Molecules

22 pages, 7281 KiB

Open AccessReview

Radiolabeled Dendrimers for Nuclear Medicine Applications

by Lingzhou Zhao¹, Meilin Zhu²

, Yujie Li¹, Yan Xing¹ and Jinhua Zhao^1,*

¹ Department of Nuclear Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China

² Basic Medical College, Ningxia Medical University, Yinchuan 750004, Ningxia, China

Molecules 2017, 22(9), 1350; https://doi.org/10.3390/molecules22091350 - 25 Aug 2017

Cited by 31 | Viewed by 7844

Abstract

Recent advances in nuclear medicine have explored nanoscale carriers for targeted delivery of various radionuclides in specific manners to improve the effect of diagnosis and therapy of diseases. Due to the unique molecular architecture allowing facile attachment of targeting ligands and radionuclides, dendrimers [...] Read more.

Recent advances in nuclear medicine have explored nanoscale carriers for targeted delivery of various radionuclides in specific manners to improve the effect of diagnosis and therapy of diseases. Due to the unique molecular architecture allowing facile attachment of targeting ligands and radionuclides, dendrimers provide versatile platforms in this filed to build abundant multifunctional radiolabeled nanoparticles for nuclear medicine applications. This review gives special focus to recent advances in dendrimer-based nuclear medicine agents for the imaging and treatment of cancer, cardiovascular and other diseases. Radiolabeling strategies for different radionuclides and several challenges involved in clinical translation of radiolabeled dendrimers are extensively discussed. Full article

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

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8 pages, 2424 KiB

Open AccessCommunication

MTLD, a Database of Multiple Target Ligands, the Updated Version

by Chao Chen¹, Meng Wu², Shan Cen², Jianhui Wu³ and Jinming Zhou^2,*

¹ North China Institute of Science and Technology, Beijing 065201, China

² Institute of Medicinal Biotechnology, Chinese Academy of Medical Science, Beijing 100050, China

³ Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, QC H3T 1E2, Canada

Molecules 2017, 22(9), 1375; https://doi.org/10.3390/molecules22091375 - 6 Sep 2017

Cited by 7 | Viewed by 5855

Abstract

Polypharmacology plays an important role in drug discovery and polypharmacology drug strategies provide a novel path in drug design. However, to develop a polypharmacology drug with the desired profile remains a challenge. Previously, we developed a free web-accessible database called Multiple Target Ligand [...] Read more.

Polypharmacology plays an important role in drug discovery and polypharmacology drug strategies provide a novel path in drug design. However, to develop a polypharmacology drug with the desired profile remains a challenge. Previously, we developed a free web-accessible database called Multiple Target Ligand Database (MTLD, www.mtdcadd.com). Herein, the MTLD database has been updated, containing 2444 Multiple Target Ligands (MTLs) that bind with 21,424 binding sites from 18,231 crystal structures. Of the MTLs, 304 entries are approved drugs, and 1911 entries are drug-like compounds. Also, we added new functions such as multiple conditional search and linkage visualization. Through querying the updated database, extremely useful information for the development of polypharmacology drugs may be provided. Full article

(This article belongs to the Special Issue Polypharmacology and Multitarget Drug Discovery)

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15 pages, 3269 KiB

Open AccessCommunication

Study on the Fluorescent Activity of N²-Indolyl-1,2,3-triazole

by You-Can Zhang, Rui Jin, Luo-Yuan Li, Zili Chen^* and Li-Min Fu^*

Department of Chemistry, Renmin University of China, Beijing 100872, China

Molecules 2017, 22(9), 1380; https://doi.org/10.3390/molecules22091380 - 5 Sep 2017

Cited by 18 | Viewed by 5415

Abstract

A new type of blue emitter, N²-Indolyl-1,2,3-triazoles (NITs), with the λ_max ranging from 420–480 nm and the Stokes shift from 89–143 nm, were synthesized through the coupling reaction of indoles with triazole derivatives. The influence of different substitution patterns on [...] Read more.

A new type of blue emitter, N²-Indolyl-1,2,3-triazoles (NITs), with the λ_max ranging from 420–480 nm and the Stokes shift from 89–143 nm, were synthesized through the coupling reaction of indoles with triazole derivatives. The influence of different substitution patterns on the optical properties (efficiency, excitation, and emission wavelengths) of the NITs was investigated. In addition, one palladium complex were synthesized by using NITs as the ligands, which, however, exhibited no fluorescent activity, but did show the enhanced co-planarity. Lastly, two bio-active molecule derivatives were explored for the potential use of these novel dyes in related chemical and biological applications. Full article

(This article belongs to the Section Photochemistry)

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14 pages, 4699 KiB

Open AccessArticle

Chemical Composition of Pinus roxburghii Bark Volatile Oil and Validation of Its Anti-Inflammatory Activity Using Molecular Modelling and Bleomycin-Induced Inflammation in Albino Mice

by Rola M. Labib^1,2,*, Fadia S. Youssef¹, Mohamed L. Ashour¹

, Mohamed M. Abdel-Daim³

and Samir A. Ross^2,4

¹ Department of Pharmacognosy, Faculty of Pharmacy, Ain-Shams University, Cairo 11566, Egypt

² National Center for Natural Products Research, University of Mississippi, University, MS 38677, USA

³ Department of Pharmacology, Faculty of Veterinary Medicine, Suez Canal University, Ismailia 41522, Egypt

⁴ Department of BioMolecular Sciences, School of Pharmacy, University of Mississippi, University, MS 38677, USA

Molecules 2017, 22(9), 1384; https://doi.org/10.3390/molecules22091384 - 29 Aug 2017

Cited by 57 | Viewed by 8328

Abstract

The chemical composition of Pinus roxburghii bark essential oil (PRO) was qualitatively and quantitatively determined using GC/FID and GC/MS. The anti-inflammatory activity was assessed in vitro by evaluating the binding percentages on the cannabinoids and opioids receptors. Bleomycin (BLM)-induced pulmonary inflammation in albino [...] Read more.

The chemical composition of Pinus roxburghii bark essential oil (PRO) was qualitatively and quantitatively determined using GC/FID and GC/MS. The anti-inflammatory activity was assessed in vitro by evaluating the binding percentages on the cannabinoids and opioids receptors. Bleomycin (BLM)-induced pulmonary inflammation in albino mice was adopted to assess PRO anti-inflammatory efficacy in vivo. In silico molecular modelling of its major components was performed on human glucocorticoids receptor (GR). Seventy-five components were identified in which longifolene (33.13%) and palmitic acid (9.34%) constituted the predominant components. No binding was observed on cannabinoid receptor type 1 (CB1), whereas mild binding was observed on cannabinoid receptor type 2 (CB2), delta, kappa, and mu receptors accounting for 2.9%, 6.9%, 10.9% and 22% binding. A significant in vivo activity was evidenced by reduction of the elevated malondialdehyde (MDA), nitric oxide (NO), myeloperoxidase (MPO), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) levels by 55.56%, 55.66%, 64.64%, 58.85% and 77.78% with concomitant elevation of superoxide dismutase (SOD) and catalase (CAT) activities comparable to BLM-treated group at 100 mg/kg body weight. In silico studies showed that palmitic acid exerted the fittest binding. PRO could serve as a potent anti-inflammatory natural candidate that should be supported by further clinical trials. Full article

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

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9 pages, 1487 KiB

Open AccessArticle

One-Pot Green Regioselesctive Synthesis of γ-Lactones from Epoxides and Ketene Silyl Acetals Using 1,3-Dimethylimidazolium Fluoride as a Recoverable Metal-Free Catalyst

by Mosadegh Keshavarz¹, Amanollah Zarei Ahmady^2,3,*

, Azar Mostoufi³ and Neda Mohtasham⁴

¹ Department of Gas and Petroleum, Yasouj University, Gachsaran 75918-74831, Iran

² Marine Pharmaceutical Science Research Center, Ahvaz JundiShapur University of Medical Sciences, Ahvaz 14536-33143, Iran

³ Department of Medicinal Chemistry, Ahvaz Jundishapur University of Medical Sciences, Ahvaz 14536-33143, Iran

⁴ Pediatric Division, Abuzar Children’s Medical Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz 14536-33143, Iran

Molecules 2017, 22(9), 1385; https://doi.org/10.3390/molecules22091385 - 28 Aug 2017

Cited by 13 | Viewed by 4793

Abstract

In a straightforward and fast protocol, a mixture of 1,3-dimethylimidazolium fluoride ([DMIM]F) and 1-butylimidazolium tetrafluoroborate ([Hbim]BF₄) efficiently catalyzed the reaction of epoxides with ketene silyl acetals (KSA) to give various γ-lactones under metal-free conditions. Diverse kinds of the desired γ-lactones were [...] Read more.

In a straightforward and fast protocol, a mixture of 1,3-dimethylimidazolium fluoride ([DMIM]F) and 1-butylimidazolium tetrafluoroborate ([Hbim]BF₄) efficiently catalyzed the reaction of epoxides with ketene silyl acetals (KSA) to give various γ-lactones under metal-free conditions. Diverse kinds of the desired γ-lactones were directly prepared with high regioselectivities and yields in a simple one-pot procedure using [DMIM]F as Si–O bond activator and [Hbim]BF₄ as solvent and acidic ionic liquid catalyst. The ionic liquid mixture was recovered and reused three times and no loss in its activity was observed. Full article

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13 pages, 1327 KiB

Open AccessFeature PaperArticle

Determination of Coenzyme A and Acetyl-Coenzyme A in Biological Samples Using HPLC with UV Detection

by Yevgeniya I. Shurubor^1,3,*, Marilena D’Aurelio¹, Joanne Clark-Matott², Elena P. Isakova³, Yulia I. Deryabina³, M. Flint Beal¹, Arthur J. L. Cooper^4,* and Boris F. Krasnikov^3,4

¹ Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY 10065, USA

² Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA

³ Bach Institute of Biochemistry, Research Center of Biotechnology of the Russian Academy of Sciences, Moscow 119071, Russia

⁴ Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, NY 10595, USA

Molecules 2017, 22(9), 1388; https://doi.org/10.3390/molecules22091388 - 23 Aug 2017

Cited by 56 | Viewed by 11304

Abstract

Coenzyme A (CoA) and acetyl-coenzyme A (acetyl-CoA) play essential roles in cell energy metabolism. Dysregulation of the biosynthesis and functioning of both compounds may contribute to various pathological conditions. We describe here a simple and sensitive HPLC-UV based method for simultaneous determination of [...] Read more.

Coenzyme A (CoA) and acetyl-coenzyme A (acetyl-CoA) play essential roles in cell energy metabolism. Dysregulation of the biosynthesis and functioning of both compounds may contribute to various pathological conditions. We describe here a simple and sensitive HPLC-UV based method for simultaneous determination of CoA and acetyl-CoA in a variety of biological samples, including cells in culture, mouse cortex, and rat plasma, liver, kidney, and brain tissues. The limits of detection for CoA and acetyl-CoA are >10-fold lower than those obtained by previously described HPLC procedures, with coefficients of variation <1% for standard solutions, and 1–3% for deproteinized biological samples. Recovery is 95–97% for liver extracts spiked with Co-A and acetyl-CoA. Many factors may influence the tissue concentrations of CoA and acetyl-CoA (e.g., age, fed, or fasted state). Nevertheless, the values obtained by the present HPLC method for the concentration of CoA and acetyl-CoA in selected rodent tissues are in reasonable agreement with literature values. The concentrations of CoA and acetyl-CoA were found to be very low in rat plasma, but easily measurable by the present HPLC method. The method should be useful for studying cellular energy metabolism under normal and pathological conditions, and during targeted drug therapy treatment. Full article

(This article belongs to the Section Metabolites)

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16 pages, 8033 KiB

Open AccessArticle

Spasmolytic Mechanism of Aqueous Licorice Extract on Oxytocin-Induced Uterine Contraction through Inhibiting the Phosphorylation of Heat Shock Protein 27

by Lu Yang^1,2,†, Cheng-Zhi Chai^1,†, Yan Yan³, Ying-Dan Duan¹, Astrid Henz², Bo-Li Zhang^4,*, Anders Backlund^2,*

and Bo-Yang Yu^1,*

¹ Department of Complex Prescription of TCM, Jiangsu Provincial Key Laboratory for TCM Evaluation and Translational Research, China Pharmaceutical University, 639 Longmian Road, Nanjing 211198, China

² Divsion of Pharmacognosy, Department of Medicinal Chemistry, Uppsala University, BMC box 574, S-751 23 Uppsala, Sweden

³ Modern Research Center for Traditional Chinese Medicine, Shanxi University, No. 92, Wucheng Road, Taiyuan 030006, China

⁴ Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China

^† These two authors equally contributed to the current work.

Molecules 2017, 22(9), 1392; https://doi.org/10.3390/molecules22091392 - 29 Aug 2017

Cited by 13 | Viewed by 8053

Abstract

Licorice derived from the roots and rhizomes of Glycyrrhiza uralensis Fisch. (Fabaceae), is one of the most widely-used traditional herbal medicines in China. It has been reported to possess significant analgesic activity for treating spastic pain. The aim of this study is [...] Read more.

Licorice derived from the roots and rhizomes of Glycyrrhiza uralensis Fisch. (Fabaceae), is one of the most widely-used traditional herbal medicines in China. It has been reported to possess significant analgesic activity for treating spastic pain. The aim of this study is to investigate the spasmolytic molecular mechanism of licorice on oxytocin-induced uterine contractions and predict the relevant bioactive constituents in the aqueous extract. The aqueous extraction from licorice inhibited the amplitude and frequency of uterine contraction in a concentration-dependent manner. A morphological examination showed that myometrial smooth muscle cells of oxytocin-stimulated group were oval-shaped and arranged irregularly, while those with a single centrally located nucleus of control and licorice-treated groups were fusiform and arranged orderly. The percentage of phosphorylation of HSP27 at Ser-15 residue increased up to 50.33% at 60 min after oxytocin stimulation. Furthermore, this increase was significantly suppressed by licorice treatment at the concentration of 0.2 and 0.4 mg/mL. Colocalization between HSP27 and α-SMA was observed in the myometrial tissues, especially along the actin bundles in the oxytocin-stimulated group. On the contrary, the colocalization was no longer shown after treatment with licorice. Additionally, employing ChemGPS-NP provided support for a preliminary assignment of liquiritigenin and isoliquiritigenin as protein kinase C (PKC) inhibitors in addition to liquiritigenin, isoliquiritigenin, liquiritin and isoliquiritin as MAPK-activated protein kinase 2 (MK2) inhibitors. These assigned compounds were docked with corresponding crystal structures of respective proteins with negative and low binding energy, which indicated a high affinity and tight binding capacity for the active site of the kinases. These results suggest that licorice exerts its spasmolytic effect through inhibiting the phosphorylation of HSP27 to alter the interaction between HSP27 and actin. Furthermore, our results provide support for the prediction that potential bioactive constituents from aqueous licorice extract inhibit the relevant up-stream kinases that phosphorylate HSP27. Full article

(This article belongs to the Section Natural Products Chemistry)

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20 pages, 4665 KiB

Open AccessArticle

High Boron-loaded DNA-Oligomers as Potential Boron Neutron Capture Therapy and Antisense Oligonucleotide Dual-Action Anticancer Agents

by Damian Kaniowski¹, Katarzyna Ebenryter-Olbińska¹

, Milena Sobczak¹, Błażej Wojtczak^2,†

, Sławomir Janczak², Zbigniew J. Leśnikowski^2,* and Barbara Nawrot^1,*

¹ Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences, Department of Bioorganic Chemistry, Sienkiewicza 112, 90-363 Lodz, Poland

² Institute of Medical Biology of the Polish Academy of Sciences, Laboratory of Molecular Virology and Biological Chemistry, 106 Lodowa St., 92-232 Lodz, Poland

^† Current address: Centre of New Technologies, University of Warsaw, S. Banacha 2c, 02-097 Warsaw, Poland.

Molecules 2017, 22(9), 1393; https://doi.org/10.3390/molecules22091393 - 23 Aug 2017

Cited by 29 | Viewed by 7686

Abstract

Boron cluster-modified therapeutic nucleic acids with improved properties are of interest in gene therapy and in cancer boron neutron capture therapy (BNCT). High metallacarborane-loaded antisense oligonucleotides (ASOs) targeting epidermal growth factor receptor (EGFR) were synthesized through post-synthetic Cu (I)-assisted “click” conjugation of alkyne-modified [...] Read more.

Boron cluster-modified therapeutic nucleic acids with improved properties are of interest in gene therapy and in cancer boron neutron capture therapy (BNCT). High metallacarborane-loaded antisense oligonucleotides (ASOs) targeting epidermal growth factor receptor (EGFR) were synthesized through post-synthetic Cu (I)-assisted “click” conjugation of alkyne-modified DNA-oligonucleotides with a boron cluster alkyl azide component. The obtained oligomers exhibited increased lipophilicity compared to their non-modified precursors, while their binding affinity to complementary DNA and RNA strands was slightly decreased. Multiple metallacarborane residues present in the oligonucleotide chain, each containing 18 B-H groups, enabled the use of IR spectroscopy as a convenient analytical method for these oligomers based on the diagnostic B-H signal at 2400–2650 cm⁻¹. The silencing activity of boron cluster-modified ASOs used at higher concentrations was similar to that of unmodified oligonucleotides. The screened ASOs, when used in low concentrations (up to 50 μM), exhibited pro-oxidative properties by inducing ROS production and an increase in mitochondrial activities in HeLa cells. In contrast, when used at higher concentrations, the ASOs exhibited anti-oxidative properties by lowering ROS species levels. In the HeLa cells (tested in the MTT assay) treated (without lipofectamine) or transfected with the screened compounds, the mitochondrial activity remained equal to the control level or only slightly changed (±30%). These findings may be useful in the design of dual-action boron cluster-modified therapeutic nucleic acids with combined antisense and anti-oxidant properties. Full article

(This article belongs to the Special Issue Synthesis and Applications of Oligonucleotide Conjugates)

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15 pages, 3175 KiB

Open AccessArticle

Development and Validation of HPLC-DAD and UHPLC-DAD Methods for the Simultaneous Determination of Guanylhydrazone Derivatives Employing a Factorial Design

by Wanessa Azevedo de Brito¹, Monique Gomes Dantas¹, Fernando Henrique Andrade Nogueira¹, Edeildo Ferreira da Silva-Júnior², João Xavier de Araújo-Júnior², Thiago Mendonça de Aquino², Êurica Adélia Nogueira Ribeiro², Lilian Grace Da Silva Solon³, Cícero Flávio Soares Aragão¹

and Ana Paula Barreto Gomes^1,*

¹ Drug Quality Control Laboratory (LCQMed), Pharmaceutical Sciences Department, Federal University of Rio Grande do Norte–UFRN, Av. General Cordeiro de Faria s/n, Natal RN 59012-570, Brazil

² Laboratory of Medicinal Chemistry, Nursing and Pharmacy School, Federal University of Alagoas, ESENFAR, Av. Lourival de Mello Motta s/n, Maceió AL 57072-970, Brazil

³ Pharmaceutical Sciences Department, Federal University of Amapá–UNIFAP, Rod Juscelino Kubitschek, Km-02, Macapá AP 68903-419, Brazil

Molecules 2017, 22(9), 1394; https://doi.org/10.3390/molecules22091394 - 30 Aug 2017

Cited by 9 | Viewed by 6228

Abstract

Guanylhydrazones are molecules with great pharmacological potential in various therapeutic areas, including antitumoral activity. Factorial design is an excellent tool in the optimization of a chromatographic method, because it is possible quickly change factors such as temperature, mobile phase composition, mobile phase pH, [...] Read more.

Guanylhydrazones are molecules with great pharmacological potential in various therapeutic areas, including antitumoral activity. Factorial design is an excellent tool in the optimization of a chromatographic method, because it is possible quickly change factors such as temperature, mobile phase composition, mobile phase pH, column length, among others to establish the optimal conditions of analysis. The aim of the present work was to develop and validate a HPLC and UHPLC methods for the simultaneous determination of guanylhydrazones with anticancer activity employing experimental design. Precise, exact, linear and robust HPLC and UHPLC methods were developed and validated for the simultaneous quantification of the guanylhydrazones LQM10, LQM14, and LQM17. The UHPLC method was more economic, with a four times less solvent consumption, and 20 times less injection volume, what allowed better column performance. Comparing the empirical approach employed in the HPLC method development to the DoE approach employed in the UHPLC method development, we can conclude that the factorial design made the method development faster, more practical and rational. This resulted in methods that can be employed in the analysis, evaluation and quality control of these new synthetic guanylhydrazones. Full article

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15 pages, 775 KiB

Open AccessFeature PaperArticle

Chemical and Antimicrobial Analyses of Sideritis romana L. subsp. purpurea (Tal. ex Benth.) Heywood, an Endemic of the Western Balkan

by Vanja Tadić^1,†, Alessandra Oliva^2,†

, Mijat Božović^3,4,*

, Alessia Cipolla², Massimiliano De Angelis², Vincenzo Vullo², Stefania Garzoli⁵

and Rino Ragno^4,5,*

¹ Institute of Medicinal Plants Research Dr Josif Pančić, Tadeuša Košćuška 1, 11000 Belgrade, Serbia

² Department of Public Health and Infectious Diseases, Sapienza University, P.le Aldo Moro 5, 00185 Rome, Italy

³ Faculty of Natural Sciences and Mathematics, University of Montenegro, Džordža Vašingtona bb, 81000 Podgorica, Montenegro

⁴ Rome Center for Molecular Design, Sapienza University, P.le Aldo Moro 5, 00185 Rome, Italy

⁵ Department of Drug Chemistry and Technology, Sapienza University, P.le Aldo Moro 5, 00185 Rome, Italy

^† These authors contributed equally to this work.

Molecules 2017, 22(9), 1395; https://doi.org/10.3390/molecules22091395 - 23 Aug 2017

Cited by 24 | Viewed by 8095

Abstract

A comprehensive study on essential oil and different solvent extracts of Sideritis romana L. subsp. purpurea (Tal. ex Benth.) Heywood (Lamiaceae) from Montenegro is reported. The gas chromatography-mass spectrometry analysis of the essential oil revealed a total of 43 components with bicyclogermacrene (23.8%), [...] Read more.

A comprehensive study on essential oil and different solvent extracts of Sideritis romana L. subsp. purpurea (Tal. ex Benth.) Heywood (Lamiaceae) from Montenegro is reported. The gas chromatography-mass spectrometry analysis of the essential oil revealed a total of 43 components with bicyclogermacrene (23.8%), germacrene D (8%), (E)-caryophyllene (7.9%) and spathulenol (5.5%) as the major ones. Sesquiterpenoid group was found to be the most dominant one (64.8%), with 19.9% of the oxygenated forms. In the crude methanol extract of the investigated plant, obtained by Sohhlet exraction, the total phenol content was 14.7 ± 0.4 mg of GA/g, the total flavonoids were 0.29 ± 0.03% expressed as hyperoside percentage, whereas the total tannins content was 0.22 ± 0.04% expressed as pyrogallol percentage. For the antimicrobial activity determination, the following microorganisms have been used: methicillin-susceptible Staphylococcus aureus (MSSA (American Type Culture Collection (ATCC) 29213)) and methicillin-resistant S. aureus (MRSA (clinical strain)), Escherichia coli (ATCC 25922), carbapenem-susceptible Klebsiella pneumoniae (clinical strain), carbapenem-resistant K. pneumoniae (clinical strain) and Candida albicans (ATCC 14053). The essential oil showed high potency against MSSA and MRSA, both at high (~5 × 10⁵ CFU/mL) and low (~5 × 10³ CFU/mL) inoculum. With respect to MSSA, the minimal inhibitory concentration (MIC) value was 0.307 mg/mL, with bactericidal activity obtained at 0.615 mg/mL, while, in the case of MRSA, the MIC and minimal bactericidal concentration (MBC) values were 0.076 and 0.153 mg/mL, respectively. Regarding anti-Candida albicans activity, the MIC value was 2.46 mg/mL without reaching fungicidal activity. In addition to the observed essential oil efficacy, different solvent extracts were analyzed for their antimicrobial activity. Similarly to the essential oil, thehighest efficacy was observed against both MSSA and MRSA strains, at high and low inoculums, in the case of the 1,2-dichloroethane and methanol extracts. A potent fungicidal activity has been also found for the n-hexane and 1,2-dichloroethane extracts. It can be concluded that Sideritis romana L. subsp. purpurea (Tal. ex Benth.) Heywood provides a wide range of application in different fields such as phytochemistry, pharmacology, toxicology or pharmacognosy. Full article

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

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18 pages, 3164 KiB

Open AccessArticle

Isolation, Characterization and Bioactivities of an Extracellular Polysaccharide Produced from Streptomyces sp. MOE6

by Marwa O. Elnahas^1,2,3, Magdy A. Amin², Mohamed M. D. Hussein³, Vinit C. Shanbhag¹, Amal E. Ali² and Judy D. Wall^1,*

¹ Department of Biochemistry, University of Missouri, Columbia, MO 65211, USA

² Department of Microbiology and Immunology, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt

³ Department of Chemistry of Natural and Microbial Products, National Research Center, Cairo 12622, Egypt

Molecules 2017, 22(9), 1396; https://doi.org/10.3390/molecules22091396 - 24 Aug 2017

Cited by 43 | Viewed by 7425

Abstract

A Streptomyces strain was isolated from soil and the sequence of 1471 nucleotides of its 16S rDNA showed 99% identity to Streptomyces sp. HV10. This newly isolated Streptomyces strain produced an extracellular polysaccharide (EPS) composed mainly of glucose and mannose in a ratio [...] Read more.

A Streptomyces strain was isolated from soil and the sequence of 1471 nucleotides of its 16S rDNA showed 99% identity to Streptomyces sp. HV10. This newly isolated Streptomyces strain produced an extracellular polysaccharide (EPS) composed mainly of glucose and mannose in a ratio of 1:4.1, as was characterized by Fourier transform infrared spectroscopy (FTIR), HPLC and ¹H-NMR. The antioxidant activities of the partially purified MOE6-EPS were determined by measuring the hydroxyl free radical scavenging activity and the scavenging of 2,2-diphenyl-2-picryl-hydrazyl (DPPH) radicals. In addition, the partially purified MOE6-EPS showed high ferrous ion (Fe²⁺) chelation activity which is another antioxidant activity. Interestingly, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays that were colorimetric assays for NAD(P)H-dependent cellular oxidoreductases and a proxy of the number of viable cells, showed that the partially purified MOE6-EPS inhibited the proliferation of the human breast cancer cells (MDA-MB-231). The scratch wound assay showed that MOE6-EPS reduced the migration of mouse breast cancer cells (4T1). This study reports the production of EPS from Streptomyces species with promising antioxidant, metal chelating and mammalian cell inhibitory activities. Full article

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

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15 pages, 2629 KiB

Open AccessFeature PaperReview

Looking Back, Looking Forward at Halogen Bonding in Drug Discovery

by Lois Mendez¹, Gabriela Henriquez², Suman Sirimulla³ and Mahesh Narayan^1,*

¹ Department of Chemistry, The University of Texas at El Paso, El Paso, TX 79968, USA

² Environmental Science and Engineering Program, The University of Texas at El Paso, El Paso, TX 79968, USA

³ School of Pharmacy, The University of Texas at El Paso, El Paso, TX 79968, USA

Molecules 2017, 22(9), 1397; https://doi.org/10.3390/molecules22091397 - 24 Aug 2017

Cited by 146 | Viewed by 13971

Abstract

Halogen bonding has emerged at the forefront of advances in improving ligand: receptor interactions. In particular the newfound ability of this extant non-covalent-bonding phenomena has revolutionized computational approaches to drug discovery while simultaneously reenergizing synthetic approaches to the field. Here we survey, via [...] Read more.

Halogen bonding has emerged at the forefront of advances in improving ligand: receptor interactions. In particular the newfound ability of this extant non-covalent-bonding phenomena has revolutionized computational approaches to drug discovery while simultaneously reenergizing synthetic approaches to the field. Here we survey, via examples of classical applications involving halogen atoms in pharmaceutical compounds and their biological hosts, the unique advantages that halogen atoms offer as both Lewis acids and Lewis bases. Full article

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

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14 pages, 3028 KiB

Open AccessArticle

Acceptor Side-Chain Effects on the Excited State Dynamics of Two-Dimensional-Like Conjugated Copolymers in Solution

by Ming-Ming Huo^1,*, Rong Hu², Wei Yan¹, Yi-Tong Wang^1,3, Kuan W. A. Chee^1,3, Yong Wang¹ and Jian-Ping Zhang⁴

¹ Qingdao Research Center for Advanced Photonic Technologies, Laser Research Institute, Shandong Academy of Sciences, Qingdao 266100, China

² Research Institute for New Materials Technology, Chongqing University of Arts and Sciences, Chongqing 402160, China

³ Department of Electrical and Electronic Engineering, Faculty of Science and Engineering, University of Nottingham Ningbo China, Ningbo 315100, China

⁴ Department of Chemistry, Renmin University of China, Beijing 100872, China

Molecules 2017, 22(9), 1398; https://doi.org/10.3390/molecules22091398 - 25 Aug 2017

Viewed by 6111

Abstract

Excited state dynamics of two-dimensional-like conjugated copolymers PFDCN and PFSDCN based on alternating fluorene and triphenylamine main chains and malononitrile pendant acceptor groups with thiophene as π-bridge, have been investigated by using transient absorption spectroscopy. There is an additional conjugated –C=C– bond in [...] Read more.

