were also calculated. Full article

(This article belongs to the Section Computational and Theoretical Chemistry)

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13 pages, 1238 KiB

Open AccessArticle

Pharmacokinetic Comparison of Seven Major Bio-Active Components in Normal and Blood Stasis Rats after Oral Administration of Herb Pair Danggui-Honghua by UPLC-TQ/MS

by Yi Jin^1,2, Yu-Ping Tang^1,2,*

, Zhen-Hua Zhu², Er-Xin Shang², Han-Qing Pang², Xu-Qin Shi², Yan-Yan Chen¹, Jin Wang¹, Xing Chang¹, An Kang^2,*, Gui-Sheng Zhou², Ya-Jun Shi¹, Jin Sun¹, Zhi-Shu Tang¹, Shao-Ping Li³ and Jin-Ao Duan²

¹ Shaanxi Collaborative Innovation Center of Chinese Medicinal Resources Industrialization and College of Pharmacy, Shaanxi University of Chinese Medicine, Xianyang 712046, China

² Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and Jiangsu Key Laboratory for High Technology Research of TCM Formulae, and National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China

³ State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau 999078, China

Molecules 2017, 22(10), 1746; https://doi.org/10.3390/molecules22101746 - 17 Oct 2017

Cited by 19 | Viewed by 5697

Abstract

The compatibility between Danggui (Angelicae Sinensis Radix) and Honghua (Carthami Flos) is a known herb pair, which could activate blood circulation and dissipate blood stasis effects. In this paper, we quantified seven main bio-active components (hydroxysafflor yellow A, caffeic acid, p-coumaric acid, [...] Read more.

The compatibility between Danggui (Angelicae Sinensis Radix) and Honghua (Carthami Flos) is a known herb pair, which could activate blood circulation and dissipate blood stasis effects. In this paper, we quantified seven main bio-active components (hydroxysafflor yellow A, caffeic acid, p-coumaric acid, kaempferol-3-O-rutinoside, ferulic acid, 3-n-butylphthalide, and ligustilide) in plasma samples in vivo by UPLC-TQ/MS method and investigatedwhether the pharmacokinetic (PK) behaviors of the seven components could be altered in blood stasis rats after oral administration of the Gui-Hong extracts. It was found that the C_max and AUC_0-t of these components in blood stasis rats had increasing tendency compared with normal rats. Most components in model and normal rats had significant difference in some pharmacokinetic parameters, which indicated that the metabolism enzymes and transporters involved in the metabolism and disposition of these bio-active componentsmay bealtered in blood stasis rats. This study was the first report about the pharmacokinetic investigation between normal and blood stasis rats after oral administrationof Gui-Hong extracts, and these results are important and valuable for better clinical applications of Gui-Hong herb pair and relatedTCM formulae. Full article

(This article belongs to the Collection Bioactive Compounds)

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10 pages, 6731 KiB

Open AccessArticle

Solvent-Free Addition of Indole to Aldehydes: Unexpected Synthesis of Novel 1-[1-(1H-Indol-3-yl) Alkyl]-1H-Indoles and Preliminary Evaluation of Their Cytotoxicity in Hepatocarcinoma Cells

by Graziella Tocco^1,*

, Gloria Zedda², Mariano Casu³, Gabriella Simbula^4,†

and Michela Begala^1,†

¹ Department of Life and Environmental Sciences, Unit of Drug Sciences, University of Cagliari, via Ospedale 72, 09124 Cagliari, Italy

² Merck Millipore, 39 Route Industrielle de la Hardt, 67120 Molsheim, France

³ Department of Physics, University of Cagliari, 09042 Monserrato CA, Italy

⁴ Department of Biomedical Science, Oncology and Molecular Pathology Unit, University of Cagliari, 09124 Cagliari, Italy

^† These authors equally contributed to the work.

Molecules 2017, 22(10), 1747; https://doi.org/10.3390/molecules22101747 - 17 Oct 2017

Cited by 16 | Viewed by 6539

Abstract

New 1-[1-(1H-indol-3-yl) alkyl]-1H-indoles, surprisingly, have been obtained from the addition of indole to a variety of aldehydes under neat conditions. CaO, present in excess, was fundamental for carrying out the reaction with paraformaldehyde. Under the same reaction conditions, aromatic [...] Read more.

New 1-[1-(1H-indol-3-yl) alkyl]-1H-indoles, surprisingly, have been obtained from the addition of indole to a variety of aldehydes under neat conditions. CaO, present in excess, was fundamental for carrying out the reaction with paraformaldehyde. Under the same reaction conditions, aromatic and heteroaromatic aldehydes afforded only classical bis (indolyl) aryl indoles. In this paper, the role of CaO, together with the regiochemistry and the mechanism of the reaction, are discussed in detail. The effect of some selected 3,3′- and 1,3′-diindolyl methane derivatives on cell proliferation of the hepatoma cell line FaO was also evaluated. Full article

(This article belongs to the Special Issue The Biomedical Importance of Indoles and Their Derivatives)

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14 pages, 1032 KiB

Open AccessArticle

Synthesis of Chiral TFA-Protected α-Amino Aryl-Ketone Derivatives with Friedel–Crafts Acylation of α-Amino Acid N-Hydroxysuccinimide Ester

by Zetryana Puteri Tachrim, Kazuhiro Oida, Haruka Ikemoto, Fumina Ohashi, Natsumi Kurokawa, Kento Hayashi, Mami Shikanai, Yasuko Sakihama, Yasuyuki Hashidoko and Makoto Hashimoto^*

Division of Applied Bioscience, Graduate School of Agriculture, Hokkaido University, Kita 9, Nishi 9, Kita-ku, Sapporo 060-8589, Japan

Molecules 2017, 22(10), 1748; https://doi.org/10.3390/molecules22101748 - 17 Oct 2017

Cited by 9 | Viewed by 10102

Abstract

Chiral N-protected α-amino aryl-ketones are one of the useful precursors used in the synthesis of various biologically active compounds and can be constructed via Friedel–Crafts acylation of N-protected α-amino acids. One of the drawbacks of this reaction is the utilization of [...] Read more.

Chiral N-protected α-amino aryl-ketones are one of the useful precursors used in the synthesis of various biologically active compounds and can be constructed via Friedel–Crafts acylation of N-protected α-amino acids. One of the drawbacks of this reaction is the utilization of toxic, corrosive and moisture-sensitive acylating reagents. In peptide construction via amide bond formation, N-hydroxysuccinimide ester (OSu), which has high storage stability, can react rapidly with amino components and produces fewer side reactions, including racemization. This study reports the first synthesis and utilization of N-trifluoroacetyl (TFA)-protected α-amino acid-OSu as a potential acyl donor for Friedel–Crafts acylation into various arenes. The TFA-protected isoleucine derivative and its diastereomer TFA-protected allo-isoleucine derivative were investigated to check the retention of α-proton chirality in the Friedel–Crafts reaction. Further utilization of OSu in other branched-chain and unbranched-chain amino acids results in an adequate yield of TFA-protected α-amino aryl-ketone without loss of optical purity. Full article

(This article belongs to the Section Organic Chemistry)

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13 pages, 692 KiB

Open AccessArticle

Health-Promoting Phytochemicals from 11 Mustard Cultivars at Baby Leaf and Mature Stages

by Marissa D. Frazie^1,†, Moo Jung Kim^2,† and Kang-Mo Ku^2,*

¹ Division of Animal and Nutritional Sciences, West Virginia University, Morgantown, WV 26506, USA

² Division of Plant and Soil Sciences, West Virginia University, Morgantown, WV 26506, USA

^† These authors contributed equally to this work.

Molecules 2017, 22(10), 1749; https://doi.org/10.3390/molecules22101749 - 17 Oct 2017

Cited by 49 | Viewed by 10192

Abstract

Mustard is a Brassica vegetable that provides a number of phytonutrients. However, the phytonutrient profile of mustard has been relatively limited. We analyzed the glucosinolates and their hydrolysis products, carotenoids, total anthocyanin and phenolic contents, and antioxidant capacity of the leaves of 11 [...] Read more.

Mustard is a Brassica vegetable that provides a number of phytonutrients. However, the phytonutrient profile of mustard has been relatively limited. We analyzed the glucosinolates and their hydrolysis products, carotenoids, total anthocyanin and phenolic contents, and antioxidant capacity of the leaves of 11 mustard cultivars grown in a greenhouse at the baby leaf and mature stages. An aliphatic glucosinolate sinigrin and its hydrolysis products allyl isothiocyanate and 1-cyano-2,3-epithiopropane were the major phytonutrients in the mustard leaves. Carotenoids β-carotene, lutein, violaxanthin, and neoxanthin were detected. We found phytonutrient concentration and their change with plant growth were cultivar-dependent. The %RDA value for vitamin A calculated using β-carotene content and retinol activity equivalents suggests that mustard cultivars used in this study can be a good source of vitamin A. Phenolic contents and antioxidant capacity also varied among cultivars and between physiological stages. Our results suggest that mustard leaves are rich in various phytochemicals and their composition depends on cultivar and the physiological stage. This is the first report on phytochemical composition in various mustard cultivars at different physiological stages. Full article

(This article belongs to the Collection Bioactive Compounds)

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8 pages, 1472 KiB

Open AccessArticle

Heat Shock Protein-Inducing Property of Diarylheptanoid Containing Chalcone Moiety from Alpinia katsumadai

by Joo-Won Nam^1,*

and Yun-Sil Lee²

¹ College of Pharmacy, Yeungnam University, Gyeongsan-si, Gyeongsangbukdo 38541, Korea

² Graduate School of Pharmaceutical Sciences, College of Pharmacy, Ewha Womans University, Seoul 03760, Korea

Molecules 2017, 22(10), 1750; https://doi.org/10.3390/molecules22101750 - 17 Oct 2017

Cited by 5 | Viewed by 3725

Abstract

A new diarylheptanoid containing a chalcone moiety, katsumain H (1), was isolated from the seeds of Alpinia katsumadai. The structure was elucidated using a combination of 1D/2D NMR spectroscopy and mass spectrometry data analysis. The absolute configurations of C-3, C-5, [...] Read more.

A new diarylheptanoid containing a chalcone moiety, katsumain H (1), was isolated from the seeds of Alpinia katsumadai. The structure was elucidated using a combination of 1D/2D NMR spectroscopy and mass spectrometry data analysis. The absolute configurations of C-3, C-5, and C-7 in 1 were assigned based on its optical rotation and after comparing its NMR chemical shifts with those of its diastereoisomers, katsumain E and katsumain F, which were previously isolated from this plant and characterized. In this study, the stimulatory effects of compounds 1 and 2 were evaluated on heat shock factor 1 (HSF1), heat shock protein 27 (HSP27), and HSP70. Compounds 1 and 2 increased the expression of HSF1 (1.056- and 1.200-fold, respectively), HSP27 (1.312- and 1.242-fold, respectively), and HSP70 (1.234- and 1.271-fold, respectively), without increased cytotoxicity. Full article

(This article belongs to the Section Natural Products Chemistry)

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7 pages, 527 KiB

Open AccessArticle

New Cassane Diterpenoids from Caesalpinia sappan and their Antiplasmodial Activity

by Nai-Liang Zhu^1,†

, Zhong-Hao Sun^1,†, Mei-Geng Hu¹, Tong-Yu Wu², Jing-Quan Yuan³, Hai-Feng Wu¹, Yu Tian¹

, Peng-Fei Li¹, Jun-Shan Yang¹, Guo-Xu Ma^1,* and Xu-Dong Xu^1,*

¹ Key Laboratory of Bioactive Substances and Resource Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Key Laboratory of Efficacy Evaluation of Chinese Medicine against Glycolipid Metabolic Disorders, State Administration of Traditional Chinese Medicine, Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100193, China

² Center of Research and Development on Life Sciences and Environment Sciences, Harbin University of Commerce, Harbin 150076, China

³ College of chemistry and materials science, Guangxi Teachers Education University, Nanning 530001, China

^† These authors contributed equally to this work.

Molecules 2017, 22(10), 1751; https://doi.org/10.3390/molecules22101751 - 17 Oct 2017

Cited by 20 | Viewed by 4360

Abstract

One new cassane diterpene possessing an unusual N bridge between C-19 and C-20 named caesalsappanin R (1), as well as another new diterpene caesalsappanin S (2), were isolated from the seeds of Caesalpinia sappanwith methanol extract. Their structures [...] Read more.

One new cassane diterpene possessing an unusual N bridge between C-19 and C-20 named caesalsappanin R (1), as well as another new diterpene caesalsappanin S (2), were isolated from the seeds of Caesalpinia sappanwith methanol extract. Their structures were determined by spectroscopic analysis and examined alongside existing data from prior studies. Their biological activities were profiled by their antiplasmodial activity. Full article

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11 pages, 1566 KiB

Open AccessArticle

Synthesis, Characterization, and Biological Evaluations of 1,3,5-Triazine Derivatives of Metformin Cyclization with Berberine and Magnolol in the Presence of Sodium Methylate

by Han Cao¹, Shili Liao¹, Wenjing Zhong¹, Xuerong Xiao¹, Jiancheng Zhu¹, Weimin Li^2,*, Xia Wu^1,* and Yifan Feng^1,*

¹ Central Laboratory of Guangdong, Pharmaceutical University, Guangzhou 510000, China

² College of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou 510000, China

Molecules 2017, 22(10), 1752; https://doi.org/10.3390/molecules22101752 - 18 Oct 2017

Cited by 25 | Viewed by 6297

Abstract

The novel target products were synthesized in the formation of a triazine ring from berberine, magnolol, and metformin catalyzed by sodium methylate. The structures of products 1–3 were firstly confirmed by extensive spectroscopic analyses and single-crystal X-ray diffraction. The crystal structures [...] Read more.

The novel target products were synthesized in the formation of a triazine ring from berberine, magnolol, and metformin catalyzed by sodium methylate. The structures of products 1–3 were firstly confirmed by extensive spectroscopic analyses and single-crystal X-ray diffraction. The crystal structures of the target product 2 and the intermediate product 7b were reported for the first time. All target products were evaluated for their anti-inflammatory and antidiabetic activities against INS-1 and RAW264.1 cells in vitro and all products showed excellent anti-inflammatory effects and anti-insulin resistance effects. Our studies indicated that new compounds 1–3 were found to be active against inflammation and insulin resistance. Full article

(This article belongs to the Section Medicinal Chemistry)

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12 pages, 1142 KiB

Open AccessFeature PaperCommunication

A New Noncanonical Anionic Peptide That Translocates a Cellular Blood–Brain Barrier Model

by Sara Neves-Coelho, Rute P. Eleutério, Francisco J. Enguita

, Vera Neves^*

and Miguel A. R. B. Castanho

Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Av. Prof. Egas Moniz, Lisboa 1649-028, Portugal

Molecules 2017, 22(10), 1753; https://doi.org/10.3390/molecules22101753 - 18 Oct 2017

Cited by 29 | Viewed by 9807

Abstract

The capacity to transport therapeutic molecules across the blood–brain barrier (BBB) represents a breakthrough in the development of tools for the treatment of many central nervous system (CNS)-associated diseases. The BBB, while being protective against infectious agents, hinders the brain uptake of many [...] Read more.

The capacity to transport therapeutic molecules across the blood–brain barrier (BBB) represents a breakthrough in the development of tools for the treatment of many central nervous system (CNS)-associated diseases. The BBB, while being protective against infectious agents, hinders the brain uptake of many drugs. Hence, finding safe shuttles able to overcome the BBB is of utmost importance. Herein, we identify a new BBB-translocating peptide with unique properties. For years it was thought that cationic sequences were mandatory for a cell-penetrating peptide (CPP) to achieve cellular internalization. Despite being anionic at physiological pH, PepNeg (sequence (SGTQEEY) is an efficient BBB translocator that is able to carry a large cargo (27 kDa), while maintaining BBB integrity. In addition, PepNeg is able to use two distinct methods of translocation, energy-dependent and -independent, suggesting that direct penetration might occur when low concentrations of peptide are presented to cells. The discovery of this new anionic trans-BBB peptide allows the development of new delivery systems to the CNS and contributes to the need to rethink the role of electrostatic attraction in BBB-translocation. Full article

(This article belongs to the Special Issue Peptide-Based Drugs and Drug Delivery Systems)

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17 pages, 7712 KiB

Open AccessArticle

Emodin Inhibition of Influenza A Virus Replication and Influenza Viral Pneumonia via the Nrf2, TLR4, p38/JNK and NF-kappaB Pathways

by Jian-Ping Dai^1,*

, Qian-Wen Wang¹, Yun Su¹, Li-Ming Gu¹, Ying Zhao¹, Xiao-Xua Chen¹, Cheng Chen¹, Wei-Zhong Li², Ge-Fei Wang¹ and Kang-Sheng Li¹

¹ Department of Microbiology and Immunology, Shantou University Medical College, Shantou 515041, China

² Department of Veterinary Medicine, University of Maryland, College Park, and Virginia-Maryland Regional College of Veterinary Medicine, College Park, MD 20742, USA

Molecules 2017, 22(10), 1754; https://doi.org/10.3390/molecules22101754 - 18 Oct 2017

Cited by 96 | Viewed by 9907

Abstract

Lasting activations of toll-like receptors (TLRs), MAPK and NF-κB pathways can support influenza A virus (IAV) infection and promote pneumonia. In this study, we have investigated the effect and mechanism of action of emodin on IAV infection using qRT-PCR, western blotting, ELISA, Nrf2 [...] Read more.