Excited state dynamics of two-dimensional-like conjugated copolymers PFDCN and PFSDCN based on alternating fluorene and triphenylamine main chains and malononitrile pendant acceptor groups with thiophene as π-bridge, have been investigated by using transient absorption spectroscopy. There is an additional conjugated –C=C– bond in PFDCN, which distinguishes it from PFSDCN. The lowest energy absorption band of each copolymer absorption spectrum is attributed to the π−π* transition with intramolecular charge-transfer, which has a lower fluorescence contribution than those of higher energy absorption bands. The optical excitation of either PFDCN or PFSDCN solution generates polaron pairs that then self-localize and evolve to a bound singlet exciton within a few picoseconds. Due to the additional conjugated –C=C– bond in the acceptor side-chain, PFDCN has a stronger intramolecular charge-transfer characteristic compared with PFSDCN, therefore exhibiting a longer self-localization time (7 ps vs. 3 ps for PFSDCN) and a shorter fluorescence lifetime (1.48 ns vs. 1.60 ns for PFSDCN). Full article

(This article belongs to the Special Issue Photoresponsive Polymers)

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21 pages, 2692 KiB

Open AccessReview

Solution NMR Spectroscopy in Target-Based Drug Discovery

by Yan Li

and Congbao Kang^*

Experimental Therapeutics Centre, Agency for Science, Technology and Research (A*STAR), 31 Biopolis Way, Nanos, #03-01, Singapore 138669, Singapore

Molecules 2017, 22(9), 1399; https://doi.org/10.3390/molecules22091399 - 23 Aug 2017

Cited by 34 | Viewed by 10893

Abstract

Solution NMR spectroscopy is a powerful tool to study protein structures and dynamics under physiological conditions. This technique is particularly useful in target-based drug discovery projects as it provides protein-ligand binding information in solution. Accumulated studies have shown that NMR will play more [...] Read more.

Solution NMR spectroscopy is a powerful tool to study protein structures and dynamics under physiological conditions. This technique is particularly useful in target-based drug discovery projects as it provides protein-ligand binding information in solution. Accumulated studies have shown that NMR will play more and more important roles in multiple steps of the drug discovery process. In a fragment-based drug discovery process, ligand-observed and protein-observed NMR spectroscopy can be applied to screen fragments with low binding affinities. The screened fragments can be further optimized into drug-like molecules. In combination with other biophysical techniques, NMR will guide structure-based drug discovery. In this review, we describe the possible roles of NMR spectroscopy in drug discovery. We also illustrate the challenges encountered in the drug discovery process. We include several examples demonstrating the roles of NMR in target-based drug discoveries such as hit identification, ranking ligand binding affinities, and mapping the ligand binding site. We also speculate the possible roles of NMR in target engagement based on recent processes in in-cell NMR spectroscopy. Full article

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

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10 pages, 2137 KiB

Open AccessArticle

Covalent Porphyrin Hybrids Linked with Dipyrrin, Bidipyrrin or Thiacorrole

by Renbao He, Huan Yue and Jiahui Kong^*

Zhejiang Yongtai Technology Co. Ltd., Taizhou 317016, China

Molecules 2017, 22(9), 1400; https://doi.org/10.3390/molecules22091400 - 23 Aug 2017

Cited by 4 | Viewed by 5630

Abstract

Novel meso-meso directly linked porphyrin hybrids were successfully targeted and synthesized, with porphyrin units linked with dipyrrin, bidipyrrin or thiacorrole, expanding the ranges of dipyrrin derivatives and showing diverse metal coordinations and further influencing the chemical shift of pyrrole units. The porphyrinyl dipyrrin [...] Read more.

Novel meso-meso directly linked porphyrin hybrids were successfully targeted and synthesized, with porphyrin units linked with dipyrrin, bidipyrrin or thiacorrole, expanding the ranges of dipyrrin derivatives and showing diverse metal coordinations and further influencing the chemical shift of pyrrole units. The porphyrinyl dipyrrin nickel complex 3 was successfully obtained in a high yield by the oxidation of porphyrinyl dipyrromethane 2 and subsequent coordination. Further oxidative coupling reactions of 3 afforded por-bidipyrrin-por hybrid 4. Interestingly, an unexpected methoxy por-bidipyrrin-por hybrid 6 was generated by treating 4 with FeCl₃ in CH₂Cl₂/MeOH and subsequent coordination. In addition to open chain hybrids, an aromatic scaffold hybrid por-thiacorrole-por 8 was synthesized by treating porphyrinyl dibromo-dipyrrin nickel complex 7 with Na₂S·9H₂O. A series of porphyrin hybrids offers a new approach for π-conjugated molecules. Full article

(This article belongs to the Collection Heterocyclic Compounds)

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21 pages, 1316 KiB

Open AccessReview

Dendrimers as Nanocarriers for Nucleic Acid and Drug Delivery in Cancer Therapy

by Livia Palmerston Mendes^1,2, Jiayi Pan¹

and Vladimir P. Torchilin^1,*

¹ Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University, Boston, MA 02115, USA

² CAPES Foundation, Ministry of Education of Brazil, Brasilia 70040-020, Brazil

Molecules 2017, 22(9), 1401; https://doi.org/10.3390/molecules22091401 - 23 Aug 2017

Cited by 569 | Viewed by 18371

Abstract

Dendrimers are highly branched polymers with easily modifiable surfaces. This makes them promising structures for functionalization and also for conjugation with drugs and DNA/RNA. Their architecture, which can be controlled by different synthesis processes, allows the control of characteristics such as shape, size, [...] Read more.

Dendrimers are highly branched polymers with easily modifiable surfaces. This makes them promising structures for functionalization and also for conjugation with drugs and DNA/RNA. Their architecture, which can be controlled by different synthesis processes, allows the control of characteristics such as shape, size, charge, and solubility. Dendrimers have the ability to increase the solubility and bioavailability of hydrophobic drugs. The drugs can be entrapped in the intramolecular cavity of the dendrimers or conjugated to their functional groups at their surface. Nucleic acids usually form complexes with the positively charged surface of most cationic dendrimers and this approach has been extensively employed. The presence of functional groups in the dendrimer’s exterior also permits the addition of other moieties that can actively target certain diseases and improve delivery, for instance, with folate and antibodies, now widely used as tumor targeting strategies. Dendrimers have been investigated extensively in the medical field, and cancer treatment is one of the greatest areas where they have been most used. This review will consider the main types of dendrimer currently being explored and how they can be utilized as drug and gene carriers and functionalized to improve the delivery of cancer therapy. Full article

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

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12 pages, 1195 KiB

Open AccessArticle

Determination and Visualization of Peimine and Peiminine Content in Fritillaria thunbergii Bulbi Treated by Sulfur Fumigation Using Hyperspectral Imaging with Chemometrics

by Juan He¹, Yong He^2,*

and And Chu Zhang^2,*

¹ Zhejiang Academy of Traditional Chinese Medicine, Key Laboratory of Research and Development of Chinese Medicine of Zhejiang Province, Hangzhou 310007, China

² College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou 310058, China

Molecules 2017, 22(9), 1402; https://doi.org/10.3390/molecules22091402 - 23 Aug 2017

Cited by 26 | Viewed by 4418

Abstract

Rapid, non-destructive, and accurate quantitative determination of the effective components in traditional Chinese medicine (TCM) is required by industries, planters, and regulators. In this study, near-infrared hyperspectral imaging was applied for determining the peimine and peiminine content in Fritillaria thunbergii bulbi under sulfur [...] Read more.

Rapid, non-destructive, and accurate quantitative determination of the effective components in traditional Chinese medicine (TCM) is required by industries, planters, and regulators. In this study, near-infrared hyperspectral imaging was applied for determining the peimine and peiminine content in Fritillaria thunbergii bulbi under sulfur fumigation. Spectral data were extracted from the hyperspectral images. High-performance liquid chromatography (HPLC) was conducted to determine the reference peimine and peiminine content. The successive projection algorithm (SPA), weighted regression coefficient (Bw), competitive adaptive reweighted sampling (CARS), and random frog (RF) were used to select optimal wavelengths, while the partial least squares (PLS), least-square support vector machine (LS–SVM) and extreme learning machine (ELM) were used to build regression models. Regression models using the full spectra and optimal wavelengths obtained satisfactory results with the correlation coefficient of calibration (r_c), cross-validation (r_cv) and prediction (r_p) of most models being over 0.8. Prediction maps of peimine and peiminine content in Fritillaria thunbergii bulbi were formed by applying regression models to the hyperspectral images. The overall results indicated that hyperspectral imaging combined with regression models and optimal wavelength selection methods were effective in determining peimine and peiminine content in Fritillaria thunbergii bulbi, which will help in the development of an online detection system for real-world quality control of Fritillaria thunbergii bulbi under sulfur fumigation. Full article

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14 pages, 1926 KiB

Open AccessArticle

Preclinical Assessment of a ⁶⁸Ga-DOTA-Functionalized Depsipeptide as a Radiodiagnostic Infection Imaging Agent

by Thomas Ebenhan¹

, Botshelo Brenda Mokaleng¹, Jacobus Daniel Venter², Hendrik Gert Kruger³

, Jan Rijn Zeevaart⁴ and Mike Sathekge^1,*

¹ University of Pretoria & Steve Biko Academic Hospital, Crn Malherbe and Steve Biko Rd, Pretoria 0001, South Africa

² South African Medical Research Council, 1 Southpansberg Road, Pretoria 0001, South Africa

³ School of Health Sciences, Catalysis and Peptide Research Unit, University of KwaZulu Natal, E-block 6th Floor, Westville Campus, University Rd, Westville, Durban 3630, South Africa

⁴ Department of Science and Technology, Preclinical Drug Development Platform, North West University, 11 Hoffman St, Potchefstroom 2520, South Africa

Molecules 2017, 22(9), 1403; https://doi.org/10.3390/molecules22091403 - 24 Aug 2017

Cited by 20 | Viewed by 7404

Abstract

The study assessed a radiolabeled depsipeptide conjugate (⁶⁸Ga-DOTA-TBIA101) for its potential as an imaging agent targeting infection or infection-associated inflammation. ⁶⁸Ga-labeled DOTA-TBIA101 imaging was performed in (NZR1) healthy rabbits; (NZR2) rabbits bearing muscular sterile inflammation and Staphylococcus aureus (SA) infection; [...] Read more.

The study assessed a radiolabeled depsipeptide conjugate (⁶⁸Ga-DOTA-TBIA101) for its potential as an imaging agent targeting infection or infection-associated inflammation. ⁶⁸Ga-labeled DOTA-TBIA101 imaging was performed in (NZR1) healthy rabbits; (NZR2) rabbits bearing muscular sterile inflammation and Staphylococcus aureus (SA) infection; and (NZR3) rabbits infected with Mycobacterium tuberculosis (MTB) combined with a subcutaneous scruff infection of SA in the same animal. All animals were imaged using a PET/CT scanner at 5 and 60 min post injection. Images showed elevated accumulation of ⁶⁸Ga-DOTA-TBIA101 in the sterile muscular inflammation site (T/NT ratio = 2.6 ± 0.37 (5 min) and 2.8 ± 2.3 (60 min)) and muscles infected with MTB (T/NT ratio = 2.6 ± 0.35 (5 min) and 2.8 ± 0.16 (60 min)). The findings suggest that ⁶⁸Ga-DOTA-TBIA101-PET/CT may detect MTB-associated inflammation, although more foundational studies need to be performed to rationalize the diagnostic value of this technique. Full article

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

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30 pages, 19384 KiB

Open AccessArticle

The Influence of Lead on Generation of Signalling Molecules and Accumulation of Flavonoids in Pea Seedlings in Response to Pea Aphid Infestation

by Agnieszka Woźniak¹, Kinga Drzewiecka², Jacek Kęsy³, Łukasz Marczak⁴, Dorota Narożna⁵, Marcin Grobela⁶, Rafał Motała⁶, Jan Bocianowski⁷ and Iwona Morkunas^1,*

¹ Department of Plant Physiology, Poznań University of Life Sciences, Wołyńska 35, 60-637 Poznań, Poland

² Department of Chemistry, Poznań University of Life Sciences, Wojska Polskiego 75, 60-625 Poznań, Poland

³ Chair of Plant Physiology and Biotechnology, Nicolaus Copernicus University, Gagarina 9, 87−100 Toruń, Poland

⁴ Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12/14, 61-704 Poznań, Poland

⁵ Department of Biochemistry and Biotechnology, Poznań University of Life Sciences, Dojazd 11, 60-632 Poznań, Poland

⁶ Department of Ecology and Environmental Protection, Laboratory of Environmental Analyses, the Institute of Plant Protection National Research Institute, Węgorka 20, 60−101 Poznań, Poland

⁷ Department of Mathematical and Statistical Methods, Poznań University of Life Sciences, Wojska Polskiego 28, 60-637 Poznań, Poland

Molecules 2017, 22(9), 1404; https://doi.org/10.3390/molecules22091404 - 24 Aug 2017

Cited by 37 | Viewed by 6727

Abstract

The aim of this study was to investigate the effect of an abiotic factor, i.e., lead at various concentrations (low causing a hormesis effect and causing high toxicity effects), on the generation of signalling molecules in pea (Pisum sativum L. cv. Cysterski) [...] Read more.

The aim of this study was to investigate the effect of an abiotic factor, i.e., lead at various concentrations (low causing a hormesis effect and causing high toxicity effects), on the generation of signalling molecules in pea (Pisum sativum L. cv. Cysterski) seedlings and then during infestation by the pea aphid (Acyrthosiphon pisum Harris). The second objective was to verify whether the presence of lead in pea seedling organs and induction of signalling pathways dependent on the concentration of this metal trigger defense responses to A. pisum. Therefore, the profile of flavonoids and expression levels of genes encoding enzymes of the flavonoid biosynthesis pathway (phenylalanine ammonialyase and chalcone synthase) were determined. A significant accumulation of total salicylic acid (TSA) and abscisic acid (ABA) was recorded in the roots and leaves of pea seedlings growing on lead-supplemented medium and next during infestation by aphids. Increased generation of these phytohormones strongly enhanced the biosynthesis of flavonoids, including a phytoalexin, pisatin. This research provides insights into the cross-talk between the abiotic (lead) and biotic factor (aphid infestation) on the level of the generation of signalling molecules and their role in the induction of flavonoid biosynthesis. Full article

(This article belongs to the Special Issue Structure, Chemical Analysis, Biosynthesis, Metabolism, Molecular Engineering and Biological Functions of Phytoalexins)

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10 pages, 1449 KiB

Open AccessArticle

Homoisoflavonoids and Chalcones Isolated from Haematoxylum campechianum L., with Spasmolytic Activity

by Armando Escobar-Ramos¹, Carlos Ernesto Lobato-García^1,*, Alejandro Zamilpa²

, Abraham Gómez-Rivera¹

, Jaime Tortoriello² and Manasés González-Cortazar^2,*

¹ Academics Division of Basic Sciences, University Juárez Autonomous of Tabasco, Highway Cunduacán-Jalpa Km. 0.5, Cunduacán Tabasco 86690, Mexico

² Southern Biomedical Research, Mexican Institute of Social Security, Argentina No. 1, Col. Centro, 62790 Xochitepec, Mexico

Molecules 2017, 22(9), 1405; https://doi.org/10.3390/molecules22091405 - 24 Aug 2017

Cited by 20 | Viewed by 6098

Abstract

Haematoxylum campechianum is a medicinal plant employed as an astringent to purify the blood and to treat stomach problems such as diarrhea and dysentery. A bio-guided chemical fractionation of the methanolic extract obtained from this plant allowed for the isolation of five compounds: [...] Read more.

Haematoxylum campechianum is a medicinal plant employed as an astringent to purify the blood and to treat stomach problems such as diarrhea and dysentery. A bio-guided chemical fractionation of the methanolic extract obtained from this plant allowed for the isolation of five compounds: two chalcones known as sappanchalcone (1); 3-deoxysappanchalcone (2); three homoisoflavonoids known as hematoxylol A (3); 4-O-methylhematoxylol (4); and, hematoxin (5). The spasmolytic activity was determined in an in vitro model (electrically induced contractions of guinea pig ileum), and allowed to demonstrate that the methanolic extract (EC₅₀ = 62.11 ± 3.23) fractions HcF7 (EC₅₀ = 61.75 ± 3.55) and HcF9 (EC₅₀ = 125.5 ± 10.65) and compounds 1 (EC₅₀ = 16.06 ± 2.15) and 2 (EC₅₀ = 25.37 ± 3.47) of Haematoxylum campechianum present significant relaxing activity as compared to papaverine (EC₅₀ = 20.08 ± 2.0) as a positive control. Full article

(This article belongs to the Collection Bioactive Compounds)

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17 pages, 1621 KiB

Open AccessReview

Phytochemistry, Pharmacology and Traditional Uses of Plants from the Genus Trachelospermum L.

by Zefeng Zhao^1,†, Xirui He^1,2,†, Yuhui Zhao¹, Ying Sun¹, Xufei Chen¹, Ye Cun¹, Linhong Huang^2,*, Yajun Bai^1,3 and Xiaohui Zheng^1,*

¹ Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Northwest University, 229 Taibai Road, Xi’an 710069, China

² Honghui Hospital, Xi’an Jiaotong University, Xi’an 710054, China

³ College of Chemistry and Materials Science, Northwest University, Xi’an 710069, China

^† These authors contributed equally to this paper and share co-first authorship.

Molecules 2017, 22(9), 1406; https://doi.org/10.3390/molecules22091406 - 24 Aug 2017

Cited by 18 | Viewed by 9202

Abstract

This paper is intended to review advances in the botanical, phytochemical, traditional uses and pharmacological studies of the genus Trachelospermum. Until now, 138 chemical constituents have been isolated and characterized from these plants, particularly from T. asiaticum and T. jasminoides. Among [...] Read more.

This paper is intended to review advances in the botanical, phytochemical, traditional uses and pharmacological studies of the genus Trachelospermum. Until now, 138 chemical constituents have been isolated and characterized from these plants, particularly from T. asiaticum and T. jasminoides. Among these compounds, lignans, triterpenoids, and flavonoids are the major bioactive constituents. Studies have shown that plants from the genus Trachelospermum exhibit an extensive range of pharmacological properties both in vivo and in vitro, including anti-inflammatory, analgesic, antitumor, antiviral and antibacterial activities. In Traditional Chinese Medicine (TCM) culture, drugs that include T. jasminoides stems have been used to cure rheumatism, gonarthritis, backache and pharyngitis, although there are few reports concerning the clinical use and toxicity of these plants. Further attention should be paid to gathering information about their toxicology data, quality-control measures, and the clinical value of the active compounds from genus Trachelospermum. Full article

(This article belongs to the Special Issue Herbal Remedies Meet Modern Day Medicine: Challenges and Opportunities)

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14 pages, 4494 KiB

Open AccessArticle

Biosynthesis of Silver Nanoparticles on Orthodontic Elastomeric Modules: Evaluation of Mechanical and Antibacterial Properties

by Alma E. Hernández-Gómora^1,2, Edith Lara-Carrillo^1,2,*

, Julio B. Robles-Navarro¹, Rogelio J. Scougall-Vilchis²

, Susana Hernández-López³, Carlo E. Medina-Solís⁴

and Raúl A. Morales-Luckie^5,*

¹ Facultad de Odontología, Universidad Autónoma del Estado de México, Jesús Carranza y Paseo Tollocan, 50120 Toluca, Estado de México, Mexico

² Centro de Investigación y Estudios Avanzados en Odontología, Universidad Autónoma del Estado de México, Jesús Carranza y Paseo Tollocan, 50130 Toluca, Estado de México, Mexico

³ Facultad de Química, Universidad Autónoma del Estado de México, Paseo Colón intersección Paseo Tollocan S/N, 50120 Toluca, Estado de México, Mexico

⁴ Área Académica de Odontología, Instituto de Ciencias de la Salud, Universidad Autónoma del Estado de Hidalgo, 42039 Pachuca, Hidalgo, Mexico

⁵ Centro Conjunto de Investigación en Química Sustentable UAEM-UNAM, Universidad Autónoma del Estado de México, Carretera Toluca-Atlacomulco Km 14.5, San Cayetano, 50200 Toluca, Estado de México, Mexico

Molecules 2017, 22(9), 1407; https://doi.org/10.3390/molecules22091407 - 25 Aug 2017

Cited by 63 | Viewed by 8297

Abstract

In the present study, silver nanoparticles (AgNPs) were synthesized in situ on orthodontic elastomeric modules (OEM) using silver nitrate salts as metal-ion precursors and extract of the plant Hetheroteca inuloides (H. inuloides) as bioreductant via a simple and eco-friendly method. The [...] Read more.

In the present study, silver nanoparticles (AgNPs) were synthesized in situ on orthodontic elastomeric modules (OEM) using silver nitrate salts as metal-ion precursors and extract of the plant Hetheroteca inuloides (H. inuloides) as bioreductant via a simple and eco-friendly method. The synthesized AgNPs were characterized by UV-visible spectroscopy; scanning electron microscopy-energy-dispersive spectroscopy (SEM-EDS) and transmission electron microscopy (TEM). The surface plasmon resonance peak found at 472 nm confirmed the formation of AgNPs. SEM and TEM images reveal that the particles are quasi-spherical. The EDS analysis of the AgNPs confirmed the presence of elemental silver. The antibacterial properties of OEM with AgNPs were evaluated against the clinical isolates Streptococcus mutans, Lactobacillus casei, Staphylococcus aureus and Escherichia coli using agar diffusion tests. The physical properties were evaluated by a universal testing machine. OEM with AgNPs had shown inhibition halos for all microorganisms in comparison with OEM control. Physical properties increased with respect to the control group. The results suggest the potential of the material to combat dental biofilm and in turn decrease the incidence of demineralization in dental enamel, ensuring their performance in patients with orthodontic treatment. Full article

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

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18 pages, 2210 KiB

Open AccessReview

Sigma Receptor (σR) Ligands with Antiproliferative and Anticancer Activity

by Markos-Orestis Georgiadis

, Olga Karoutzou

, Angeliki-Sofia Foscolos

and Ioannis Papanastasiou^*

School of Health Sciences, Department of Pharmacy, Division of Pharmaceutical Chemistry, National and Kapodistrian University of Athens, Panepistimioupoli-Zografou, 15784 Athens, Greece

Molecules 2017, 22(9), 1408; https://doi.org/10.3390/molecules22091408 - 25 Aug 2017

Cited by 44 | Viewed by 9373

Abstract

Sigma receptor (σR) ligands have proven to be useful as cancer diagnostics and anticancer therapeutics and their ligands have been developed as molecular probes in oncology. Moreover, various σR ligands generate cancer cell death in vitro and in vivo. These σR ligands have [...] Read more.

Sigma receptor (σR) ligands have proven to be useful as cancer diagnostics and anticancer therapeutics and their ligands have been developed as molecular probes in oncology. Moreover, various σR ligands generate cancer cell death in vitro and in vivo. These σR ligands have exhibited promising results against numerous human and rodent cancers and are investigated under preclinical and clinical study trials, indicating a new category of drugs in cancer therapy. 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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15 pages, 5530 KiB

Open AccessArticle

Purification, Preliminary Characterization and Hepatoprotective Effects of Polysaccharides from Dandelion Root

by Liangliang Cai, Dongwei Wan, Fanglian Yi and Libiao Luan^*

Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, China

Molecules 2017, 22(9), 1409; https://doi.org/10.3390/molecules22091409 - 25 Aug 2017

Cited by 64 | Viewed by 47880

Abstract

In this study, purification, preliminary characterization and hepatoprotective effects of water-soluble polysaccharides from dandelion root (DRP) were investigated. Two polysaccharides, DRP1 and DRP2, were isolated from DRP. The two polysaccharides were α-type polysaccharides and didn’t contain protein. DRP1, with a molecular weight of [...] Read more.

In this study, purification, preliminary characterization and hepatoprotective effects of water-soluble polysaccharides from dandelion root (DRP) were investigated. Two polysaccharides, DRP1 and DRP2, were isolated from DRP. The two polysaccharides were α-type polysaccharides and didn’t contain protein. DRP1, with a molecular weight of 5695 Da, was composed of glucose, galactose and arabinose, whereas DRP2, with molecular weight of 8882 Da, was composed of rhamnose, galacturonic acid, glucose, galactose and arabinose. The backbone of DRP1 was mainly composed of (1→6)-linked-α-d-Glc and (1→3,4)-linked-α-d-Glc. DRP2 was mainly composed of (1→)-linked-α-d-Ara and (1→)-linked-α-d-Glc. A proof-of-concept study was performed to assess the therapeutic potential of DRP1 and DRP2 in a mouse model that mimics acetaminophen (APAP) -induced liver injury (AILI) in humans. The present study shows DRP1 and DRP2 could protect the liver from APAP-induced hepatic injury by activating the Nrf2-Keap1 pathway. These conclusions demonstrate that the DRP1 and DRP2 might be suitable as functional foods and natural drugs in preventing APAP-induced liver injury. Full article

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

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13 pages, 2958 KiB

Open AccessArticle

Enantiomeric-Enriched Ferrocenes: Synthesis, Chiral Resolution, and Mathematic Evaluation of CD-chiral Selector Energies with Ferrocene-Conjugates

by Lubov V. Snegur^1,*, Yurii A. Borisov¹, Yuliya V. Kuzmenko¹, Vadim A. Davankov¹, Mikhail M. Ilyin¹, Mikhail M. Ilyin, Jr.¹, Dmitry E. Arhipov¹, Alexander A. Korlyukov^1,2

, Sergey S. Kiselev¹ and Alexander A. Simenel^1,3

¹ A.N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, 28 Vavilov St., 119991 Moscow, Russian

² N.I. Pirogov Russian National Research Medical University, 1 Ostrovityanov St., 117997 Moscow, Russian

³ Moscow Institute of Steel and Alloys National University of Science and Technology, 4 Leninskii Av., 119049 Moscow, Russian

Molecules 2017, 22(9), 1410; https://doi.org/10.3390/molecules22091410 - 25 Aug 2017

Cited by 8 | Viewed by 5766

Abstract

Enantiomeric-enriched ferrocene-modified pyrazoles were synthesized via the reaction of the ferrocene alcohol, (S)-FcCH(OH)CH₃ (Fc = ferrocenyl), with various pyrazoles in acidic conditions at room temperature within several minutes. X-ray structural data for racemic (R,S)-1N-(3,5-dimethyl [...] Read more.

Enantiomeric-enriched ferrocene-modified pyrazoles were synthesized via the reaction of the ferrocene alcohol, (S)-FcCH(OH)CH₃ (Fc = ferrocenyl), with various pyrazoles in acidic conditions at room temperature within several minutes. X-ray structural data for racemic (R,S)-1N-(3,5-dimethyl pyrazolyl)ethyl ferrocene (1) and its (S)-enantiomer (S)-1 were determined. A series of racemic pyrazolylalkyl ferrocenes was separated into enantiomers by analytical HPLC on β- and γ-cyclodextrins (CD) chiral stationary phases. The quantum chemical calculations of interaction energies of β-CD were carried out for both (R)- and (S)-enantiomers. A high correlation between experimental HPLC data and calculated interaction energies values was obtained. Full article

(This article belongs to the Special Issue Chirality in Health and Environment: Recent developments)

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14 pages, 1144 KiB

Open AccessReview

The Role of Kinase Modulators in Cellular Senescence for Use in Cancer Treatment

by Chang Sup Lee^†, Juhwa Baek^† and Sun-Young Han^*

¹ College of Pharmacy and Research Institute of Pharmaceutical Sciences, Gyeongsang National University, 501 Jinju-daero, Jinju, Gyeongnam 52828, Korea

^† These authors contributed equally to the work.

Molecules 2017, 22(9), 1411; https://doi.org/10.3390/molecules22091411 - 25 Aug 2017

Cited by 25 | Viewed by 8462

Abstract

Recently, more than 30 small molecules and eight monoclonal antibodies that modulate kinase signaling have been approved for the treatment of several pathological conditions, including cancer, idiopathic pulmonary fibrosis, and rheumatoid arthritis. Among them, kinase modulators have been a primary focus for use [...] Read more.

Recently, more than 30 small molecules and eight monoclonal antibodies that modulate kinase signaling have been approved for the treatment of several pathological conditions, including cancer, idiopathic pulmonary fibrosis, and rheumatoid arthritis. Among them, kinase modulators have been a primary focus for use in cancer treatment. Cellular senescence is believed to protect cells from tumorigenesis by irreversibly halting cell cycle progression and avoiding the growth of damaged cells and tissues. Senescence can also contribute to tumor suppression and be utilized as a mechanism by anti-cancer agents. Although the role of kinase modulators in cancer treatment and their effects on senescence in tumor development have been extensively studied, the relationship between kinase modulators for cancer treatment and senescence has not been fully discussed. In this review, we discuss the pro- and anti-tumorigenesis functions of senescence and summarize the key roles of kinase modulators in the regulation of senescence against tumors. Full article

(This article belongs to the Special Issue Kinase Inhibitors)

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14 pages, 4630 KiB

Open AccessArticle

Structure Identification and In Vitro Anticancer Activity of Lathyrol-3-phenylacetate-5,15-diacetate

by Jian-ye Zhang^1,*

, Wen-jing Huang¹, Hong-mei Sun², Yun Liu¹, Xiao-qin Zhao³, Si-li Tang¹, Ming-na Sun¹, Sheng Wang¹, Jia-jun Li¹, Ling-ling Zhang¹, Jun-hua Zhou¹, Qian-rong Pan¹ and Hu-biao Chen^4,*

¹ Key Laboratory of Molecular and Clinical Pharmacology, School of Pharmaceutical Sciences and the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou 511436, China

² Infinitus (China) Company Ltd., Jiangmen 529156, China

³ Pediatric Department, Guangdong Women and Children Hospital and Health Institute, Guangzhou 511400, China

⁴ School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China

Molecules 2017, 22(9), 1412; https://doi.org/10.3390/molecules22091412 - 25 Aug 2017

Cited by 15 | Viewed by 6484

Abstract

Natural products from the genus Euphorbia show attention-attracting activities, such as anticancer activity. In this article, classical isolation and structure identification were used in a study on Caper Euphorbia Seed. Subsequently, MTT and wound healing assays, flow cytometry, western blotting, Hoechst 33258 staining [...] Read more.

Natural products from the genus Euphorbia show attention-attracting activities, such as anticancer activity. In this article, classical isolation and structure identification were used in a study on Caper Euphorbia Seed. Subsequently, MTT and wound healing assays, flow cytometry, western blotting, Hoechst 33258 staining and fluorescence microscopy examination were applied to investigate the anticancer activity of the obtained compounds. In a result, lathyrol-3-phenyl- acetate-5,15-diacetate (deoxy Euphorbia factor L1, DEFL1) was isolated from Caper Euphorbia Seed. Moreover, the NMR signals were totally assigned. DEFL1 showed potent inhibition against lung cancer A549 cells, with an IC₅₀ value of 17.51 ± 0.85 μM. Furthermore, DEFL1 suppressed wound healing of A549 cells in a concentration-dependent manner. Mechanically, DEFL1 induced apoptosis, with involvement of an increase of reactive oxygen species (ROS), decrease of mitochondrial membrane potential (ΔΨm), release of cytochrome c, activity raise of caspase-9 and 3. Characteristic features of apoptosis were observed by fluorescence microscopy. In summary, DEFL1 inhibited growth and induced apoptosis in lung cancer A549 cells via a mitochondrial pathway. Full article

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

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8 pages, 1040 KiB

Open AccessShort Note

Dihydrochalcones and Diterpenoids from Pteris ensiformis and Their Bioactivities

by Yu-Sheng Shi^1,2,†, Yan Zhang^3,*,†, Wen-Zhong Hu^1,*, Xiu-Fu Zhang¹, Xin Fu⁴ and Xia Lv¹

¹ Key Laboratory of Biotechnology and Bioresources Utilization, Educational of Minister, College of Life Science, Dalian Nationalities University, Dalian 116600, 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 100050, China

³ Jiamusi College, Heilongjiang University of Chinese Medicine, Jiamusi 154007, China

⁴ Department of Pharmacognosy, Heilongjiang University of Chinese Medicine, Harbin 150040, China

^† These authors contributed equally to this work.

Molecules 2017, 22(9), 1413; https://doi.org/10.3390/molecules22091413 - 25 Aug 2017

Cited by 15 | Viewed by 4479

Abstract

Two new dihydrochalcone enantiomers (+)-1 and (−)-1, along with eight known compounds 3–10, were obtained from Pteris ensiformis. The planar structures were determined on the basis of extensive 1D and 2DNMR and HRESIMS. The resolution of [...] Read more.

Two new dihydrochalcone enantiomers (+)-1 and (−)-1, along with eight known compounds 3–10, were obtained from Pteris ensiformis. The planar structures were determined on the basis of extensive 1D and 2DNMR and HRESIMS. The resolution of (+)-1 and (−)-1 was achieved by chiral HPLC analysis. The absolute configurations of (+)-1 and (−)-1 were established by the bulkiness rule using Rh₂(O₂CCF₃)₄-induced circular dichroism (ICD) method. Compounds (+)-1, (−)-1, 8, 9 and 10 exhibited the inhibitory assay of NO production in mouse macrophages stimulated by LPS, with IC₅₀ values of 2.0, 2.5, 8.0, 9.5 and 5.6 μM, respectively. Otherwise, compound 10 showed moderate cytotoxic activity against HCT-116, HepG-2 and BGC-823 cell lines with IC₅₀ values of 3.0, 10.5 and 6.3 μM, respectively. Full article

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12 pages, 5778 KiB

Open AccessArticle

Interactions Controlling the Slow Dynamic Conformational Motions of Ubiquitin

by Soichiro Kitazawa¹, Maho Yagi-Utsumi^2,3, Koichi Kato^2,3 and Ryo Kitahara^1,*

¹ College of Pharmaceutical Sciences, Ritsumeikan University, Noji-higashi 1-1-1, Kusatsu 525-8577, Japan

² Okazaki Institute for Integrative Bioscience and Institute for Molecular Science, National Institutes of Natural Sciences, Myodaiji-cho, Aza-higashiyama 5-1, Okazaki 444-8787, Japan

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

Molecules 2017, 22(9), 1414; https://doi.org/10.3390/molecules22091414 - 28 Aug 2017

Cited by 4 | Viewed by 5012

Abstract

Rational mutation of proteins based on their structural and dynamic characteristics is a useful strategy for amplifying specific fluctuations in proteins. Here, we show the effects of mutation on the conformational fluctuations and thermodynamic stability of ubiquitin. In particular, we focus on the [...] Read more.

Rational mutation of proteins based on their structural and dynamic characteristics is a useful strategy for amplifying specific fluctuations in proteins. Here, we show the effects of mutation on the conformational fluctuations and thermodynamic stability of ubiquitin. In particular, we focus on the salt bridge between K11 and E34 and the hydrogen bond between I36 and Q41, which are predicted to control the fluctuation between the basic folded state, N₁, and the alternatively folded state, N₂, of the protein, using high-pressure NMR spectroscopy. The E34A mutation, which disrupts the salt bridge, did not alter picosecond–to–nanosecond, microsecond–to–millisecond dynamic motions, and stability of the protein, while the Q41N mutation, which destabilizes the hydrogen bond, specifically amplified the N₁–N₂ conformational fluctuation and decreased stability. Based on the observed thermodynamic stabilities of the various conformational states, we showed that in the Q41N mutant, the N₁ state is more significantly destabilized than the N₂ state, resulting in an increase in the relative population of N₂. Identifying the interactions controlling specific motions of a protein will facilitate molecular design to achieve functional dynamics beyond native state dynamics. Full article

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

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12 pages, 2528 KiB

Open AccessArticle

Bis(1-pyrenylmethyl)-2-benzyl-2-methyl-malonate as a Cu²⁺ Ion-Selective Fluoroionophore

by Takayo Moriuchi-Kawakami^1,*

, Youji Hisada¹, Akihisa Higashikado¹, Tsubasa Inoue¹, Keiichi Fujimori¹ and Toshiyuki Moriuchi²

¹ Department of Applied Chemistry, Faculty of Engineering, Osaka Institute of Technology, 5-16-1 Omiya, Asahi, Osaka 535-8585, Japan

² Department of Applied Chemistry, Graduate School of Engineering, Osaka University, 2-1 Yamada-oka, Suita, Osaka 565-0871, Japan

Molecules 2017, 22(9), 1415; https://doi.org/10.3390/molecules22091415 - 25 Aug 2017

Cited by 3 | Viewed by 5631

Abstract

A new malonate possessing two pyrene moieties was synthesized as a fluoroionophore, and its structure and fluorescence spectroscopic properties were investigated. When excited at 344 nm in acetonitrile/chloroform (9:1, v/v), the synthesized bispyrenyl malonate has the fluorescence of intramolecular excimer [...] Read more.

A new malonate possessing two pyrene moieties was synthesized as a fluoroionophore, and its structure and fluorescence spectroscopic properties were investigated. When excited at 344 nm in acetonitrile/chloroform (9:1, v/v), the synthesized bispyrenyl malonate has the fluorescence of intramolecular excimer (λ_em = 467 nm) emissions and not a pyrene monomer emission (λ_em = 394 nm). A large absolute fluorescence quantum yield was obtained in the solid state (Φ_PL = 0.65) rather than in solution (Φ_PL = 0.13). X-ray crystallography analysis clarified the molecular structure and alignment of the bispyrenyl malonate in the crystal phase, elucidating its fluorescence spectroscopic properties. Such analysis also suggests there are intramolecular C–H···π interactions and intermolecular π···π interactions between the pyrenyl rings. Interestingly, the synthesized bispyrenyl malonate exhibits excellent fluorescence sensing for the Cu²⁺ ion. Remarkable fluorescence intensity enhancement was only observed with the addition of the Cu²⁺ ion. Full article

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17 pages, 993 KiB

Open AccessArticle

Identification of Optically Active Pyrimidine Derivatives as Selective 5-HT_2C Modulators

by Juhyeon Kim^1,2

, Hanbyeol Jo³, Hyunseung Lee³, Hyunah Choo^1,4, Hak Joong Kim², Ae Nim Pae^4,5, Yong Seo Cho^1,4,* and Sun-Joon Min^3,*

¹ Center for Neuro-Medicine, Korea Institute of Science and Technology (KIST), 5 Hwarangno 14-gil, Seongbuk-gu, Seoul 02792, Korea

² Department of Chemistry, Korea University, Seoul 02841, Korea

³ Department of Chemical & Molecular Engineering/Applied Chemistry, Hanyang University, Ansan, Gyeonggi-do 15588, Korea

⁴ Department of Biological Chemistry, Korea University of Science and Technology (UST), 217 Gajungro, Yuseong-gu, Daejeon 34113, Korea

⁵ Convergence Research Center for Diagnosis, Treatment and Care System of Dementia, KIST, Seoul 02792, Korea

Molecules 2017, 22(9), 1416; https://doi.org/10.3390/molecules22091416 - 26 Aug 2017

Cited by 2 | Viewed by 5690

Abstract

A series of pyrimidine derivatives 4a–i were synthesized and evaluated for their binding affinities towards 5-HT_2C receptors. With regard to designed molecules 4a–i, the influence of the size of alkyl ether and the absolute configuration of a [...] Read more.

A series of pyrimidine derivatives 4a–i were synthesized and evaluated for their binding affinities towards 5-HT_2C receptors. With regard to designed molecules 4a–i, the influence of the size of alkyl ether and the absolute configuration of a stereogenic center on the 5-HT_2C binding affinity and selectivity was studied. The most promising diasteromeric mixtures 4d and 4e were selected in the initial radioligand binding assay and they were further synthesized as optically active forms starting from optically active alcohols 5d and 5e, prepared by an enzymatic kinetic resolution. Pyrimidine analogue (R,R)-4e displayed an excellent 5-HT_2C binding affinity with good selectivity values against a broad range of other 5-HT receptor subtypes. Full article

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

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0 pages, 4004 KiB

Open AccessArticle

RETRACTED: Pyrene-Phosphonate Conjugate: Aggregation-Induced Enhanced Emission, and Selective Fe³⁺ Ions Sensing Properties

by Sachin D. Padghan¹, Rajesh S. Bhosale^1,*, Sidhanath V. Bhosale¹, Frank Antolasic², Mohammad Al Kobaisi² and Sheshanath V. Bhosale^2,*

¹ Polymers and Functional Materials Division, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, Telangana, India

² School of Science, Royal Melbourne Institute of Technology University, GPO Box 2476, Melbourne, VIC 3001, Australia

Molecules 2017, 22(9), 1417; https://doi.org/10.3390/molecules22091417 - 29 Aug 2017

Cited by 17 | Viewed by 7815 | Retraction

Abstract

A new pyrene-phosphonate colorimetric receptor 1 has been designed and synthesized in a one-step process via amide bond formation between pyrene butyric acid chloride and phosphonate-appended aniline. The pyrene-phosphonate receptor 1 showed aggregation-induced enhanced emission (AIEE) properties in water/acetonitrile (ACN) solutions. Dynamic light [...] Read more.

A new pyrene-phosphonate colorimetric receptor 1 has been designed and synthesized in a one-step process via amide bond formation between pyrene butyric acid chloride and phosphonate-appended aniline. The pyrene-phosphonate receptor 1 showed aggregation-induced enhanced emission (AIEE) properties in water/acetonitrile (ACN) solutions. Dynamic light scattering (DLS) characterization revealed that the aggregates of receptor 1 at 80% water fraction have an average size of ≈142 nm. Field emission scanning electron microscopy (FE-SEM) analysis confirmed the formation of spherical aggregates upon solvent evaporation. The sensing properties of receptor 1 were investigated by UV-vis, fluorescence emission spectroscopy, and other optical methods. Among the tested metal ions, receptor 1 is capable of recognizing the Fe³⁺ ion selectively. The changes in spectral measurements were explained on the basis of complex formation. The composition of receptor 1 and Fe³⁺ ions was determined by using Job’s plot and found to be 1:1. The receptor 1–Fe³⁺ complex showed a reversible UV-vis response in the presence of EDTA. Full article

(This article belongs to the Collection Heterocyclic Compounds)

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30 pages, 627 KiB

Open AccessReview

In Vitro Innervation as an Experimental Model to Study the Expression and Functions of Acetylcholinesterase and Agrin in Human Skeletal Muscle

by Katarina Mis¹, Zoran Grubic^1,*, Paola Lorenzon², Marina Sciancalepore²

, Tomaz Mars¹ and Sergej Pirkmajer^1,*

¹ Institute of Pathophysiology, Faculty of Medicine, University of Ljubljana, Zaloška 4, SI-1000 Ljubljana, Slovenia

² Department of Life Sciences, University of Trieste, via A. Fleming 22, I-34127 Trieste, Italy

Molecules 2017, 22(9), 1418; https://doi.org/10.3390/molecules22091418 - 27 Aug 2017

Cited by 13 | Viewed by 7893

Abstract

Acetylcholinesterase (AChE) and agrin, a heparan-sulfate proteoglycan, reside in the basal lamina of the neuromuscular junction (NMJ) and play key roles in cholinergic transmission and synaptogenesis. Unlike most NMJ components, AChE and agrin are expressed in skeletal muscle and α-motor neurons. AChE and [...] Read more.

Acetylcholinesterase (AChE) and agrin, a heparan-sulfate proteoglycan, reside in the basal lamina of the neuromuscular junction (NMJ) and play key roles in cholinergic transmission and synaptogenesis. Unlike most NMJ components, AChE and agrin are expressed in skeletal muscle and α-motor neurons. AChE and agrin are also expressed in various other types of cells, where they have important alternative functions that are not related to their classical roles in NMJ. In this review, we first focus on co-cultures of embryonic rat spinal cord explants with human skeletal muscle cells as an experimental model to study functional innervation in vitro. We describe how this heterologous rat-human model, which enables experimentation on highly developed contracting human myotubes, offers unique opportunities for AChE and agrin research. We then highlight innovative approaches that were used to address salient questions regarding expression and alternative functions of AChE and agrin in developing human skeletal muscle. Results obtained in co-cultures are compared with those obtained in other models in the context of general advances in the field of AChE and agrin neurobiology. Full article

(This article belongs to the Special Issue The Cholinesterases—Structure, Mechanism, Function and Drug Design: The 25th Anniversary of the Solution of the Crystal Structure of Acetylcholinesterase by Joel L. Sussman and Israel Silman)

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11 pages, 1765 KiB

Open AccessArticle

Acetylation of Microcrystalline Cellulose by Transesterification in AmimCl/DMSO Cosolvent System

by Huihui Wang, Xiaoxiang Wen, Xueqin Zhang and Chuanfu Liu^*

State Key Laboratory of Pulp and Paper Engineering, South China University of Technology, Guangzhou 510640, China

Molecules 2017, 22(9), 1419; https://doi.org/10.3390/molecules22091419 - 27 Aug 2017

Cited by 28 | Viewed by 7449

Abstract

Recently, IL/cosolvent systems have generated a lot of interest as cellulose-dissolving solvents and reaction media for various kinds of cellulose modification. In the present study, both 1-allyl-3-methylimidazolium chloride (AmimCl)/dimethyl sulfoxide (DMSO) and AmimCl/N,N-dimethylformamide (DMF) systems were employed to synthesize [...] Read more.

Recently, IL/cosolvent systems have generated a lot of interest as cellulose-dissolving solvents and reaction media for various kinds of cellulose modification. In the present study, both 1-allyl-3-methylimidazolium chloride (AmimCl)/dimethyl sulfoxide (DMSO) and AmimCl/N,N-dimethylformamide (DMF) systems were employed to synthesize cellulose acetate by transesterification. Microcrystalline cellulose, 1,8-diazabicyclo[5.4.0]undec-7-ene and isopropenyl acetate were chosen as the raw material, catalyst and acetylation reagent, respectively. The results revealed that DMSO was a suitable cosolvent for the transesterification in the homogeneous solution. Moreover, DMSO had a positive effect on the reaction as the cosolvent under the given conditions and the degree of the substitution of cellulose acetate could be significantly enhanced through increasing the molar ratio of DMSO. The synthesized products were characterized by Fourier transform infrared (FT-IR) spectroscopy, ¹H and ¹³C nuclear magnetic resonance spectroscopy (¹H-NMR and ¹³C-NMR), correlation spectroscopy (COSY), heteronuclear single quantum correlation (HSQC) spectroscopy, and X-ray diffraction (XRD) to confirm the chemical and physical structure of the cellulose acetate generated. The thermal properties were also evaluated using thermogravimetric analysis (TGA)/derivative thermogravimetry (DTG). Full article

(This article belongs to the Special Issue Cellulose Chemical Modifications—Towards Sustainable Materials)

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12 pages, 1318 KiB

Open AccessReview

An Overview of LEDs’ Effects on the Production of Bioactive Compounds and Crop Quality

by Md. Mohidul Hasan¹, Tufail Bashir¹, Ritesh Ghosh¹

, Sun Keun Lee² and Hanhong Bae^1,*

¹ Department of Biotechnology, Yeungnam University, Gyeongsan, Gyeongbuk 38541, Korea

² Division of Forest Insect Pest and Diseases, Korea Forest Research Institute, Seoul 02455, Korea

Molecules 2017, 22(9), 1420; https://doi.org/10.3390/molecules22091420 - 27 Aug 2017

Cited by 169 | Viewed by 13425

Abstract

Light-emitting diodes (LEDs) are characterized by their narrow-spectrum, non-thermal photon emission, greater longevity, and energy-saving characteristics, which are better than traditional light sources. LEDs thus hold the potential to revolutionize horticulture lighting technology for crop production, protection, and preservation. Exposure to different LED [...] Read more.

Light-emitting diodes (LEDs) are characterized by their narrow-spectrum, non-thermal photon emission, greater longevity, and energy-saving characteristics, which are better than traditional light sources. LEDs thus hold the potential to revolutionize horticulture lighting technology for crop production, protection, and preservation. Exposure to different LED wavelengths can induce the synthesis of bioactive compounds and antioxidants, which in turn can improve the nutritional quality of horticultural crops. Similarly, LEDs increase the nutrient contents, reduce microbial contamination, and alter the ripening of postharvest fruits and vegetables. LED-treated agronomic products can be beneficial for human health due to their good nutrient value and high antioxidant properties. Besides that, the non-thermal properties of LEDs make them easy to use in closed-canopy or within-canopy lighting systems. Such configurations minimize electricity consumption by maintaining optimal incident photon fluxes. Interestingly, red, blue, and green LEDs can induce systemic acquired resistance in various plant species against fungal pathogens. Hence, when seasonal clouds restrict sunlight, LEDs can provide a controllable, alternative source of selected single or mixed wavelength photon source in greenhouse conditions. Full article

(This article belongs to the Collection Bioactive Compounds)

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11 pages, 2026 KiB

Open AccessArticle

Sensitive and Selective Detection of Oxo-Form Organophosphorus Pesticides Based on CdSe/ZnS Quantum Dots

by Jinchao Wei¹, Jiliang Cao¹, Hao Hu^1,2, Qing Yang², Fengqing Yang³, Jianbo Wan¹, Huanxing Su¹, Chengwei He¹, Peng Li^1,* and Yitao Wang^1,*

¹ State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau 999078, China

² State Key Laboratory of Hydraulics and Mountain River Engineering, Sichuan University, Chengdu 610000, Sichuan, China

³ School of Chemistry and Chemical Engineering, Chongqing University, Chongqing 400015, China

Molecules 2017, 22(9), 1421; https://doi.org/10.3390/molecules22091421 - 28 Aug 2017

Cited by 18 | Viewed by 6294

Abstract

A rapid, sensitive and enzyme-based optical biosensor was applied for the determination of seven organophosphorus pesticides (OPPs), including the oxo forms (malaoxon, paraoxon, dibrom, and dichlorvos), the thio forms (malathion and parathion) and the mixed form (demeton) in Panax ginseng. The principal [...] Read more.

A rapid, sensitive and enzyme-based optical biosensor was applied for the determination of seven organophosphorus pesticides (OPPs), including the oxo forms (malaoxon, paraoxon, dibrom, and dichlorvos), the thio forms (malathion and parathion) and the mixed form (demeton) in Panax ginseng. The principal of the proposed method is that the fluorescence quenching effect of quantum dots (QDs) can be observed by enzyme-generated H₂O₂. The active centers of acetylcholinesterase (AChE) could be inhibited in the presence of pesticides, which caused decrease of the generated H₂O₂. Then, the inhibition efficiency of pesticide to AChE activity could be evaluated by measuring the fluorescence changes. Different from biosensors based on immobilized enzyme or self-assembling technique, the proposed biosensor demonstrated a good selectivity for the detection of oxo forms of OPPs. In the present study, the important experimental conditions of the proposed biosensor were investigated. Under the optimized conditions (incubation temperature, 35 °C; incubation time, 20 min; pH value, 8.0; detection time, 30 min; AChE concentration, 40.9 U/L; and choline oxidase (ChOx) concentration, 637.5 U/L), the limit of detection for the investigated oxo-form OPPs was no more than 0.05 μM, which suggested that the proposed method could be used for sensitive and selective determination of trace amounts of OPPs residues in real samples with complex matrices. Full article

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12 pages, 2463 KiB

Open AccessArticle

Multienzyme Biosynthesis of Dihydroartemisinic Acid

by Xixian Chen^1,2,*, Congqiang Zhang^1,2 and Heng-Phon Too^1,2,*

¹ Biotransformation Innovation Platform, Agency for Science Technology and Research, Singapore 138673, Singapore

² Department of Biochemistry, National University of Singapore, Singapore 117598, Singapore

Molecules 2017, 22(9), 1422; https://doi.org/10.3390/molecules22091422 - 28 Aug 2017

Cited by 24 | Viewed by 6858

Abstract

One-pot multienzyme biosynthesis is an attractive method for producing complex, chiral bioactive compounds. It is advantageous over step-by-step synthesis, as it simplifies the process, reduces costs and often leads to higher yield due to the synergistic effects of enzymatic reactions. In this study, [...] Read more.

One-pot multienzyme biosynthesis is an attractive method for producing complex, chiral bioactive compounds. It is advantageous over step-by-step synthesis, as it simplifies the process, reduces costs and often leads to higher yield due to the synergistic effects of enzymatic reactions. In this study, dihydroartemisinic acid (DHAA) pathway enzymes were overexpressed in Saccharomyces cerevisiae, and whole-cell biotransformation of amorpha-4,11-diene (AD) to DHAA was demonstrated. The first oxidation step by cytochrome P450 (CYP71AV1) is the main rate-limiting step, and a series of N-terminal truncation and transcriptional tuning improved the enzymatic activity. With the co-expression of artemisinic aldehyde dehydrogenase (ALDH1), which recycles NADPH, a significant 8-fold enhancement of DHAA production was observed. Subsequently, abiotic conditions were optimized to further enhance the productivity of the whole-cell biocatalysts. Collectively, approximately 230 mg/L DHAA was produced by the multi-step whole-cell reaction, a ~50% conversion from AD. This study illustrates the feasibility of producing bioactive compounds by in vitro one-pot multienzyme reactions. Full article

(This article belongs to the Special Issue Multicomponent Reaction-Based Synthesis of Bioactive Molecules)

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8 pages, 2586 KiB

Open AccessCommunication

Enhancement of Glucose Uptake by Meso-Dihydroguaiaretic Acid through GLUT4 Up-Regulation in 3T3-L1 Adipocytes

by Anna Lee^1,†, Kyeong-Mi Choi^1,†, Won-Beom Jung¹, Heejin Jeong¹, Ga-Yeong Kim¹, Ju Hyun Lee¹, Mi Kyeong Lee¹, Jin Tae Hong¹

, Yoon-Seok Roh¹, Sang-Hyun Sung²

and Hwan-Soo Yoo^1,*

¹ College of Pharmacy, Chungbuk National University, Osongsaengmyeong 1-ro, Heungduk-gu, Cheongju 28160, Korea

² College of Pharmacy, Seoul National University, Seoul 08826, Korea

^† These authors contributed equally to this work.

Molecules 2017, 22(9), 1423; https://doi.org/10.3390/molecules22091423 - 28 Aug 2017

Cited by 11 | Viewed by 6864

Abstract

Type 2 diabetes is characterized by insulin resistance, which leads to increased blood glucose levels. Adipocytes are involved in the development of insulin resistance, resulting from the dysfunction of the insulin signaling pathway. In this study, we investigated whether meso-dihydroguaiaretic acid (MDGA) [...] Read more.

Type 2 diabetes is characterized by insulin resistance, which leads to increased blood glucose levels. Adipocytes are involved in the development of insulin resistance, resulting from the dysfunction of the insulin signaling pathway. In this study, we investigated whether meso-dihydroguaiaretic acid (MDGA) may modulate glucose uptake in adipocytes, and examined its mechanism of action. MDGA enhanced adipogenesis through up-regulation of peroxisome proliferator-activated receptor γ and CCAAT/enhancer-binding protein α in 3T3-L1 adipocytes partially differentiated with sub-optimal concentrations of insulin. MDGA also increased glucose uptake by stimulating expression and translocation of glucose transporter 4 (GLUT4) in adipocytes. These results suggest that MDGA may increase GLUT4 expression and its translocation by promoting insulin sensitivity, leading to enhanced glucose uptake. Full article

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

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12 pages, 3790 KiB

Open AccessArticle

The Effect of Pressure and Solvent on the Supercritical Fluid Chromatography Separation of Tocol Analogs in Palm Oil

by Mei Han Ng^* and Ahmad Kushairi

Engineering and Processing Research Division, Malaysian Palm Oil Board, 6, Persiaran Institusi, Bandar Baru Bangi, Kajang 43000, Selangor, Malaysia

Molecules 2017, 22(9), 1424; https://doi.org/10.3390/molecules22091424 - 29 Aug 2017

Cited by 3 | Viewed by 4467

Abstract

There are six tocol analogs present in palm oil, namely α-tocopherol (α-T), α-tocomonoenol (α-T₁), α-tocotrienol (α-T₃), γ-tocotrienol (γ-T₃), β-tocotrioenol (β-T₃) and δ-tocotrienol (δ-T₃). These analogs were difficult to separate chromatographically due to their [...] Read more.

There are six tocol analogs present in palm oil, namely α-tocopherol (α-T), α-tocomonoenol (α-T₁), α-tocotrienol (α-T₃), γ-tocotrienol (γ-T₃), β-tocotrioenol (β-T₃) and δ-tocotrienol (δ-T₃). These analogs were difficult to separate chromatographically due to their similar structures, physical and chemical properties. This paper reports on the effect of pressure and injection solvent on the separation of the tocol analogs in palm oil. Supercritical CO₂ modified with ethanol was used as the mobile phase. Both total elution time and resolution of the tocol analogs decreased with increased pressure. Ethanol as an injection solvent resulted in peak broadening of the analogs within the entire pressure range studied. Solvents with an eluent strength of 3.4 or less were more suitable for use as injecting solvents. Full article

(This article belongs to the Special Issue Sub- and Supercritical Fluids and Green Chemistry)

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10 pages, 1438 KiB

Open AccessArticle

Identification and Analysis of Amygdalin, Neoamygdalin and Amygdalin Amide in Different Processed Bitter Almonds by HPLC-ESI-MS/MS and HPLC-DAD

by Shuya Xu¹, Xinfang Xu¹

, Shaoxiong Yuan², Huan Liu¹, Mengnan Liu¹, Ying Zhang¹, Hui Zhang¹, Yan Gao¹, Ruichao Lin¹ and Xiangri Li^1,*

¹ School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100102, China

² Marketing Department, Leading Pharm Medical Technology, Inc., Beijing 100083, China

Molecules 2017, 22(9), 1425; https://doi.org/10.3390/molecules22091425 - 30 Aug 2017

Cited by 36 | Viewed by 8522

Abstract

Processing is a traditional pharmacy technology based on traditional Chinese medicine theory. The traditional Chinese medicine (TCM) ingredients should be processed before being used as a medicine. Processed bitter almonds are widely used in the clinic in TCM for the treatment of cough [...] Read more.

Processing is a traditional pharmacy technology based on traditional Chinese medicine theory. The traditional Chinese medicine (TCM) ingredients should be processed before being used as a medicine. Processed bitter almonds are widely used in the clinic in TCM for the treatment of cough and asthma. In this work the amygdalin profile of three producing areas in China was determined, with respect to three differently processed bitter almond products: raw, stir-fried and scalded. Identification of the compounds was done by using high performance liquid chromatography coupled to electrospray ionization mass spectrometry (HPLC-ESI-MS/MS). Results indicated that amygdalin, neoamygdalin and amygdalin amide were identified in the different processed bitter almonds. Meanwhile, amygdalin was used as a standard to calculate the quantification of amygdalin and the concentration ratio of neoamygdalin and total amygdalin by HPLC-DAD. The data suggested that composition of amygdalin isomers in bitter almonds was influenced by the processing method. It also gives a new understanding of the processing principle of bitter almonds. Moreover, the classification of different processed bitter almonds can be achieved on the basis of amygdalin isomers levels. Full article

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9 pages, 2205 KiB

Open AccessArticle

NO-Donor Iron Nitrosyl Complex with N-Ethylthiourea Ligand Exhibits Selective Toxicity to Glioma A172 Cells

by Nataliya Sanina^1,2,3,*, Natal’ya Shmatko¹, Tatiyana Stupina¹, Anastasiya Balakina¹ and Alexei Terent’ev^1,2,3

¹ Institute of Problems of Chemical Physics RAS, Chernogolovka 142432, Russia

² Medicinal Chemistry Research and Education Center, Moscow Region State University, Moscow 105005, Russia

³ Faculty of Fundamental Physical and Chemical Engineering, M.V. Lomonosov Moscow State University, Moscow 119991, Russia

Molecules 2017, 22(9), 1426; https://doi.org/10.3390/molecules22091426 - 29 Aug 2017

Cited by 18 | Viewed by 5166

Abstract

We studied effects of NO-donor iron nitrosyl complex with N-ethylthiourea ligand (ETM) on normal or tumor-derived cell lines. ETM was mildly toxic to most cell lines studied except the human glioma cell line A172 that proved to be highly sensitive to the [...] Read more.