Lasting activations of toll-like receptors (TLRs), MAPK and NF-κB pathways can support influenza A virus (IAV) infection and promote pneumonia. In this study, we have investigated the effect and mechanism of action of emodin on IAV infection using qRT-PCR, western blotting, ELISA, Nrf2 luciferase reporter, siRNA and plaque inhibition assays. The results showed that emodin could significantly inhibit IAV (ST169, H1N1) replication, reduce IAV-induced expressions of TLR2/3/4/7, MyD88 and TRAF6, decrease IAV-induced phosphorylations of p38/JNK MAPK and nuclear translocation of NF-κB p65. Emodin also activated the Nrf2 pathway, decreased ROS levels, increased GSH levelss and GSH/GSSG ratio, and upregulated the activities of SOD, GR, CAT and GSH-Px after IAV infection. Suppression of Nrf2 via siRNA markedly blocked the inhibitory effects of emodin on IAV-induced activations of TLR4, p38/JNK, and NF-κB pathways and on IAV-induced production of IL-1β, IL-6 and expression of IAV M2 protein. Emodin also dramatically increased the survival rate of mice, reduced lung edema, pulmonary viral titer and inflammatory cytokines, and improved lung histopathological changes. In conclusion, emodin can inhibit IAV replication and influenza viral pneumonia, at least in part, by activating Nrf2 signaling and inhibiting IAV-induced activations of the TLR4, p38/JNK MAPK and NF-κB pathways. Full article

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14 pages, 12382 KiB

Open AccessArticle

Hepatoprotective Effects of Kaempferol-3-O-α-l-Arabinopyranosyl-7-O-α-l-Rhamnopyranoside on d-Galactosamine and Lipopolysaccharide Caused Hepatic Failure in Mice

by Lin Dong^1,2, Lei Yin², Hongfeng Quan², Yuankui Chu³ and Jincai Lu^1,*

¹ School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China

² School of Pharmacy, Ningxia Medical University, Yinchuan 750004, China

³ Department of Laboratory Medicine, General Hospital of Ningxia Medical University, Ningxia Medical University, Yinchuan 750004, China

Molecules 2017, 22(10), 1755; https://doi.org/10.3390/molecules22101755 - 18 Oct 2017

Cited by 18 | Viewed by 5447

Abstract

Fulminant hepatic failure (FHF), associated with high mortality, is characterized by extensive death of hepatocytes and hepatic dysfunction. There is no effective treatment for FHF. Several studies have indicated that flavonoids can protect the liver from different factor-induced injury. Previously, we found that [...] Read more.

Fulminant hepatic failure (FHF), associated with high mortality, is characterized by extensive death of hepatocytes and hepatic dysfunction. There is no effective treatment for FHF. Several studies have indicated that flavonoids can protect the liver from different factor-induced injury. Previously, we found that the extracts of Elaeagnus mollis leaves had favorable protective effects on acute liver injury. However, the role and mechanisms behind that was elusive. This study examined the hepatoprotective mechanisms of kaempferol-3-O-α-l-arabinopyranosyl-7-O-α-l-rhamnopyra-noside (KAR), a major flavonol glycoside of E. mollis, against d-galactosamine (GalN) and lipopolysaccharide (LPS)-induced hepatic failure. KAR reduces the mouse mortality, protects the normal liver structure, inhibits the serum aspartate aminotransferase (AST) and alamine aminotransferase (ALT) activity and decreases the production of malondialdehyde (MDA) and reactive oxygen species (ROS) and inflammatory cytokines, TNF-α, IL-6, and IL-1β. Furthermore, KAR inhibits the apoptosis of hepatocytes and reduces the expression of TLR4 and NF-κB signaling pathway-related proteins induced by GalN/LPS treatment. These findings suggest that the anti-oxidative, anti-inflammatory, and anti-apoptotic effects of KAR on GalN/LPS-induced acute liver injury were performed through down-regulating the activity of the TLR4 and NF-κB signaling pathways. Full article

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17 pages, 1226 KiB

Open AccessArticle

Analysis of Non-Volatile Chemical Constituents of Menthae Haplocalycis Herba by Ultra-High Performance Liquid Chromatography-High Resolution Mass Spectrometry

by Lu-Lu Xu¹, Jing-Jing Xu¹, Kun-Rui Zhong¹, Zhan-Peng Shang¹, Fei Wang¹, Ru-Feng Wang¹, Le Zhang¹, Jia-Yu Zhang^2,* and Bin Liu^1,*

¹ School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 100029, China

² Beijing Research Institution of Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China

Molecules 2017, 22(10), 1756; https://doi.org/10.3390/molecules22101756 - 19 Oct 2017

Cited by 63 | Viewed by 8665

Abstract

Menthae Haplocalycis herba, one kind of Chinese edible herbs, has been widely utilized for the clinical use in China for thousands of years. Over the last decades, studies on chemical constituents of Menthae Haplocalycis herba have been widely performed. However, less attention has [...] Read more.

Menthae Haplocalycis herba, one kind of Chinese edible herbs, has been widely utilized for the clinical use in China for thousands of years. Over the last decades, studies on chemical constituents of Menthae Haplocalycis herba have been widely performed. However, less attention has been paid to non-volatile components which are also responsible for its medical efficacy than the volatile constituents. Therefore, a rapid and sensitive method was developed for the comprehensive identification of the non-volatile constituents in Menthae Haplocalycis herba using ultra-high performance liquid chromatography coupled with linear ion trap-Orbitrap mass spectrometry (UHPLC-LTQ-Orbitrap). Separation was performed with Acquity UPLC^® BEH C₁₈ column (2.1 mm × 100 mm, 1.7 μm) with 0.2% formic acid aqueous solution and acetonitrile as the mobile phase under gradient conditions. Based on the accurate mass measurement (<5 ppm), MS/MS fragmentation patterns and different chromatographic behaviors, a total of 64 compounds were unambiguously or tentatively characterized, including 30 flavonoids, 20 phenolic acids, 12 terpenoids and two phenylpropanoids. Finally, target isolation of three compounds named Acacetin, Rosmarinic acid and Clemastanin A (first isolated from Menthae Haplocalycis herba) were performed based on the obtained results, which further confirmed the deduction of fragmentation patterns and identified the compounds profile in Menthae Haplocalycis herba. Our research firstly systematically elucidated the non-volatile components of Menthae Haplocalycis herba, which laid the foundation for further pharmacological and metabolic studies. Meanwhile, our established method was useful and efficient to screen and identify targeted constituents from traditional Chinese medicine extracts. Full article

(This article belongs to the Special Issue New Methodologies in Natural Product Analytics and Structure Elucidation)

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15 pages, 3100 KiB

Open AccessArticle

Genistein Binding to Copper(II)—Solvent Dependence and Effects on Radical Scavenging

by Jing Yang¹, Yi Xu¹, Hao-Yu Liu¹

, Rui-Min Han^1,*

, Jian-Ping Zhang¹ and Leif H. Skibsted^2,*

¹ Department of Chemistry, Renmin University of China, No. 59, ZhongGuanCun Street, Beijing 100872, China

² Department of Food Science, University of Copenhagen, Rolighedsvej 30, DK-1058 Frederiksberg C, Denmark

Molecules 2017, 22(10), 1757; https://doi.org/10.3390/molecules22101757 - 18 Oct 2017

Cited by 19 | Viewed by 5321

Abstract

Genistein, but not daidzein, binds to copper(II) with a 1:2 stoichiometry in ethanol and with a 1:1 stoichiometry in methanol, indicating chelation by the 5-phenol and the 4-keto group of the isoflavonoid as demonstrated by the Jobs method and UV-visible absorption spectroscopy. In [...] Read more.

Genistein, but not daidzein, binds to copper(II) with a 1:2 stoichiometry in ethanol and with a 1:1 stoichiometry in methanol, indicating chelation by the 5-phenol and the 4-keto group of the isoflavonoid as demonstrated by the Jobs method and UV-visible absorption spectroscopy. In ethanol, the stability constants had the value 1.12 × 10¹¹ L²∙mol⁻² for the 1:2 complex and in methanol 6.0 × 10⁵ L∙mol⁻¹ for the 1:1 complex at 25 °C. Binding was not detected in water, as confirmed by an upper limit for the 1:1 stability constant of K = 5 mol⁻¹ L as calculated from the difference in solvation free energy of copper(II) between methanol and the more polar water. Solvent molecules compete with genistein as demonstrated in methanol where binding stoichiometry changes from 1:2 to 1:1 compared to ethanol and methanol/chloroform (7/3, v/v). Genistein binding to copper(II) increases the scavenging rate of the stable, neutral 2,2-diphenyl-1-picrylhydrazyl radical by more than a factor of four, while only small effects were seen for the short-lived but more oxidizing β-carotene radical cation using laser flash photolysis. The increased efficiency of coordinated genistein is concluded to depend on kinetic rather than on thermodynamic factors, as confirmed by the small change in reduction potential of −0.016 V detected by cyclic voltammetry upon binding of genistein to copper(II) in methanol/chloroform solutions. Full article

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15 pages, 3229 KiB

Open AccessArticle

Novel Bioactive Paulomycin Derivatives Produced by Streptomyces albus J1074

by Jorge Fernández-De la Hoz

, Carmen Méndez, José A. Salas

and Carlos Olano^*

Departamento de Biología Funcional e Instituto Universitario de Oncología del Principado de Asturias (I.U.O.P.A), Universidad de Oviedo, C/Julian Claveria s/n, 33006, Oviedo (Asturias), Spain

Molecules 2017, 22(10), 1758; https://doi.org/10.3390/molecules22101758 - 18 Oct 2017

Cited by 8 | Viewed by 6449

Abstract

Four novel paulomycin derivatives have been isolated from S. albus J1074 grown in MFE culture medium. These compounds are structural analogs of antibiotics 273a_2α and 273a_2β containing a thiazole moiety, probably originated through an intramolecular Michael addition. The novel, thiazole, moiety-containing [...] Read more.

Four novel paulomycin derivatives have been isolated from S. albus J1074 grown in MFE culture medium. These compounds are structural analogs of antibiotics 273a_2α and 273a_2β containing a thiazole moiety, probably originated through an intramolecular Michael addition. The novel, thiazole, moiety-containing paulomycins show a lower antibiotic activity than paulomycins A and B against Gram-positive bacteria. However, two of them show an improved activity against Gram-negative bacteria. In addition, the four novel compounds are more stable in culture than paulomycins A and B. Thus, the presence of an N-acetyl-l-cysteine moiety linked to the carbon atom of the paulic acid isothiocyanate moiety, via a thioester bond, and the subsequent intramolecular cyclization of the paulic acid to generate a thiazole heterocycle confer to paulomycins a higher structural stability that otherwise will conduce to paulomycin degradation and into inactive paulomenols. Full article

(This article belongs to the Collection Antibiotics & Superbugs: New Strategies to Combat Antimicrobial Resistance)

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12 pages, 1661 KiB

Open AccessArticle

Synthesis and Antitumor Activity of Triazole-Containing Sorafenib Analogs

by Wenjing Ye, Qi Yao, Simiao Yu, Ping Gong and Mingze Qin^*

Key Laboratory of Structure-Based Drug Design and Discovery (Shenyang Pharmaceutical University), Ministry of Education, 103 Wenhua Road, Shenyang 110016, China

Molecules 2017, 22(10), 1759; https://doi.org/10.3390/molecules22101759 - 24 Oct 2017

Cited by 14 | Viewed by 5576

Abstract

Using a highly effective binuclear Cu complex as the catalyst, the 1,3-dipolar cycloaddition reactions between 16 alkynes and two azides were successfully performed and resulted in the production of 25 new triazole-containing sorafenib analogs. Several compounds were evaluated as potent antitumor agents. Among [...] Read more.

Using a highly effective binuclear Cu complex as the catalyst, the 1,3-dipolar cycloaddition reactions between 16 alkynes and two azides were successfully performed and resulted in the production of 25 new triazole-containing sorafenib analogs. Several compounds were evaluated as potent antitumor agents. Among them, 4-(4-(4-(3-fluorophenyl)-1H-1,2,3-triazol-1-yl)phenoxy)-N-methylpicolinamide (8f) potently suppressed the proliferation of HT-29 cancer cells by inducing apoptosis and almost completely inhibited colony formation at a low micromolar concentration. Full article

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15 pages, 2238 KiB

Open AccessFeature PaperArticle

Glucopyranosylidene-Spiro-Thiazolinones: Synthetic Studies and Determination of Absolute Configuration by TDDFT-ECD Calculations

by Katalin E. Szabó, Sándor Kun

, Attila Mándi

, Tibor Kurtán and László Somsák^*

Department of Organic Chemistry, University of Debrecen, PO Box 400, H-4002 Debrecen, Hungary

Molecules 2017, 22(10), 1760; https://doi.org/10.3390/molecules22101760 - 19 Oct 2017

Cited by 6 | Viewed by 5187

Abstract

Reactions of O-peracylated C-(1-bromo-β-d-glucopyranosyl)formamides with thioamides furnished the corresponding glucopyranosylidene-spiro-thiazolin-4-one. While O-debenzoylations under a variety of conditions resulted in decomposition, during O-deacetylations the addition of MeOH to the thiazolinone moiety was observed, and with EtOH and water [...] Read more.

Reactions of O-peracylated C-(1-bromo-β-d-glucopyranosyl)formamides with thioamides furnished the corresponding glucopyranosylidene-spiro-thiazolin-4-one. While O-debenzoylations under a variety of conditions resulted in decomposition, during O-deacetylations the addition of MeOH to the thiazolinone moiety was observed, and with EtOH and water similar adducts were isolated or detected. The structure and stereochemistry of the new compounds were established by means of NMR and electronic circular dichroism (ECD) data supported by time-dependent density functional theory ECD (TDDFT-ECD) calculations. TDDFT-ECD calculations could efficiently distinguish the proposed epimeric products having different absolute configuration in the spiro heterocyclic ring. Full article

(This article belongs to the Special Issue Advances in Spiro Compounds)

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11 pages, 1224 KiB

Open AccessReview

Hop Phytochemicals and Their Potential Role in Metabolic Syndrome Prevention and Therapy

by Pavel Dostálek^*

, Marcel Karabín

and Lukáš Jelínek

Department of Biotechnology, University of Chemistry and Technology, Prague, Technická 5, 166 28 Prague 6, Czech Republic

Molecules 2017, 22(10), 1761; https://doi.org/10.3390/molecules22101761 - 19 Oct 2017

Cited by 60 | Viewed by 10536

Abstract

Historically, hop cones (Humulus lupulus) have been used since ancient times as a remedy for many ailments and, as a source of polyphenols and bitter acids, is very effective in the treatment of metabolic syndrome (MS). Hop flavonoids, particularly xanthohumol (XN), [...] Read more.

Historically, hop cones (Humulus lupulus) have been used since ancient times as a remedy for many ailments and, as a source of polyphenols and bitter acids, is very effective in the treatment of metabolic syndrome (MS). Hop flavonoids, particularly xanthohumol (XN), are substances with hypoglycemic, antihyperlipidemic, and antiobesity activities. Iso-α-acids (IAA) and matured hop bitter acids (MHBA) improve health by influencing lipid metabolism, glucose tolerance, and body weight. The modulatory effect of IAA and MHBA on lipid metabolism may also be responsible for a loss in body weight. These results suggest promising applications for IAA, MHBA, and XN in humans, particularly in the prevention of diet-induced obesity and diabetes. Full article

(This article belongs to the Special Issue Bioactive Compounds for Metabolic Syndrome and Type 2 Diabetes)

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13 pages, 2808 KiB

Open AccessFeature PaperArticle

Self-Assembly with 2,6-Bis(1-(pyridin-4-ylmethyl)-1H-1,2,3-triazol-4-yl)pyridine: Silver(I) and Iron(II) Complexes

by Daniel A. W. Ross

, Dan Preston^* and James D. Crowley^*

Department of Chemistry, University of Otago, P.O. Box 56, Dunedin 9016, Otago, New Zealand

Molecules 2017, 22(10), 1762; https://doi.org/10.3390/molecules22101762 - 19 Oct 2017

Cited by 9 | Viewed by 6479

Abstract

A new “click” ligand, 2,6-bis(1-(pyridin-4-ylmethyl)-1H-1,2,3-triazol-4-yl)pyridine (L) featuring a tridentate 2,6-bis(1,2,3-triazol-4-yl)pyridine (tripy) pocket and two pyridyl (py) units was synthesized in modest yield (42%) using the copper(I) catalyzed azide-alkyne cycloaddition (CuAAC) reaction. The coordination chemistry of the ligand with silver(I) [...] Read more.

A new “click” ligand, 2,6-bis(1-(pyridin-4-ylmethyl)-1H-1,2,3-triazol-4-yl)pyridine (L) featuring a tridentate 2,6-bis(1,2,3-triazol-4-yl)pyridine (tripy) pocket and two pyridyl (py) units was synthesized in modest yield (42%) using the copper(I) catalyzed azide-alkyne cycloaddition (CuAAC) reaction. The coordination chemistry of the ligand with silver(I) and iron(II) ions was examined using a battery of solution (¹H and DOSY (diffusion ordered spectroscopy) nuclear magnetic resonance (NMR), infrared and absorption spectroscopies, high-resolution electrospray ionization mass spectrometry (HR-ESI-MS)), and solid state (X-ray crystallography, elemental analysis) techniques. When treated with silver(I) ions, the ligand forms discrete [Ag(L)]⁺ (X⁻, where X⁻ = BF₄⁻, NO₃⁻ or SbF₆⁻) complexes in dimethyl sulfoxide (DMSO) solution but these complexes crystallize as coordination polymers. The addition of [Fe(H₂O)₆](BF₄)₂ to an acetonitrile solution of the ligand forms the expected monomeric octahedral [Fe(L)₂]²⁺ complex and treatment of the iron(II) complex with AgBF₄ generates a heterometallic linear coordination polymer. Full article

(This article belongs to the Section Organic Chemistry)

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13 pages, 2661 KiB

Open AccessArticle

Cellulase-Assisted Extraction of Polysaccharides from White Hyacinth Bean: Characterization of Antioxidant Activity and Promotion for Probiotics Proliferation

by Guo-Wei Shu¹

, Yun-Xia He^1,*, Ni Lei¹, Ji-Li Cao², He Chen¹ and Li Chen^3,*

¹ School of Food and Biological Engineering, Shaanxi University of Science and Technology, Xi’an 710021, China

² Department of Research and Development, Xi’an Oriental Dairy Co., Ltd., Xi’an 710027, China

³ College of Food Engineering and Nutritional Science, Shaanxi Normal University, Xi’an 710119, China

Molecules 2017, 22(10), 1764; https://doi.org/10.3390/molecules22101764 - 20 Oct 2017

Cited by 24 | Viewed by 5474

Abstract

Food-derived polysaccharides have advantages over synthetical compounds and have attracted interest globally for decades. In this study, we optimized the cellulase-assisted extraction of polysaccharides from white hyacinth bean (PWBs) with the aid of response surface methodology (RSM). The optimum extraction parameters were a [...] Read more.

Food-derived polysaccharides have advantages over synthetical compounds and have attracted interest globally for decades. In this study, we optimized the cellulase-assisted extraction of polysaccharides from white hyacinth bean (PWBs) with the aid of response surface methodology (RSM). The optimum extraction parameters were a pH of 7.79, a cellulase of 2.73%, and a ratio of water to material of 61.39, producing a high polysaccharide yield (3.32 ± 0.03)%. The scavenging ability of PWBs varied on three radicals (hydroxyl > 2,2-diphenyl-1-picrylhydrazyl (DPPH) > superoxide). Furthermore, PWBs contributed to the proliferation of three probiotic bacteria (Lactobacillus acidophilus LA5, Bifidobacterium bifidum BB01, and Lactobacillus bulgaricus LB6). These investigations of PWBs provide a novel bioresource for the exploitation of antioxidant and probiotic bacterial proliferation. Full article

(This article belongs to the Special Issue Polysaccharide-based Materials)

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16 pages, 1313 KiB

Open AccessArticle

Discovery of Novel N-Substituted Prolinamido Indazoles as Potent Rho Kinase Inhibitors and Vasorelaxation Agents

by Yangyang Yao^1,†, Renze Li^1,†, Xiaoyu Liu¹, Feilong Yang¹, Ying Yang¹, Xiaoyu Li¹, Xiang Shi¹, Tianyi Yuan², Lianhua Fang², Guanhua Du², Xiaozhen Jiao^1,* and Ping Xie^1,*

¹ State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Beijing Key Laboratory of Active Substances Discovery and Druggability Evaluation, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China

² State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Beijing Key Laboratory of Drug Targets Identification and Drug Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China

^† These authors contributed equally to this work.

Molecules 2017, 22(10), 1766; https://doi.org/10.3390/molecules22101766 - 19 Oct 2017

Cited by 16 | Viewed by 5422

Abstract

Inhibitors of Rho kinase (ROCK) have potential therapeutic applicability in a wide range of diseases, such as hypertension, stroke, asthma and glaucoma. In a previous article, we described the lead discovery of DL0805, a new ROCK I inhibitor, showing potent inhibitory activity (IC [...] Read more.

Inhibitors of Rho kinase (ROCK) have potential therapeutic applicability in a wide range of diseases, such as hypertension, stroke, asthma and glaucoma. In a previous article, we described the lead discovery of DL0805, a new ROCK I inhibitor, showing potent inhibitory activity (IC₅₀ 6.7 μM). Herein, we present the lead optimization of compound DL0805, resulting in the discovery of 24- and 39-fold more-active analogues 4a (IC₅₀ 0.27 μM) and 4b (IC₅₀ 0.17 μM), among other active analogues. Moreover, ex-vivo studies demonstrated that 4a and 4b exhibited comparable vasorelaxant activity to the approved drug fasudil in rat aortic rings. The research of a preliminary structure–activity relationship (SAR) indicated that the target compounds containing a β-proline moiety have improved activity against ROCK I relative to analogues bearing an α-proline moiety, and among the series of the derivatives with a β-proline-derived indazole scaffold, the inhibitory activity of the target compounds with a benzyl substituent is superior to those with a benzoyl substituent. Full article

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15 pages, 2630 KiB

Open AccessArticle

Rapid Screening of Active Components with an Osteoclastic Inhibitory Effect in Herba epimedii Using Quantitative Pattern–Activity Relationships Based on Joint-Action Models

by Xiao-Yan Yuan¹

, Meng Wang², Sheng Lei², Qian-Xu Yang^2,* and Yan-Qiu Liu^3,*

¹ Department of Analytical Chem istry of School of Pharmacy, Zunyi Medical University, Zunyi 563000, China

² R & D Center, China Tobacco Yunnan Industrial Co., Ltd., Kunming 650231, China

³ Institute (College) of Integrative Medicine, Dalian Medical University, Dalian 116044, China

Molecules 2017, 22(10), 1767; https://doi.org/10.3390/molecules22101767 - 19 Oct 2017

Cited by 6 | Viewed by 4390

Abstract

Screening of bioactive components is important for modernization and quality control of herbal medicines, while the traditional bioassay-guided phytochemical approach is time-consuming and laborious. The presented study proposes a strategy for rapid screening of active components from herbal medicines. As a case study, [...] Read more.

Screening of bioactive components is important for modernization and quality control of herbal medicines, while the traditional bioassay-guided phytochemical approach is time-consuming and laborious. The presented study proposes a strategy for rapid screening of active components from herbal medicines. As a case study, the quantitative pattern–activity relationship (QPAR) between compounds and the osteoclastic inhibitory effect of Herba epimedii, a widely used herbal medicine in China, were investigated based on joint models. For model construction, standard mixtures data showed that the joint-action models are better than the partial least-squares (PLS) model. Then, the Good2bad value, which could reflect components’ importance based on Monte Carlo sampling, was coupled with the joint-action models for screening of active components. A compound (baohuoside I) and a component composed of compounds with retention times in the 6.9–7.9 min range were selected by our method. Their inhibition rates were higher than icariin, the key bioactive compound in Herba epimedii, which could inhibit osteoclast differentiation and bone resorption in a previous study. Meanwhile, the half-maximal effective concentration, namely, EC₅₀ value of the selected component was 7.54 μg/mL, much smaller than that of baohuoside I—77 μg/mL—which indicated that there is synergistic action between compounds in the selected component. The results clearly show our proposed method is simple and effective in screening the most-bioactive components and compounds, as well as drug-lead components, from herbal medicines. Full article

(This article belongs to the Special Issue Frontiers in Computational Chemistry for Drug Discovery)

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12 pages, 1481 KiB

Open AccessReview

Synthesis and Properties of MQ Copolymers: Current State of Knowledge

by Elena Tatarinova¹, Nataliya Vasilenko¹ and Aziz Muzafarov^1,2,*

¹ Enikolopov Institute of Synthetic Polymer Materials of Russian Academy of Sciences Profsoyuznaya st. 70, Moscow 117393, Russia

² Nesmeyanov Institute of Organoelement Compounds of Russian Academy of Sciences Russia, Vavilova St., 28, GSP-1, V-334, Moscow 119991, Russia

Molecules 2017, 22(10), 1768; https://doi.org/10.3390/molecules22101768 - 23 Oct 2017

Cited by 29 | Viewed by 8668

Abstract

In this review, we discuss currently available studies on the synthesis and properties of MQ copolymers. The data on methods of producing hydrolytic and heterofunctional polycondensation of functional organosilanes as well as the obtaining MQ copolymers based on silicic acids and nature silicates [...] Read more.

In this review, we discuss currently available studies on the synthesis and properties of MQ copolymers. The data on methods of producing hydrolytic and heterofunctional polycondensation of functional organosilanes as well as the obtaining MQ copolymers based on silicic acids and nature silicates are considered. The ratio of M and Q monomers and the production method determine the structure of MQ copolymers and, accordingly, their physicochemical characteristics. It is shown that the most successful synthetic approach is a polycondensation of organoalkoxysilanes in the medium of anhydrous acetic acid, which reduces the differences in reactivity of M and Q monomers and leads to obtaining a product with uniform composition in all fractions, with full absence of residual alkoxy-groups. The current concept of MQ copolymers is that of organo-inorganic hybrid systems with nanosized crosslinked inorganic regions limited by triorganosilyl groups and containing residual hydroxyl groups. The systems can be considered as a peculiar molecular composites consisting of separate parts that play the role of a polymer matrix, a plasticizer, and a nanosized filler. Full article

(This article belongs to the Special Issue Progress in Silicon and Organosilicon Chemistry)

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8 pages, 1140 KiB

Open AccessArticle

α-Synuclein Regulates Neuronal Cholesterol Efflux

by Jen-Hsiang T. Hsiao^1,2,3, Glenda M. Halliday^1,2,3 and Woojin Scott Kim^1,2,3,*

¹ Brain and Mind Centre, Sydney Medical School, The University of Sydney, Sydney NSW 2050, Australia

² Neuroscience Research Australia, Sydney NSW 2031, Australia

³ School of Medical Sciences, University of New South Wales, Sydney NSW 2052, Australia

Molecules 2017, 22(10), 1769; https://doi.org/10.3390/molecules22101769 - 19 Oct 2017

Cited by 31 | Viewed by 6082

Abstract

α-Synuclein is a neuronal protein that is at the center of focus in understanding the etiology of a group of neurodegenerative diseases called α-synucleinopathies, which includes Parkinson’s disease (PD). Despite much research, the exact physiological function of α-synuclein is still unclear. α-Synuclein has [...] Read more.

α-Synuclein is a neuronal protein that is at the center of focus in understanding the etiology of a group of neurodegenerative diseases called α-synucleinopathies, which includes Parkinson’s disease (PD). Despite much research, the exact physiological function of α-synuclein is still unclear. α-Synuclein has similar biophysical properties as apolipoproteins and other lipid-binding proteins and has a high affinity for cholesterol. These properties suggest a possible role for α-synuclein as a lipid acceptor mediating cholesterol efflux (the process of removing cholesterol out of cells). To test this concept, we “loaded” SK-N-SH neuronal cells with fluorescently-labelled cholesterol, applied exogenous α-synuclein, and measured the amount of cholesterol removed from the cells using a classic cholesterol efflux assay. We found that α-synuclein potently stimulated cholesterol efflux. We found that the process was dose and time dependent, and was saturable at 1.0 µg/mL of α-synuclein. It was also dependent on the transporter protein ABCA1 located on the plasma membrane. We reveal for the first time a novel role of α-synuclein that underscores its importance in neuronal cholesterol regulation, and identify novel therapeutic targets for controlling cellular cholesterol levels. Full article

(This article belongs to the Special Issue Neuroprotective Agents)

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8 pages, 1549 KiB

Open AccessArticle

Construction of a Bivalent Thrombin Binding Aptamer and Its Antidote with Improved Properties

by Quintin W. Hughes^1,2,*, Bao T. Le^3,4, Grace Gilmore^1,2, Ross I. Baker^1,2 and Rakesh N. Veedu^3,4,*

¹ Western Australian Centre for Thrombosis and Haemostasis, Discovery Way, Murdoch University, Perth, WA 6150, Australia

² Perth Blood Institute, Hollywood Private Hospital, Monash Avenue, Perth, WA 6009, Australia

³ Centre for Comparative Genomics, Discovery Way, Murdoch University, Perth, WA 6150, Australia

⁴ Perron Institute for Neurological and Translational Science, Perth, WA 6009, Australia

Molecules 2017, 22(10), 1770; https://doi.org/10.3390/molecules22101770 - 19 Oct 2017

Cited by 28 | Viewed by 5521

Abstract

Aptamers are short synthetic DNA or RNA oligonucleotides that adopt secondary and tertiary conformations based on Watson–Crick base-pairing interactions and can be used to target a range of different molecules. Two aptamers, HD1 and HD22, that bind to exosites I and II of [...] Read more.

Aptamers are short synthetic DNA or RNA oligonucleotides that adopt secondary and tertiary conformations based on Watson–Crick base-pairing interactions and can be used to target a range of different molecules. Two aptamers, HD1 and HD22, that bind to exosites I and II of the human thrombin molecule, respectively, have been extensively studied due to their anticoagulant potentials. However, a fundamental issue preventing the clinical translation of many aptamers is degradation by nucleases and reduced pharmacokinetic properties requiring higher dosing regimens more often. In this study, we have chemically modified the design of previously described thrombin binding aptamers targeting exosites I, HD1, and exosite II, HD22. The individual aptamers were first modified with an inverted deoxythymidine nucleotide, and then constructed bivalent aptamers by connecting the HD1 and HD22 aptamers either through a triethylene glycol (TEG) linkage or four consecutive deoxythymidines together with an inverted deoxythymidine nucleotide at the 3′-end. The anticoagulation potential, the reversal of coagulation with different antidote sequences, and the nuclease stability of the aptamers were then investigated. The results showed that a bivalent aptamer RNV220 containing an inverted deoxythymidine and a TEG linkage chemistry significantly enhanced the anticoagulation properties in blood plasma and nuclease stability compared to the existing aptamer designs. Furthermore, a bivalent antidote sequence RNV220AD efficiently reversed the anticoagulation effect of RNV220 in blood plasma. Based on our results, we believe that RNV220 could be developed as a potential anticoagulant therapeutic molecule. Full article

(This article belongs to the Special Issue Nucleic Acid Chemistry and Nucleic Acid Drugs: A Themed Issue in Honor of Professor Lihe Zhang on the Occasion of His 80th Birthday)

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12 pages, 980 KiB

Open AccessArticle

Lipase-Catalyzed Transesterification of Egg-Yolk Phophatidylcholine with Concentrate of n-3 Polyunsaturated Fatty Acids from Cod Liver Oil

by Anna Chojnacka^*, Witold Gładkowski and Aleksandra Grudniewska

Department of Chemistry, Wroclaw University of Environmental and Life Sciences, Norwida 25, 50-375 Wroclaw, Poland

Molecules 2017, 22(10), 1771; https://doi.org/10.3390/molecules22101771 - 19 Oct 2017

Cited by 22 | Viewed by 5838

Abstract

Phospholipids containing PUFAs are important vehicles for their delivering to the targeted tissues. In our research project we established enzymatic methods for the enrichment of natural egg-yolk PC with n-3 PUFAs. Instead of synthetic PUFA ethyl esters, the new strategy was developed using [...] Read more.