We studied effects of NO-donor iron nitrosyl complex with N-ethylthiourea ligand (ETM) on normal or tumor-derived cell lines. ETM was mildly toxic to most cell lines studied except the human glioma cell line A172 that proved to be highly sensitive to the complex and underwent cell death after ETM exposure. The high susceptibility of A172 cells to ETM was attributed to its NO-donor properties since no toxicity was detected for the N-ethylthiourea ligand. Full article

(This article belongs to the Special Issue Metal Based Drugs: Opportunities and Challenges)

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12 pages, 1664 KiB

Open AccessArticle

Stringent Nucleotide Recognition by the Ribosome at the Middle Codon Position

by Wei Liu¹, Dongwon Shin², Martin Ng¹, Karissa Y. Sanbonmatsu³, Yitzhak Tor² and Barry S. Cooperman^1,*

¹ Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104, USA

² Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093, USA

³ Theoretical Biology and Biophysics Group, Los Alamos National Laboratory, Los Alamos, NM 87545, USA

Molecules 2017, 22(9), 1427; https://doi.org/10.3390/molecules22091427 - 29 Aug 2017

Cited by 4 | Viewed by 4375

Abstract

Accurate translation of the genetic code depends on mRNA:tRNA codon:anticodon base pairing. Here we exploit an emissive, isosteric adenosine surrogate that allows direct measurement of the kinetics of codon:anticodon University of California base formation during protein synthesis. Our results suggest that codon:anticodon base [...] Read more.

Accurate translation of the genetic code depends on mRNA:tRNA codon:anticodon base pairing. Here we exploit an emissive, isosteric adenosine surrogate that allows direct measurement of the kinetics of codon:anticodon University of California base formation during protein synthesis. Our results suggest that codon:anticodon base pairing is subject to tighter constraints at the middle position than at the 5′- and 3′-positions, and further suggest a sequential mechanism of formation of the three base pairs in the codon:anticodon helix. Full article

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

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21 pages, 5543 KiB

Open AccessArticle

Discovery of Phylloseptins that Defense against Gram-Positive Bacteria and Inhibit the Proliferation of the Non-Small Cell Lung Cancer Cell Line, from the Skin Secretions of Phyllomedusa Frogs

by Jia Liu^1,2, Qing Wu^1,*, Lei Li^2,*

, Xinping Xi², Di Wu²

, Mei Zhou²

, Tianbao Chen²

, Chris Shaw² and Lei Wang²

¹ School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China

² Natural Drug Discovery Group, School of Pharmacy, Queen’s University, Belfast BT9 7BL, UK

Molecules 2017, 22(9), 1428; https://doi.org/10.3390/molecules22091428 - 29 Aug 2017

Cited by 21 | Viewed by 5985

Abstract

The growing occurrence of bacterial resistance to conventional antibiotics has called for the development of new classes of antimicrobial agents. Antimicrobial peptides (AMPs) with broad antimicrobial spectrum derived from frog skin secretions have been demonstrated to be promising candidates for new antibiotic development. [...] Read more.

The growing occurrence of bacterial resistance to conventional antibiotics has called for the development of new classes of antimicrobial agents. Antimicrobial peptides (AMPs) with broad antimicrobial spectrum derived from frog skin secretions have been demonstrated to be promising candidates for new antibiotic development. A proven rich source of these compounds are the skin secretions of the frogs in the Phyllomedusa genus. In this study, two novel phylloseptin peptides—phylloseptin-PTa and phylloseptin-PHa—were isolated from the skin secretions of the South American frogs, Phyllomedusa tarsius (P. tarsius) and Phyllomedusa hypochondrialis (P. hypochondrialis) through parallel transcriptomic and peptidomic studies. Replicates obtained by chemical synthesis were structurally analysed and shown to adopt an α-helix configuration in an amphiphilic environment. Both peptides demonstrated antimicrobial activities against planktonic Gram-positive bacteria strains, including Staphylococcus aureus, Enterococcus faecalis and methicillin-resistant Staphylococcus aureus , biofilms, as well as cytostatic effects on the non-small cell lung cancer cell line, NCI-H157, with relatively low haemolysis on horse erythrocytes and low cytotoxicity on the human microvascular endothelial cell line, HMEC-1. The discovery of phylloseptin peptides may further inspire the development of new types of antibiotics. Full article

(This article belongs to the Special Issue Bioactive Natural Peptides As A Pipeline For Therapeutics)

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13 pages, 1024 KiB

Open AccessReview

The Role of Metal Binding in the Amyotrophic Lateral Sclerosis-Related Aggregation of Copper-Zinc Superoxide Dismutase

by Ivana Sirangelo and Clara Iannuzzi^*

Department of Biochemistry, Biophysics and General Pathology, Università degli Studi della Campania “Luigi Vanvitelli”, 80138 Naples, Italy

Molecules 2017, 22(9), 1429; https://doi.org/10.3390/molecules22091429 - 29 Aug 2017

Cited by 67 | Viewed by 8443

Abstract

Protein misfolding and conformational changes are common hallmarks in many neurodegenerative diseases involving formation and deposition of toxic protein aggregates. Although many players are involved in the in vivo protein aggregation, physiological factors such as labile metal ions within the cellular environment are [...] Read more.

Protein misfolding and conformational changes are common hallmarks in many neurodegenerative diseases involving formation and deposition of toxic protein aggregates. Although many players are involved in the in vivo protein aggregation, physiological factors such as labile metal ions within the cellular environment are likely to play a key role. In this review, we elucidate the role of metal binding in the aggregation process of copper-zinc superoxide dismutase (SOD1) associated to amyotrophic lateral sclerosis (ALS). SOD1 is an extremely stable Cu-Zn metalloprotein in which metal binding is crucial for folding, enzymatic activity and maintenance of the native conformation. Indeed, demetalation in SOD1 is known to induce misfolding and aggregation in physiological conditions in vitro suggesting that metal binding could play a key role in the pathological aggregation of SOD1. In addition, this study includes recent advances on the role of aberrant metal coordination in promoting SOD1 aggregation, highlighting the influence of metal ion homeostasis in pathologic aggregation processes. Full article

(This article belongs to the Special Issue Metallopeptides)

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60 pages, 6583 KiB

Open AccessReview

Advances in Development of Antimicrobial Peptidomimetics as Potential Drugs

by Natalia Molchanova, Paul R. Hansen^*

and Henrik Franzyk^*

Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Jagtvej 162, DK-2100 Copenhagen, Denmark

Molecules 2017, 22(9), 1430; https://doi.org/10.3390/molecules22091430 - 29 Aug 2017

Cited by 234 | Viewed by 18532

Abstract

The rapid emergence of multidrug-resistant pathogens has evolved into a global health problem as current treatment options are failing for infections caused by pan-resistant bacteria. Hence, novel antibiotics are in high demand, and for this reason antimicrobial peptides (AMPs) have attracted considerable interest, [...] Read more.

The rapid emergence of multidrug-resistant pathogens has evolved into a global health problem as current treatment options are failing for infections caused by pan-resistant bacteria. Hence, novel antibiotics are in high demand, and for this reason antimicrobial peptides (AMPs) have attracted considerable interest, since they often show broad-spectrum activity, fast killing and high cell selectivity. However, the therapeutic potential of natural AMPs is limited by their short plasma half-life. Antimicrobial peptidomimetics mimic the structure and biological activity of AMPs, but display extended stability in the presence of biological matrices. In the present review, focus is on the developments reported in the last decade with respect to their design, synthesis, antimicrobial activity, cytotoxic side effects as well as their potential applications as anti-infective agents. Specifically, only peptidomimetics with a modular structure of residues connected via amide linkages will be discussed. These comprise the classes of α-peptoids (N-alkylated glycine oligomers), β-peptoids (N-alkylated β-alanine oligomers), β³-peptides, α/β³-peptides, α-peptide/β-peptoid hybrids, α/γ N-acylated N-aminoethylpeptides (AApeptides), and oligoacyllysines (OAKs). Such peptidomimetics are of particular interest due to their potent antimicrobial activity, versatile design, and convenient optimization via assembly by standard solid-phase procedures. Full article

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

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9 pages, 1316 KiB

Open AccessArticle

New Antifeedant Grayanane Diterpenoids from the Flowers of Pieris formosa

by Chun-Huan Li^1,†, Shi-Hong Luo^2,†, Sheng-Hong Li^2,*,† and Jin-Ming Gao^1,*,†

¹ Shaanxi Key Labotory of Natural Products & Chemical Biology, College of Chemistry & Pharmacy, Northwest A & F University, Yangling 712100, China

² State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Lanhei Road 132, Kunming 650201, China

^† These authors contributed equally.

Molecules 2017, 22(9), 1431; https://doi.org/10.3390/molecules22091431 - 31 Aug 2017

Cited by 16 | Viewed by 5124

Abstract

Three new grayanane diterpenoids, pierisoids C‒E (1–3), as well as 10 known ones (4–13), were evaluated from the flowers of Pieris formosa, which is used as an insecticide in rural areas of China. Their [...] Read more.

Three new grayanane diterpenoids, pierisoids C‒E (1–3), as well as 10 known ones (4–13), were evaluated from the flowers of Pieris formosa, which is used as an insecticide in rural areas of China. Their structures were elucidated on the basis of extensive 1D and 2D NMR spectroscopic data analyses. Significant antifeedant activity of 1, 3 and 10 against the beet armyworm (Spodoptera exigua) was found, indicating that these diterpenoids might also be involved in the plant defense against insect herbivores. Full article

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10 pages, 1672 KiB

Open AccessArticle

Soluble Epoxide Hydrolase Inhibitory Activity of Components Isolated from Apios americana Medik

by Jang Hoon Kim¹

, Hyo Young Kim¹, Si Yong Kang¹, Young Ho Kim² and Chang Hyun Jin^1,*

¹ Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeoungeup, Jeollabuk-do 56212, Korea

² College of Pharmacy, Chungnam National University, Daejeon 34134, Korea

Molecules 2017, 22(9), 1432; https://doi.org/10.3390/molecules22091432 - 30 Aug 2017

Cited by 11 | Viewed by 5354

Abstract

A new compound 1, 5-methoxy-2,5,7,4′-tetrahydroxy-coumaronochromone, along with seven known compounds (2–8), were isolated from Apios americana using open column chromatography. Their structures were established based on an analysis of 1D and 2D NMR, and MS spectra. Among these, [...] Read more.

A new compound 1, 5-methoxy-2,5,7,4′-tetrahydroxy-coumaronochromone, along with seven known compounds (2–8), were isolated from Apios americana using open column chromatography. Their structures were established based on an analysis of 1D and 2D NMR, and MS spectra. Among these, two compounds 1 and 2 showed inhibitory activity on soluble epoxide hydrolase (sEH) at a concentration below 50 μM. The respective competitive (1) and mixed (2) inhibitors were revealed to have K_i values of 21.0 ± 0.8 and 14.5 ± 1.5 μM, based on the Dixon plot. The potential inhibitor (2) was visually presented in a predicted binding pose in the receptor by molecular docking. Additionally, molecular dynamics were performed for a detailed understanding of their complex by Gromacs 4.6.5 package. Full article

(This article belongs to the Collection Bioactive Compounds)

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12 pages, 3070 KiB

Open AccessFeature PaperArticle

An Unusual Dimeric Inhibitor of Acetylcholinesterase: Cooperative Binding of Crystal Violet

by Anders Allgardsson^1,†, C. David Andersson^2,†, Christine Akfur¹, Franz Worek³, Anna Linusson² and Fredrik Ekström^1,*

¹ Swedish Defence Research Agency, SE-90281 Umeå, Sweden

² Department of Chemistry, Umeå University, SE-90187 Umeå, Sweden

³ Department of Toxicological Enzymology, Bundeswehr Institute of Pharmacology and Toxicology, 80937 Munich, Germany

^† These authors contributed equally to this work.

Molecules 2017, 22(9), 1433; https://doi.org/10.3390/molecules22091433 - 30 Aug 2017

Cited by 6 | Viewed by 7484

Abstract

Acetylcholinesterase (AChE) is an essential enzyme that terminates cholinergic transmission by a rapid hydrolysis of the neurotransmitter acetylcholine. AChE is an important target for treatment of various cholinergic deficiencies, including Alzheimer’s disease and myasthenia gravis. In a previous high throughput screening campaign, we [...] Read more.

Acetylcholinesterase (AChE) is an essential enzyme that terminates cholinergic transmission by a rapid hydrolysis of the neurotransmitter acetylcholine. AChE is an important target for treatment of various cholinergic deficiencies, including Alzheimer’s disease and myasthenia gravis. In a previous high throughput screening campaign, we identified the dye crystal violet (CV) as an inhibitor of AChE. Herein, we show that CV displays a significant cooperativity for binding to AChE, and the molecular basis for this observation has been investigated by X-ray crystallography. Two monomers of CV bind to residues at the entrance of the active site gorge of the enzyme. Notably, the two CV molecules have extensive intermolecular contacts with each other and with AChE. Computational analyses show that the observed CV dimer is not stable in solution, suggesting the sequential binding of two monomers. Guided by the structural analysis, we designed a set of single site substitutions, and investigated their effect on the binding of CV. Only moderate effects on the binding and the cooperativity were observed, suggesting a robustness in the interaction between CV and AChE. Taken together, we propose that the dimeric cooperative binding is due to a rare combination of chemical and structural properties of both CV and the AChE molecule itself. Full article

(This article belongs to the Special Issue The Cholinesterases—Structure, Mechanism, Function and Drug Design: The 25th Anniversary of the Solution of the Crystal Structure of Acetylcholinesterase by Joel L. Sussman and Israel Silman)

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20 pages, 7861 KiB

Open AccessFeature PaperReview

Synthesis of Glycosides by Glycosynthases

by Marc R. Hayes¹ and Jörg Pietruszka^1,2,*

¹ Institut für Bioorganische Chemie, Heinrich-Heine-Universität Düsseldorf im Forschungszentrum Jülich, 52426 Jülich, Germany

² Forschungszentrum Jülich, IBG-1: Biotechnology, 52426 Jülich, Germany

Molecules 2017, 22(9), 1434; https://doi.org/10.3390/molecules22091434 - 30 Aug 2017

Cited by 70 | Viewed by 14309

Abstract

The many advances in glycoscience have more and more brought to light the crucial role of glycosides and glycoconjugates in biological processes. Their major influence on the functionality and stability of peptides, cell recognition, health and immunity and many other processes throughout biology [...] Read more.

The many advances in glycoscience have more and more brought to light the crucial role of glycosides and glycoconjugates in biological processes. Their major influence on the functionality and stability of peptides, cell recognition, health and immunity and many other processes throughout biology has increased the demand for simple synthetic methods allowing the defined syntheses of target glycosides. Additional interest in glycoside synthesis has arisen with the prospect of producing sustainable materials from these abundant polymers. Enzymatic synthesis has proven itself to be a promising alternative to the laborious chemical synthesis of glycosides by avoiding the necessity of numerous protecting group strategies. Among the biocatalytic strategies, glycosynthases, genetically engineered glycosidases void of hydrolytic activity, have gained much interest in recent years, enabling not only the selective synthesis of small glycosides and glycoconjugates, but also the production of highly functionalized polysaccharides. This review provides a detailed overview over the glycosylation possibilities of the variety of glycosynthases produced until now, focusing on the transfer of the most common glucosyl-, galactosyl-, xylosyl-, mannosyl-, fucosyl-residues and of whole glycan blocks by the different glycosynthase enzyme variants. Full article

(This article belongs to the Special Issue Synthesis and Biological Applications of Glycoconjugates)

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16 pages, 2657 KiB

Open AccessArticle

Cytotoxic Activity of Origanum Vulgare L. on Hepatocellular Carcinoma cell Line HepG2 and Evaluation of its Biological Activity

by Hazem S. Elshafie¹

, Maria F. Armentano², Monica Carmosino², Sabino A. Bufo²

, Vincenzo De Feo³

and Ippolito Camele^1,*

¹ School of Agricultural, Forestry, Food and Environmental Sciences, University of Basilicata, Potenza 85100, Italy

² Department of Sciences, University of Basilicata, Potenza 85100, Italy

³ Department of Pharmacy, University of Salerno, Salerno 84084, Italy

Molecules 2017, 22(9), 1435; https://doi.org/10.3390/molecules22091435 - 30 Aug 2017

Cited by 118 | Viewed by 14053

Abstract

The potential of plant essential oils (EOs) in anticancer treatment has recently received many research efforts to overcome the development of multidrug resistance and their negative side effects. The aims of the current research are to study (i) the cytotoxic effect of the [...] Read more.

The potential of plant essential oils (EOs) in anticancer treatment has recently received many research efforts to overcome the development of multidrug resistance and their negative side effects. The aims of the current research are to study (i) the cytotoxic effect of the crude EO extracted from Origanum vulgare subsp hirtum and its main constituents (carvacrol, thymol, citral and limonene) on hepatocarcinoma HepG2 and healthy human renal cells HEK293; (ii) the antibacterial and phytotoxic activities of the above EO and its main constituents. Results showed that cell viability percentage of treated HepG2 by EO and its main constituents was significantly decreased when compared to untreated cells. The calculated inhibition concentration (IC₅₀) values for HepG2 were lower than healthy renal cells, indicating the sort of selectivity of the studied substances. Citral is not potentially recommended as an anticancer therapeutic agent, since there are no significant differences between IC₅₀ values against both tested cell lines. Results showed also that oregano EO and its main constituents have a significant antibacterial activity and a moderate phytotoxic effect. The current research verified that oregano EO and its main constituents could be potentially utilized as anticancer therapeutic agents. Full article

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

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21 pages, 10122 KiB

Open AccessArticle

Molecular Dynamic Analysis of Hyaluronic Acid and Phospholipid Interaction in Tribological Surgical Adjuvant Design for Osteoarthritis

by Jacek Siódmiak¹, Piotr Bełdowski¹, Wayne K. Augé II², Damian Ledziński³, Sandra Śmigiel^4,*

and Adam Gadomski¹

¹ Institute of Mathematics and Physics, UTP University of Science and Technology, 85-796 Bydgoszcz, Poland

² Department of Research and Development, NuOrtho Surgical, Inc., Boston, MA 02723, USA

³ Faculty of Telecommunications, Computer Science and Technology, UTP University of Science and Technology, 85-796 Bydgoszcz, Poland

⁴ Faculty of Mechanical Engineering, UTP University of Science and Technology, 85-796 Bydgoszcz, Poland

Molecules 2017, 22(9), 1436; https://doi.org/10.3390/molecules22091436 - 4 Sep 2017

Cited by 32 | Viewed by 6921

Abstract

Tribological surgical adjuvants constitute a therapeutic discipline made possible by surgical advances in the treatment of damaged articular cartilage beyond palliative care. The purpose of this study is to analyze interactions between hyaluronic acid and phospholipid molecules, and the formation of geometric forms, [...] Read more.

Tribological surgical adjuvants constitute a therapeutic discipline made possible by surgical advances in the treatment of damaged articular cartilage beyond palliative care. The purpose of this study is to analyze interactions between hyaluronic acid and phospholipid molecules, and the formation of geometric forms, that play a role in the facilitated lubrication of synovial joint organ systems. The analysis includes an evaluation of the pathologic state to detail conditions that may be encountered by adjuvants during surgical convalescence. The synovial fluid changes in pH, hyaluronic acid polydispersity, and phospholipid concentration associated with osteoarthritis are presented as features that influence the lubricating properties of adjuvant candidates. Molecular dynamic simulation studies are presented, and the Rouse model is deployed, to rationalize low molecular weight hyaluronic acid behavior in an osteoarthritic environment of increased pH and phospholipid concentration. The results indicate that the hyaluronic acid radius of gyration time evolution is both pH- and phospholipid concentration-dependent. Specifically, dipalmitoylphosphatidylcholine induces hydrophobic interactions in the system, causing low molecular weight hyaluronic acid to shrink and at high concentration be absorbed into phospholipid vesicles. Low molecular weight hyaluronic acid appears to be insufficient for use as a tribological surgical adjuvant because an increased pH and phospholipid concentration induces decreased crosslinking that prevents the formation of supramolecular lubricating forms. Dipalmitoylphosphatidylcholine remains an adjuvant candidate for certain clinical situations. The need to reconcile osteoarthritic phenotypes is a prerequisite that should serve as a framework for future adjuvant design and subsequent tribological testing. Full article

(This article belongs to the Special Issue Hyaluronic Acid and its Derivatives for Biomedical Applications)

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12 pages, 1003 KiB

Open AccessArticle

Alkaloid Constituents of the Amaryllidaceae Plant Amaryllis belladonna L

by Luciana R. Tallini¹

, Jean Paulo de Andrade², Marcel Kaiser^3,4, Francesc Viladomat¹, Jerald J. Nair¹, José Angelo S. Zuanazzi⁵

and Jaume Bastida^1,*

¹ Departament de Biologia, Sanitat i Medi Ambient, Facultat de Farmàcia, Universitat de Barcelona, Av. Joan XXIII 27–31, 08028 Barcelona, Spain

² Departamento de Química Orgânica, Universidade Federal do Espírito Santo, Av. Fernando Ferrari 845, Victoria 29075-015, Brazil

³ Medicinal Parasitology and Infection Biology, Swiss Tropical Institute, Socinstrasse 57, 4051 Basel, Switzerland

⁴ University of Basel, Petersplatz 1, 4001 Basel, Switzerland

⁵ Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Av. Ipiranga 2752, Porto Alegre 90610-000, Brazil

Molecules 2017, 22(9), 1437; https://doi.org/10.3390/molecules22091437 - 31 Aug 2017

Cited by 45 | Viewed by 8985

Abstract

The plant family Amaryllidaceae is well-known for its unique alkaloid constituents, which exhibit a wide range of biological activities. Its representative, Amaryllis belladonna, has a geographical distribution covering mainly southern Africa, where it has significant usage in the traditional medicine of the [...] Read more.

The plant family Amaryllidaceae is well-known for its unique alkaloid constituents, which exhibit a wide range of biological activities. Its representative, Amaryllis belladonna, has a geographical distribution covering mainly southern Africa, where it has significant usage in the traditional medicine of the native people. In this study, A. belladonna samples collected in Brazil were examined for alkaloid content. Alkaloid profiles of A. belladonna bulbs were generated by a combination of chromatographic, spectroscopic and spectrometric methods, including GC–MS and 2D NMR. In vitro screening against four different parasitic protozoa (Trypanosoma cruzi, T. brucei rhodesiense, Leishmania donovani and Plasmodium falciparum) was carried out using the A. belladonna crude methanol extract, as well as three of its alkaloid isolates. Twenty-six different Amaryllidaceae alkaloids were identified in the A. belladonna bulb samples, and three of them were isolated. Evidence for their respective biosynthetic pathways was afforded via their mass-spectral fragmentation data. Improved data for 1-O-acetylcaranine was provided by 2D NMR experiments, together with new ¹H-NMR data for buphanamine. The crude extract and 3-O-acetylhamayne exhibited good antiprotozoal activity in vitro, although both with a high cytotoxic index. Full article

(This article belongs to the Collection Herbal Medicine Research)

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14 pages, 2943 KiB

Open AccessArticle

Preparation and Characterization of Novel Cationic Chitosan Derivatives Bearing Quaternary Ammonium and Phosphonium Salts and Assessment of Their Antifungal Properties

by Wenqiang Tan^1,2, Qing Li¹, Fang Dong¹, Qiuhong Chen¹ and Zhanyong Guo^1,2,*

¹ Key Laboratory of Coastal Biology and Bioresource Utilization, Yantai Institute of Coastal Zone Research, Chinese Academy of Sciences, Yantai 264003, China

² University of Chinese Academy of Sciences, Beijing 100049, China

Molecules 2017, 22(9), 1438; https://doi.org/10.3390/molecules22091438 - 31 Aug 2017

Cited by 47 | Viewed by 8081

Abstract

Chitosan is an abundant and renewable polysaccharide, its derivatives exhibit attractive bioactivities and the wide applications in various biomedical fields. In this paper, two novel cationic chitosan derivatives modified with quaternary phosphonium salts were successfully synthesized via trimethylation, chloride acetylation, and quaternization with [...] Read more.

Chitosan is an abundant and renewable polysaccharide, its derivatives exhibit attractive bioactivities and the wide applications in various biomedical fields. In this paper, two novel cationic chitosan derivatives modified with quaternary phosphonium salts were successfully synthesized via trimethylation, chloride acetylation, and quaternization with tricyclohexylphosphine and triphenylphosphine. The structures and properties of synthesized products in the reactions were characterized by FTIR spectroscopy, ¹H-NMR, ³¹P-NMR, elemental and thermogravimetric analysis. The antifungal activities of chitosan derivatives against four kinds of phytopathogens, including Phomopsis asparagi, Watermelon fusarium, Colletotrichum lagenarium, and Fusarium oxysporum were tested using the radial growth assay in vitro. The results revealed that the synthesized cationic chitosan derivatives showed significantly improved antifungal efficiency compared to chitosan. It was reasonably suggested that quaternary phosphonium groups enabled the obviously stronger antifungal activity of the synthesized chitosans. Especially, the triphenylphosphonium-functionalized chitosan derivative inhibited the growth of Phomopsis asparagi most effectively, with inhibitory indices of about 80% at 0.5 mg/mL. Moreover, the data demonstrated that the substituted groups with stronger electron-withdrawing ability relatively possessed greater antifungal activity. The results suggest the possibility that cationic chitosan derivatives bearing quaternary phosphonium salts could be effectively employed as novel antifungal biomaterials for application in the field of agriculture. Full article

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

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16 pages, 266 KiB

Open AccessReview

Toxicity Effects of Functionalized Quantum Dots, Gold and Polystyrene Nanoparticles on Target Aquatic Biological Models: A Review

by Giovanni Libralato¹

, Emilia Galdiero^1,*, Annarita Falanga²

, Rosa Carotenuto¹

, Elisabetta De Alteriis¹ and Marco Guida¹

¹ Department of Biology, University of Naples Federico II, Complesso Universitario di Monte S. Angelo, via Cinthia ed. 7, 80126 Naples, Italy

² Department of Pharmacy, University of Naples Federico II, Via Mezzocannone 16, 80134 Naples, Italy

Molecules 2017, 22(9), 1439; https://doi.org/10.3390/molecules22091439 - 31 Aug 2017

Cited by 97 | Viewed by 9404

Abstract

Nano-based products are widespread in several sectors, including textiles, medical-products, cosmetics, paints and plastics. Nanosafety and safe-by-design are driving nanoparticle (NP) production and applications through NP functionalization (@NPs). Indeed, @NPs frequently present biological effects that differ from the parent material. This paper reviews [...] Read more.

Nano-based products are widespread in several sectors, including textiles, medical-products, cosmetics, paints and plastics. Nanosafety and safe-by-design are driving nanoparticle (NP) production and applications through NP functionalization (@NPs). Indeed, @NPs frequently present biological effects that differ from the parent material. This paper reviews the impact of quantum dots (QDs), gold nanoparticles (AuNPs), and polystyrene-cored NPs (PSNPs), evidencing the role of NP functionalization in toxicity definition. Key biological models were taken into consideration for NP evaluation: Saccharomyces cerevisiae, fresh- (F) and saltwater (S) microalgae (Raphidocelis subcapitata (F), Scenedesmus obliquus (F) and Chlorella spp. (F), and Phaeodactylum tricornutum (S)), Daphnia magna, and Xenopus laevis. QDs are quite widespread in technological devices, and they are known to induce genotoxicity and oxidative stress that can drastically change according to the coating employed. For example, AuNPs are frequently functionalized with antimicrobial peptides, which is shown to both increase their activity and decrease the relative environmental toxicity. P-NPs are frequently coated with NH₂⁻ for cationic and COOH⁻ for anionic surfaces, but when positively charged toxicity effects can be observed. Careful assessment of functionalized and non-functionalized NPs is compulsory to also understand their potential direct and indirect effects when the coating is removed or degraded. Full article

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

50 pages, 2820 KiB

Open AccessArticle

Novel Selective Estrogen Receptor Ligand Conjugates Incorporating Endoxifen-Combretastatin and Cyclofenil-Combretastatin Hybrid Scaffolds: Synthesis and Biochemical Evaluation

by Patrick M. Kelly¹, Niall O. Keely², Sandra A. Bright³, Bassem Yassin², Gloria Ana¹, Darren Fayne³, Daniela M. Zisterer³ and Mary J. Meegan^1,2,*

¹ School of Pharmacy and Pharmaceutical Sciences, Trinity Biomedical Sciences Institute, 152-160 Pearse Street, Trinity College Dublin, Dublin 2, Ireland

² School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin, Dublin 2, Ireland

³ School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, 152-160 Pearse Street, Trinity College Dublin, Dublin 2, Ireland

Molecules 2017, 22(9), 1440; https://doi.org/10.3390/molecules22091440 - 31 Aug 2017

Cited by 29 | Viewed by 7247

Abstract

Nuclear receptors such as the estrogen receptors (ERα and ERβ) modulate the effects of the estrogen hormones and are important targets for design of innovative chemotherapeutic agents for diseases such as breast cancer and osteoporosis. Conjugate and bifunctional compounds which incorporate an ER [...] Read more.