Phospholipids containing PUFAs are important vehicles for their delivering to the targeted tissues. In our research project we established enzymatic methods for the enrichment of natural egg-yolk PC with n-3 PUFAs. Instead of synthetic PUFA ethyl esters, the new strategy was developed using polyunsaturated fatty acids enriched fraction (PUFA-EF) from cod liver oil as the natural acyl donors. PUFA-EF was produced by urea-complexation and contained 86.9% PUFA including 8.5% stearidonic acid (SDA; 18:4(n-3)), 26.7% EPA, and 45.2% DHA. The transesterification of PC with PUFA was catalyzed by lipases. After screening of enzymes the effect of reaction medium; molar ratio of substrates and etc. was investigated. The highest incorporation of PUFA was 45.6%; including 36.8% DHA and 5.8% EPA at the following reaction conditions: hexane; 55 °C; PUFA-EF/PC acyl ratio of 10; 48 h of reaction time and lipase B from Candida antarctica as a biocatalyst (20% of enzyme load). Full article

(This article belongs to the Special Issue Lipases and Lipases Modification)

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21 pages, 5276 KiB

Open AccessArticle

Ni(II) Complexes with Schiff Base Ligands: Preparation, Characterization, DNA/Protein Interaction and Cytotoxicity Studies

by Hui Yu^1,2, Wei Zhang², Qing Yu², Fu-Ping Huang^2,*, He-Dong Bian^1,2,* and Hong Liang²

¹ Guangxi Key Laboratory of Chemistry and Engineering of Forest Products, School of Chemistry and Chemical Engineering, Guangxi University for Nationalities, Nanning 530008, China

² Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources (Ministry of Education of China), School of Chemistry and Pharmacy, Guangxi Normal University, Guilin 541004, China

Molecules 2017, 22(10), 1772; https://doi.org/10.3390/molecules22101772 - 24 Oct 2017

Cited by 49 | Viewed by 6621

Abstract

In this study, two Ni(II) complexes, namely [Ni(HL1)₂(OAc)₂] (1) and [Ni(L2)₂] (2) (where HL1 and HL2 are (E)-1-((1-(2-hydroxyethyl)-1H-pyrazol-5-ylimino)methyl)-naphthalen-2-ol) and (E)-ethyl-5-((2-hydroxynaphthalen-1-yl)methyleneamino)-1-methyl-1H-pyrazole-4-carboxylate, respectively), were synthesized and characterized [...] Read more.

In this study, two Ni(II) complexes, namely [Ni(HL1)₂(OAc)₂] (1) and [Ni(L2)₂] (2) (where HL1 and HL2 are (E)-1-((1-(2-hydroxyethyl)-1H-pyrazol-5-ylimino)methyl)-naphthalen-2-ol) and (E)-ethyl-5-((2-hydroxynaphthalen-1-yl)methyleneamino)-1-methyl-1H-pyrazole-4-carboxylate, respectively), were synthesized and characterized by X-ray crystallography, Electrospray Ionization Mass Spectrometry (ESI-MS), elemental analysis, and IR. Their uptake in biological macromolecules and cancer cells were preliminarily investigated through electronic absorption (UV-Vis), circular dichroism (CD) and fluorescence quenching measurements. Bovine serum albumin (BSA) interaction experiments were investigated by spectroscopy which showed that the complexes and ligands could quench the intrinsic fluorescence of BSA through an obvious static quenching process. The spectroscopic studies indicated that these complexes could bind to DNA via groove, non-covalent, and electrostatic interactions. Furthermore, in vitro methyl thiazolyl tetrazolium (MTT) assays and Annexin V/PI flow cytometry experiments were performed to assess the antitumor capacity of the complexes against eight cell lines. The results show that both of the complexes possess reasonable cytotoxicities. Full article

(This article belongs to the Special Issue Metal Complexes of Biological Ligands)

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17 pages, 4135 KiB

Open AccessArticle

Self-Nanoemulsifying Drug Delivery Systems Containing Plantago lanceolata—An Assessment of Their Antioxidant and Antiinflammatory Effects

by Azin Kalantari¹, Dóra Kósa¹, Dániel Nemes¹

, Zoltán Ujhelyi¹, Pálma Fehér¹, Miklós Vecsernyés¹, Judit Váradi¹, Ferenc Fenyvesi¹, Ákos Kuki², Sándor Gonda³, Gábor Vasas³, Rudolf Gesztelyi⁴, Anayatollah Salimi⁵ and Ildikó Bácskay^1,*

¹ Department of Pharmaceutical Technology (www.pharm.unideb.hu), University of Debrecen, Nagyerdei körút 98, 4032 Debrecen, Hungary

² Department of Applied Chemistry (www.pharm.unideb.hu), University of Debrecen, Nagyerdei körút 98, 4032 Debrecen, Hungary

³ Department of Pharmacognosy (www.pharm.unideb.hu), University of Debrecen, Nagyerdei körút 98, 4032 Debrecen, Hungary

⁴ Department of Pharmacology (www.med.unideb.hu), University of Debrecen, Nagyerdei körút 98, 4032 Debrecen, Hungary

⁵ Nanotechnology Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz 61357-33184, Iran

Molecules 2017, 22(10), 1773; https://doi.org/10.3390/molecules22101773 - 20 Oct 2017

Cited by 27 | Viewed by 7864

Abstract

The most important components of Plantago lanceolata L. leaves are catalpol, aucubin, and acteoside (=verbascoside). These bioactive compounds possess different pharmacological effects: anti-inflammatory, antioxidant, antineoplastic, and hepatoprotective. The aim of this study was to protect Plantago lanceolata extract from hydrolysis and to improve [...] Read more.

The most important components of Plantago lanceolata L. leaves are catalpol, aucubin, and acteoside (=verbascoside). These bioactive compounds possess different pharmacological effects: anti-inflammatory, antioxidant, antineoplastic, and hepatoprotective. The aim of this study was to protect Plantago lanceolata extract from hydrolysis and to improve its antioxidant effect using self-nano-emulsifying drug delivery systems (SNEDDS). Eight SNEDDS compositions were prepared, and their physical properties, in vitro cytotoxicity, and in vivo AST/ALT values were investigated. MTT cell viability assay was performed on Caco-2 cells. The well-diluted samples (200 to 1000-fold dilutions) proved to be non-cytotoxic. The acute administration of PL-SNEDDS compositions resulted in minor changes in hepatic markers (AST, ALT), except for compositions 4 and 8 due to their high Transcutol contents (80%). The non-toxic compositions showed a significant increase in free radical scavenger activity measured by the DPPH test compared to the blank SNEDDS. An indirect dissolution test was performed, based on the result of the DPPH antioxidant assay; the dissolution profiles of Plantago lancolata extract were statistically different from each SNEDDS. The anti-inflammatory effect of PL-SNEDDS compositions was confirmed by the ear inflammation test. For the complete examination period, all compositions decreased ear edema as compared to the positive (untreated) control. It can be concluded that PL-SNEDDS compositions could be used to deliver active natural compounds in a stable, efficient, and safe manner. Full article

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27 pages, 3842 KiB

Open AccessReview

Valorization Challenges to Almond Residues: Phytochemical Composition and Functional Application

by Iva Prgomet^1,*, Berta Gonçalves¹, Raúl Domínguez-Perles¹, Núria Pascual-Seva²

and Ana I. R. N. A. Barros¹

¹ Centre for the Research and Technology of Agro-Environmental and Biological Sciences, CITAB, University of Trás-os-Montes e Alto Douro, UTAD, Quinta de Prados, 5000-801 Vila Real, Portugal

² Department of Plant Production, Universitat Politècnica de València, 46022 València, Spain

Molecules 2017, 22(10), 1774; https://doi.org/10.3390/molecules22101774 - 20 Oct 2017

Cited by 96 | Viewed by 14947

Abstract

Almond is characterized by its high nutritional value; although information reported so far mainly concerns edible kernel. Even though the nutritional and commercial relevance of the almond is restricted to almond meat; to date; increasing attention has been paid to other parts of [...] Read more.

Almond is characterized by its high nutritional value; although information reported so far mainly concerns edible kernel. Even though the nutritional and commercial relevance of the almond is restricted to almond meat; to date; increasing attention has been paid to other parts of this fruit (skin; shell; and hull); considered by-products that are scarcely characterized and exploited regarding their properties as valuable sources of bioactive compounds (mainly represented by phenolic acids and flavonoids). This lack of proper valorization procedures entails the continuation of the application of traditional procedures to almond residues that nowadays are mainly addressed to livestock feed and energy production. In this sense; data available on the physicochemical and phytochemical composition of almond meat and its related residues suggest promising applications; and allow one to envisage new uses as functional ingredients towards value-added foods and feeds; as well as a source of bioactive phytochemicals to be included in cosmetic formulations. This objective has prompted investigators working in the field to evaluate their functional properties and biological activity. This approach has provided interesting information concerning the capacity of polyphenolic extracts of almond by-products to prevent degenerative diseases linked to oxidative stress and inflammation in human tissues and cells; in the frame of diverse pathophysiological situations. Hence; this review deals with gathering data available in the scientific literature on the phytochemical composition and bioactivity of almond by-products as well as on their bioactivity so as to promote their functional application. Full article

(This article belongs to the Section Natural Products Chemistry)

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17 pages, 7976 KiB

Open AccessArticle

Differential Interaction of Antimicrobial Peptides with Lipid Structures Studied by Coarse-Grained Molecular Dynamics Simulations

by Galo E. Balatti¹, Ernesto E. Ambroggio², Gerardo D. Fidelio², M. Florencia Martini³ and Mónica Pickholz^1,*

¹ Departamento de Física, Facultad de Ciencias Exactas y Naturales, CONICET-Universidad de Buenos Aires, IFIBA, Buenos Aires C1428BFA, Argentina

² Centro de Investigaciones en Química Biológica de Córdoba (CIQUIBIC), Departamento de Química Biológica “Dr. Ranwel Caputto”, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba X500HUA, Argentina

³ Departamento de Farmacología, Instituto de la Química y Metabolismo del Fármaco (IQUIMIFA), Facultad de Farmacia y Bioquímica, Cátedra de Química Medicinal, CONICET-Universidad de Buenos Aires, Buenos Aires C1113AAD, Argentina

Molecules 2017, 22(10), 1775; https://doi.org/10.3390/molecules22101775 - 20 Oct 2017

Cited by 28 | Viewed by 7705

Abstract

In this work; we investigated the differential interaction of amphiphilic antimicrobial peptides with 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) lipid structures by means of extensive molecular dynamics simulations. By using a coarse-grained (CG) model within the MARTINI force field; we simulated the peptide–lipid system from three different [...] Read more.

In this work; we investigated the differential interaction of amphiphilic antimicrobial peptides with 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) lipid structures by means of extensive molecular dynamics simulations. By using a coarse-grained (CG) model within the MARTINI force field; we simulated the peptide–lipid system from three different initial configurations: (a) peptides in water in the presence of a pre-equilibrated lipid bilayer; (b) peptides inside the hydrophobic core of the membrane; and (c) random configurations that allow self-assembled molecular structures. This last approach allowed us to sample the structural space of the systems and consider cooperative effects. The peptides used in our simulations are aurein 1.2 and maculatin 1.1; two well-known antimicrobial peptides from the Australian tree frogs; and molecules that present different membrane-perturbing behaviors. Our results showed differential behaviors for each type of peptide seen in a different organization that could guide a molecular interpretation of the experimental data. While both peptides are capable of forming membrane aggregates; the aurein 1.2 ones have a pore-like structure and exhibit a higher level of organization than those conformed by maculatin 1.1. Furthermore; maculatin 1.1 has a strong tendency to form clusters and induce curvature at low peptide–lipid ratios. The exploration of the possible lipid–peptide structures; as the one carried out here; could be a good tool for recognizing specific configurations that should be further studied with more sophisticated methodologies. Full article

(This article belongs to the Special Issue Phospholipids: Structure and Function)

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14 pages, 2437 KiB

Open AccessArticle

Synthesis of Siloxyalumoxanes and Alumosiloxanes Based on Organosilicon Diols

by Galina Shcherbakova^*, Pavel Storozhenko and Alexander Kisin

State Research Institute for Chemistry and Technology of Organoelement Compounds, Shosse Entuziastov 38, Moscow 105118, Russia

Molecules 2017, 22(10), 1776; https://doi.org/10.3390/molecules22101776 - 20 Oct 2017

Cited by 1 | Viewed by 4667

Abstract

We have drawn a few interesting conclusions while studying reaction products of Ph₂Si(OH)₂ with Al(ⁱBu)₃ and tetraisobutylalumoxane. In the first place, this is the production (at a Ph₂Si(OH)₂ and Al(ⁱBu)₃ equimolar [...] Read more.

We have drawn a few interesting conclusions while studying reaction products of Ph₂Si(OH)₂ with Al(ⁱBu)₃ and tetraisobutylalumoxane. In the first place, this is the production (at a Ph₂Si(OH)₂ and Al(ⁱBu)₃ equimolar ratio) of an oligomer siloxyalumoxane structure with alternating four- and six-member rings. In addition, it shows isobutyl and phenyl group migration between aluminum and silicon due to the formation of an intramolecular four-member cyclic complex [Ph₂(OH)SiO]Al(ⁱBu)₂ → [(ⁱBu)Ph(OH)SiO]Al(ⁱBu)Ph. Ph₂Si(OH)₂ interaction with Al(ⁱBu)₃ not only starts from intramolecular complex production, but the chain is terminated for the same reason, which in the case of the Ph₂Si(OH)₂ reaction with tetraisobutylalumoxane results in failure of to obtain high-polymer siloxyalumoxane compounds. When Al(ⁱBu)₃ interacts with α- and γ-diols, no oligomer compounds are produced. In the Al(ⁱBu)₃ reaction with α, γ-diols are created in monomer compounds that are likely to have a cyclic structure. Notably, when Al(ⁱBu)₃ interacts with only α-diol, a double excess of Al(ⁱBu)₃ allows for full replacement of hydrogen in the α-diol hydroxyl groups by aluminum alkyl residue with 1,3-bis(diisobutylalumoxymethyl)-1,1,3,3-tetramethyldisiloxane production. At an equimolar ratio of initial reagents, the second isobutyl radical at Al does not interact with the second hydroxyl group of α-diol, apparently due to the steric hindrance, and 1-(diisobutylalumoxymethyl)-3-(hydroxymethyl)-1,1,3,3-tetramethyl-disiloxane is produced. Al(ⁱBu)₃ reactions with γ-diol also result in monomer compounds, but the presence of a chain consisting of three CH₂-groups between Si and the hydroxyl group facilitates interaction between the second hydroxyl group of γ-diol and the second isobutyl radical Al(ⁱBu)₃. Tetraisobutylalumoxane reactions with α- and γ-diols result in oligomer compounds. Full article

(This article belongs to the Special Issue Progress in Silicon and Organosilicon Chemistry)

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27 pages, 1011 KiB

Open AccessReview

A Systematic Review of Computational Drug Discovery, Development, and Repurposing for Ebola Virus Disease Treatment

by James Schuler^†, Matthew L. Hudson^†, Diane Schwartz and Ram Samudrala^*

¹ Department of Biomedical Informatics, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, The State University of New York, Buffalo, NY 14203, USA

^† These authors contributed equally to this work.

Molecules 2017, 22(10), 1777; https://doi.org/10.3390/molecules22101777 - 20 Oct 2017

Cited by 24 | Viewed by 10103

Abstract

Ebola virus disease (EVD) is a deadly global public health threat, with no currently approved treatments. Traditional drug discovery and development is too expensive and inefficient to react quickly to the threat. We review published research studies that utilize computational approaches to find [...] Read more.

Ebola virus disease (EVD) is a deadly global public health threat, with no currently approved treatments. Traditional drug discovery and development is too expensive and inefficient to react quickly to the threat. We review published research studies that utilize computational approaches to find or develop drugs that target the Ebola virus and synthesize its results. A variety of hypothesized and/or novel treatments are reported to have potential anti-Ebola activity. Approaches that utilize multi-targeting/polypharmacology have the most promise in treating EVD. Full article

(This article belongs to the Special Issue Polypharmacology and Multitarget Drug Discovery)

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17 pages, 1532 KiB

Open AccessArticle

Rapid Classification and Identification of Chemical Components of Schisandra Chinensis by UPLC-Q-TOF/MS Combined with Data Post-Processing

by Shenshen Yang^*, Lanlan Shan, Houmin Luo, Xue Sheng, Jun Du and Yubo Li^*

Tianjin State Key Laboratory of Modern Chinese Medicine, School of Traditional Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, 312 Anshan West Road, Tianjin 300193, China

Molecules 2017, 22(10), 1778; https://doi.org/10.3390/molecules22101778 - 20 Oct 2017

Cited by 65 | Viewed by 6419

Abstract

Schisandra chinensis (known in Chinese as WuWeiZi, WWZ) has observable effects such as astringing the lung to stop coughs, arresting sweating, preserving semen and preventing diarrhea. The major components of WWZ include lignans, triterpenoids, organic acids and fatty acids. In this paper, a [...] Read more.