Nuclear receptors such as the estrogen receptors (ERα and ERβ) modulate the effects of the estrogen hormones and are important targets for design of innovative chemotherapeutic agents for diseases such as breast cancer and osteoporosis. Conjugate and bifunctional compounds which incorporate an ER ligand offer a useful method of delivering cytotoxic drugs to tissue sites such as breast cancers which express ERs. A series of novel conjugate molecules incorporating both the ER ligands endoxifen and cyclofenil-endoxifen hybrids covalently linked to the antimitotic and tubulin targeting agent combretastatin A-4 were synthesised and evaluated as ER ligands. A number of these compounds demonstrated pro-apoptotic effects, with potent antiproliferative activity in ER-positive MCF-7 breast cancer cell lines and low cytotoxicity. These conjugates displayed binding affinity towards ERα and ERβ isoforms at nanomolar concentrations e.g., the cyclofenil-amide compound 13e is a promising lead compound of a clinically relevant ER conjugate with IC₅₀ in MCF-7 cells of 187 nM, and binding affinity to ERα (IC₅₀ = 19 nM) and ERβ (IC₅₀ = 229 nM) while the endoxifen conjugate 16b demonstrates antiproliferative activity in MCF-7 cells (IC₅₀ = 5.7 nM) and binding affinity to ERα (IC₅₀ = 15 nM) and ERβ (IC₅₀ = 115 nM). The ER binding effects are rationalised in a molecular modelling study in which the disruption of the ER helix-12 in the presence of compounds 11e, 13e and 16b is presented These conjugate compounds have potential application for further development as antineoplastic agents in the treatment of ER positive breast cancers. Full article

(This article belongs to the Special Issue Polypharmacology and Multitarget Drug Discovery)

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13 pages, 1174 KiB

Open AccessArticle

Evaluation of Rhamnetin as an Inhibitor of the Pharmacological Effect of Secretory Phospholipase A2

by Mariana Novo Belchor^1,2, Henrique Hessel Gaeta², Caroline Fabri Bittencourt Rodrigues², Caroline Ramos da Cruz Costa², Daniela De Oliveira Toyama³, Luiz Felipe Domingues Passero², Marcia Dalastra Laurenti⁴ and Marcos Hikari Toyama^2,*

¹ Postgraduate Program in Food, Nutrition and Health, Federal University of São Paulo, Santos 11015-020, São Paulo, Brazil

² Bioscience Institute, Paulista State University, São Vicente 11330-900, São Paulo, Brazil

³ Pro-rector of Research, Brazil University, Itaquera 08230-030, São Paulo, Brazil

⁴ Pathology Laboratory of Infectious Diseases (LIM50), Department of Pathology, Medical School of the University of São Paulo, São Paulo 01246-903, Brazil

Molecules 2017, 22(9), 1441; https://doi.org/10.3390/molecules22091441 - 31 Aug 2017

Cited by 37 | Viewed by 7326

Abstract

Rhamnetin (Rhm), 3-O-methylquercetin (3MQ), and Rhamnazin (Rhz) are methylated derivatives of quercetin commonly found in fruits and vegetables that possess antioxidant and anti-inflammatory properties. Phospholipase A2 (PLA2) displays several important roles during acute inflammation; therefore, this study aimed at investigating new [...] Read more.

Rhamnetin (Rhm), 3-O-methylquercetin (3MQ), and Rhamnazin (Rhz) are methylated derivatives of quercetin commonly found in fruits and vegetables that possess antioxidant and anti-inflammatory properties. Phospholipase A2 (PLA2) displays several important roles during acute inflammation; therefore, this study aimed at investigating new compounds able to inhibit this enzyme, besides evaluating creatine kinase (CK) levels and citotoxicity. Methylated quercetins were compared with quercetin (Q) and were incubated with secretory PLA2 (sPLA2) from Bothrops jararacussu to determine their inhibitory activity. Cytotoxic studies were performed by using the J774 cell lineage incubated with quercertins. In vivo tests were performed with Swiss female mice to evaluate decreasing paw edema potential and compounds’ CK levels. Structural modifications on sPLA2 were made with circular dichroism (CD). Despite Q and Rhz showing greater enzymatic inhibitory potential, high CK was observed. Rhm exhibited sPLA2 inhibitory potential, no toxicity and, remarkably, it decreased CK levels. The presence of 3OH on the C-ring of Rhm may contribute to both its anti-inflammatory and enzymatic inhibition of sPLA2, and the methylation of ring A may provide the increase in cell viability and low CK level induced by sPLA2. These results showed that Rhm can be a candidate as a natural compound for the development of new anti-inflammatory drugs. Full article

(This article belongs to the Special Issue Phospholipases and Lipases: Targets for Drug Development)

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16 pages, 3960 KiB

Open AccessArticle

Voltammetric Study of Some 3-Aryl-quinoxaline-2-carbonitrile 1,4-di-N-oxide Derivatives with Anti-Tumor Activities

by Eric M. Miller^1,†, Qing Xia^2,†, Mariah E. Cella¹, Austin W. Nenninger¹

, Monica N. Mruzik¹, Krystina A. Brillos-Monia¹, Yong Zhou Hu³, Rong Sheng³, Christina M. Ragain¹ and Philip W. Crawford^1,*

¹ Department of Chemistry, Southeast Missouri State University, Cape Girardeau, MO 63701, USA

² Department of Pharmacology, Ningbo College of Health Sciences, No. 51, Xuefu Road, Yinzhou, Ningbo 315000, China

³ College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China

^† These authors contributed equally to this work.

Molecules 2017, 22(9), 1442; https://doi.org/10.3390/molecules22091442 - 31 Aug 2017

Cited by 10 | Viewed by 5279

Abstract

The electrochemical properties of twenty 3-aryl-quinoxaline-2-carbonitrile 1,4-di-N-oxide derivatives with varying degrees of cytotoxic activity were investigated in dimethylformamide (DMF) using cyclic voltammetry and first derivative cyclic voltammetry. With one exception, the first reduction of these compounds was found to be reversible [...] Read more.

The electrochemical properties of twenty 3-aryl-quinoxaline-2-carbonitrile 1,4-di-N-oxide derivatives with varying degrees of cytotoxic activity were investigated in dimethylformamide (DMF) using cyclic voltammetry and first derivative cyclic voltammetry. With one exception, the first reduction of these compounds was found to be reversible or quasireversible and is attributed to reduction of the N-oxide moiety to form a radical anion. The second reduction of the diazine ring was found to be irreversible. Compounds containing a nitro group on the 3-phenyl ring also exhibited a reduction process that may be attributed to that group. There was good correlation between molecular structure and reduction potential, with reduction being facilitated by an enhanced net positive charge at the electroactive site created by electron withdrawing substituents. Additionally, the reduction potential was calculated using two common basis sets, 6-31g and lanl2dz, for five of the test molecules. There was a strong correlation between the computational data and the experimental data, with the exception of the derivative containing the nitro functionality. No relationship between the experimentally measured reduction potentials and reported cytotoxic activities was evident upon comparison of the data. Full article

(This article belongs to the Collection Heterocyclic Compounds)

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14 pages, 3266 KiB

Open AccessArticle

Identification of a Quality Marker (Q-Marker) of Danhong Injection by the Zebrafish Thrombosis Model

by Yuqing Qi¹

, Xiaoping Zhao^2,*, Hao Liu¹, Yimin Wang³, Chao Zhao³, Tao Zhao³, Buchang Zhao³ and Yi Wang^1,*

¹ College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China

² College of Preclinical Medicine, Zhejiang Chinese Medical University, Hangzhou 310053, China

³ Shandong Buchang Pharmaceutical Co., Ltd., Heze 274000, China

Molecules 2017, 22(9), 1443; https://doi.org/10.3390/molecules22091443 - 31 Aug 2017

Cited by 32 | Viewed by 7341

Abstract

Quality-marker (Q-marker) is an emerging concept to ensure the quality and batch-to-batch consistency of Chinese medicine (CM). However, significant difficulties remain in the identification of Q-markers due to the unclear relationship between complex chemical compositions and the pharmacological efficacy of CM. In the [...] Read more.

Quality-marker (Q-marker) is an emerging concept to ensure the quality and batch-to-batch consistency of Chinese medicine (CM). However, significant difficulties remain in the identification of Q-markers due to the unclear relationship between complex chemical compositions and the pharmacological efficacy of CM. In the present study, we proposed a novel strategy to identify the potential Q-marker of danhong injection (DHI) by an in vivo zebrafish thrombosis model. The anti-thrombotic effects of DHI and its major constituents were evaluated by the zebrafish model of arachidonic acid (AA)-induced thrombosis. The results indicated that DHI can attenuate tail venous thrombus and recover the decrease of heart red blood cell (RBC) intensity in a dose-dependent manner. The result that DHI prevented the formulation of thrombosis in zebrafish was also validated in the zebrafish thrombosis model with green fluorescence protein (GFP)-labeled hemoglobin. The major components of DHI, namely danshen (DS) and honghua (HH), as well as the major chemical constituents of DHI, also exerted anti-thrombotic effects, among which rosmarinic acid (RA) and p-coumaric acid (pCA) showed moderate anti-thrombotic effects. This is the first time that pCA from HH has been found as an active compound exerting an anti-thrombotic effect in a dose-dependent manner, whose IC₅₀ value is approximately 147 μg/mL. By analyzing 10 batches of normal DHI samples and five abnormal samples by high-performance liquid chromatography (HPLC), we found the contents of pCA and RA can be positively correlated to the anti-thrombotic effect of DHI, suggesting that pCA and RA could be potential Q-markers of DHI to ensure batch-to-batch consistency. Our findings illustrated that discovering major active compounds from CM by in vivo pharmacological models can be a useful approach to identifying Q-markers of CM, and in vivo pharmacological models can be a potential tool to evaluate batch-to-batch consistency of CMs. Full article

(This article belongs to the Collection Herbal Medicine Research)

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18 pages, 6034 KiB

Open AccessArticle

Andrographolide Suppresses MV4-11 Cell Proliferation through the Inhibition of FLT3 Signaling, Fatty Acid Synthesis and Cellular Iron Uptake

by Xiao Chen^1,†, Jianbin Zhang^2,†, Lixia Yuan^3,†, Yifei Lay⁴, Yin Kwan Wong⁴, Teck Kwang Lim⁴, Chye Sun Ong⁵, Qingsong Lin^4,*, Jigang Wang^4,6,*

and Zichun Hua^1,6,*

¹ The State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210023, China

² Department of Oncology, Clinical Research Institute, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou 310014, China

³ School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China

⁴ Department of Biological Sciences, National University of Singapore, Singapore 117543, Singapore

⁵ Institute of Mental Health, Education Office, Singapore 539747, Singapore

⁶ Changzhou High-Tech Research Institute of Nanjing University, Institute of Biotechnology, Jiangsu Industrial Technology Research Institute and Jiangsu Target Pharma Laboratories Inc., Changzhou 213164, China

^† These authors contributed equally to this work.

Molecules 2017, 22(9), 1444; https://doi.org/10.3390/molecules22091444 - 31 Aug 2017

Cited by 16 | Viewed by 9326

Abstract

Background: Andrographolide (ADR), the main active component of Andrographis paniculata, displays anticancer activity in various cancer cell lines, among which leukemia cell lines exhibit the highest sensitivity to ADR. In particular, ADR was also reported to have reduced drug resistance in [...] Read more.

Background: Andrographolide (ADR), the main active component of Andrographis paniculata, displays anticancer activity in various cancer cell lines, among which leukemia cell lines exhibit the highest sensitivity to ADR. In particular, ADR was also reported to have reduced drug resistance in multidrug resistant cell lines. However, the mechanism of action (MOA) of ADR’s anticancer and anti-drug-resistance activities remain elusive. Methods: In this study, we used the MV4-11 cell line, a FLT3 positive acute myeloid leukemia (AML) cell line that displays multidrug resistance, as our experimental system. We first evaluated the effect of ADR on MV4-11 cell proliferation. Then, a quantitative proteomics approach was applied to identify differentially expressed proteins in ADR-treated MV4-11 cells. Finally, cellular processes and signal pathways affected by ADR in MV4-11 cell were predicted with proteomic analysis and validated with in vitro assays. Results: ADR inhibits MV4-11 cell proliferation in a dose- and time-dependent manner. With a proteomic approach, we discovered that ADR inhibited fatty acid synthesis, cellular iron uptake and FLT3 signaling pathway in MV4-11 cells. Conclusions: ADR inhibits MV4-11 cell proliferation through inhibition of fatty acid synthesis, iron uptake and protein synthesis. Furthermore, ADR reduces drug resistance by blocking FLT3 signaling. Full article

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

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13 pages, 1782 KiB

Open AccessReview

Unique Roles of Gold Nanoparticles in Drug Delivery, Targeting and Imaging Applications

by Fen-Ying Kong, Jin-Wei Zhang, Rong-Fang Li, Zhong-Xia Wang, Wen-Juan Wang and Wei Wang^*

School of Chemistry and Chemical Engineering, Yancheng Institute of Technology, Yancheng 224051, China

Molecules 2017, 22(9), 1445; https://doi.org/10.3390/molecules22091445 - 31 Aug 2017

Cited by 545 | Viewed by 22810

Abstract

Nanotechnology has become more and more potentially used in diagnosis or treatment of diseases. Advances in nanotechnology have led to new and improved nanomaterials in biomedical applications. Common nanomaterials applicable in biomedical applications include liposomes, polymeric micelles, graphene, carbon nanotubes, quantum dots, ferroferric [...] Read more.

Nanotechnology has become more and more potentially used in diagnosis or treatment of diseases. Advances in nanotechnology have led to new and improved nanomaterials in biomedical applications. Common nanomaterials applicable in biomedical applications include liposomes, polymeric micelles, graphene, carbon nanotubes, quantum dots, ferroferric oxide nanoparticles, gold nanoparticles (Au NPs), and so on. Among them, Au NPs have been considered as the most interesting nanomaterial because of its unique optical, electronic, sensing and biochemical properties. Au NPs have been potentially applied for medical imaging, drug delivery, and tumor therapy in the early detection, diagnosis, and treatment of diseases. This review focuses on some recent advances in the use of Au NPs as drug carriers for the intracellular delivery of therapeutics and as molecular nanoprobes for the detection and monitoring of target molecules. Full article

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15 pages, 4422 KiB

Open AccessArticle

Comparison of Chemical Profiles, Anti-Inflammatory Activity, and UPLC-Q-TOF/MS-Based Metabolomics in Endotoxic Fever Rats between Synthetic Borneol and Natural Borneol

by Liang Zou^1,†, Yan Zhang^1,†, Wei Li¹, Jinming Zhang², Dan Wang¹, Jia Fu^1,* and Ping Wang^2,*

¹ School of Medicine, Chengdu University, Chengdu 610106, China

² Department of Pharmacology, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China

^† These authors contributed equally to this work.

Molecules 2017, 22(9), 1446; https://doi.org/10.3390/molecules22091446 - 31 Aug 2017

Cited by 50 | Viewed by 7071

Abstract

Natural borneol (NB, called “Bingpian”) is an important traditional Chinese medicine to restore consciousness, remove heat and relieve pain, all of which are inflammation-related diseases. Recently, due to the limited source of NB, synthetic borneol (SB) is widely used as a substitute for [...] Read more.

Natural borneol (NB, called “Bingpian”) is an important traditional Chinese medicine to restore consciousness, remove heat and relieve pain, all of which are inflammation-related diseases. Recently, due to the limited source of NB, synthetic borneol (SB) is widely used as a substitute for NB in clinics. However, little is known about the effects of SB instead of NB. Herein, the aim of the present study was to compare NB and SB on chemical profiles by gas chromatography-mass spectrometer (GC-MS) analysis, anti-inflammatory activity in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages, and ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) metabolomic approaches in endotoxic fever induced in rats. Results showed that, in total, 13 volatile components could be identified in NB and SB by GC-MS analysis, in which a significant difference between them still existed. The main constituents in SB were iso-borneol and borneol, while borneol contributes to 98.96% of the amount in NB. Additionally, both NB and SB exhibited remarkable anti-inflammatory effects to reduce the level of inflammatory factors including NO, TNF-α and IL-6 in LPS-induced RAW 264.7 macrophages, and lower the high body temperature in rats with endotoxic fever induced by LPS. Moreover, it seems that NB exhibited higher efficacy than SB. The unequal bioactive efficiency between NB and SB was also indicated by means of non-targeting metabolomics. Based on UPLC-Q-TOF/MS technology, 12 biomarkers in the serum of fever rats were identified. Pathway analysis revealed that the anti-fever effect of NB and SB was related to regulating the abnormal glycerophospholipid, linoleic acid and alpha-linoleic acid metabolism pathways in the fever model. Results indicated that there was still a great difference between NB and SB involving chemical constituents, anti-inflammation activity and the ability to regulate the abnormal metabolism pathways of the fever model. Certainly, further studies are warranted to better understand the replacement rationale in medicinal application. Full article

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21 pages, 3806 KiB

Open AccessFeature PaperReview

Solution NMR Studies of Mycobacterium tuberculosis Proteins for Antibiotic Target Discovery

by Do-Hee Kim^†, Sung-Min Kang^† and Bong-Jin Lee^*

¹ Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, Korea

^† These authors contributed equally to this work.

Molecules 2017, 22(9), 1447; https://doi.org/10.3390/molecules22091447 - 31 Aug 2017

Cited by 3 | Viewed by 5612

Abstract

Tuberculosis is an infectious disease caused by Mycobacterium tuberculosis, which triggers severe pulmonary diseases. Recently, multidrug/extensively drug-resistant tuberculosis strains have emerged and continue to threaten global health. Because of the development of drug-resistant tuberculosis, there is an urgent need for novel antibiotics [...] Read more.

Tuberculosis is an infectious disease caused by Mycobacterium tuberculosis, which triggers severe pulmonary diseases. Recently, multidrug/extensively drug-resistant tuberculosis strains have emerged and continue to threaten global health. Because of the development of drug-resistant tuberculosis, there is an urgent need for novel antibiotics to treat these drug-resistant bacteria. In light of the clinical importance of M. tuberculosis, 2067 structures of M. tuberculsosis proteins have been determined. Among them, 52 structures have been solved and studied using solution nuclear magnetic resonance (NMR). The functional details based on structural analysis of M. tuberculosis using NMR can provide essential biochemical data for the development of novel antibiotic drugs. In this review, we introduce diverse structural and biochemical studies on M. tuberculosis proteins determined using NMR spectroscopy. Full article

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

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16 pages, 1525 KiB

Open AccessArticle

Different Covalent Immobilizations Modulate Lipase Activities of Hypocrea pseudokoningii

by Marita G. Pereira¹, Susana Velasco-Lozano², Sonia Moreno-Perez^3,4, Aline M. Polizeli¹, Paulo R. Heinen⁵, Fernanda D. A. Facchini⁵, Ana C. Vici¹, Mariana Cereia¹, Benevides C. Pessela³, Gloria Fernandez-Lorente³, Jose M. Guisan⁴

, João A. Jorge¹ and Maria De Lourdes T. M. Polizeli^1,*

¹ Departamento de Biologia, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Av. Bandeirantes, 3900, Ribeirão Preto-SP 14040-901, Brazil

² Heterogeneous Biocatalysis Group, CIC Biomagune, Parque Tecnológico de San Sebastián Edificio Empresarial “C”, Paseo Miramón 182, 20009 Donostia-San Sebastián Guipúzcoa, Spain

³ Departamento de Biotecnología y Microbiología de los Alimentos, Instituto de Ciências de la Alimentación, CIAL-CSIC, Calle Nicolás Cabrera 9, Campus UAM, Cantoblanco, 28049 Madrid, Spain

⁴ Departamento de Biocatálisis, Instituto de Catálisis y Petroleoquímica, CSIC, Campus UAM, Cantoblanco, 28049 Madrid, Spain

⁵ Departamento de Bioquímica e Imunologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto-SP 14040-900, Brazil

Molecules 2017, 22(9), 1448; https://doi.org/10.3390/molecules22091448 - 4 Sep 2017

Cited by 8 | Viewed by 4923

Abstract

Enzyme immobilization can promote several advantages for their industrial application. In this work, a lipase from Hypocrea pseudokoningii was efficiently linked to four chemical supports: agarose activated with cyanogen bromide (CNBr), glyoxyl-agarose (GX), MANAE-agarose activated with glutaraldehyde (GA) and GA-crosslinked with glutaraldehyde. Results [...] Read more.

Enzyme immobilization can promote several advantages for their industrial application. In this work, a lipase from Hypocrea pseudokoningii was efficiently linked to four chemical supports: agarose activated with cyanogen bromide (CNBr), glyoxyl-agarose (GX), MANAE-agarose activated with glutaraldehyde (GA) and GA-crosslinked with glutaraldehyde. Results showed a more stable lipase with both the GA-crosslinked and GA derivatives, compared to the control (CNBr), at 50 °C, 60 °C and 70 °C. Moreover, all derivatives were stabilized when incubated with organic solvents at 50%, such as ethanol, methanol, n-propanol and cyclohexane. Furthermore, lipase was highly activated (4-fold) in the presence of cyclohexane. GA-crosslinked and GA derivatives were more stable than the CNBr one in the presence of organic solvents. All derivatives were able to hydrolyze sardine, açaí (Euterpe oleracea), cotton seed and grape seed oils. However, during the hydrolysis of sardine oil, GX derivative showed to be 2.3-fold more selectivity (eicosapentaenoic acid (EPA)/docosahexaenoic acid (DHA) ratio) than the control. Additionally, the types of immobilization interfered with the lipase enantiomeric preference. Unlike the control, the other three derivatives preferably hydrolyzed the R-isomer of 2-hydroxy-4-phenylbutanoic acid ethyl ester and the S-isomer of 1-phenylethanol acetate racemic mixtures. On the other hand, GX and CNBr derivatives preferably hydrolyzed the S-isomer of butyryl-2-phenylacetic acid racemic mixture while the GA and GA-crosslink derivatives preferably hydrolyzed the R-isomer. However, all derivatives, including the control, preferably hydrolyzed the methyl mandelate S-isomer. Moreover, the derivatives could be used for eight consecutive cycles retaining more than 50% of their residual activity. This work shows the importance of immobilization as a tool to increase the lipase stability to temperature and organic solvents, thus enabling the possibility of their application at large scale processes. Full article

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

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11 pages, 3881 KiB

Open AccessArticle

Molecular Cloning and Characterization of Carotenoid Pathway Genes and Carotenoid Content in Ixeris dentata var. albiflora

by Chinreddy Subramanyam Reddy^1,†

, Sang-Hoon Lee^1,†, Jeong Su Yoon², Jae Kwang Kim², Sang Won Lee¹, Mok Hur¹, Sung Cheol Koo¹, Jin Meilan¹, Woo Moon Lee¹, Jae Ki Jang¹, Yoonkang Hur³, Sang Un Park⁴

and And Yeon Bok Kim^1,5,*

¹ Department of Herbal Crop Resources, National Institute of Horticultural & Herbal Science, RDA, Eumseong-gun 27709, Korea

² Division of Life Sciences, College of Life Sciences and Bioengineering, Incheon National University, Incheon 22012, Korea

³ Department of Biology, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon 34134, Korea

⁴ Department of Crop Science, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon 34134, Korea

⁵ Department of Medicinal and Industrial Crops, Korea National College of Agriculture and Fisheries, Jeonju 54874, Korea

^† This authors contributed equally to this work.

Molecules 2017, 22(9), 1449; https://doi.org/10.3390/molecules22091449 - 31 Aug 2017

Cited by 8 | Viewed by 5548

Abstract

Ixeris dentata var. albiflora is considered as a potential therapeutic agent against mithridatism, calculous, indigestion, pneumonia, hepatitis, and tumors as well as good seasoned vegetable in Far East countries. Phytoene synthase (PSY), phytoene desaturase (PDS) ξ-carotene desaturase (ZDS), lycopene β-cyclase (LCYB), lycopene ε-cyclase [...] Read more.

Ixeris dentata var. albiflora is considered as a potential therapeutic agent against mithridatism, calculous, indigestion, pneumonia, hepatitis, and tumors as well as good seasoned vegetable in Far East countries. Phytoene synthase (PSY), phytoene desaturase (PDS) ξ-carotene desaturase (ZDS), lycopene β-cyclase (LCYB), lycopene ε-cyclase (LCYE), ε-ring carotene hydroxylase (CHXB), and zeaxanthin epoxidase (ZDS) are vital enzymes in the carotenoid biosynthesis pathway. We have examined these seven genes from I. dentata that are participated in carotenoid biosynthesis utilizing an Illumina/Solexa HiSeq 2000 platform. In silico analysis of the seven deduced amino acid sequences were revealed its closest homology with other Asteracea plants. Further, we explored transcript levels and carotenoid accumulation in various organs of I. dentata using quantitative real time PCR and high-performance liquid chromatography, respectively. The highest transcript levels were noticed in the leaf for all the genes while minimal levels were noticed in the root. The maximal carotenoid accumulation was also detected in the leaf. We proposed that these genes expressions are associated with the accumulation of carotenoids. Our findings may suggest the fundamental clues to unravel the molecular insights of carotenoid biosynthesis in various organs of I. dentata. Full article

(This article belongs to the Section Natural Products Chemistry)

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9 pages, 874 KiB

Open AccessArticle

Synthesis and Detailed Examination of Spectral Properties of (S) and (R)-Higenamine 4′-O-β-d-Glucoside and HPLC Analytical Conditions to Distinguish the Diastereomers

by Eisuke Kato^*, Ryohei Iwata and Jun Kawabata

Laboratory of Food Biochemistry, Division of Applied Bioscience, Graduate School of Agriculture, Hokkaido University, Kita-ku, Sapporo, Hokkaido 060-8589, Japan

Molecules 2017, 22(9), 1450; https://doi.org/10.3390/molecules22091450 - 31 Aug 2017

Cited by 6 | Viewed by 5041

Abstract

Higenamine is a tetrahydroisoquinoline present in several plants that has β-adrenergic receptor agonist activity. Study of the biosynthesis of higenamine has shown the participation of norcoclaurine synthase, which controls the stereochemistry to construct the (S)-isomer. However, when isolated from nature, higenamine [...] Read more.

Higenamine is a tetrahydroisoquinoline present in several plants that has β-adrenergic receptor agonist activity. Study of the biosynthesis of higenamine has shown the participation of norcoclaurine synthase, which controls the stereochemistry to construct the (S)-isomer. However, when isolated from nature, higenamine is found as the racemate, or even the (R)-isomer. We recently reported the isolation of higenamine 4′-O-β-d-glucoside. Herein, its (R)- and (S)-isomers were synthesized and compared to precisely determine the stereochemistry of the isolate. Owing to their similar spectral properties, determination of the stereochemistry based on NMR data was considered inappropriate. Therefore, a high-performance liquid chromatography method was established to separate the isomers, and natural higenamine 4′-O-β-d-glucoside was determined to be a mixture of isomers. Full article

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19 pages, 23194 KiB

Open AccessArticle

Coordination Mechanism and Bio-Evidence: Reactive γ-Ketoenal Intermediated Hepatotoxicity of Psoralen and Isopsoralen Based on Computer Approach and Bioassay

by Yue Hai^1,†, Shan Feng^1,2,†, Lili Wang¹, Yetao Ma¹, Yiran Zhai¹, Zijun Wu¹, Sichao Zhang¹ and Xin He^1,3,*

¹ School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Nankai District, Tianjin 300193, China

² College of Pharmaceutical Sciences and Chinese Medicine, Southwest University, Chongqing 400715, China

³ Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin 300193, China

^† These authors contributed equally to this manuscript.

Molecules 2017, 22(9), 1451; https://doi.org/10.3390/molecules22091451 - 4 Sep 2017

Cited by 14 | Viewed by 5242

Abstract

Psoralen and isopsoralen are secondary plant metabolites found in many fruits, vegetables, and medicinal herbs. Psoralen-containing plants (Psoralea corylifolia L.) have been reported to cause hepatotoxicity. Herein, we found that psoralen and isopsoralen were oxidized by CYP450s to reactive furanoepoxide or γ-ketoenal [...] Read more.

Psoralen and isopsoralen are secondary plant metabolites found in many fruits, vegetables, and medicinal herbs. Psoralen-containing plants (Psoralea corylifolia L.) have been reported to cause hepatotoxicity. Herein, we found that psoralen and isopsoralen were oxidized by CYP450s to reactive furanoepoxide or γ-ketoenal intermediates, causing a mechanism-based inhibition of CYP3A4. Furthermore, in GSH-depleted mice, the hepatotoxicity of these reactive metabolites has been demonstrated by pre-treatment with a well-known GSH synthesis inhibitor, L-buthionine-S, Rsulfoxinine (BSO). Moreover, a molecular docking simulation of the present study was undertaken to understand the coordination reaction that plays a significant role in the combination of unstable intermediates and CYP3A4. These results suggested that psoralen and isopsoralen are modest hepatotoxic agents, as their reactive metabolites could be deactivated by H₂O and GSH in the liver, which partly contributes to the ingestion of psoralen-containing fruits and vegetables being safe. Full article

(This article belongs to the Section Medicinal Chemistry)

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16 pages, 1241 KiB

Open AccessArticle

Identification of Polar Constituents in the Decoction of Juglans mandshurica and in the Medicated Egg Prepared with the Decoction by HPLC-Q-TOF MS²

by Tian-Min Wang¹, Ying Fu¹, Wen-Jie Yu¹, Chen Chen¹, Xue Di¹, Hui Zhang¹, Yan-Jun Zhai^1,*, Zheng-Yun Chu¹, Ting-Guo Kang¹ and Hu-Biao Chen^2,*

¹ School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian 116600, China

² School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong 999077, Hong Kong, China

Molecules 2017, 22(9), 1452; https://doi.org/10.3390/molecules22091452 - 1 Sep 2017

Cited by 16 | Viewed by 4778

Abstract

As a folk medicinal plant, Juglans mandshurica has been used for the treatment of cancer in China and Korea. Traditionally, J. mandshurica is decocted together with chicken eggs. Both the decoction and medicated eggs possess anti-tumor properties. Clarifying the constituents of the decoction [...] Read more.