Schisandra chinensis (known in Chinese as WuWeiZi, WWZ) has observable effects such as astringing the lung to stop coughs, arresting sweating, preserving semen and preventing diarrhea. The major components of WWZ include lignans, triterpenoids, organic acids and fatty acids. In this paper, a reliable method for the rapid identification of multiple components in WWZ by their characteristic fragments and neutral losses using UPLC-Q-TOF/MS technology was developed. After review of the literature and some reference experiments, the fragmentation pattern of several compounds were studied and summarized. Then, according to the corresponding characteristic fragments coupled with neutral losses in the positive or negative ion mode produced by different types of substances a rapid identification of target compounds was achieved. Finally, a total of 30 constituents of WWZ were successfully identified, including 15 lignans, nine triterpenoids, three organic acids and three fatty acids. The method established in this study not only provides a comprehensive analysis of the chemical ingredients of WWZ, providing a basis for further phytochemical studies on WWZ but also provides a more efficient way to solve the problem of identification of complex chemical constituents in traditional Chinese medicines. Full article

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24 pages, 1069 KiB

Open AccessReview

Traditional Uses, Origins, Chemistry and Pharmacology of Bombyx batryticatus: A Review

by Meibian Hu¹, Zhijie Yu¹, Jiaolong Wang¹, Wenxiang Fan¹, Yujie Liu¹, Jianghua Li¹, He Xiao², Yongchuan Li², Wei Peng^1,* and Chunjie Wu^1,3,*

¹ College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China

² Chengdu Min-Jiang-Yuan Pharmaceutical Co., Ltd., Chengdu 611000, China

³ Key Research Laboratory of Traditional Chinese Medicine Processing Technology, State Administration of Traditional Chinese Medicine of People’s Republic of China, Chengdu 611137, China

Molecules 2017, 22(10), 1779; https://doi.org/10.3390/molecules22101779 - 20 Oct 2017

Cited by 54 | Viewed by 9694

Abstract

Bombyx batryticatus (B. batryticatus), a well-known traditional animal Chinese medicine, has been commonly used in China for thousands of years. The present paper reviewed advances in traditional uses, origin, chemical constituents, pharmacology and toxicity studies of B. batryticatus. The aim [...] Read more.

Bombyx batryticatus (B. batryticatus), a well-known traditional animal Chinese medicine, has been commonly used in China for thousands of years. The present paper reviewed advances in traditional uses, origin, chemical constituents, pharmacology and toxicity studies of B. batryticatus. The aim of the paper is to provide more comprehensive references for modern B. batryticatus study and application. In Traditional Chinese Medicine (TCM) culture, drugs containing B. batryticatus have been used to treat convulsions, headaches, skin prurigo, scrofula, tonsillitis and fever. Many studies indicate B. batryticatus contains various compounds, including protein and peptides, fatty acids, flavonoids, nucleosides, steroids, coumarin, polysaccharide and others. Numerous investigations also have shown that extracts and compounds from B. batryticatus exert a wide spectrum of pharmacological effects both in vivo and in vitro, including effects on the nervous system, anticoagulant effects, antitumor effects, antibacterial and antifungal effects, antioxidant effects, hypoglycemic effects, as well as other effects. However, further studies should be undertaken to investigate bioactive compounds (especially proteins and peptides), toxic constituents, using forms and the quality evaluation and control of B. batryticatus. Furthermore, it will be interesting to study the mechanism of biological activities and structure-function relationships of bioactive constituents in B. batryticatus. Full article

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9 pages, 804 KiB

Open AccessArticle

Residue Dynamics and Risk Assessment of Prochloraz and Its Metabolite 2,4,6-Trichlorophenol in Apple

by Qingkui Fang¹, Gengyou Yao², Yanhong Shi², Chenchun Ding¹, Yi Wang²

, Xiangwei Wu², Rimao Hua² and Haiqun Cao^1,*

¹ School of Plant Protection, Provincial Key Laboratory for Agri-Food Safety, Anhui Agricultural University, Hefei 230036, China

² School of Resource & Environment, Provincial Key Laboratory for Agri-Food Safety, Anhui Agricultural University, Hefei 230036, China

Molecules 2017, 22(10), 1780; https://doi.org/10.3390/molecules22101780 - 20 Oct 2017

Cited by 17 | Viewed by 4501

Abstract

The residue dynamics and risk assessment of prochloraz and its metabolite 2,4,6-trichlorophenol (2,4,6-TCP) in apple under different treatment concentrations were investigated using a GC-ECD method. The derivatization percent of prochloraz to 2,4,6-TCP was stable and complete. The recoveries of prochloraz and 2,4,6-TCP were [...] Read more.

The residue dynamics and risk assessment of prochloraz and its metabolite 2,4,6-trichlorophenol (2,4,6-TCP) in apple under different treatment concentrations were investigated using a GC-ECD method. The derivatization percent of prochloraz to 2,4,6-TCP was stable and complete. The recoveries of prochloraz and 2,4,6-TCP were 82.9%–114.4%, and the coefficients of variation (CV) were 0.7%–8.6% for the whole fruit, apple pulp, and apple peel samples. Under the application of 2 °C 2.0 g/L, 2 °C 1.0 g/L, 20 °C 2.0 g/L, and 20 °C 1.0 g/L treatment, the half-life for the degradation of prochloraz was 57.8–86.6 d in the whole fruit and apple peel, and the prochloraz concentration in the apple pulp increased gradually until a peak (0.72 mg·kg⁻¹) was reached. The concentration of 2,4,6-TCP was below 0.1 mg·kg⁻¹ in four treatment conditions and not detected (<LOD) in apple pulp. Finally, based on the detection of market samples in Hefei (China), we believe that the residual level of prochloraz in apples meets the requirements of the Chinese standards. Full article

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18 pages, 11442 KiB

Open AccessArticle

Protective Effect of Flavonoids from Ziziphus jujuba cv. Jinsixiaozao against Acetaminophen-Induced Liver Injury by Inhibiting Oxidative Stress and Inflammation in Mice

by Weizhen Huang¹, Yongjie Wang¹, Xiaoyan Jiang¹, Yueyue Sun¹, Zhongxi Zhao^1,2,3,* and Siying Li^4,*

¹ School of Pharmaceutical Sciences, Shandong University, 44 West Wenhua Road, Jinan 50012, Shandong, China

² Shandong Engineering & Technology Research Center for Jujube Food and Drug, 44 West Wenhua Road, Jinan 250012, Shandong, China

³ Shandong Provincial Key Laboratory of Mucosal and Transdermal Drug Delivery Technologies, Shandong Academy of Pharmaceutical Sciences, 989 Xinluo Street, Jinan 250101, Shandong, China

⁴ Department of Pathology and Pathophysiology, School of Basic Medicine, Shandong University, 44 West Wenhua Road, Jinan 250012, Shandong, China

Molecules 2017, 22(10), 1781; https://doi.org/10.3390/molecules22101781 - 20 Oct 2017

Cited by 61 | Viewed by 7695

Abstract

This study was aimed to investigate the chemical composition, antioxidant activities and hepatoprotective effect of flavonoids from Ziziphus jujuba cv. Jinsixiaozao (ZJF). The composition of ZJF was analyzed by high performance liquid chromatography (HPLC) and Liquid chromatography–mass spectrometry (LC–MS), and antioxidant properties [...] Read more.

This study was aimed to investigate the chemical composition, antioxidant activities and hepatoprotective effect of flavonoids from Ziziphus jujuba cv. Jinsixiaozao (ZJF). The composition of ZJF was analyzed by high performance liquid chromatography (HPLC) and Liquid chromatography–mass spectrometry (LC–MS), and antioxidant properties were investigated by biological assays in vitro. The hepatoprotective activity of ZJF was evaluated in acetaminophen (APAP)-treated BALB/c mice. Results indicate that ZJF displayed significant antioxidant capacity. Pretreatment with ZJF significantly decreased APAP-elevated serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and total bilirubin (TB). Activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were enhanced with ZJF administration, while malondialdehyde (MDA) level and glutathione (GSH) depletion were reduced. Meanwhile, ZJF reversed the suppression of nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear translocation, and up-regulated the protein expression of NAD(P)H: quinone oxidoreductase 1(NQO1) in liver damage mice. Furthermore, ZJF attenuated APAP-induced inflammatory mediator production, such as nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β). Expression of p65 showed that ZJF dampened nuclear factor-κB (NF-κB) activation. The results strongly indicate that the hepatoprotective role of ZJF in APAP-induced hepatotoxicity might result from its induction of antioxidant defense via activation of Nrf2 and reduction of inflammation via inhibition of NF-κB. Full article

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12 pages, 2025 KiB

Open AccessArticle

Protective Effect of Prunus Cerasus (Sour Cherry) Seed Extract on the Recovery of Ischemia/Reperfusion-Induced Retinal Damage in Zucker Diabetic Fatty Rat

by Balázs Varga¹, Dániel Priksz¹, Nóra Lampé¹, Mariann Bombicz¹, Andrea Kurucz¹, Adrienn Mónika Szabó², Anikó Pósa³, Renáta Szabó³, Ádám Kemény-Beke⁴, Judit Remenyik⁵, Rudolf Gesztelyi¹

and Béla Juhász^1,*

¹ Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Debrecen, Debrecen H4032, Hungary

² Department of Internal Medicine, Building C, Faculty of Medicine, University of Debrecen, Debrecen H4032, Hungary

³ Department of Physiology, Anatomy and Neuroscience, Faculty of Science and Informatics, University of Szeged, Szeged H6726, Hungary

⁴ Department of Ophtalmology, Faculty of Medicine, University of Debrecen, Debrecen H4032, Hungary

⁵ Institute of Food Technology, Faculty of Agricultural and Food Sciences and Environmental Management, University of Debrecen, Debrecen H4032, Hungary

Molecules 2017, 22(10), 1782; https://doi.org/10.3390/molecules22101782 - 21 Oct 2017

Cited by 22 | Viewed by 6272

Abstract

Among diabetes patients, ophthalmological complications are very frequent. High blood glucose and (consequential) ischemia-reperfusion (I/R) injury contribute significantly to the severity of retinopathies. Diabetic retinopathy is among the leading causes of blindness. Our study demonstrates the effect of sour cherry seed extract (SCSE) [...] Read more.

Among diabetes patients, ophthalmological complications are very frequent. High blood glucose and (consequential) ischemia-reperfusion (I/R) injury contribute significantly to the severity of retinopathies. Diabetic retinopathy is among the leading causes of blindness. Our study demonstrates the effect of sour cherry seed extract (SCSE) on blood glucose and function of the retina with electroretinography (ERG) in a diabetic setting with or without ischemia-reperfusion (I/R) injury in Zucker Diabetic Fatty (ZDF) rats. Our results prove that the SCSE has a retinoprotective effect in diabetic rats: according to ERG measurements, SCSE treatment mitigated the retinal function-damaging effect of diabetes, and proved to be protective in the diabetic eye against ischemia-reperfusion injuries of the retina. Outcomes suggest that the protective effects of SCSE may occur through several pathways, including HO-1 dependent mechanisms. The observation that SCSE treatment decreases blood glucose is also novel. These findings offer the possibility for development of novel therapeutic strategies utilizing this emerging functional food, in particular in the prevention of conditions resulting from high blood glucose or I/R injury, such as deterioration of retinal microcirculation. Full article

(This article belongs to the Special Issue Bioactive Compounds for Metabolic Syndrome and Type 2 Diabetes)

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14 pages, 1556 KiB

Open AccessCommunication

Cinnamic Acid Analogs as Intervention Catalysts for Overcoming Antifungal Tolerance

by Jong H. Kim^*

, Kathleen L. Chan and Luisa W. Cheng

Foodborne Toxin Detection and Prevention Research Unit, Western Regional Research Center, USDA-ARS, 800 Buchanan St., Albany, CA 94710, USA

Molecules 2017, 22(10), 1783; https://doi.org/10.3390/molecules22101783 - 21 Oct 2017

Cited by 9 | Viewed by 6570

Abstract

Disruption of fungal cell wall should be an effective intervention strategy. However, the cell wall-disrupting echinocandin drugs, such as caspofungin (CAS), cannot exterminate filamentous fungal pathogens during treatment. For potency improvement of cell wall-disrupting agents (CAS, octyl gallate (OG)), antifungal efficacy of thirty-three [...] Read more.

Disruption of fungal cell wall should be an effective intervention strategy. However, the cell wall-disrupting echinocandin drugs, such as caspofungin (CAS), cannot exterminate filamentous fungal pathogens during treatment. For potency improvement of cell wall-disrupting agents (CAS, octyl gallate (OG)), antifungal efficacy of thirty-three cinnamic acid derivatives was investigated against Saccharomyces cerevisiae slt2Δ, bck1Δ, mutants of the mitogen-activated protein kinase (MAPK), and MAPK kinase kinase, respectively, in cell wall integrity system, and glr1Δ, mutant of CAS-responsive glutathione reductase. Cell wall mutants were highly susceptible to four cinnamic acids (4-chloro-α-methyl-, 4-methoxy-, 4-methyl-, 3-methylcinnamic acids), where 4-chloro-α-methyl- and 4-methylcinnamic acids possessed the highest activity. Structure-activity relationship revealed that 4-methylcinnamic acid, the deoxygenated structure of 4-methoxycinnamic acid, overcame tolerance of glr1Δ to 4-methoxycinnamic acid, indicating the significance of para substitution of methyl moiety for effective fungal control. The potential of compounds as chemosensitizers (intervention catalysts) to cell wall disruptants (viz., 4-chloro-α-methyl- or 4-methylcinnamic acids + CAS or OG) was assessed according to Clinical Laboratory Standards Institute M38-A. Synergistic chemosensitization greatly lowers minimum inhibitory concentrations of the co-administered drug/agents. 4-Chloro-α-methylcinnamic acid further overcame fludioxonil tolerance of Aspergillus fumigatus antioxidant MAPK mutants (sakAΔ, mpkCΔ). Collectively, 4-chloro-α-methyl- and 4-methylcinnamic acids possess chemosensitizing capability to augment antifungal efficacy of conventional drug/agents, thus could be developed as target-based (i.e., cell wall disruption) intervention catalysts. Full article

(This article belongs to the Special Issue Small Molecule Catalysts with Therapeutic Potential)

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20 pages, 4540 KiB

Open AccessArticle

Effect of Steam Deactivation Severity of ZSM-5 Additives on LPG Olefins Production in the FCC Process

by Andrey A. Gusev^1,2, Antonios C. Psarras¹, Konstantinos S. Triantafyllidis², Angelos A. Lappas^1,* and Paul A. Diddams³

¹ Centre for Research and Technology Hellas, Chemical Process and Energy Resources Institute, 6th km Charilaou-Thermi Road, Thessaloniki 57001, Greece

² Aristotle University of Thessaloniki, Department of Chemistry, University Campus, Thessaloniki 54124, Greece

³ Johnson Matthey Process Technologies, Technology Center, Bourne Blvd, Savannah, GA 31408, USA

Molecules 2017, 22(10), 1784; https://doi.org/10.3390/molecules22101784 - 21 Oct 2017

Cited by 24 | Viewed by 9127

Abstract

ZSM-5-containing catalytic additives are widely used in oil refineries to boost light olefin production and improve gasoline octanes in the Fluid Catalytic Cracking (FCC) process. Under the hydrothermal conditions present in the FCC regenerator (typically >700 °C and >8% steam), FCC catalysts and [...] Read more.

ZSM-5-containing catalytic additives are widely used in oil refineries to boost light olefin production and improve gasoline octanes in the Fluid Catalytic Cracking (FCC) process. Under the hydrothermal conditions present in the FCC regenerator (typically >700 °C and >8% steam), FCC catalysts and additives are subject to deactivation. Zeolites (e.g., Rare Earth USY in the base catalyst and ZSM-5 in Olefins boosting additives) are prone to dealumination and partial structural collapse, thereby losing activity, micropore surface area, and undergoing changes in selectivity. Fresh catalyst and additives are added at appropriate respective levels to the FCC unit on a daily basis to maintain overall targeted steady-state (equilibrated) activity and selectivity. To mimic this process under accelerated laboratory conditions, a commercial P/ZSM-5 additive was hydrothermally equilibrated via a steaming process at two temperatures: 788 °C and 815 °C to simulate moderate and more severe equilibration industrial conditions, respectively. n-Dodecane was used as probe molecule and feed for micro-activity cracking testing at 560 °C to determine the activity and product selectivity of fresh and equilibrated P-doped ZSM-5 additives. The fresh/calcined P/ZSM-5 additive was very active in C₁₂ cracking while steaming limited its activity, i.e., at catalyst-to-feed (C/F) ratio of 1, about 70% and 30% conversion was obtained with the fresh and steamed additives, respectively. A greater activity drop was observed upon increasing the hydrothermal deactivation severity due to gradual decrease of total acidity and microporosity of the additives. However, this change in severity did not result in any selectivity changes for the LPG (liquefied petroleum gas) olefins as the nature (Brønsted-to-Lewis ratio) of the acid/active sites was not significantly altered upon steaming. Steam deactivation of ZSM-5 had also no significant effect on aromatics formation which was enhanced at higher conversion levels. Coke remained low with both fresh and steam-deactivated P/ZSM-5 additives. Full article

(This article belongs to the Special Issue Zeolites and Related Nanoporous Materials: Synthesis, Characterization and Applications in Catalysis and Green Chemistry)

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18 pages, 4072 KiB

Open AccessArticle

Inhibitory Effects of Siegesbeckia orientalis Extracts on Advanced Glycation End Product Formation and Key Enzymes Related to Metabolic Syndrome

by Wei-Chin Hung¹, Xue-Hua Ling^2,3, Chi-Chang Chang³, Hsia-Fen Hsu⁴, Shih-Wei Wang⁵, Yi-Chen Lee⁶, Ci Luo⁴, Yun-Tzu Lee⁴ and Jer-Yiing Houng^2,4,*

¹ Division of Cardiology, E-Da Hospital, Kaohsiung 82445, Taiwan

² Graduate Institute of Biotechnology and Chemical Engineering, I-Shou University, Kaohsiung 84001, Taiwan

³ Department of Obstetrics & Gynecology, E-Da Hospital/I-Shou University, Kaohsiung 82445, Taiwan

⁴ Department of Nutrition, I-Shou University, Kaohsiung 82445, Taiwan

⁵ Division of Allergy, Immunology, and Rheumatology, Department of Internal Medicine, E-Da Hospital/I-Shou University, Kaohsiung 82445, Taiwan

⁶ Department of Nutrition Therapy, E-Da Hospital, Kaohsiung 82445, Taiwan

Molecules 2017, 22(10), 1785; https://doi.org/10.3390/molecules22101785 - 21 Oct 2017

Cited by 18 | Viewed by 7782

Abstract

Metabolic syndrome typically includes Type 2 diabetes associated with hyperglycemia, central obesity, dyslipidemia and hypertension. It is highly related to oxidative stress, formation of advanced glycated end products (AGEs) and key enzymes, such as carbohydrate digesting enzymes like pancreatic α-amylase and intestinal α-glucosidase, [...] Read more.

Metabolic syndrome typically includes Type 2 diabetes associated with hyperglycemia, central obesity, dyslipidemia and hypertension. It is highly related to oxidative stress, formation of advanced glycated end products (AGEs) and key enzymes, such as carbohydrate digesting enzymes like pancreatic α-amylase and intestinal α-glucosidase, pancreatic lipase and angiotensin I-converting enzyme (ACE). This study used an in vitro approach to assess the potential of four extracts of Siegesbeckia orientalis linne on key enzymes relevant to metabolic syndrome. In this research, S. orientailis was firstly extracted by ethanol. The ethanol extract (SE) was then partitioned sequentially with hexane, ethyl acetate and methanol, and these extracts were named SE-Hex, SE-EA and SE-MeOH, respectively. The experimental results showed that SE-EA had the highest total phenolic content (TPC, 76.9 ± 1.8 mg/g) and the total flavonoids content (TFC, 5.3 ± 0.3 mg/g). This extract exhibited the most significant antioxidant activities, including DPPH radical-scavenging capacity (IC₅₀ = 161.8 ± 2.4 μg/mL), ABTS radical-scavenging capacity (IC₅₀ = 13.9 ± 1.5 μg/mL) and reducing power. For anti-glycation activities, SE-EA showed the best results in the inhibition of AGEs, as well as inhibitory activities against α-glucosidase (IC₅₀ = 362.3 ± 9.2 μg/mL) and α-amylase (IC₅₀ = 119.0 ± 17.7 μg/mL). For anti-obesity activities, SE-EA indicated the highest suppression effect on pancreatic lipase (IC₅₀ = 3.67 ± 0.52 mg/mL). Finally, for anti-hypertension activity, SE-EA also demonstrated the strongest inhibitory activity on ACE (IC₅₀ = 626.6 ± 15.0 μg/mL). Close relationships were observed among the parameters of TPC, antioxidant activities, inhibitory activities on α-amylase, α-glucosidase, lipase and ACE (R > 0.9). Moderate correlations were found among the parameters of TFC, antioxidant activities, and suppression of dicarbonyl compounds formation (R = 0.5–0.9). Taken together these in vitro studies reveal the therapeutic potential of SE-EA extract in the prevention and treatment of metabolic disorders. Full article

(This article belongs to the Special Issue Bioactive Compounds for Metabolic Syndrome and Type 2 Diabetes)

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14 pages, 1961 KiB

Open AccessArticle

Nucleophilicities of Lewis Bases B and Electrophilicities of Lewis Acids A Determined from the Dissociation Energies of Complexes B⋯A Involving Hydrogen Bonds, Tetrel Bonds, Pnictogen Bonds, Chalcogen Bonds and Halogen Bonds

by Ibon Alkorta^1,*

and Anthony C. Legon^2,*

¹ Instituto de Química Médica (IQM-CSIC), Juan de la Cierva, 3, E-28006 Madrid, Spain

² School of Chemistry, University of Bristol, Cantock’s Close, Bristol BS8 1TS, UK

Molecules 2017, 22(10), 1786; https://doi.org/10.3390/molecules22101786 - 23 Oct 2017

Cited by 40 | Viewed by 5827

Abstract

It is shown that the dissociation energy

D_{e}

for the process B⋯A = B + A for 250 complexes B⋯A composed of 11 Lewis bases B (N₂, CO, HC≡CH, CH₂=CH₂, C₃H₆, PH [...] Read more.

It is shown that the dissociation energy

D_{e}

for the process B⋯A = B + A for 250 complexes B⋯A composed of 11 Lewis bases B (N₂, CO, HC≡CH, CH₂=CH₂, C₃H₆, PH₃, H₂S, HCN, H₂O, H₂CO and NH₃) and 23 Lewis acids (HF, HCl, HBr, HC≡CH, HCN, H₂O, F₂, Cl₂, Br₂, ClF, BrCl, H₃SiF, H₃GeF, F₂CO, CO₂, N₂O, NO₂F, PH₂F, AsH₂F, SO₂, SeO₂, SF₂, and SeF₂) can be represented to good approximation by means of the equation

D_{e} = c^{'} N_{B} E_{A}

, in which

N_{B}

is a numerical nucleophilicity assigned to B,

E_{A}

is a numerical electrophilicity assigned to A, and

c^{'}

is a constant, conveniently chosen to have the value 1.00 kJ mol⁻¹ here. The 250 complexes were chosen to cover a wide range of non-covalent interaction types, namely: (1) the hydrogen bond; (2) the halogen bond; (3) the tetrel bond; (4) the pnictogen bond; and (5) the chalcogen bond. Since there is no evidence that one group of non-covalent interaction was fitted any better than the others, it appears the equation is equally valid for all the interactions considered and that the values of

N_{B}

and

E_{A}

so determined define properties of the individual molecules. The values of

N_{B}

and

E_{A}

can be used to predict the dissociation energies of a wide range of binary complexes B⋯A with reasonable accuracy. Full article

(This article belongs to the Special Issue Halogen Bonds and Beyond)

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17 pages, 8576 KiB

Open AccessArticle

Trace Oxygen Sensitive Material Based on Two Porphyrin Derivatives in a Heterodimeric Complex

by Eugenia Fagadar-Cosma^1,*

, Valentin Badea², Gheorghe Fagadar-Cosma^2,*, Anca Palade¹, Anca Lascu¹, Ionela Fringu¹ and Mihaela Birdeanu^1,3

¹ Institute of Chemistry Timisoara of Romanian Academy, M. Viteazul Ave, No. 24, 300223 Timisoara, Romania

² Faculty of Industrial Chemistry and Environmental Engineering, Politehnica University Timisoara, PtaVictoriei 2, 300006 Timisoara, Romania

³ National Institute for Research and Development in Electrochemistry and Condensed Matter, P. Andronescu Street, No. 1, 300224 Timisoara, Romania

Molecules 2017, 22(10), 1787; https://doi.org/10.3390/molecules22101787 - 21 Oct 2017

Cited by 6 | Viewed by 7224

Abstract

The successful preparation of a novel dimer complex formed between 5,10,15,20-tetrakis(3,4-dimethoxyphenyl)-porphyrin Fe(III) chloride and (5,10,15,20-tetraphenylporphinato) dichlorophosphorus(V) chloride using the well-known reactivity of the P–X bond is reported. The obtained complex was characterized by UV-vis, Fourier transform infrared spectroscopy (FT-IR), fluorescence, ¹H-NMR, ¹³ [...] Read more.

The successful preparation of a novel dimer complex formed between 5,10,15,20-tetrakis(3,4-dimethoxyphenyl)-porphyrin Fe(III) chloride and (5,10,15,20-tetraphenylporphinato) dichlorophosphorus(V) chloride using the well-known reactivity of the P–X bond is reported. The obtained complex was characterized by UV-vis, Fourier transform infrared spectroscopy (FT-IR), fluorescence, ¹H-NMR, ¹³C-NMR, and ³¹P-NMR spectroscopic techniques and also by additional Heteronuclear Single Quantum Coherence (HSQC) and Heteronuclear Multiple Bond Correlation (HMBC) experiments in order to correctly assign the NMR signals. Scanning electron microscopy (SEM) and EDX quantifications completed the characterizations. This novel porphyrin dimer complex demonstrated fluorescence sensing of H₂O₂ in water for low oxygen concentrations in the range of 40–90 µM proving medical relevance for early diagnosis of diseases such as Alzheimer’s, Parkinson’s, Huntington’s, and even cancer because higher concentrations of H₂O₂ than 50 μM are consideredcytotoxic for life. Due to its optical properties, this novel metalloporphyrin–porphyrin based complex is expected to show PDT and bactericidal activity under visible-light irradiation. Full article

(This article belongs to the Section Molecular Diversity)

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14 pages, 1621 KiB

Open AccessArticle

Recovery of Oil with Unsaturated Fatty Acids and Polyphenols from Chaenomelessinensis (Thouin) Koehne: Process Optimization of Pilot-Scale Subcritical Fluid Assisted Extraction

by Zhenzhou Zhu^1,†, Rui Zhang^1,†, Shaoying Zhan¹, Jingren He^1,*, Francisco J. Barba^2,*

, Giancarlo Cravotto³

, Weizhong Wu¹ and Shuyi Li¹

¹ College of Food Science and Engineering, Wuhan Polytechnic University, Wuhan 430023, China

² Nutrition and Food Science Area, Preventive Medicine and Public Health, Food Science, Toxicology and Forensic Medicine Department, Faculty of Pharmacy, Universitat de València, Avda. Vicent Andrés Estellés, s/n, Burjassot 46100, Spain

³ Dipartimento di Scienza e Tecnologia del Farmaco, University of Turin, Via P. Giuria 9, Turin 10125, Italy

^† These authors contributed equally to this work.

Molecules 2017, 22(10), 1788; https://doi.org/10.3390/molecules22101788 - 22 Oct 2017

Cited by 7 | Viewed by 6471

Abstract

The potential effects of three modern extraction technologies (cold-pressing, microwaves and subcritical fluids) on the recovery of oil from Chaenomelessinensis (Thouin) Koehne seeds have been evaluated and compared to those of conventional chemical extraction methods (Soxhlet extraction). This oil contains unsaturated fatty acids [...] Read more.

The potential effects of three modern extraction technologies (cold-pressing, microwaves and subcritical fluids) on the recovery of oil from Chaenomelessinensis (Thouin) Koehne seeds have been evaluated and compared to those of conventional chemical extraction methods (Soxhlet extraction). This oil contains unsaturated fatty acids and polyphenols. Subcritical fluid extraction (SbFE) provided the highest yield—25.79 g oil/100 g dry seeds—of the three methods. Moreover, the fatty acid composition in the oil samples was analysed using gas chromatography–mass spectrometry. This analysis showed that the percentages of monounsaturated (46.61%), and polyunsaturated fatty acids (42.14%), after applying SbFE were higher than those obtained by Soxhlet, cold-pressing or microwave-assisted extraction. In addition, the oil obtained under optimized SbFE conditions (35 min extraction at 35 °C with four extraction cycles), showed significant polyphenol (527.36 mg GAE/kg oil), and flavonoid (15.32 mg RE/kg oil), content, had a good appearance and was of high quality. Full article

(This article belongs to the Special Issue Green Extraction of Natural Product: Innovative Techniques, Alternative Solvents and Original Procedures)

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14 pages, 2511 KiB

Open AccessArticle

Analysis of Floral Volatile Components and Antioxidant Activity of Different Varieties of Chrysanthemum morifolium

by Lu Yang^1,2, Aobulikasimu·Nuerbiye³, Ping Cheng^1,2, Jin-Hui Wang³ and Hong Li^1,*

¹ Xinjiang Academy of Forestry, Urumqi 830000, China

² Economic forest product quality inspection and testing center of the State Forestry Administration (Urumqi), Urumqi 830052, China

³ Xinjiang Medical University, Urumqi 830000, China

Molecules 2017, 22(10), 1790; https://doi.org/10.3390/molecules22101790 - 23 Oct 2017

Cited by 57 | Viewed by 8892

Abstract

This study investigated the volatile flavor compounds and antioxidant properties of the essential oil of chrysanthemums that was extracted from the fresh flowers of 10 taxa of Chrysanthemum morifolium from three species; namely Dendranthema morifolium (Ramat.) Yellow, Dendranthema morifolium (Ramat.) Red, Dendranthema morifolium [...] Read more.

This study investigated the volatile flavor compounds and antioxidant properties of the essential oil of chrysanthemums that was extracted from the fresh flowers of 10 taxa of Chrysanthemum morifolium from three species; namely Dendranthema morifolium (Ramat.) Yellow, Dendranthema morifolium (Ramat.) Red, Dendranthema morifolium (Ramat.) Pink, Dendranthema morifolium (Ramat.) White, Pericallis hybrid Blue, Pericallis hybrid Pink, Pericallis hybrid Purple, Bellis perennis Pink, Bellis perennis Yellow, and Bellis perennis White. The antioxidant capacity of the essential oil was assayed by spectrophotometric analysis. The volatile flavor compounds from the fresh flowers were collected using dynamic headspace collection, analyzed using auto thermal desorber–gas chromatography/mass spectrometry, and identified with quantification using the external standard method. The antioxidant activities of Chrysanthemum morifolium were evaluated by DPPH and FRAP assays, and the results showed that the antioxidant activity of each sample was not the same. The different varieties of fresh Chrysanthemum morifolium flowers were distinguished and classified by fingerprint similarity evaluation, principle component analysis (PCA), and cluster analysis. The results showed that the floral volatile component profiles were significantly different among the different Chrysanthemum morifolium varieties. A total of 36 volatile flavor compounds were identified with eight functional groups: hydrocarbons, terpenoids, aromatic compounds, alcohols, ketones, ethers, aldehydes, and esters. Moreover, the variability among Chrysanthemum morifolium in basis to the data, and the first three principal components (PC1, PC2, and PC3) accounted for 96.509% of the total variance (55.802%, 30.599%, and 10.108%, respectively). PCA indicated that there were marked differences among Chrysanthemum morifolium varieties. The cluster analysis confirmed the results of the PCA analysis. In conclusion, the results of this study provide a basis for breeding Chrysanthemum cultivars with desirable floral scents, and they further support the view that some plants are promising sources of natural antioxidants. Full article

(This article belongs to the Special Issue Selected Papers from the 6th International Conference on Biotechnology and Bioengineering (6-ICBB 2017))

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7 pages, 2357 KiB

Open AccessCommunication

Cadmium Disrupts Subcellular Organelles, Including Chloroplasts, Resulting in Melatonin Induction in Plants

by Hyoung-Yool Lee and Kyoungwhan Back^*

Department of Biotechnology, Bioenergy Research Center, College of Agriculture and Life Sciences, Chonnam National University, 77 Yongbong-ro, Buk-gu, Gwangju 61186, Korea

Molecules 2017, 22(10), 1791; https://doi.org/10.3390/molecules22101791 - 23 Oct 2017

Cited by 43 | Viewed by 6231

Abstract

Cadmium is a well-known elicitor of melatonin synthesis in plants, including rice. However, the mechanisms by which cadmium induces melatonin induction remain elusive. To investigate whether cadmium influences physical integrities in subcellular organelles, we treated tobacco leaves with either CdCl₂ or AlCl [...] Read more.