As a folk medicinal plant, Juglans mandshurica has been used for the treatment of cancer in China and Korea. Traditionally, J. mandshurica is decocted together with chicken eggs. Both the decoction and medicated eggs possess anti-tumor properties. Clarifying the constituents of the decoction and absorbed by the medicated eggs is essential for the investigation of the active principles of J. mandshurica. Herein, the medicated eggs were prepared by decocting raw chicken eggs, having unbroken shells, with the decoction of J. mandshurica. A systematic investigation of the chemical profile of the J. mandshurica decoction and the medicated egg extraction was conducted by HPLC-Q-TOF-MS². In total, 93 peaks, including 45 tannins, 14 naphthalene derivatives, 17 organic acids, 3 diarylheptanoids, 4 lignans, 3 anthraquinones, 1 flavonoid glycoside, 3 amino acids, and 3 nitrogenous compounds, were tentatively identified in the decoction. In the medicated egg extraction, 44 peaks including 11 organic acids, 3 amino acids, 3 nitrogenous compounds, 8 naphthalene derivatives, 3 diarylheptanoids, 15 tannins, and 1 lignan were tentatively identified. The chemical profile presented provided a detailed overview of the polar chemical constituents in J. mandshurica and useful information for the research of bioactive compounds of this plant. Full article

(This article belongs to the Section Natural Products Chemistry)

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18 pages, 1604 KiB

Open AccessArticle

Changes in Tannin Composition of Syrah Grape Skins and Seeds during Fruit Ripening under Contrasting Water Conditions

by Maria Kyraleou¹, Stamatina Kallithraka¹

, Nikolaos Theodorou², Pierre-Louis Teissedre^3,4, Yorgos Kotseridis¹ and Stefanos Koundouras^2,*

¹ Laboratory of Enology, Department of Food Science and Technology, Agricultural University of Athens, 75 Iera Odos, 11855 Athens, Greece

² Laboratory of Viticulture, School of Agriculture, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece

³ Institut des Sciences de la Vigne et du Vin (ISVV), EA 4577, Œnologie, 210 Chemin de Leysotte, University Bordeaux, 33140 Villenave d’Ornon, France

⁴ INRA, ISVV, USC 1366 Œnologie, 210 Chemin de Leysotte, 33140 Villenave d’Ornon, France

Molecules 2017, 22(9), 1453; https://doi.org/10.3390/molecules22091453 - 1 Sep 2017

Cited by 49 | Viewed by 6545

Abstract

Tannin accumulation and composition were determined in skins and seeds isolated from Vitis vinifera cv. Syrah grapes submitted to contrasting water regimes under semiarid climatic conditions. Three irrigation treatments were conducted, starting at berry set through harvest of two growing seasons, 2011 and [...] Read more.

Tannin accumulation and composition were determined in skins and seeds isolated from Vitis vinifera cv. Syrah grapes submitted to contrasting water regimes under semiarid climatic conditions. Three irrigation treatments were conducted, starting at berry set through harvest of two growing seasons, 2011 and 2012: irrigation at 100% of crop evapotranspiration ETc (FI), irrigation at 50% of ETc (DI) and non-irrigated (NI). Seed total tannins did not vary with maturity but those of skins underwent a progressive decline (especially in 2011), expressed both on a fresh weight and on a per berry basis. Skin total tannin concentration and content per berry were increased under NI and DI conditions, mainly in 2012. In contrast, seed total tannins (in 2012) and flavan-3-ol monomers and tannin oligomers (both years) were higher in the fully irrigated vines (FI). Skin polymer size increased during ripening, NI and DI skins showing higher mean degree of polymerization (mDP) compared to FI at harvest. NI was also associated with a lower percentage of galloylation (%G) in skin oligomeric fraction (in 2012) and a lower percentage of prodelphinidins in the skin polymeric fraction (both years) at harvest. The mDP and %G of seed extracts did not vary during ripening and were higher in NI but only in 2012. According to the results, management of vine water status was shown to influence tannin amount and composition of Syrah grapes grown under semiarid conditions. Full article

(This article belongs to the Collection Wine Chemistry)

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9 pages, 719 KiB

Open AccessArticle

Constituents of the Fruits of Citrus medica L. var. sarcodactylis and the Effect of 6,7-Dimethoxy-coumarin on Superoxide Anion Formation and Elastase Release

by Yu-Yi Chan¹, Tsong-Long Hwang^2,3,4

, Ping-Chung Kuo⁵

, Hsin-Yi Hung⁵ and Tian-Shung Wu^5,6,*

¹ Department of Biotechnology, Southern Taiwan University of Science and Technology, Tainan 71005, Taiwan

² Graduate Institute of Natural Products, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan

³ Research Center for Chinese Herbal Medicine, Research Center for Food and Cosmetic Safety, and Graduate Institute of Health Industry Technology, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan 333, Taiwan

⁴ Department of Anesthesiology, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan

⁵ School of Pharmacy, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan

⁶ Department of Pharmacy, College of Pharmacy and Health Care, Tajen University, Pingtung 907, Taiwan

Molecules 2017, 22(9), 1454; https://doi.org/10.3390/molecules22091454 - 1 Sep 2017

Cited by 18 | Viewed by 5458

Abstract

Investigation of the chemical constituents from the fruits of Citrus medica L. var. sarcodactylis Swingle has led to the characterization of a new sesquiterpene 1 along with thirty-two known compounds. The structure of 1 was established on the basis of 2D NMR spectroscopic [...] Read more.

Investigation of the chemical constituents from the fruits of Citrus medica L. var. sarcodactylis Swingle has led to the characterization of a new sesquiterpene 1 along with thirty-two known compounds. The structure of 1 was established on the basis of 2D NMR spectroscopic and mass spectrometric analyses, and the known compounds were identified by comparison of their physical and spectroscopic data with those reported in the literature. In addition, most of the isolated compounds were evaluated for the activity assayed by the in vitro inhibition of superoxide anion generation and elastase release by human neutrophils. The results showed that only 6,7-dimethoxycoumarin (5) exhibited significant inhibition of superoxide anion generation, with IC₅₀ value of 3.8 ± 1.4 μM. Full article

(This article belongs to the Section Natural Products Chemistry)

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10 pages, 1415 KiB

Open AccessArticle

Zeamide, a Glycosylinositol Phosphorylceramide with the Novel Core Arap(1β→6)Ins Motif from the Marine Sponge Svenzea zeai

by Gerardo Della Sala¹

, Roberta Teta¹, Germana Esposito¹

, Joseph R. Pawlik², Alfonso Mangoni¹

and Valeria Costantino^1,*

¹ The NeaNat Group, Dipartimento di Farmacia, Università degli Studi di Napoli Federico II, via D. Montesano 49, Napoli 80131, Italy

² Department of Biology and Marine Biology, University of North Carolina Wilmington, Center for Marine Science, 5600 Marvin K Moss Lane, Wilmington, NC 28409, USA

Molecules 2017, 22(9), 1455; https://doi.org/10.3390/molecules22091455 - 1 Sep 2017

Cited by 3 | Viewed by 7361

Abstract

Glycosylinositol phosphorylceramides (GIPCs) show a great structural diversity, but all share a small number of core structures, with a glucosamine, a mannose, or a glucuronic acid as the first sugar linked to the inositol. The Caribbean sponge Svenzea zeai was shown to consistently [...] Read more.

Glycosylinositol phosphorylceramides (GIPCs) show a great structural diversity, but all share a small number of core structures, with a glucosamine, a mannose, or a glucuronic acid as the first sugar linked to the inositol. The Caribbean sponge Svenzea zeai was shown to consistently contain zeamide (1), the first example of a new class of GIPCs, in which the inositol is glycosylated by a d-arabinose. The structure of zeamide was determined by spectroscopic analysis (NMR, MS, ECD) and microscale chemical degradation. The 6-O-β-d-arabinopyranosyl-myo-inositol (d-Arap(1β→6)Ins) core motif of zeamide is unprecedented not only among GIPCs, but also in any natural glycoconjugate. Full article

(This article belongs to the Section Metabolites)

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13 pages, 2360 KiB

Open AccessArticle

Origin and Formation Mechanism Investigation of Compound Precipitation from the Traditional Chinese Prescription Huang-Lian-Jie-Du-Tang by Isothermal Titration Calorimetry

by Hui Wang^1,†, Tong Li^1,†, Hongjun Xiang¹, Xinyu Zhang¹, Kang Fang¹, Gaorong Wu¹, Mengmeng Yan¹, Nannan Xue¹, Meng Chen¹, Tianxin Xie¹, Yuzhong Zhang², Penglong Wang^1,*

and Haimin Lei^1,*

¹ School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 100102, China

² Department of Pathology, Beijing University of Chinese Medicine, Beijing 100102, China

^† These authors contributed equally to this work.

Molecules 2017, 22(9), 1456; https://doi.org/10.3390/molecules22091456 - 1 Sep 2017

Cited by 29 | Viewed by 5880

Abstract

Previous studies have shown that compounds in the form of precipitate (CFP) from Huang-Lian-Jie-Du-Tang (HLJDT) were stable, and the CFP content reached 2.63% of the whole decoction and had good neuroprotective effects. However, there has been no research on their specific source. In [...] Read more.

Previous studies have shown that compounds in the form of precipitate (CFP) from Huang-Lian-Jie-Du-Tang (HLJDT) were stable, and the CFP content reached 2.63% of the whole decoction and had good neuroprotective effects. However, there has been no research on their specific source. In this study, it was found that HLJDT CFP mainly came from the reaction of Scutellaria baicalensis and Coptis chinensis by studying the separated prescription components (accounting for 81.33% of HLJDT CFP). Unlike previous studies on HLJDT CFP, in this research the chemical composition of Scutellaria baicalensis–Coptis chinensis (SB–CC) CFP was identified by high performance liquid chromatography coupled with mass spectrometry (HPLC-MSⁿ), which further proved that the main source of HLJDT CFP was Scutellaria baicalensis–Coptis chinensis CFP compared with previous HLJDT CFP studies. To explain the reaction mechanism between the decoctions of Scutellaria baicalensis and Coptis chinensis, isothermal titration calorimetry (ITC) was used to analyze their binding heat and the thermodynamic parameters (ΔH, ΔS, ΔG, n, Ka) of the reaction between baicalin and berberine, which are the main components of Scutellaria baicalensis and Coptis chinensis, respectively. The results showed that the reaction between decoctions of Scutellaria baicalensis and Coptis chinensis was exothermic and the reaction between baicalin and berberine was a spontaneous and enthalpy-driven chemical reaction, the binding ratio being 1:1. In addition, HLJDT CFP (EC₅₀ = 14.71 ± 0.91 µg/mL) and SB-CC CFP (EC₅₀ = 6.11 ± 0.12 µg/mL) showed similar protective activities on PC12 cells injured by cobalt chloride (CoCl₂). This study provided a new angle to research on the main chemical components and therapeutic values of CFP in Traditional Chinese Medicine compounds. Full article

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

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27 pages, 9621 KiB

Open AccessArticle

Mechanochemical Synthesis and Biological Evaluation of Novel Isoniazid Derivatives with Potent Antitubercular Activity

by Paulo F. M. Oliveira^1,2,3,†

, Brigitte Guidetti^2,3, Alain Chamayou¹, Christiane André-Barrès^2,3, Jan Madacki⁴, Jana Korduláková^4,*, Giorgia Mori⁵, Beatrice Silvia Orena⁵, Laurent Roberto Chiarelli⁵

, Maria Rosalia Pasca^5,*

, Christian Lherbet^2,3, Chantal Carayon^2,3, Stéphane Massou², Michel Baron¹ and Michel Baltas^2,3,*

¹ Department of Process Engineering, Université de Toulouse, Mines-Albi, CNRS UMR 5302, Centre RAPSODEE, Campus Jarlard, 81013 Albi, France

² Department of Chemistry, Université de Toulouse, UPS, CNRS UMR 5068, LSPCMIB, 118 Route de Narbonne, 31062 Toulouse, France

³ CNRS, Laboratoire de Synthèse et Physico-Chimie de Molécules d’Intérêt Biologique, LSPCMIB, UMR-5068, 118 Route de Narbonne, 31062 Toulouse, France

⁴ Department of Biochemistry, Comenius University in Bratislava, Faculty of Natural Sciences, Mlynská Dolina, Ilkovičova 6, 84215 Bratislava, Slovakia

⁵ Department of Biology and Biotechnology “Lazzaro Spallanzani”, University of Pavia; via Ferrata 1, 27100 Pavia, Italy

^† Current address: Université de Lille, UMET, Unité Matériaux et Transformations, CNRS UMR 8207, F-59000 Lille, France.

Molecules 2017, 22(9), 1457; https://doi.org/10.3390/molecules22091457 - 1 Sep 2017

Cited by 80 | Viewed by 10128

Abstract

A series of isoniazid derivatives bearing a phenolic or heteroaromatic coupled frame were obtained by mechanochemical means. Their pH stability and their structural (conformer/isomer) analysis were checked. The activity of prepared derivatives against Mycobacterium tuberculosis cell growth was evaluated. Some compounds such as [...] Read more.

A series of isoniazid derivatives bearing a phenolic or heteroaromatic coupled frame were obtained by mechanochemical means. Their pH stability and their structural (conformer/isomer) analysis were checked. The activity of prepared derivatives against Mycobacterium tuberculosis cell growth was evaluated. Some compounds such as phenolic hydrazine 1a and almost all heteroaromatic ones, especially 2, 5 and 7, are more active than isoniazid, and their activity against some M. tuberculosis MDR clinical isolates was determined. Compounds 1a and 7 present a selectivity index >1400 evaluated on MRC5 human fibroblast cells. The mechanism of action of selected hydrazones was demonstrated to block mycolic acid synthesis due to InhA inhibition inside the mycobacterial cell. Full article

(This article belongs to the Section Medicinal Chemistry)

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12 pages, 7072 KiB

Open AccessArticle

Dramatic Influence of Ionic Liquid and Ultrasound Irradiation on the Electrophilic Sulfinylation of Aromatic Compounds by Sulfinic Esters

by Ngoc-Lan Thi Nguyen¹, Hong-Thom Vo¹, Fritz Duus² and Thi Xuan Thi Luu^1,*

¹ Department of Organic Chemistry, VNUHCM-University of Science, 227 Nguyen Van Cu St., Dist. 5, 700000 Ho Chi Minh City, Vietnam

² Department of Science and Environment, Roskilde University, P.O. Box 260, DK-4000 Roskilde, Denmark

Molecules 2017, 22(9), 1458; https://doi.org/10.3390/molecules22091458 - 4 Sep 2017

Cited by 22 | Viewed by 5670

Abstract

The sulfinylation reaction of aromatic and hetero-aromatic compounds with sulfinic esters as electrophiles has been investigated in different ionic liquids and by means of different Lewis acid salts in order to get moderate to good yields of asymmetrical sulfoxides. Mixtures of 1-butyl-3-methylimidazolium chloride [...] Read more.

The sulfinylation reaction of aromatic and hetero-aromatic compounds with sulfinic esters as electrophiles has been investigated in different ionic liquids and by means of different Lewis acid salts in order to get moderate to good yields of asymmetrical sulfoxides. Mixtures of 1-butyl-3-methylimidazolium chloride and aluminum chloride were found to be the most efficient and recyclable reaction framework. Ultrasound sonication appeared to be the most useful and green activation method to afford the sulfoxides in yields better than or equivalent to those obtained under the longer-lasting conventional stirring conditions. Full article

(This article belongs to the Section Organic Chemistry)

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13 pages, 1368 KiB

Open AccessArticle

Diuretic Activity of Compatible Triterpene Components of Alismatis rhizoma

by Xue Zhang^1,2,†, Xiao-Yan Li^1,†, Na Lin¹, Wan-Li Zhao¹, Xiao-Qiang Huang¹, Ying Chen¹, Ming-Qing Huang^1,2, Wen Xu^1,2,* and Shui-Sheng Wu^1,2,*

¹ College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China

² Centre of Biomedical Research & Development, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China

^† These authors contributed equally to this work.

Molecules 2017, 22(9), 1459; https://doi.org/10.3390/molecules22091459 - 6 Sep 2017

Cited by 58 | Viewed by 8295

Abstract

Alismatis rhizoma (AR), the dried rhizoma of Alisma orientale Juzepzuk (Alismataceae), is a traditional Chinese medicine. AR is an important part of many prescriptions and is commonly used as a diuretic agent in Asia. This study aimed to evaluate the diuretic effects of [...] Read more.

Alismatis rhizoma (AR), the dried rhizoma of Alisma orientale Juzepzuk (Alismataceae), is a traditional Chinese medicine. AR is an important part of many prescriptions and is commonly used as a diuretic agent in Asia. This study aimed to evaluate the diuretic effects of total triterpene extract (TTE) and triterpene component compatibility (TCC, the mixture of alisol B 23-acetate, alisol B, alisol A 24-acetate, alisol A, and alisol C 23-acetate) of AR in saline-loaded rats. The optimal diuretic TCC of AR was optimized using a uniform design. Different doses (5, 20, and 40 mg/kg) of TTE and TCC groups (N1–N8) were orally administered to rats. Urinary excretion rate, pH, and electrolyte excretion were measured in the urine of saline-loaded rats. Results showed that TTE doses increased urine volume and electrolyte excretion compared with the control group. All uniformly designed groups of TCC also increased urine excretion. In addition, optimal diuretic TCC was calculated (alisol B 23-acetate: alisol B: alisol A 24-acetate: alisol A: alisol C 23-acetate 7.2:0.6:2.8:3.0:6.4) and further validated by saline-loaded rats. This study demonstrated that TTE presented a notable diuretic effect by increasing Na⁺, K⁺, and Cl⁻ displacements. The most suitable TTC compatible proportion of alisol B 23-acetate: alisol B: alisol A 24-acetate: alisol A: alisol C 23-acetate for diuretic activity was validated, and triterpenes were the material basis for the diuretic activity of AR. Full article

(This article belongs to the Collection Herbal Medicine Research)

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15 pages, 1374 KiB

Open AccessArticle

Statistical Methodologies for the Optimization of Lipase and Biosurfactant by Ochrobactrum intermedium Strain MZV101 in an Identical Medium for Detergent Applications

by Gholamhossein Ebrahimipour, Hossein Sadeghi and Mina Zarinviarsagh^*

Department of Microbiology and Microbial Biotechnology, Faculty of Biological Sciences and Technology, University of Shahid-Beheshty, Tehran 1983963113, Iran

Molecules 2017, 22(9), 1460; https://doi.org/10.3390/molecules22091460 - 11 Sep 2017

Cited by 15 | Viewed by 5188

Abstract

The Plackett–Burman design and the Box–Behnken design, statistical methodologies, were employed for the optimization lipase and biosurfactant production by Ochrobactrum intermedium strain MZV101 in an identical broth medium for detergent applications. Environmental factor pH determined to be most mutual significant variables on production. [...] Read more.

The Plackett–Burman design and the Box–Behnken design, statistical methodologies, were employed for the optimization lipase and biosurfactant production by Ochrobactrum intermedium strain MZV101 in an identical broth medium for detergent applications. Environmental factor pH determined to be most mutual significant variables on production. A high concentration of molasses at high temperature and pH has a negative effect on lipase and biosurfactant production by O. intermedium strain MZV101. The chosen mathematical method of medium optimization was sufficient for improving the industrial production of lipase and biosurfactant by bacteria, which were respectively increased 3.46- and 1.89-fold. The duration of maximum production became 24 h shorter, so it was fast and cost-saving. In conclusion, lipase and biosurfactant production by O. intermedium strain MZV101 in an identical culture medium at pH 10.5–11 and 50–60 °C, with 1 g/L of molasses, seemed to be economical, fast, and effective for the enhancement of yield percentage for use in detergent applications. Full article

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

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12 pages, 259 KiB

Open AccessArticle

Persimmon Fruit Powder May Substitute Indolbi, a Synthetic Growth Regulator, in Soybean Sprout Cultivation

by Il-Doo Kim¹, Sanjeev Kumar Dhungana²

, Yong-Sung Park², Dong Joon Kim³ and Dong-Hyun Shin^2,*

¹ International Institute of Agricultural Research & Development, Kyungpook National University, Daegu 41566, Korea

² School of Applied Biosciences, Kyungpook National University, Daegu 41566, Korea

³ Department of Tourism Management, Yeungnam University College, Daegu 42415, Korea

Molecules 2017, 22(9), 1462; https://doi.org/10.3390/molecules22091462 - 3 Sep 2017

Cited by 8 | Viewed by 4763

Abstract

Soybean sprouts are a major food item in Korea. Various studies have been carried out to enhance their yield and nutritional values. The objective of the present study was to examine the influence of persimmon fruit powder and Indolbi, a synthetic plant growth [...] Read more.

Soybean sprouts are a major food item in Korea. Various studies have been carried out to enhance their yield and nutritional values. The objective of the present study was to examine the influence of persimmon fruit powder and Indolbi, a synthetic plant growth regulator, on the yield and nutritional value of soybean sprouts. Seeds were soaked in tap water containing 0.5%, 1.0%, 2.5% and 5.0% (w/v) persimmon fruit powder and the samples were named as PT-1, PT-2, PT-3, and PT-4, respectively. The yield increment was almost doubled in PT-3 and PT-4 than in the Indolbi treated sprouts on basis of the control. Vitamin C, isoflavones, and total phenolic contents as well as antioxidant potentials (determined by 1,1-diphenyl-2-picrylhydrazyl and superoxide anion radical scavenging assays) were also significantly (p < 0.05) higher in PT-3 compared to the Indolbi treatment and the control. However, total free amino acid and magnesium contents of Indolbi- applied sprouts were higher than in the fruit powder treatments. The overall results of the present study showed that persimmon fruit powder can be an option to enhance the yield and nutritional value of soybean sprouts since, due to potential health hazards, the use of synthetic chemicals like Indolbi is less preferred than the natural products. Full article

(This article belongs to the Section Natural Products Chemistry)

10 pages, 665 KiB

Open AccessArticle

EPuL: An Enhanced Positive-Unlabeled Learning Algorithm for the Prediction of Pupylation Sites

by Xuanguo Nan¹, Lingling Bao¹, Xiaosa Zhao¹

, Xiaowei Zhao¹, Arun Kumar Sangaiah²

, Gai-Ge Wang^3,*

and Zhiqiang Ma^1,*

¹ School of Information Science and Technology, Northeast Normal University, Changchun 130117, China

² School of Computing Science and Engineering, VIT University, Vellore 632014, Tamil Nadu, India

³ School of Computer Science and Technology, Jiangsu Normal University, Xuzhou 221116, China

Molecules 2017, 22(9), 1463; https://doi.org/10.3390/molecules22091463 - 5 Sep 2017

Cited by 27 | Viewed by 4779

Abstract

Protein pupylation is a type of post-translation modification, which plays a crucial role in cellular function of bacterial organisms in prokaryotes. To have a better insight of the mechanisms underlying pupylation an initial, but important, step is to identify pupylation sites. To date, [...] Read more.

Protein pupylation is a type of post-translation modification, which plays a crucial role in cellular function of bacterial organisms in prokaryotes. To have a better insight of the mechanisms underlying pupylation an initial, but important, step is to identify pupylation sites. To date, several computational methods have been established for the prediction of pupylation sites which usually artificially design the negative samples using the verified pupylation proteins to train the classifiers. However, if this process is not properly done it can affect the performance of the final predictor dramatically. In this work, different from previous computational methods, we proposed an enhanced positive-unlabeled learning algorithm (EPuL) to the pupylation site prediction problem, which uses only positive and unlabeled samples. Firstly, we separate the training dataset into the positive dataset and the unlabeled dataset which contains the remaining non-annotated lysine residues. Then, the EPuL algorithm is utilized to select the reliably negative initial dataset and then iteratively pick out the non-pupylation sites. The performance of the proposed method was measured with an accuracy of 90.24%, an Area Under Curve (AUC) of 0.93 and an MCC of 0.81 by 10-fold cross-validation. A user-friendly web server for predicting pupylation sites was developed and was freely available at http://59.73.198.144:8080/EPuL Full article

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

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6 pages, 738 KiB

Open AccessReview

Why is Aged Acetylcholinesterase So Difficult to Reactivate?

by Daniel M. Quinn^*, Joseph Topczewski, Nilanthi Yasapala and Alexander Lodge

Department of Chemistry, University of Iowa, Iowa City, IA 52242, USA

Molecules 2017, 22(9), 1464; https://doi.org/10.3390/molecules22091464 - 4 Sep 2017

Cited by 35 | Viewed by 7285

Abstract

Organophosphorus agents are potent inhibitors of acetylcholinesterase. Inhibition involves successive chemical events. The first is phosphylation of the active site serine to produce a neutral adduct, which is a close structural analog of the acylation transition state. This adduct is unreactive toward spontaneous [...] Read more.

Organophosphorus agents are potent inhibitors of acetylcholinesterase. Inhibition involves successive chemical events. The first is phosphylation of the active site serine to produce a neutral adduct, which is a close structural analog of the acylation transition state. This adduct is unreactive toward spontaneous hydrolysis, but in many cases can be reactivated by nucleophilic medicinal agents, such as oximes. However, the initial phosphylation reaction may be followed by a dealkylation reaction of the incipient adduct. This reaction is called aging and produces an anionic phosphyl adduct with acetylcholinesterase that is refractory to reactivation. This review considers why the anionic aged adduct is unreactive toward nucleophiles. An alternate approach is to realkylate the aged adduct, which would render the adduct reactivatable with oxime nucleophiles. However, this approach confronts a considerable—and perhaps intractable—challenge: the aged adduct is a close analog of the deacylation transition state. Consequently, the evolutionary mechanisms that have led to transition state stabilization in acetylcholinesterase catalysis are discussed herein, as are the challenges that they present to reactivation of aged acetylcholinesterase. Full article

(This article belongs to the Special Issue The Cholinesterases—Structure, Mechanism, Function and Drug Design: The 25th Anniversary of the Solution of the Crystal Structure of Acetylcholinesterase by Joel L. Sussman and Israel Silman)

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13 pages, 3008 KiB

Open AccessArticle

Synergic Anti-Pruritus Mechanisms of Action for the Radix Sophorae Flavescentis and Fructus Cnidii Herbal Pair

by Jiali Zhong^1,†, Zhihong Liu^2,†

, Xinxin Zhou^1,* and Jun Xu^2,*

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

² School of Pharmaceutical Sciences, Sun Yat-Sen University, 132 East Circle Road at University City, Guangzhou 510006, China

^† These authors contribute equally.

Molecules 2017, 22(9), 1465; https://doi.org/10.3390/molecules22091465 - 4 Sep 2017

Cited by 34 | Viewed by 6595

Abstract

Radix Sophorae Flavescentis (RSF) and Fructus Cnidii (FC) compose a typical herbal synergic pair in traditional Chinese medicine (TCM) for pruritus symptom treatments. The mechanisms of action for the synergy are not understood. This paper aims at predicting the anti-pruritus targets and the [...] Read more.

Radix Sophorae Flavescentis (RSF) and Fructus Cnidii (FC) compose a typical herbal synergic pair in traditional Chinese medicine (TCM) for pruritus symptom treatments. The mechanisms of action for the synergy are not understood. This paper aims at predicting the anti-pruritus targets and the main active ingredients for the RSF and FC herbal pair. We demonstrate that the RSF–FC herbal pair can be elucidated by mining the chemical structures of compounds derived from RSF and FC. Based on chemical structure data, the putative targets for RSF and FC were predicted. Additional putative targets that interact with the anti-pruritus targets were derived by mapping the putative targets onto a PPI network. By examining the annotations of these proteins, we conclude that (1) RSF’s active compounds are mainly alkaloids and flavonoids. The representative putative targets of the alkaloids are inflammation-related proteins (MAPK14, PTGS2, PTGS2, and F2) and pruritus-related proteins (HRH1, TRPA1, HTR3A, and HTR6). The representative putative targets of the flavonoids are inflammation-related proteins (TNF, NF-κB, F2, PTGS2, and PTGS2) and pruritus-related proteins (NR3C1 and IL2). (2) FC’s active compounds are mainly coumarins. Their representative putative targets are CNS-related proteins (AChE and OPRK1) and inflammation-related proteins (PDE4D, TLR9, and NF-κB). (3) Both RSF and FC display anti-inflammatory effects, though they exhibit their anti-pruritus effects in different ways. Their synergy shows that RSF regulates inflammation-related pruritus and FC regulates CNS-related pruritus. Full article

(This article belongs to the Special Issue Herbal Remedies Meet Modern Day Medicine: Challenges and Opportunities)

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49 pages, 4033 KiB

Open AccessReview

Forsythiae Fructus: A Review on its Phytochemistry, Quality Control, Pharmacology and Pharmacokinetics

by Zhanglu Dong, Xianyuan Lu, Xueli Tong, Yaqian Dong, Lan Tang^* and Menghua Liu^*

Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China

Molecules 2017, 22(9), 1466; https://doi.org/10.3390/molecules22091466 - 4 Sep 2017

Cited by 101 | Viewed by 8458

Abstract

Forsythiae Fructus, as a traditional Chinese medicine, has been widely used both as a single herb and in compound prescriptions in Asia, mainly due to its heat-clearing and detoxifying effects. Modern pharmacology has proved Forsythiae Fructus possesses various therapeutic effects, both in [...] Read more.