Cadmium is a well-known elicitor of melatonin synthesis in plants, including rice. However, the mechanisms by which cadmium induces melatonin induction remain elusive. To investigate whether cadmium influences physical integrities in subcellular organelles, we treated tobacco leaves with either CdCl₂ or AlCl₃ and monitored the structures of subcellular organelles—such as chloroplasts, mitochondria, and the endoplasmic reticulum (ER)—using confocal microscopic analysis. Unlike AlCl₃ treatment, CdCl₂ (0.5 mM) treatment significantly disrupted chloroplasts, mitochondria, and ER. In theory, the disruption of chloroplasts enabled chloroplast-expressed serotonin N-acetyltransferase (SNAT) to encounter serotonin in the cytoplasm, leading to the synthesis of N-acetylserotonin followed by melatonin synthesis. In fact, the disruption of chloroplasts by cadmium, not by aluminum, gave rise to a huge induction of melatonin in rice leaves, which suggests that cadmium-treated chloroplast disruption plays an important role in inducing melatonin in plants by removing physical barriers, such as chloroplast double membranes, allowing SNAT to gain access to the serotonin substrate enriched in the cytoplasm. Full article

(This article belongs to the Special Issue Melatonin as an Antioxidant and a Functionally Pleiotropic Molecule: Synthesis, Metabolism and Activities in Organisms)

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11 pages, 983 KiB

Open AccessArticle

Phenolic Compounds Present Schinus terebinthifolius Raddi Influence the Lowering of Blood Pressure in Rats

by Lorena De Lima Glória¹, Mariana Barreto de Souza Arantes¹, Silvia Menezes de Faria Pereira¹, Guilherme De Souza Vieira², Camilla Xavier Martins², Almir Ribeiro de Carvalho Junior³

, Fernanda Antunes², Raimundo Braz-Filho³

, Ivo José Curcino Vieira³, Larissa Leandro da Cruz¹, Douglas Siqueira de Almeida Chaves⁴, Silvério De Paiva Freitas⁵ and Daniela Barros de Oliveira^1,*

¹ Laboratório de Tecnologia de Alimentos, CCTA, Universidade Estadual do Norte Fluminense Darcy Ribeiro, Campos dos Goytacazes 28013-602, Brazil

² Laboratório de Clínica e Cirurgia Animal, CCTA, Universidade Estadual do Norte Fluminense Darcy Ribeiro, Campos dos Goytacazes 28013-602, Brazil

³ Laboratório de Ciências Químicas, CCT, Universidade Estadual do Norte Fluminense Darcy Ribeiro, Campos dos Goytacazes 28013-602, Brazil

⁴ Laboratório de Química de Bioativos Naturais, Departamento de Ciências Farmacêuticas, Universidade Federal Rural do Rio de Janeiro, Seropédica 23897-000, Brazil

⁵ Laboratório de Fitotecnia, Universidade Estadual do Norte Fluminense Darcy Ribeiro, Campos dos Goytacazes 28013-602, Brazil

Molecules 2017, 22(10), 1792; https://doi.org/10.3390/molecules22101792 - 23 Oct 2017

Cited by 24 | Viewed by 6267

Abstract

This study identified two phenolic compounds in Schinus terebinthifolius Raddi fruits: naringenin (first report in this species) and gallic acid. Their structures were elucidated by nuclear magnetic resonance (NMR) data (¹H-, ¹³C-NMR) and a high-performance liquid chromatography (HPLC) technique. A [...] Read more.

This study identified two phenolic compounds in Schinus terebinthifolius Raddi fruits: naringenin (first report in this species) and gallic acid. Their structures were elucidated by nuclear magnetic resonance (NMR) data (¹H-, ¹³C-NMR) and a high-performance liquid chromatography (HPLC) technique. A high content of phenolics (659.21 mg of gallic acid equivalents/g of sample—Folin-Ciocalteau method) and total flavonoids (140.69 mg of rutin equivalents/g of sample—aluminum chloride method) were quantified in S. terebinthifolius, as well as high antioxidant activity (77.47%—2,2-diphenyl-1-picrylhydrazyl, DPPH method). The antihypertensive activity related to its phenolic content was investigated. After intravenous infusion in Wistar rats, these phenolics significantly reduced (p < 0.05) the systolic, median, and diastolic arterial pressures of individuals. The rotarod test was performed to determine the mechanism of action of the sample vasorelaxant effect. It was found that its action exceeded that of the positive control used (diazepam). This confirmed the vasodilatory activity exerted by S. terebinthifolius fruits is related to the phenolic compounds present in the plant, which are potent antioxidants and inhibit oxidative stress, mainly in the central nervous system. Full article

(This article belongs to the Collection Bioactive Compounds)

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13 pages, 2661 KiB

Open AccessArticle

The Regulatory Mechanism of MLT/MT1 Signaling on the Growth of Antler Mesenchymal Cells

by Feifei Yang^1,2, Changjiu He¹, Xuyang Sun¹, Jing Wang³, Can Luo¹, Guoshi Liu³

, Liguo Yang¹, Jiajun Xiong^1,* and Lijun Huo^1,*

¹ Key Lab of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, China

² Department of Animal Husbandry and Veterinary, Wuhan Agricultural School, Wuhan 430043, China

³ National Engineering Laboratory for Animal Breeding, Key Laboratory of Animal Genetics and Breeding of the Ministry of Agriculture, Beijing Key Laboratory for Animal Genetic Improvement, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China

Molecules 2017, 22(10), 1793; https://doi.org/10.3390/molecules22101793 - 23 Oct 2017

Cited by 9 | Viewed by 6246

Abstract

Melatonin (MLT) plays an important role in regulating the physiological cycle of seasonal breeding animals. Melatonin receptor I (MT1) is effectively expressed in the cambium layer of deer antler. However, the function and metabolic mechanism of MLT/MT1 signaling in the mesenchymal cells of [...] Read more.

Melatonin (MLT) plays an important role in regulating the physiological cycle of seasonal breeding animals. Melatonin receptor I (MT1) is effectively expressed in the cambium layer of deer antler. However, the function and metabolic mechanism of MLT/MT1 signaling in the mesenchymal cells of sika deer remain to be further elucidated. In this work, we detected the effects of MLT/MT1 signaling on mesenchymal cells proliferation and the interaction between MLT/MT1 and IGF1/IGF1-R signaling. The results show that (1) deer antler mesenchymal cells actually express MT1; (2) exogenous melatonin significantly promotes mesenchymal cells proliferation, while MT1 knock-down significantly impairs the positive effects of melatonin; and (3) melatonin significantly enhanced IGF1/IGF1-R signaling, as both the expression of IGF1 and IGF-1R increased, while MT1 knock-down significantly decreased IGF1-R expression and IGF1 synthesis. In summary, these data verified that MLT/MT1 signaling plays a crucial role in antler mesenchymal proliferation, which may be mediated by IGF1/IGF1-R. Full article

(This article belongs to the Special Issue Melatonin as an Antioxidant and a Functionally Pleiotropic Molecule: Synthesis, Metabolism and Activities in Organisms)

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19 pages, 8082 KiB

Open AccessArticle

Silver Nanoparticles Stabilised by Cationic Gemini Surfactants with Variable Spacer Length

by Martin Pisárčik^1,*, Josef Jampílek²

, Miloš Lukáč¹, Renáta Horáková¹, Ferdinand Devínsky^1,3

, Marián Bukovský⁴, Michal Kalina⁵

, Jakub Tkacz⁵

and Tomáš Opravil⁵

¹ Department of Chemical Theory of Drugs, Faculty of Pharmacy, Comenius University, Kalinčiakova 8, Bratislava SK-83232, Slovakia

² Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Comenius University, Bratislava SK-83232, Slovakia

³ Faculty of Pharmacy, Comenius University, Kalinčiakova 8, Bratislava SK-83232, Slovakia

⁴ Department of Cell and Molecular Biology of Drugs, Faculty of Pharmacy, Comenius University, Bratislava SK-83232, Slovakia

⁵ Materials Research Centre, Faculty of Chemistry, Brno University of Technology, CZ-61200 Brno, Czech Republic

Molecules 2017, 22(10), 1794; https://doi.org/10.3390/molecules22101794 - 23 Oct 2017

Cited by 38 | Viewed by 8092

Abstract

The present study is focused on the synthesis and investigation of the physicochemical and biological properties of silver nanoparticles stabilized with a series of cationic gemini surfactants having a polymethylene spacer of variable length. UV-VIS spectroscopy, dynamic light scattering, scanning electron microscopy and [...] Read more.

The present study is focused on the synthesis and investigation of the physicochemical and biological properties of silver nanoparticles stabilized with a series of cationic gemini surfactants having a polymethylene spacer of variable length. UV-VIS spectroscopy, dynamic light scattering, scanning electron microscopy and zeta potential measurements were applied to provide physicochemical characterization of the silver nanoparticles. The mean size values of the nanoparticles were found to be in the 50 to 115 nm range. From the nanoparticle size distributions and scanning electron microscopy images it results that a population of small nanoparticles with the size of several nanometers was confirmed if the nanoparticles were stabilized with gemini molecules with either a short methylene spacer (two or four −CH₂− groups) or a long spacer (12 −CH₂− groups). The average zeta potential value for silver nanoparticles stabilized with gemini molecules is roughly independent of gemini surfactant spacer length and is approx. +58 mV. An interaction model between silver nanoparticles and gemini molecules which reflects the gained experimental data, is suggested. Microbicidal activity determinations revealed that the silver nanoparticles stabilized with gemini surfactants are more efficient against Gram-negative bacteria and yeasts, which has a direct relation to the interaction mechanism of nanoparticles with the bacterial cell membrane and its structural composition. Full article

(This article belongs to the Special Issue Selected Papers from the 46th EuroCongress on Drug Synthesis and Analysis (ECDSA-2017))

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18 pages, 613 KiB

Open AccessReview

Pharmabiotics as an Emerging Medication for Metabolic Syndrome and Its Related Diseases

by Thi Thanh Binh Nguyen^1,†

, Yan Yan Jin^1,†, Hea-Jong Chung² and Seong-Tschool Hong^1,*

¹ Department of Biomedical Sciences and Institute for Medical Science, Chonbuk National University Medical School, Jeonju, Chonbuk 54907, Korea

² Department of Microbiology, Seonam University Medical School, Namwon, Chonbuk 55321, Korea

^† These authors contributed equally to this work.

Molecules 2017, 22(10), 1795; https://doi.org/10.3390/molecules22101795 - 24 Oct 2017

Cited by 29 | Viewed by 8932

Abstract

Metabolic syndrome (MetS) is a cluster of metabolic risk factors associated with central obesity, hyperglycemia, insulin resistance, dyslipidemia and high blood pressure. In recent decades, because of the remarkable increase in both prevalence and severity, MetS and its related diseases such as cardiovascular [...] Read more.

Metabolic syndrome (MetS) is a cluster of metabolic risk factors associated with central obesity, hyperglycemia, insulin resistance, dyslipidemia and high blood pressure. In recent decades, because of the remarkable increase in both prevalence and severity, MetS and its related diseases such as cardiovascular diseases (CVDs), obesity, hypertension and diabetes have become the main global burden and challenge in strategic management involving prevention and treatment. However, currently, the preventions and treatments based on pharmaceutical interventions do not provide a solution for MetS and its related diseases. Recently, gut microbiota showed clear evidence of preventing and/or treating MetS, shedding light on treating MetS and its related diseases through a completely different approach. In this review, we will interpret the effects of current pharmaceutical drugs used in preventing and treating MetS and its related diseases to understand remaining issues of those interventions. We will explore the possibility of developing gut microbiota as pharmabiotics in a completely new medication option for treating MetS and its related diseases. Full article

(This article belongs to the Special Issue Bioactive Compounds for Metabolic Syndrome and Type 2 Diabetes)

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13 pages, 1239 KiB

Open AccessReview

Cyclodipeptides: An Overview of Their Biosynthesis and Biological Activity

by Awdhesh Kumar Mishra^1,†

, Jaehyuk Choi^1,†, Seong-Jin Choi² and Kwang-Hyun Baek^1,*

¹ Department of Biotechnology, Yeungnam University, Gyeongsan, Gyeongbuk 38541, Korea

² Department of Biotechnology, Daegu Catholic University, Gyeongsan 38430, Korea

^† These authors contributed equally to this work.

Molecules 2017, 22(10), 1796; https://doi.org/10.3390/molecules22101796 - 23 Oct 2017

Cited by 101 | Viewed by 11765

Abstract

Cyclodipeptides (CDP) represent a diverse family of small, highly stable, cyclic peptides that are produced as secondary functional metabolites or side products of protein metabolism by bacteria, fungi, and animals. They are widespread in nature, and exhibit a broad variety of biological and [...] Read more.

Cyclodipeptides (CDP) represent a diverse family of small, highly stable, cyclic peptides that are produced as secondary functional metabolites or side products of protein metabolism by bacteria, fungi, and animals. They are widespread in nature, and exhibit a broad variety of biological and pharmacological activities. CDP synthases (CDPSs) and non-ribosomal peptide synthetases (NRPSs) catalyze the biosynthesis of the CDP core structure, which is further modified by tailoring enzymes often associated with CDP biosynthetic gene clusters. In this review, we provide a comprehensive summary of CDP biosynthetic pathways and modifying enzymes. We also discuss the biological properties of some known CDPs and their possible applications in metabolic engineering. Full article

(This article belongs to the Collection Phytochemicals: Biosynthesis, Metabolism and Biological Activities)

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16 pages, 1658 KiB

Open AccessArticle

Ureidopyrazine Derivatives: Synthesis and Biological Evaluation as Anti-Infectives and Abiotic Elicitors

by Ghada Bouz^*

, Martin Juhás

, Pavlína Niklová, Ondřej Janďourek

, Pavla Paterová, Jiří Janoušek

, Lenka Tůmová, Zuzana Kovalíková, Petr Kastner, Martin Doležal

and Jan Zitko^*

Faculty of Pharmacy in Hradec Kralove, Charles University, Heyrovskeho 1203, Hradec Kralove 50005, Czech Republic

Molecules 2017, 22(10), 1797; https://doi.org/10.3390/molecules22101797 - 23 Oct 2017

Cited by 7 | Viewed by 5262

Abstract

Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) has become a frequently deadly infection due to increasing antimicrobial resistance. This serious issue has driven efforts worldwide to discover new drugs effective against Mtb. One research area is the synthesis and evaluation [...] Read more.

Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) has become a frequently deadly infection due to increasing antimicrobial resistance. This serious issue has driven efforts worldwide to discover new drugs effective against Mtb. One research area is the synthesis and evaluation of pyrazinamide derivatives as potential anti-TB drugs. In this paper we report the synthesis and biological evaluations of a series of ureidopyrazines. Compounds were synthesized by reacting alkyl/aryl isocyanates with aminopyrazine or with propyl 5-aminopyrazine-2-carboxylate. Reactions were performed in pressurized vials using a CEM Discover microwave reactor with a focused field. Purity and chemical structures of products were assessed, and the final compounds were tested in vitro for their antimycobacterial, antibacterial, and antifungal activities. Propyl 5-(3-phenylureido)pyrazine-2-carboxylate (compound 4, MIC_Mtb = 1.56 μg/mL, 5.19 μM) and propyl 5-(3-(4-methoxyphenyl)ureido)pyrazine-2-carboxylate (compound 6, MIC_Mtb = 6.25 μg/mL, 18.91 μM) had high antimycobacterial activity against Mtb H37Rv with no in vitro cytotoxicity on HepG2 cell line. Therefore 4 and 6 are suitable for further structural modifications that might improve their biological activity and physicochemical properties. Based on the structural similarity to 1-(2-chloropyridin-4-yl)-3-phenylurea, a known plant growth regulator, two selected compounds were evaluated for similar activity as abiotic elicitors. Full article

(This article belongs to the Special Issue Selected Papers from the 46th EuroCongress on Drug Synthesis and Analysis (ECDSA-2017))

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14 pages, 1731 KiB

Open AccessArticle

Pharmacological Effects of Two Novel Bombesin-Like Peptides from the Skin Secretions of Chinese Piebald Odorous Frog (Odorrana schmackeri) and European Edible Frog (Pelophylax kl. esculentus) on Smooth Muscle

by Xiaowei Zhou^1,2, Chengbang Ma², Mei Zhou²

, Yuning Zhang², Xinping Xi^2,*, Ruimin Zhong^1,*, Tianbao Chen²

, Chris Shaw² and Lei Wang²

¹ Department of Nutrition, Henry Fok School of Food Science and Engineering, Shaoguan University, Shaoguan 512005, China

² Natural Drug Discovery Group, School of Pharmacy, Queen’s University, Belfast BT9 7BL, Northern Ireland, UK

Molecules 2017, 22(10), 1798; https://doi.org/10.3390/molecules22101798 - 23 Oct 2017

Cited by 7 | Viewed by 5843

Abstract

Bombesin-like peptides, which were identified from a diversity of amphibian skin secretions, have been demonstrated to possess several biological functions such as stimulation of smooth muscle contraction and regulation of food intake. Here, we report two novel bombesin-like peptides, bombesin-OS and bombesin-PE, which [...] Read more.