Forsythiae Fructus, as a traditional Chinese medicine, has been widely used both as a single herb and in compound prescriptions in Asia, mainly due to its heat-clearing and detoxifying effects. Modern pharmacology has proved Forsythiae Fructus possesses various therapeutic effects, both in vitro and in vivo, such as anti-inflammatory, antibacterial and antiviral activities. Up to now, three hundred and twenty-one compounds have been identified and sensitive analytical methods have been established for its quality control. Recently, the pharmacokinetics of Forsythiae Fructus and its bioactive compounds have been reported, providing valuable information for its clinical application. Therefore, this systematic review focused on the newest scientific reports on Forsythiae Fructus and extensively summarizes its phytochemistry, pharmacology, pharmacokinetics and standardization procedures, especially the difference between the two applied types—unripe Forsythiae Fructus and ripe Forsythiae Fructus—in the hope of providing a helpful reference and guide for its clinical applications and further studies. Full article

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14 pages, 1276 KiB

Open AccessArticle

Phenolics Isolated from Aframomum meleguta Enhance Proliferation and Ossification Markers in Bone Cells

by Ashraf B. Abdel-Naim^1,2,*, Abdullah A. Alghamdi³, Mardi M. Algandaby^1,4, Fahad A. Al-Abbasi^1,3, Ahmed M. Al-Abd^2,5

, Hossam M. Abdallah^6,7

, Ali M. El-Halawany⁷ and Masao Hattori⁸

¹ Medicinal Plants Research Unit, Deanship of Scientific Research, King Abdulaziz University, Jeddah 80230, Saudi Arabia

² Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia

³ Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah 21523, Saudi Arabia

⁴ Department of Biological Sciences, Faculty of Science, King Abdulaziz University, Jeddah 21523, Saudi Arabia

⁵ Pharmacology Department, Medical Division, National Research Centre, Giza 12622, Egypt

⁶ Department of Natural Products, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia

⁷ Department of Pharmacognosy, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt

⁸ Institute of Natural Medicine, University of Toyama, Toyama 930-0194, Japan

Molecules 2017, 22(9), 1467; https://doi.org/10.3390/molecules22091467 - 4 Sep 2017

Cited by 12 | Viewed by 6459

Abstract

Osteoporosis is a serious health problem characterized by decreased bone mineral density and deterioration of bone microarchitecture. Current antiosteoporotic agents exhibit a wide range of adverse effects; meanwhile, phytochemicals are effective and safer alternatives. In the current work, nine compounds belonging to hydroxyphenylalkane [...] Read more.

Osteoporosis is a serious health problem characterized by decreased bone mineral density and deterioration of bone microarchitecture. Current antiosteoporotic agents exhibit a wide range of adverse effects; meanwhile, phytochemicals are effective and safer alternatives. In the current work, nine compounds belonging to hydroxyphenylalkane and diarylheptanoid groups were isolated from Aframomum meleguea seeds and identified as 6-gingerol (1), 6-paradol (2), 8-dehydrogingerdione (3), 8-gingerol (4), dihydro-6-paradol (5), dihydrogingerenone A (6), dihydrogingerenone C (7), 1,7-bis(3,4-dihydroxy-5-methoxyphenyl)heptane-3,5-diyl diacetate (8), and 1-(3,4-dihydroxy-5-methoxyphenyl)-7-(3,4-dihydroxyphenyl)heptane-3,5-diyl diacetate (9). The structures of isolated compounds were established by NMR and mass spectral data, in addition to referring to literature data. Exposure of MCF-7, MG-63, and SAOS-2 cells to subcytotoxic concentrations of the compounds under investigation resulted in accelerated proliferation. Among them, paradol was selected for further detailed biochemical analysis in SAOS-2 cells. DNA flowcytometric analysis of cell cycle distribution revealed that paradol did not induce any significant change in the proliferation index of SAOS-2 cells. Assessment of osteogenic gene expression revealed that paradol enhanced the expression of osteocyte and osteoblast-related genes and inhibited osteoclast and RUNX suppressor genes. Biochemically, paradol enhanced alkaline phosphatase activity and vitamin D content and decreased the osteoporotic marker acid phosphatase. In conclusion, paradol, which is a major constituents of A. melegueta seeds, exhibited potent proliferative and ossification characteristics in bone cells. Full article

(This article belongs to the Collection Bioactive Compounds)

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13 pages, 2428 KiB

Open AccessArticle

The Variation of Oncidium Rosy Sunset Flower Volatiles with Daily Rhythm, Flowering Period, and Flower Parts

by Yi-Tien Chiu¹, Hsin-Chun Chen^2,*

and Chen Chang^1,*

¹ Department of Horticulture, National Chung Hsing University, 145 Xingda Rd., South Dist., Taichung 402, Taiwan

² Department of Cosmeceutics, China Medical University, 91 Hsueh-Shih Rd., Taichung 404, Taiwan

Molecules 2017, 22(9), 1468; https://doi.org/10.3390/molecules22091468 - 4 Sep 2017

Cited by 16 | Viewed by 5425

Abstract

Oncidium is an important ornamental crop worldwide, and in recent years, the characteristics of the flower aroma have become a concern for breeders. This study used headspace solid-phase microextraction (HS-SPME) and gas chromatography/mass spectrometry (GC-MS) analysis of the volatile compounds to study the [...] Read more.

Oncidium is an important ornamental crop worldwide, and in recent years, the characteristics of the flower aroma have become a concern for breeders. This study used headspace solid-phase microextraction (HS-SPME) and gas chromatography/mass spectrometry (GC-MS) analysis of the volatile compounds to study the aroma characteristics of Onc. Rosy Sunset. A total of 45 compounds were identified, with the major compound being linalool. Onc. Rosy Sunset had the highest odor concentration from 10:00 to 12:00 and lowest from 20:00 to 24:00. The inflorescence emitted the highest quantities of volatile compounds during stages 3–6, which then decreased with the aging of the flowers. In Onc. Rosy Sunset, the sepals and petals were the major parts for the floral fragrance emission, in which linalool content was the highest, whereas the lip and column had a different composition of major volatile compounds, of which benzaldehyde, β-myrcene, and β-caryophyllene dominated. Full article

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17 pages, 1282 KiB

Open AccessReview

Fructus Ligustri Lucidi in Osteoporosis: A Review of its Pharmacology, Phytochemistry, Pharmacokinetics and Safety

by Beibei Chen^1,†, Lili Wang^2,3,†, Lin Li^1,†, Ruyuan Zhu¹, Haixia Liu¹, Chenyue Liu², Rufeng Ma¹, Qiangqiang Jia¹, Dandan Zhao³, Jianzhao Niu¹, Min Fu⁴, Sihua Gao³ and Dongwei Zhang^3,*

¹ Traditional Chinese Medicine School, Beijing University of Chinese Medicine, Beijing 100029, China

² Chinese Material Medica School, Beijing University of Chinese Medicine, Beijing 100029, China

³ Diabetes Research Center, Beijing University of Chinese Medicine, Beijing 100029, China

⁴ The Research Institute of McGill University Health Center, Montreal, QC H4A 3J1, Canada

^† These authors contributed equally to this work.

Molecules 2017, 22(9), 1469; https://doi.org/10.3390/molecules22091469 - 5 Sep 2017

Cited by 67 | Viewed by 10926

Abstract

Background: Fructus Ligustri Lucidi (FLL) has now attracted increasing attention as an alternative medicine in the prevention and treatment of osteoporosis. This study aimed to provide a general review of traditional interpretation of the actions of FLL in osteoporosis, main phytochemical constituents, [...] Read more.

Background: Fructus Ligustri Lucidi (FLL) has now attracted increasing attention as an alternative medicine in the prevention and treatment of osteoporosis. This study aimed to provide a general review of traditional interpretation of the actions of FLL in osteoporosis, main phytochemical constituents, pharmacokinetics, pharmacology in bone improving effect, and safety. Materials and Methods: Several databases, including PubMed, China National Knowledge Infrastructure, National Science and Technology Library, China Science and Technology Journal Database, and Web of Science were consulted to locate publications pertaining to FLL. The initial inquiry was conducted for the presence of the following keywords combinations in the abstracts: Fructus Ligustri Lucidi, osteoporosis, phytochemistry, pharmacokinetics, pharmacology, osteoblasts, osteoclasts, salidroside. About 150 research papers and reviews were consulted. Results: FLL is assumed to exhibit anti-osteoporotic effects by improving liver and kidney deficiencies and reducing lower back soreness in Traditional Chinese Medicine (TCM). The data from animal and cell experiments demonstrate that FLL is able to improve bone metabolism and bone quality in ovariectomized, growing, aged and diabetic rats through the regulation of PTH/FGF-23/1,25-(OH)₂D₃/CaSR, Nox4/ROS/NF-κB, and OPG/RANKL/cathepsin K signaling pathways. More than 100 individual compounds have been isolated from this plant. Oleanolic acid, ursolic acid, salidroside, and nuzhenide have been reported to exhibit the anti-osteoporosis effect. The pharmacokinetics data reveals that salidroside is one of the active constituents, and that tyrosol is hard to detect under physiological conditions. Acute and subacute toxicity studies show that FLL is well tolerated and presents no safety concerns. Conclusions: FLL provides a new option for the prevention and treatment of osteoporosis, which attracts rising interests in identifying potential anti-osteoporotic compounds and fractions from this plant. Further scientific evidences are expected from well-designed clinical trials on its bone protective effects and safety. Full article

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

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14 pages, 1823 KiB

Open AccessArticle

Design and Antiproliferative Evaluation of Novel Sulfanilamide Derivatives as Potential Tubulin Polymerization Inhibitors

by Dong-Jun Fu^1,†, Ji-Feng Liu^1,†, Ruo-Han Zhao^1,†, Jia-Huan Li¹, Sai-Yang Zhang^2,* and Yan-Bing Zhang^1,*

¹ School of Pharmaceutical Sciences & Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou University, Zhengzhou 450001, China

² School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, China

^† These authors contributed equally to this work.

Molecules 2017, 22(9), 1470; https://doi.org/10.3390/molecules22091470 - 5 Sep 2017

Cited by 23 | Viewed by 5970

Abstract

A series of sulfanilamide-1,2,3-triazole hybrids were designed by a molecular hybridization strategy and evaluated for antiproliferative activity against three selected cancer cell lines (MGC-803, MCF-7 and PC-3). The detailed structure-activity relationships for these sulfanilamide-1,2,3-triazole hybrids were investigated. All these sulfanilamide-1,2,3-triazole hybrids exhibited moderate [...] Read more.

A series of sulfanilamide-1,2,3-triazole hybrids were designed by a molecular hybridization strategy and evaluated for antiproliferative activity against three selected cancer cell lines (MGC-803, MCF-7 and PC-3). The detailed structure-activity relationships for these sulfanilamide-1,2,3-triazole hybrids were investigated. All these sulfanilamide-1,2,3-triazole hybrids exhibited moderate to potent activity against all cell lines. In particular 4-methyl-N-((1-(3-phenoxybenzyl)-1H-1,2,3-triazol-4-yl)methyl)benzenesulfonamide (11f) showed the most potent inhibitory effect against PC-3 cells, with an IC₅₀ value of 4.08 μM. Furthermore, the tubulin polymerization inhibitory activity in vitro of compound 11f was 2.41 μM. These sulfanilamide hybrids might serve as bioactive fragments for developing more potent antiproliferative agents. 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, 3764 KiB

Open AccessCommunication

A New Monoterpene from the Leaves of a Radiation Mutant Cultivar of Perilla frutescens var. crispa with Inhibitory Activity on LPS-Induced NO Production

by Bomi Nam, Yangkang So, Hyo-Young Kim, Jin-Baek Kim, Chang Hyun Jin

and Ah-Reum Han^*

Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup-si, Jeollabuk-do 56212, Korea

Molecules 2017, 22(9), 1471; https://doi.org/10.3390/molecules22091471 - 4 Sep 2017

Cited by 18 | Viewed by 5809

Abstract

The leaves of Perilla frutescens var. crispa (Lamiaceae)—known as ‘Jureum-soyeop’ or ‘Cha-jo-ki’ in Korean, ‘ZI SU YE’ in Chinese, and ‘Shiso’ in Japan—has been used as a medicinal herb. Recent gamma irradiated mutation breeding on P. frutescens var. crispa in our research group [...] Read more.

The leaves of Perilla frutescens var. crispa (Lamiaceae)—known as ‘Jureum-soyeop’ or ‘Cha-jo-ki’ in Korean, ‘ZI SU YE’ in Chinese, and ‘Shiso’ in Japan—has been used as a medicinal herb. Recent gamma irradiated mutation breeding on P. frutescens var. crispa in our research group resulted in the development of a new perilla cultivar, P. frutescens var. crispa (cv. Antisperill; PFCA), which has a higher content of isoegomaketone. The leaves of PFCA were extracted by supercritical carbon dioxide (SC-CO₂) extraction, and phytochemical investigation on this extract led to the isolation and identification of a new compound, 9-hydroxy-isoegomaketone [(2E)-1-(3-furanyl)-4-hydroxy-4-methyl-2-penten-1-one; 1]. Compound 1 exhibited inhibitory activity on nitric oxide (NO) production in lipopolysaccharide (LPS)-activated RAW264.7 cells with an IC₅₀ value of 14.4 μM. The compounds in the SC-CO₂ extracts of the radiation mutant cultivar and the original plant were quantified by high-performance liquid chromatography with diode array detection. Full article

(This article belongs to the Collection Bioactive Compounds)

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8 pages, 1224 KiB

Open AccessArticle

Targeting PDE10A GAF Domain with Small Molecules: A Way for Allosteric Modulation with Anti-Inflammatory Effects

by Ana M. García¹, José Brea², Alejandro González-García², Concepción Pérez³

, María Isabel Cadavid², María Isabel Loza², Ana Martinez¹ and Carmen Gil^1,*

¹ Centro de Investigaciones Biológicas (CSIC), Ramiro de Maeztu 9, 28040 Madrid, Spain

² Instituto de Farmacia Industrial, Facultad de Farmacia, Universidad de Santiago de Compostela, Campus Universitario Sur s/n, 15782 Santiago de Compostela, Spain

³ Instituto de Química Médica (CSIC), Juan de la Cierva 3, 28006 Madrid, Spain

Molecules 2017, 22(9), 1472; https://doi.org/10.3390/molecules22091472 - 4 Sep 2017

Cited by 5 | Viewed by 4465

Abstract

Phosphodiesterase (PDE) enzymes regulate the levels of cyclic nucleotides, cAMP, and/or cGMP, being attractive therapeutic targets. In order to modulate PDE activity in a selective way, we focused our efforts on the search of allosteric modulators. Based on the crystal structure of the [...] Read more.

Phosphodiesterase (PDE) enzymes regulate the levels of cyclic nucleotides, cAMP, and/or cGMP, being attractive therapeutic targets. In order to modulate PDE activity in a selective way, we focused our efforts on the search of allosteric modulators. Based on the crystal structure of the PDE10A GAF-B domain, a virtual screening study allowed the discovery of new hits that were also tested experimentally, showing inhibitory activities in the micromolar range. Moreover, these new PDE10A inhibitors were able to decrease the nitrite production in LPS-stimulated cells, thus demonstrating their potential as anti-inflammatory agents. Full article

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

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16 pages, 703 KiB

Open AccessArticle

Medicinal Plants Based Products Tested on Pathogens Isolated from Mastitis Milk

by Claudia Pașca¹, Liviu Mărghitaș¹, Daniel Dezmirean¹, Otilia Bobiș²

, Victorița Bonta², Flore Chirilă³, Ioana Matei^3,* and Nicodim Fiț³

¹ Department of Apiculture and Sericiculture, University of Agricultural Sciences and Veterinary Medicine, Cluj-Napoca 400372, Romania

² Life Science Institute “King Michael I of Romania”, University of Agricultural Sciences and Veterinary Medicine, Cluj-Napoca 400372, Romania

³ Department of Microbiology (Veterinary Medicine), University of Agricultural Sciences and Veterinary Medicine, Cluj-Napoca 400372, Romania

Molecules 2017, 22(9), 1473; https://doi.org/10.3390/molecules22091473 - 4 Sep 2017

Cited by 44 | Viewed by 6035

Abstract

Bovine mastitis a major disease that is commonly associated with bacterial infection. The common treatment is with antibiotics administered intramammary into infected quarters of the udder. The excessive use of antibiotics leads to multidrug resistance and associated risks for human health. In this [...] Read more.

Bovine mastitis a major disease that is commonly associated with bacterial infection. The common treatment is with antibiotics administered intramammary into infected quarters of the udder. The excessive use of antibiotics leads to multidrug resistance and associated risks for human health. In this context, the search for alternative drugs based on plants has become a priority in livestock medicine. These products have a low manufacturing cost and no reports of antimicrobial resistance to these have been documented. In this context, the main objective of this study was to determine the antimicrobial effect of extracts and products of several indigenous, or acclimatized plants on pathogens isolated from bovine mastitis. A total of eleven plant alcoholic extracts and eight plant-derived products were tested against 32 microorganisms isolated from milk. The obtained results have shown an inhibition of bacterial growth for all tested plants, with better results for Evernia prunastri, Artemisia absinthium, and Lavandula angustifolia. Moreover, E. prunastri, Populus nigra, and L. angustifolia presented small averages of minimum inhibitory and bactericidal concentrations. Among the plant-derived products, three out of eight have shown a strong anti-microbial effect comparable with the effect of florfenicol and enrofloxacin, and better than individual plant extracts possibly due to synergism. These results suggest an important anti-microbial effect of these products on pathogens isolated from bovine mastitis with a possible applicability in this disease. Full article

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24 pages, 3017 KiB

Open AccessReview

Vegetable Oils as Alternative Solvents for Green Oleo-Extraction, Purification and Formulation of Food and Natural Products

by Edinson Yara-Varón^1,2,*, Ying Li^3,*

, Mercè Balcells²

, Ramon Canela-Garayoa²

, Anne-Sylvie Fabiano-Tixier¹ and Farid Chemat¹

¹ Laboratoire GREEN, Université d’Avignon et des Pays de Vaucluse, INRA, UMR408, GREEN Extraction Team, F-84000 Avignon, France

² Department of Chemistry, University of Lleida, Av. Alcalde Rovira Roure 191, 25198 Lleida, Spain

³ Department of Food Science and Engineering, College of Science and Engineering, Jinan University, Guangzhou 510632, China

Molecules 2017, 22(9), 1474; https://doi.org/10.3390/molecules22091474 - 5 Sep 2017

Cited by 156 | Viewed by 35308

Abstract

Since solvents of petroleum origin are now strictly regulated worldwide, there is a growing demand for using greener, bio-based and renewable solvents for extraction, purification and formulation of natural and food products. The ideal alternative solvents are non-volatile organic compounds (VOCs) that have [...] Read more.

Since solvents of petroleum origin are now strictly regulated worldwide, there is a growing demand for using greener, bio-based and renewable solvents for extraction, purification and formulation of natural and food products. The ideal alternative solvents are non-volatile organic compounds (VOCs) that have high dissolving power and flash point, together with low toxicity and less environmental impact. They should be obtained from renewable resources at a reasonable price and be easy to recycle. Based on the principles of Green Chemistry and Green Engineering, vegetable oils could become an ideal alternative solvent to extract compounds for purification, enrichment, or even pollution remediation. This review presents an overview of vegetable oils as solvents enriched with various bioactive compounds from natural resources, as well as the relationship between dissolving power of non-polar and polar bioactive components with the function of fatty acids and/or lipid classes in vegetable oils, and other minor components. A focus on simulation of solvent-solute interactions and a discussion of polar paradox theory propose a mechanism explaining the phenomena of dissolving polar and non-polar bioactive components in vegetable oils as green solvents with variable polarity. Full article

(This article belongs to the Section Green Chemistry)

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17 pages, 6849 KiB

Open AccessReview

Cyclodextrin-Catalyzed Organic Synthesis: Reactions, Mechanisms, and Applications

by Chang Cai Bai^1,†

, Bing Ren Tian^1,†, Tian Zhao¹, Qing Huang^1,2,* and Zhi Zhong Wang^1,2,*

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

² Key Laboratory of Hui Ethnic Medicine Modernization, Ministry of Education, Yinchuan 750004, China

^† These authors contributed equally to this work.

Molecules 2017, 22(9), 1475; https://doi.org/10.3390/molecules22091475 - 7 Sep 2017

Cited by 89 | Viewed by 11003

Abstract

Cyclodextrins are well-known macrocyclic oligosaccharides that consist of α-(1,4) linked glucose units and have been widely used as artificial enzymes, chiral separators, chemical sensors, and drug excipients, owing to their hydrophobic and chiral interiors. Due to their remarkable inclusion capabilities with small organic [...] Read more.

Cyclodextrins are well-known macrocyclic oligosaccharides that consist of α-(1,4) linked glucose units and have been widely used as artificial enzymes, chiral separators, chemical sensors, and drug excipients, owing to their hydrophobic and chiral interiors. Due to their remarkable inclusion capabilities with small organic molecules, more recent interests focus on organic reactions catalyzed by cyclodextrins. This contribution outlines the current progress in cyclodextrin-catalyzed organic reactions. Particular emphases are given to the organic reaction mechanisms and their applications. In the end, the future directions of research in this field are proposed. Full article

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20 pages, 4634 KiB

Open AccessArticle

Synthesis and DFT Calculations of Novel Vanillin-Chalcones and Their 3-Aryl-5-(4-(2-(dimethylamino)-ethoxy)-3-methoxyphenyl)-4,5-dihydro-1H-pyrazole-1-carbaldehyde Derivatives as Antifungal Agents

by Luis Alberto Illicachi¹, Joel José Montalvo-Acosta², Alberto Insuasty³, Jairo Quiroga¹

, Rodrigo Abonia¹, Maximiliano Sortino⁴

, Susana Zacchino⁴

and Braulio Insuasty^1,*

¹ Grupo de Investigación de Compuestos Heterocíclicos, Departamento de Química, Universidad del Valle, A. A. 25360 Cali, Colombia

² Laboratoire d’Ingénierie des Fonctions Moléculaires, Institut de Science et d’Ingénierie Supramoléculaires, UMR 7006, CNRS, F-6700 Strasbourg, France

³ Departamento de Química y Biología, Universidad del Norte, Km 5 vía Puerto Colombia, Barranquilla 081007, Colombia

⁴ Área Farmacognosia, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional del Rosario, Suipacha 531, 2000 Rosario, Argentina

Molecules 2017, 22(9), 1476; https://doi.org/10.3390/molecules22091476 - 5 Sep 2017

Cited by 28 | Viewed by 8545

Abstract

Novel (E)-1-(aryl)-3-(4-(2-(dimethylamino)ethoxy)-3-methoxyphenyl) prop-2-en-1-ones 4 were synthesized by a Claisen-Schmidt reaction of 4-(2-(dimethylamino)ethoxy)-3-methoxy-benzaldehyde (2) with several acetophenone derivatives 3. Subsequently, cyclocondensation reactions of chalcones 4 with hydrazine hydrate afforded the new racemic 3-aryl-5-(4-(2-(dimethylamino)ethoxy)-3-methoxyphenyl)-4,5-dihydro-1H-pyrazole-1-carbaldehydes 5 when the reaction [...] Read more.

Novel (E)-1-(aryl)-3-(4-(2-(dimethylamino)ethoxy)-3-methoxyphenyl) prop-2-en-1-ones 4 were synthesized by a Claisen-Schmidt reaction of 4-(2-(dimethylamino)ethoxy)-3-methoxy-benzaldehyde (2) with several acetophenone derivatives 3. Subsequently, cyclocondensation reactions of chalcones 4 with hydrazine hydrate afforded the new racemic 3-aryl-5-(4-(2-(dimethylamino)ethoxy)-3-methoxyphenyl)-4,5-dihydro-1H-pyrazole-1-carbaldehydes 5 when the reaction was carried out in formic acid. The antifungal activity of both series of compounds against eight fungal species was determined. In general, chalcone derivatives 4 showed better activities than pyrazolines 5 against all tested fungi. None of the compounds 4a–g and 5a–g showed activity against the three Aspergillus spp. In contrast, most of the compounds 4 showed moderate to high activities against three dermatophytes (MICs 31.25–62.5 µg/mL), being 4a followed by 4c the most active structures. Interestingly, 4a and 4c possess fungicidal rather than fungistatic activities, with MFC values between 31.25 and 62.5 μg/mL. The comparison of the percentages of inhibition of C. neoformans by the most active compounds 4, allowed us to know the role played by the different substituents of the chalcones’ A-ring. Also the most anti-cryptococcal compounds 4a–c and 4g, were tested in a second panel of five clinical C. neoformans strains in order to have an overview of their inhibition capacity not only of standardized but also of clinical C. neoformans strains. DFT calculations showed that the electrophilicity is the main electronic property to explain the differences in antifungal activities for the synthesized chalcones and pyrazolines compounds. Furthermore, a quantitative reactivity analysis showed that electron-withdrawing substituted chalcones presented the higher electrophilic character and hence, the greater antifungal activities among compounds of series 4. Full article

(This article belongs to the Collection Heterocyclic Compounds)

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9 pages, 1250 KiB

Open AccessArticle

Ginger Phytochemicals Inhibit Cell Growth and Modulate Drug Resistance Factors in Docetaxel Resistant Prostate Cancer Cell

by Chi-Ming Liu¹

, Chiu-Li Kao¹, Yu-Ting Tseng²

, Yi-Ching Lo^2,3,*

and Chung-Yi Chen^4,*

¹ Department of Nursing, Tzu Hui Institute of Technology, Pingtung County 92641, Taiwan

² Department of Pharmacology, School of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan

³ Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan

⁴ School of Medical and Health Sciences, Fooyin University, Ta-Liao District, Kaohsiung 83102, Taiwan

Molecules 2017, 22(9), 1477; https://doi.org/10.3390/molecules22091477 - 5 Sep 2017

Cited by 68 | Viewed by 9370

Abstract

Ginger has many bioactive compounds with pharmacological activities. However, few studies are known about these bioactive compounds activity in chemoresistant cells. The aim of the present study was to investigate the anticancer properties of ginger phytochemicals in docetaxel-resistant human prostate cancer cells in [...] Read more.

Ginger has many bioactive compounds with pharmacological activities. However, few studies are known about these bioactive compounds activity in chemoresistant cells. The aim of the present study was to investigate the anticancer properties of ginger phytochemicals in docetaxel-resistant human prostate cancer cells in vitro. In this study, we isolated 6-gingerol, 10-gingerol, 4-shogaol, 6-shogaol, 10-shogaol, and 6-dehydrogingerdione from ginger. Further, the antiproliferation activity of these compounds was examined in docetaxel-resistant (PC3R) and sensitive (PC3) human prostate cancer cell lines. 6-gingerol, 10-gingerol, 6-shogaol, and 10-shogaol at the concentration of 100 μM significantly inhibited the proliferation in PC3R but 6-gingerol, 6-shogaol, and 10-shogaol displayed similar activity in PC3. The protein expression of multidrug resistance associated protein 1 (MRP1) and glutathione-S-transferase (GSTπ) is higher in PC3R than in PC3. In summary, we isolated the bioactive compounds from ginger. Our results showed that 6-gingerol, 10-gingerol, 6-shogaol, and 10-shogaol inhibit the proliferation of PC3R cells through the downregulation of MRP1 and GSTπ protein expression. Full article

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

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13 pages, 2043 KiB

Open AccessArticle

Non-Polar Natural Products from Bromelia laciniosa, Neoglaziovia variegata and Encholirium spectabile (Bromeliaceae)

by Ole Johan Juvik¹, Bjarte Holmelid¹, George W. Francis¹, Heidi Lie Andersen², Ana Paula De Oliveira³, Raimundo Gonçalves de Oliveira Júnior³

, Jackson Roberto Guedes da Silva Almeida³ and Torgils Fossen^1,*

¹ Department of Chemistry and Centre for Pharmacy, University of Bergen, Allégaten 41, 5007 Bergen, Norway

² Arboretum and Botanical Gardens, University of Bergen, Allégaten 41, 5007 Bergen, Norway

³ Centre for Studies and Research of Medicinal Plants, Federal University of Vale do São Francisco, 56.304-205 Petrolina, Pernambuco, Brazil

Molecules 2017, 22(9), 1478; https://doi.org/10.3390/molecules22091478 - 6 Sep 2017

Cited by 10 | Viewed by 6241

Abstract

Extensive regional droughts are already a major problem on all inhabited continents and severe regional droughts are expected to become an increasing and extended problem in the future. Consequently, extended use of available drought resistant food plants should be encouraged. Bromelia laciniosa, [...] Read more.