Bombesin-like peptides, which were identified from a diversity of amphibian skin secretions, have been demonstrated to possess several biological functions such as stimulation of smooth muscle contraction and regulation of food intake. Here, we report two novel bombesin-like peptides, bombesin-OS and bombesin-PE, which were isolated from Odorrana schmackeri and Pelophylax kl. esculentus, respectively. The mature peptides were identified and structurally confirmed by high performance Scliquid chromatography (HPLC) and tandem mass spectrometry (MS/MS). Subsequently, the effects of these purified chemically-synthetic peptides on smooth muscle were determined in bladder, uterus, and ileum. The synthetic replications were revealed to have significant pharmacological effects on these tissues. The EC₅₀ values of bombesin-OS for bladder, uterus and ileum, were 10.8 nM, 33.64 nM, and 12.29 nM, respectively. Furthermore, compared with bombesin-OS, bombesin-PE showed similar contractile activity on ileum smooth muscle and uterus smooth muscle, but had a higher potency on bladder smooth muscle. The EC₅₀value of bombesin-OS for bladder was around 1000-fold less than that of bombesin-PE. This suggests that bombesin-OS and bombesin-PE have unique binding properties to their receptors. The precursor of bombesin-OS was homologous with that of a bombesin-like peptide, odorranain-BLP-5, and bombesin-PE belongs to the ranatensin subfamily. We identified the structure of bombesin-OS and bombesin-PE, two homologues peptides whose actions may provide a further clue in the classification of ranid frogs, also in the provision of new drugs for human health. Full article

(This article belongs to the Special Issue Bioactive Natural Peptides As A Pipeline For Therapeutics)

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14 pages, 5037 KiB

Open AccessArticle

Equol, a Clinically Important Metabolite, Inhibits the Development and Pathogenicity of Magnaporthe oryzae, the Causal Agent of Rice Blast Disease

by Jiaoyu Wang^1,*, Ling Li^1,2, Yeshi Yin¹, Zhuokan Gu¹, Rongyao Chai¹, Yanli Wang¹ and Guochang Sun^1,*

¹ State Key Laboratory Breeding Base for Zhejiang Sustainable Pest and Disease Control, Institute of Plant Protection and Microbiology, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, China

² The Key Laboratory for Quality Improvement of Agricultural Products of Zhejiang Province, School of Agricultural and Food Sciences, Zhejiang Agriculture and Forest University, Hangzhou 311300, China

Molecules 2017, 22(10), 1799; https://doi.org/10.3390/molecules22101799 - 24 Oct 2017

Cited by 8 | Viewed by 6885

Abstract

Equol, a metabolite of soybean isoflavone daidzein, has been proven to have various bioactivities related to human health, but little is known on its antifungal activity to plant fungal pathogens. Magnaporthe oryzae is a phytopathogenic fungus that causes rice blast, a devastating disease [...] Read more.

Equol, a metabolite of soybean isoflavone daidzein, has been proven to have various bioactivities related to human health, but little is known on its antifungal activity to plant fungal pathogens. Magnaporthe oryzae is a phytopathogenic fungus that causes rice blast, a devastating disease on rice. Here, we demonstrated that equol influences the development and pathogenicity of M. oryzae. Equol showed a significant inhibition to the mycelial growth, conidial generation and germination, and appressorial formation of M. oryzae. As a result, equol greatly reduced the virulence of M. oryzae on rice and barley leaves. The antifungal activity of equol was also found in several other plant fungal pathogens. These findings expand our knowledge on the bioactivities of equol. Full article

(This article belongs to the Collection Bioactive Compounds)

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13 pages, 1472 KiB

Open AccessArticle

GC-MS Profiling of Volatile Components in Different Fermentation Products of Cordyceps Sinensis Mycelia

by Hongyang Zhang^1,2, Yahui Li¹, Jianing Mi³, Min Zhang², Yuerong Wang¹, Zhihong Jiang³ and Ping Hu^1,*

¹ School of Chemistry and Molecular Engineering, East China University of Science and Technology, Shanghai 200237, China

² Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China

³ State Key Laboratory of Quality Research in Chinese Medicine, Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Taipa, Macau 999078, China

Molecules 2017, 22(10), 1800; https://doi.org/10.3390/molecules22101800 - 24 Oct 2017

Cited by 36 | Viewed by 8665

Abstract

The fermentation products of Cordyceps sinensis (C. sinensis) mycelia are sustainable substitutes for natural C. sinensis. However, the volatile compositions of the commercial products are still unclear. In this paper, we have developed a simultaneous distillation-extraction (SDE) and gas chromatography-mass [...] Read more.

The fermentation products of Cordyceps sinensis (C. sinensis) mycelia are sustainable substitutes for natural C. sinensis. However, the volatile compositions of the commercial products are still unclear. In this paper, we have developed a simultaneous distillation-extraction (SDE) and gas chromatography-mass spectrometry (GC-MS) method for the profiling of volatile components in five fermentation products. A total of 64, 39, 56, 52, and 44 components were identified in the essential oils of Jinshuibao capsule (JSBC), Bailing capsule (BLC), Zhiling capsule (ZLC), Ningxinbao capsule (NXBC), and Xinganbao capsule (XGBC), respectively. 5,6-Dihydro-6-pentyl-2H-pyran-2-one (massoia lactone) was first discovered as the dominant component in JSBC volatiles. Fatty acids including palmitic acid (C16:0) and linoleic acid (C18:2) were also found to be major volatile compositions of the fermentation products. The multivariate partial least squares-discriminant analysis (PLS-DA) showed a clear discrimination among the different commercial products as well as the counterfeits. This study may provide further chemical evidences for the quality evaluation of the fermentation products of C. sinensis mycelia. Full article

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15 pages, 2228 KiB

Open AccessArticle

Association, Distribution, Liberation, and Rheological Balances of Alkyldimethylbenzylammonium Chlorides (C12–C16)

by Zuzana Vitková^1,*, Jarmila Oremusová², Petra Herdová¹, Oľga Ivánková³ and Anton Vitko⁴

¹ Department of Galenic Pharmacy, Faculty of Pharmacy, Comenius University in Bratislava, Odbojárov 10, 832 32 Bratislava, Slovakia

² Department of Physical Chemistry of Drugs, Faculty of Pharmacy, Comenius University in Bratislava, Odbojárov 10, 832 32 Bratislava, Slovakia

³ Department of Structural Mechanics, Faculty of Civil Engineering, Slovak University of Technology in Bratislava, 810 05 Bratislava, Slovakia

⁴ Institute of Robotics and Cybernetics, Faculty of Electrical Engineering and Information Technology, 812 19 Bratislava, Slovakia

Molecules 2017, 22(10), 1802; https://doi.org/10.3390/molecules22101802 - 24 Oct 2017

Cited by 5 | Viewed by 3860

Abstract

It is known that cationic surfactants have an antimicrobial effect and act as enhancers. This paper studies three cationic surfactants from the group of alkyldimethylbenzylammonium chlorides (dodecyl-, tetradecyl-, and hexadecyl). Interest is focused on the association of the surfactants with respect to temperature, [...] Read more.

It is known that cationic surfactants have an antimicrobial effect and act as enhancers. This paper studies three cationic surfactants from the group of alkyldimethylbenzylammonium chlorides (dodecyl-, tetradecyl-, and hexadecyl). Interest is focused on the association of the surfactants with respect to temperature, partition balances and their influence on drug release, rheological properties, and the pH of hydrogels. The critical micelle concentrations (CMC) of the surfactants were estimated from dependencies of conductivity, density, spectrofluorimetry, and UV–VIS spectrophotometry on molarity in the temperature range of 25–50 °C. It was found that the temperature dependence of a CMC is U-shaped, with its minimum at 30 °C, and the CMC value decreases as the length of the chain increases. The pseudo-phase separation model was used for the calculation of various thermodynamic parameters, such as the Gibbs free energies (spontaneous process), enthalpies (exothermic process), and entropies of the micelles’ formation, CMCs, and the degree of counterion binding. All thermodynamic parameters, as functions of the temperature, were estimated. It was found that partition coefficients increase as the length of the alkyl chain and the pH = (5.0–7.0) increase. The influences of surfactants, below and above the CMC, on drug (chlorhexidine dihydrochloride) release from hydrogels, rheological properties, and pH at 30 °C were studied. Also, the amounts of the released drug increase as the alkyl chains of the surfactants prolongate. The amounts of the released drug with the surfactant below the CMC are greater than that above the CMC. All hydrogels (regardless of the length of the alkyl chain) exhibit a non-Newtonian pseudo-plastic flow. The results obtained will be used in the formulation of the drug and surfactants into dosage forms. Full article

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12 pages, 1869 KiB

Open AccessArticle

Single Actin Bundle Rheology

by Dan Strehle^1,†, Paul Mollenkopf^1,2,†, Martin Glaser^1,2, Tom Golde¹, Carsten Schuldt^1,2, Josef A. Käs¹ and Jörg Schnauß^1,2,*

¹ Faculty of Physics and Earth Sciences, Peter Debye Institute, Leipzig University, Linnéstr. 5, 04103 Leipzig, Germany

² Fraunhofer Institute for Cell Therapy and Immunology (IZI), DNA Nanodevices Group, Perlickstraße 1, 04103 Leipzig, Germany

^† These authors contributed equally to this work.

Molecules 2017, 22(10), 1804; https://doi.org/10.3390/molecules22101804 - 24 Oct 2017

Cited by 11 | Viewed by 5366

Abstract

Bundled actin structures play an essential role in the mechanical response of the actin cytoskeleton in eukaryotic cells. Although responsible for crucial cellular processes, they are rarely investigated in comparison to single filaments and isotropic networks. Presenting a highly anisotropic structure, the determination [...] Read more.

Bundled actin structures play an essential role in the mechanical response of the actin cytoskeleton in eukaryotic cells. Although responsible for crucial cellular processes, they are rarely investigated in comparison to single filaments and isotropic networks. Presenting a highly anisotropic structure, the determination of the mechanical properties of individual bundles was previously achieved through passive approaches observing bending deformations induced by thermal fluctuations. We present a new method to determine the bending stiffness of individual bundles, by measuring the decay of an actively induced oscillation. This approach allows us to systematically test anisotropic, bundled structures. Our experiments revealed that thin, depletion force-induced bundles behave as semiflexible polymers and obey the theoretical predictions determined by the wormlike chain model. Thickening an individual bundle by merging it with other bundles enabled us to study effects that are solely based on the number of involved filaments. These thicker bundles showed a frequency-dependent bending stiffness, a behavior that is inconsistent with the predictions of the wormlike chain model. We attribute this effect to internal processes and give a possible explanation with regard to the wormlike bundle theory. Full article

(This article belongs to the Special Issue Natural Polymers and Biopolymers)

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18 pages, 5073 KiB

Open AccessArticle

Dermaseptin-PH: A Novel Peptide with Antimicrobial and Anticancer Activities from the Skin Secretion of the South American Orange-Legged Leaf Frog, Pithecopus (Phyllomedusa) hypochondrialis

by Linyuan Huang^†, Dong Chen^1,†, Lei Wang¹, Chen Lin^1,2, Chengbang Ma^1,*, Xinping Xi^1,*, Tianbao Chen¹

, Chris Shaw¹ and Mei Zhou¹

¹ Natural Drug Discovery Group, School of Pharmacy, Queen’s University, Belfast BT9 7BL, Northern Ireland, UK

² College of Basic Medical Science, Zhejiang Chinese Medial University, Hangzhou 310053, China

^† Theses authors contributed equally to this work.

Molecules 2017, 22(10), 1805; https://doi.org/10.3390/molecules22101805 - 24 Oct 2017

Cited by 65 | Viewed by 8977

Abstract

The dermaseptin peptides, mainly derived from the skin secretions of Hylidae frogs, belong to a superfamily of antimicrobial peptides and exhibit diverse antimicrobial and anticancer activities with low cytotoxicity. Here, we reported a novel dermaseptin peptide, from the South American orange-legged leaf frogs, [...] Read more.

The dermaseptin peptides, mainly derived from the skin secretions of Hylidae frogs, belong to a superfamily of antimicrobial peptides and exhibit diverse antimicrobial and anticancer activities with low cytotoxicity. Here, we reported a novel dermaseptin peptide, from the South American orange-legged leaf frogs, Pithecopus (Phyllomedusa) hypochondrialis, processing the shortest peptide length, namely Dermaseptin-PH. The complementary DNA (cDNA) encoding biosynthetic precursor of Dermaseptin-PH was initially identified by the rapid amplification of cDNA ends PCR (RACE-PCR) technique from the skin secretion. The predicted primary structure was confirmed by a combination of reverse-phase high performance liquid chromatography (RP-HPLC) and MS/MS fragmentation from the skin secretion. Chemically-synthetic Dermaseptin-PH was investigated using a range of bioactivity assessment assays to evaluate the biological activities and cytotoxicity of Dermaseptin-PH. Dermaseptin-PH inhibited the growth of Gram-negative bacteria, Gram-positive bacteria, and pathogenic yeast Candida albicans. In addition, Dermaseptin-PH showed a broad-spectrum of anticancer activities against several cancer cell lines including MCF-7, H157, U251MG, MDA-MB-435S, and PC-3. The potent antimicrobial and anticancer activities of Dermaseptin-PH make it a promising candidate in the discovery of new drugs for clinical applications, and the relatively short sequence of Dermaseptin-PH can provide new insight for the research and structural modification of new peptide drugs. Full article

(This article belongs to the Special Issue Bioactive Natural Peptides As A Pipeline For Therapeutics)

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15 pages, 453 KiB

Open AccessArticle

Enhanced Glucose Uptake in Human Liver Cells and Inhibition of Carbohydrate Hydrolyzing Enzymes by Nordic Berry Extracts

by Giang Thanh Thi Ho^1,*

, Thi Kim Yen Nguyen^1,2, Eili Tranheim Kase²

, Margey Tadesse¹, Hilde Barsett¹ and Helle Wangensteen¹

¹ Department of Pharmaceutical Chemistry, School of Pharmacy, University of Oslo, P.O. Box 1068 Blindern, 0316 Oslo, Norway

² Department of Pharmaceutical Biosciences, School of Pharmacy, University of Oslo, P.O. Box 1068 Blindern, 0316 Oslo, Norway

Molecules 2017, 22(10), 1806; https://doi.org/10.3390/molecules22101806 - 24 Oct 2017

Cited by 31 | Viewed by 6533

Abstract

A Western lifestyle with low physical activity and a diet rich in sugar, fat and processed food contribute to higher incidences of diabetes and obesity. Enhanced glucose uptake in human liver cells was observed after treatment with phenolic extracts from different Nordic berries. [...] Read more.

A Western lifestyle with low physical activity and a diet rich in sugar, fat and processed food contribute to higher incidences of diabetes and obesity. Enhanced glucose uptake in human liver cells was observed after treatment with phenolic extracts from different Nordic berries. All berry extracts showed higher inhibition against α-amylase and α-glucosidase than the anti-diabetic agent acarbose. Total phenolic content and phenolic profiles in addition to antioxidant activities, were also investigated. The berries were extracted with 80% methanol on an accelerated solvent extraction system (ASE) and then purified by C-18 solid phase extraction (SPE). Among the ASE methanol extracts, black chokeberry, crowberry and elderberry extracts showed high stimulation of glucose uptake in HepG2 cells and also considerable inhibitory effect towards carbohydrate hydrolyzing enzymes. SPE extracts with higher concentrations of phenolics, resulted in increased glucose uptake and enhanced inhibition of α-amylase and α-glucosidase compared to the ASE extracts. Crowberry and cloudberry were the most potent 15-lipoxygenase inhibitors, while bog whortleberry and lingonberry were the most active xanthine oxidase inhibitors. These results increase the value of these berries as a component of a healthy Nordic diet and have a potential benefit against diabetes. Full article

(This article belongs to the Collection Bioactive Compounds)

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Molecules, Volume 22, Issue 10 (October 2017) – 225 articles

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