Extensive regional droughts are already a major problem on all inhabited continents and severe regional droughts are expected to become an increasing and extended problem in the future. Consequently, extended use of available drought resistant food plants should be encouraged. Bromelia laciniosa, Neoglaziovia variegata and Encholirium spectabile are excellent candidates in that respect because they are established drought resistant edible plants from the semi-arid Caatinga region. From a food safety perspective, increased utilization of these plants would necessitate detailed knowledge about their chemical constituents. However, their chemical compositions have previously not been determined. For the first time, the non-polar constituents of B. laciniosa, N. variegata and E. spectabile have been identified. This is the first thorough report on natural products from N. variegata, E. spectabile, and B. laciniosa. Altogether, 20 non-polar natural products were characterized. The identifications were based on hyphenated gas chromatography-high resolution mass spectrometry (GC-HRMS) and supported by 1D and 2D Nuclear Magnetic Resonance (NMR) plant metabolomics. Full article

(This article belongs to the Section Natural Products Chemistry)

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12 pages, 4896 KiB

Open AccessArticle

Masticadienonic and 3α-OH Masticadienoic Acids Induce Apoptosis and Inhibit Cell Proliferation and Tumor Growth in Prostate Cancer Xenografts in Vivo

by Ma. Beatriz Sánchez-Monroy¹, Nadia J. Jacobo-Herrera², Alejandro Zentella-Dehesa^2,4, Beatriz Hernández-Téllez³ and Mariano Martínez-Vázquez^1,*

¹ Departamento de Productos Naturales, Instituto de Química, Universidad Nacional Autónoma de México, Circuito Exterior, Ciudad Universitaria, Delegación Coyoacán C.P., CDMX 04510, Mexico

² Departamento de Bioquímica, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga 15, Sección XVI, Delegación Tlalpan C.P., CDMX 14000, Mexico

³ Departamento de Biología Celular y Tisular, Facultad de Medicina, Universidad Nacional Autónoma de México, Circuito Exterior, Ciudad Universitaria, Delegación Coyoacán C.P., CDMX 04510, Mexico

⁴ Departamento de Medicina Genómica y Toxicología Ambiental & Programa Institucional de Cáncer de Mama, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Circuito Deportivo, Ciudad Universitaria, Delegación Coyoacán C.P., CDMX 04510, Mexico

Molecules 2017, 22(9), 1479; https://doi.org/10.3390/molecules22091479 - 6 Sep 2017

Cited by 12 | Viewed by 5949

Abstract

The triterpenes have been constituted as a group of interesting molecules as possible antitumor agents. Despite several of them not presenting a potent cytotoxic activity in vitro against cancer cells, in vivo in xenotransplant tumors studies, they show promising results. Based on the [...] Read more.

The triterpenes have been constituted as a group of interesting molecules as possible antitumor agents. Despite several of them not presenting a potent cytotoxic activity in vitro against cancer cells, in vivo in xenotransplant tumors studies, they show promising results. Based on the above considerations, we investigated the antitumor activity of both masticadienonic (MDA) and 3α-OH masticadienoic (3α-OH MDA) acids in a mouse prostate cancer xenograft model. Immunohistochemical assays were used to evaluate the decrease in the expression of the Proliferating Cell Nuclear Antigen (PCNA) and the Ki-67 induced by MDA and 3α-OH MDA. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay was performed to demonstrate the fragmentation of DNA. Our results showed that the two triterpenes inhibited tumor growth, had anti-proliferative effect in vivo and induced cell death by apoptosis. Collectively, our data suggested that the antitumor mechanism of MDA and 3α-OH MDA involves several molecular targets related to cell proliferation and apoptosis. Full article

(This article belongs to the Section Natural Products Chemistry)

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10 pages, 1593 KiB

Open AccessArticle

Anti-Melanogenic Effects of Flavonoid Glycosides from Limonium tetragonum (Thunb.) Bullock via Inhibition of Tyrosinase and Tyrosinase-Related Proteins

by Seul-Gi Lee¹, Fatih Karadeniz²

, Youngwan Seo^3,4 and Chang-Suk Kong^1,2,*

¹ Department of Food and Nutrition, College of Medical and Life Sciences, Silla University, Baegyang-dero 700beon-gil 140, Sasang-gu, Busan 46958, Korea

² Marine Biotechnology Center for Pharmaceuticals and Foods, Silla University, Baegyang-dero 700beon-gil 140, Sasang-gu, Busan 46958, Korea

³ Division of Marine Bioscience, College of Ocean Science and Technology, Korea Maritime and Ocean University, Busan 49112, Korea

⁴ Department of Convergence Study on the Ocean Science and Technology, Ocean Science and Technology School, Korea Maritime and Ocean University, Busan 49112, Korea

Molecules 2017, 22(9), 1480; https://doi.org/10.3390/molecules22091480 - 5 Sep 2017

Cited by 44 | Viewed by 6322

Abstract

Overproduction and stimulation of tyrosinase result in increased melanogenesis of which several skin disorders such as freckles, spots, and hyperpigmentation appear as complications. Limonium tetragonum is a halophyte well-known for its antioxidative properties. This study investigated the anti-melanogenic effects of solvent-partitioned L. tetragonum [...] Read more.

Overproduction and stimulation of tyrosinase result in increased melanogenesis of which several skin disorders such as freckles, spots, and hyperpigmentation appear as complications. Limonium tetragonum is a halophyte well-known for its antioxidative properties. This study investigated the anti-melanogenic effects of solvent-partitioned L. tetragonum extracts (LTEs) and its bioactive constituents, two isolated flavonoid glycosides. Current study followed a set of experiments on B16-F10 mouse melanoma cell model with a focus on tyrosinase activity and production. The anti-melanogenic capacity of LTEs was confirmed by their tyrosinase inhibitory effects, prevention of DOPA oxidation, and suppression of melanin production. The inhibition of tyrosinase and DOPA oxidation by LTEs was suggested to be related with the downregulation of microphthalmia-associated transcription factor, tyrosinase, tyrosinase-related protein-1, and tyrosinase-related protein-2, verified with mRNA and protein expression levels. Among all tested LTEs, 85% aq. MeOH and n-BuOH were found to be the most active fractions which later yielded the two known compounds, myricetin 3-galactoside and quercetin 3-O-β-galactopyronaside. The anti-melanogenic potential of the compounds were confirmed by their tyrosinase inhibitory effects. These results suggested that L. tetragonum may serve as a potential source of bioactive substances with effective anti-melanogenesis properties. Full article

(This article belongs to the Special Issue Metalloenzyme Inhibitors and Activators)

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16 pages, 3037 KiB

Open AccessArticle

Microwave-Assisted Extraction of Natural Antioxidants from the Exotic Gordonia axillaris Fruit: Optimization and Identification of Phenolic Compounds

by Ya Li¹

, Sha Li^2,*, Sheng-Jun Lin³, Jiao-Jiao Zhang¹, Cai-Ning Zhao¹ and Hua-Bin Li^1,4,*

¹ Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-Sen University, Guangzhou 510080, China

² School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong 999077, China

³ Zhongshan Center for Disease Control and Prevention, Zhongshan 528403, China

⁴ South China Sea Bioresource Exploitation and Utilization Collaborative Innovation Center, Sun Yat-Sen University, Guangzhou 510006, China

Molecules 2017, 22(9), 1481; https://doi.org/10.3390/molecules22091481 - 6 Sep 2017

Cited by 86 | Viewed by 7132

Abstract

Our previous study reported that the fruit of Gordonia axillaris, an edible wild fruit, possessed strong antioxidant activity. In this study, a microwave-assisted extraction (MAE) method was established to extract antioxidants from the fruit of Gordonia axillaris. The influence of five [...] Read more.

Our previous study reported that the fruit of Gordonia axillaris, an edible wild fruit, possessed strong antioxidant activity. In this study, a microwave-assisted extraction (MAE) method was established to extract antioxidants from the fruit of Gordonia axillaris. The influence of five parameters, including ethanol concentration, solvent/material ratio, extraction time, extraction temperature and microwave power, was investigated by single-factor experiments. Three factors, namely ethanol concentration, solvent/material ratio, extraction time, were found to exert a major influence on extraction efficacy, and were further studied by response surface methodology to investigate their interactions. Ethanol concentration of 36.89%, solvent/material ratio of 29.56 mL/g, extraction time of 71.04 min, temperature of 40 °C, and microwave power of 400 W were found to be the optimal condition. The TEAC value was 198.16 ± 5.47 µmol Trolox/g DW under the optimal conditions, which was in conformity to the predicted value (200.28 µmol Trolox/g DW). In addition, the MAE method was compared with two conventional methods (Soxhlet extraction and maceration extraction). Results showed that the antioxidant capacity of the extract obtained by MAE method was stronger than that obtained by maceration (168.67 ± 3.88 µmol Trolox/g DW) or Soxhlet extraction (114.09 ± 2.01 µmol Trolox/g DW). Finally, several phenolic compounds in the extract were identified and quantified by UPLC-MS/MS, which were rutin, gallic acid, protocatechuic acid, epicatechin, epicatechin gallate, 2-hydrocinnamic acid, p-coumaric acid, quercetin, chlorogenic acid and ferulic acid. 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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15 pages, 2687 KiB

Open AccessArticle

Deep Eutectic Solvents as Convenient Media for Synthesis of Novel Coumarinyl Schiff Bases and Their QSAR Studies

by Maja Molnar¹, Mario Komar¹, Harshad Brahmbhatt¹, Jurislav Babić¹, Stela Jokić¹

and Vesna Rastija^2,*

¹ Faculty of Food Technology Osijek, Josip Juraj Strossmayer University of Osijek, Franje Kuhaca 20, Osijek 31000, Croatia

² Faculty of Agriculture in Osijek, Josip Juraj Strossmayer University of Osijek, Vladimira Preloga 1, Osijek 31000, Croatia

Molecules 2017, 22(9), 1482; https://doi.org/10.3390/molecules22091482 - 5 Sep 2017

Cited by 24 | Viewed by 6744

Abstract

Deep eutectic solvents, as green and environmentally friendly media, were utilized in the synthesis of novel coumarinyl Schiff bases. Novel derivatives were synthesized from 2-((4-methyl-2-oxo-2H-chromen-7-yl)oxy)acetohydrazide and corresponding aldehyde in choline chloride:malonic acid (1:1) based deep eutectic solvent. In these reactions, deep [...] Read more.

Deep eutectic solvents, as green and environmentally friendly media, were utilized in the synthesis of novel coumarinyl Schiff bases. Novel derivatives were synthesized from 2-((4-methyl-2-oxo-2H-chromen-7-yl)oxy)acetohydrazide and corresponding aldehyde in choline chloride:malonic acid (1:1) based deep eutectic solvent. In these reactions, deep eutectic solvent acted as a solvent and catalyst as well. Novel Schiff bases were synthesized in high yields (65–75%) with no need for further purification, and their structures were confirmed by mass spectra, ¹H and ¹³C NMR. Furthermore, their antioxidant activity was determined and compared to antioxidant activity of previously synthesized derivatives, thus investigating their structure–activity relationship utilizing quantitative structure-activity relationship QSAR studies. Calculation of molecular descriptors has been performed by DRAGON software. The best QSAR model (R_tr = 0.636; R_ext = 0.709) obtained with three descriptors (MATS3m, Mor22u, Hy) implies that the pairs of atoms higher mass at the path length 3, three-dimensional arrangement of atoms at scattering parameter s = 21 Å⁻¹, and higher number of hydrophilic groups (-OH, -NH) enhanced antioxidant activity. Electrostatic potential surface of the most active compounds showed possible regions for donation of electrons to 1,1-diphenyl-2-picryhydrazyl (DPPH) radicals. Full article

(This article belongs to the Special Issue Versatile Coumarins)

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11 pages, 3713 KiB

Open AccessArticle

Ultrasonic Assisted Extraction of Paclitaxel from Taxus x media Using Ionic Liquids as Adjuvants: Optimization of the Process by Response Surface Methodology

by Zhijian Tan^1,*

, Qiao Li², Chaoyun Wang^1,*, Wanlai Zhou¹, Yuanru Yang¹, Hongying Wang¹, Yongjian Yi¹ and Fenfang Li²

¹ Institute of Bast Fiber Crops and Center of Southern Economic Crops, Chinese Academy of Agricultural Sciences, Changsha 410205, China

² College of Chemistry and Chemical Engineering, Central South University, Changsha 410083, China

Molecules 2017, 22(9), 1483; https://doi.org/10.3390/molecules22091483 - 11 Sep 2017

Cited by 26 | Viewed by 5815

Abstract

(1) Background: Ionic liquids (ILs) are considered “green” solvents and have been widely used in the extraction and separation field in recent years; (2) Methods: In this study, some common ILs and functionalized magnetic ionic liquids (MILs) were used as adjuvants for the [...] Read more.

(1) Background: Ionic liquids (ILs) are considered “green” solvents and have been widely used in the extraction and separation field in recent years; (2) Methods: In this study, some common ILs and functionalized magnetic ionic liquids (MILs) were used as adjuvants for the solvent extraction of paclitaxel from Taxus x media (T. x media) using methanol solution. The extraction conditions of methanol concentration, IL type and amount, solid–liquid ratio, extraction temperature, and ultrasonic irradiation time were investigated in single factor experiments. Then, three factors of IL amount, solid–liquid ratio, and ultrasonic irradiation time were optimized by response surface methodology (RSM); (3) Results: The MIL [C₄MIM]FeCl₃Br was screened as the optimal adjuvant. Under the optimization conditions of 1.2% IL amount, 1:10.5 solid–liquid ratio, and 30 min ultrasonic irradiation time, the extraction yield reached 0.224 mg/g; and (4) Conclusions: Compared with the conventional solvent extraction, this ultrasonic assisted extraction (UAE) using methanol and MIL as adjuvants can significantly improve the extraction yield, reduce the use of methanol, and shorten the extraction time, which has the potentiality of being used in the extraction of some other important bioactive compounds from natural plant resources. 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, 1098 KiB

Open AccessArticle

Synthesis and Biological Activity of Novel O-Alkyl Derivatives of Naringenin and Their Oximes

by Joanna Kozłowska^1,*

, Bartłomiej Potaniec¹

, Barbara Żarowska² and Mirosław Anioł¹

¹ Department of Chemistry, Wrocław University of Environmental and Life Sciences, Norwida 25, 50-375 Wrocław, Poland

² Department of Biotechnology and Food Microbiology, Wrocław University of Environmental and Life Sciences, Chełmońskiego 37/41, 51-630 Wrocław, Poland

Molecules 2017, 22(9), 1485; https://doi.org/10.3390/molecules22091485 - 6 Sep 2017

Cited by 40 | Viewed by 7296

Abstract

O-Alkyl derivatives of naringenin (1a–10a) were prepared from naringenin using the corresponding alkyl iodides and anhydrous potassium carbonate. The resulting products were used to obtain oximes (1b–10b). All compounds were tested for antimicrobial activity [...] Read more.

O-Alkyl derivatives of naringenin (1a–10a) were prepared from naringenin using the corresponding alkyl iodides and anhydrous potassium carbonate. The resulting products were used to obtain oximes (1b–10b). All compounds were tested for antimicrobial activity against Escherichia coli ATCC10536, Staphylococcus aureus DSM799, Candida albicans DSM1386, Alternaria alternata CBS1526, Fusarium linii KB-F1, and Aspergillus niger DSM1957. The resulting biological activity was expressed as the increase in optical density (ΔOD). The highest inhibitory effect against E. coli ATCC10536 was observed for 7,4′-di-O-pentylnaringenin (8a), 7-O-dodecylnaringenin (9a), naringenin oxime (NG-OX), 7,4′-di-O-pentylnaringenin oxime (8b), and 7-O-dodecylnaringenin oxime (9b) (ΔOD = 0). 7-O-dodecylnaringenin oxime (9b) also inhibited the growth of S. aureus DSM799 (ΔOD = 0.35) and C. albicans DSM1386 (ΔOD = 0.22). The growth of A. alternata CBS1526 was inhibited as a result of the action of 7,4′-di-O-methylnaringenin (2a), 7-O-ethylnaringenin (4a), 7,4′-di-O-ethylnaringenin (5a), 5,7,4′-tri-O-ethylnaringenin (6a), 7,4′-di-O-pentylnaringenin (8a), and 7-O-dodecylnaringenin (9a) (ΔOD in the range of 0.49–0.42) in comparison to that of the control culture (ΔOD = 1.87). In the case of F. linii KB-F1, naringenin (NG), 7,4′-di-O-dodecylnaringenin (10a), 7-O-dodecylnaringenin oxime (9b), and 7,4′-di-O-dodecylnaringenin oxime (10b) showed the strongest effect (ΔOD = 0). 7,4′-Di-O-pentylnaringenin (8a) and naringenin oxime (NG-OX) hindered the growth of A. niger DSM1957 (ΔOD = 0). Full article

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

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1 pages, 124 KiB

Open AccessErratum

Erratum: Xu, Y., et al. Computational Studies on Acetylcholinesterases. Molecules 2017, 22, 1324.

by Molecules Editorial Office

MDPI AG, St. Alban-Anlage 66, 4052 Basel, Switzerland

Molecules 2017, 22(9), 1486; https://doi.org/10.3390/molecules22091486 - 6 Sep 2017

Viewed by 3419

Abstract

n/a Full article

(This article belongs to the Special Issue The Cholinesterases—Structure, Mechanism, Function and Drug Design: The 25th Anniversary of the Solution of the Crystal Structure of Acetylcholinesterase by Joel L. Sussman and Israel Silman)

15 pages, 4495 KiB

Open AccessArticle

Silver Oxide Coatings with High Silver-Ion Elution Rates and Characterization of Bactericidal Activity

by Sarah S. Goderecci^1,†, Eric Kaiser^2,†, Michael Yanakas², Zachary Norris², Jeffrey Scaturro², Robert Oszust², Clarence D. Medina¹, Fallon Waechter¹, Min Heon³, Robert R. Krchnavek⁴, Lei Yu¹, Samuel E. Lofland²

, Renee M. Demarest⁵, Gregory A. Caputo^1,6,*

and Jeffrey D. Hettinger^2,6,*

¹ Department of Chemistry and Biochemistry, Rowan University, Glassboro, NJ 08028, USA

² Department of Physics and Astronomy, Rowan University, Glassboro, NJ 08028, USA

³ Department of Materials Science and Engineering, Drexel University, Philadelphia, PA 19104, USA

⁴ Department of Electrical and Computer Engineering, Rowan University, Glassboro, NJ 08028, USA

⁵ Department of Molecular Biology, Rowan University, Stratford, NJ 08084, USA

⁶ Department of Molecular and Cellular Biosciences, Rowan University, Glassboro, NJ 08028, USA

^† These authors contributed equally to this work.

Molecules 2017, 22(9), 1487; https://doi.org/10.3390/molecules22091487 - 7 Sep 2017

Cited by 33 | Viewed by 7870

Abstract

This paper reports the synthesis and characterization of silver oxide films for use as bactericidal coatings. Synthesis parameters, dissolution/elution rate, and bactericidal efficacy are reported. Synthesis conditions were developed to create AgO, Ag₂O, or mixtures of AgO and Ag₂O [...] Read more.

This paper reports the synthesis and characterization of silver oxide films for use as bactericidal coatings. Synthesis parameters, dissolution/elution rate, and bactericidal efficacy are reported. Synthesis conditions were developed to create AgO, Ag₂O, or mixtures of AgO and Ag₂O on surfaces by reactive magnetron sputtering. The coatings demonstrate strong adhesion to many substrate materials and impede the growth of all bacterial strains tested. The coatings are effective in killing Escherichia coli and Staphylococcus aureus, demonstrating a clear zone-of-inhibition against bacteria growing on solid media and the ability to rapidly inhibit bacterial growth in planktonic culture. Additionally, the coatings exhibit very high elution of silver ions under conditions that mimic dynamic fluid flow ranging between 0.003 and 0.07 ppm/min depending on the media conditions. The elution of silver ions from the AgO/Ag₂O surfaces was directly impacted by the complexity of the elution media, with a reduction in elution rate when examined in complex cell culture media. Both E. coli and S. aureus were shown to bind ~1 ppm Ag⁺/mL culture. The elution of Ag⁺ resulted in no increases in mammalian cell apoptosis after 24 h exposure compared to control, but apoptotic cells increased to ~35% by 48 and 72 h of exposure. Taken together, the AgO/Ag₂O coatings described are effective in eliciting antibacterial activity and have potential for application on a wide variety of surfaces and devices. Full article

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

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12 pages, 1295 KiB

Open AccessArticle

Effect of Sipjeondaebo-Tang on the Pharmacokinetics of S-1, an Anticancer Agent, in Rats Evaluated by Population Pharmacokinetic Modeling

by Tae Hwan Kim^1,†

, Soyoung Shin^2,†

, Jeong Cheol Shin³, Jürgen B. Bulitta¹

, Kwon-Yeon Weon³, Sun Dong Yoo⁴, Gi-Young Park⁵, Seok Won Jeong³, Dong Rak Kwon⁵, Byung Sun Min³, Mi Hee Woo³ and Beom Soo Shin^4,*

¹ Center for Pharmacometrics and Systems Pharmacology, Department of Pharmaceutics, College of Pharmacy, University of Florida, Orlando, FL 32827, USA

² College of Pharmacy, Wonkwang University, Iksan, Jeonbuk 54538, Korea

³ College of Pharmacy, Catholic University of Daegu, 13-13 Hayang-ro, Hayang-eup, Gyeongsan-si, Gyeongbuk 38430, Korea

⁴ School of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi-do 16419, Korea

⁵ Department of Rehabilitation Medicine, School of Medicine, Catholic University of Daegu, Daegu 42472, Korea

^† Tae Hwan Kim and Soyoung Shin contributed equally to this work.

Molecules 2017, 22(9), 1488; https://doi.org/10.3390/molecules22091488 - 7 Sep 2017

Cited by 6 | Viewed by 5538

Abstract

S-1 (TS-1^®) is an oral fluoropyrimidine anticancer agent containing tegafur, oteracil, and gimeracil. Sipjeondaebo-tang (SDT) is a traditional oriental herbal medicine that has potential to alleviate chemotherapy-related adverse effects. The aim of the present study was to evaluate the effect of [...] Read more.

S-1 (TS-1^®) is an oral fluoropyrimidine anticancer agent containing tegafur, oteracil, and gimeracil. Sipjeondaebo-tang (SDT) is a traditional oriental herbal medicine that has potential to alleviate chemotherapy-related adverse effects. The aim of the present study was to evaluate the effect of SDT on the pharmacokinetics of S-1. Sprague-Dawley rats were pretreated with a single dose or repeated doses of SDT for seven consecutive days (1200 mg/kg/day). After the completion of pretreatment with SDT, S-1 was orally administered and plasma concentrations of tegafur, its active metabolite 5-FU, and gimeracil were determined by liquid chromatography-tandem mass spectrometry (LC/MS/MS). A population pharmacokinetic model was developed to evaluate the effect of SDT on pharmacokinetics of tegafur and 5-FU. Although a single dose of SDT did not have any significant effect, the absorption rate of tegafur decreased, and the plasma levels of 5-FU reduced significantly in rats pretreated with SDT for seven days in parallel to the decreased gimeracil concentrations. Population pharmacokinetic modeling also showed the enhanced elimination of 5-FU in the SDT-pretreated group. Repeated doses of SDT may inhibit the absorption of gimeracil, an inhibitor of 5-FU metabolism, resulting in enhanced elimination of 5-FU and decrease its plasma level. Full article

(This article belongs to the Special Issue Herbal Remedies Meet Modern Day Medicine: Challenges and Opportunities)

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14 pages, 1765 KiB

Open AccessArticle

Quantitative Analysis, Extraction Optimization, and Biological Evaluation of Cudrania tricuspidata Leaf and Fruit Extracts

by Seung-Hui Song^1,†, Sung Hwan Ki^2,†, Dae-Hun Park³, Hong-Seop Moon¹, Chang-Dai Lee⁴, In-Soo Yoon^5,*

and Seung-Sik Cho^1,*

¹ Department of Pharmacy, College of Pharmacy, Mokpo National University, Muan-gun, Jeonnam 58554, Korea

² Laboratory of Toxicology, College of Pharmacy, Chosun University, Dong-gu, Gwangju 61452, Korea

³ Department of Nursing, Dongshin University, Naju-si, Jeonnam 58245, Korea

⁴ Department of Business Administration, Mokpo National University, Muan-gun, Jeonnam 58554, Korea

⁵ Department of Manufacturing Pharmacy, College of Pharmacy, Pusan National University, Geumjeong-gu, Busan 46241, Korea

^† These authors contributed equally to this work.

Molecules 2017, 22(9), 1489; https://doi.org/10.3390/molecules22091489 - 7 Sep 2017

Cited by 31 | Viewed by 6774

Abstract

Cudrania tricuspidata Bureau (Moraceae) shows numerous pharmacological effects and has been used in traditional herbal remedies for inflammation, gastritis, tumors, and liver diseases. However, no validated analytical method for the standardization and optimization of the biological properties of C. tricuspidata preparations has been [...] Read more.

Cudrania tricuspidata Bureau (Moraceae) shows numerous pharmacological effects and has been used in traditional herbal remedies for inflammation, gastritis, tumors, and liver diseases. However, no validated analytical method for the standardization and optimization of the biological properties of C. tricuspidata preparations has been reported. We developed and validated a reverse-phase high-performance liquid chromatography (HPLC) method for the separation and quantification of active markers. Ethanolic extracts of C. tricuspidata leaves were prepared and evaluated for chemical profiles and biological activities. The 80% ethanolic extract demonstrated the greatest antioxidant activity and phenolic content, while the 100% ethanolic extract had the greatest total flavonoid content and xanthine oxidase (XO) inhibitory activity. The validated HPLC method confirmed that chlorogenic acid, rutin, and kaempferol were present in C. tricuspidata leaf extracts. We postulated that the antioxidant and anti-hyperuricemic/gout effects of C. tricuspidata extract could be attributed to these marker compounds. Our results suggested that the flavonoid-rich fraction of the leaf extract may be utilized for the treatment and prevention of hyperuricemia-related diseases, and the validated method and marker compounds could be applied for the quality control of C. tricuspidata preparations. Full article

(This article belongs to the Section Natural Products Chemistry)

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14 pages, 1429 KiB

Open AccessArticle

Synthesis and Antidepressant Activity Profile of Some Novel Benzothiazole Derivatives

by Ümide Demir Özkay^1,*, Ceren Kaya¹, Ulviye Acar Çevik² and Özgür Devrim Can¹

¹ Department of Pharmacology, Faculty of Pharmacy, Anadolu University, 26470 Eskişehir, Turkey

² Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, 26470 Eskişehir, Turkey

Molecules 2017, 22(9), 1490; https://doi.org/10.3390/molecules22091490 - 7 Sep 2017

Cited by 38 | Viewed by 6935

Abstract

Within the scope of our new antidepressant drug development efforts, in this study, we synthesized eight novel benzothiazole derivatives 3a–3h. The chemical structures of the synthesized compounds were elucidated by spectroscopic methods. Test compounds were administered orally at a dose [...] Read more.

Within the scope of our new antidepressant drug development efforts, in this study, we synthesized eight novel benzothiazole derivatives 3a–3h. The chemical structures of the synthesized compounds were elucidated by spectroscopic methods. Test compounds were administered orally at a dose of 40 mg/kg to mice 24, 5 and 1 h before performing tail suspension, modified forced swimming, and activity cage tests. The obtained results showed that compounds 3c, 3d, 3f–3h reduced the immobility time of mice as assessed in the tail suspension test. Moreover, in the modified forced swimming tests, the same compounds significantly decreased the immobility, but increased the swimming frequencies of mice, without any alteration in the climbing frequencies. These results, similar to the results induced by the reference drug fluoxetine (20 mg/kg, po), indicated the antidepressant-like activities of the compounds 3c, 3d, 3f–3h. Owing to the fact that test compounds did not induce any significant alteration in the total number of spontaneous locomotor activities, the antidepressant-like effects of these derivatives seemed to be specific. In order to predict ADME parameters of the synthesized compounds 3a–3h, some physicochemical parameters were calculated. The ADME prediction study revealed that all synthesized compounds may possess good pharmacokinetic profiles. Full article

(This article belongs to the Section Medicinal Chemistry)

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17 pages, 775 KiB

Open AccessArticle

Design, Synthesis, Antimycobacterial Evaluation, and In Silico Studies of 3-(Phenylcarbamoyl)-pyrazine-2-carboxylic Acids

by Lucia Semelková^1,*, Petra Janošcová¹, Carlos Fernandes¹

, Ghada Bouz¹

, Ondřej Janďourek¹

, Klára Konečná¹

, Pavla Paterová², Lucie Navrátilová¹, Jiří Kuneš¹, Martin Doležal¹

and Jan Zitko^1,*

¹ Faculty of Pharmacy in Hradec Králové, Charles University, Heyrovského 1203, Hradec Králové 500 05, Czech Republic

² Department of Clinical Microbiology, University Hospital, Sokolská 581, Hradec Králové 500 05, Czech Republic

Molecules 2017, 22(9), 1491; https://doi.org/10.3390/molecules22091491 - 7 Sep 2017

Cited by 13 | Viewed by 7239

Abstract

Pyrazinamide, the first-line antitubercular drug, has been regarded the basic component of tuberculosis treatment for over sixty years. Researchers have investigated its effect on Mycobacterium tuberculosis for this long time, and as a result, new potential targets of pyrazinamide or its active form, [...] Read more.

Pyrazinamide, the first-line antitubercular drug, has been regarded the basic component of tuberculosis treatment for over sixty years. Researchers have investigated its effect on Mycobacterium tuberculosis for this long time, and as a result, new potential targets of pyrazinamide or its active form, pyrazinoic acid, have been found. We have designed and prepared 3-(phenyl-carbamoyl)pyrazine-2-carboxylic acids as more lipophilic derivatives of pyrazinoic acid. We also prepared methyl and propyl derivatives as prodrugs with further increased lipophilicity. Antimycobacterial, antibacterial and antifungal growth inhibiting activity was investigated in all prepared compounds. 3-[(4-Nitrophenyl)carbamoyl]pyrazine-2-carboxylic acid (16) exerted high antimycobacterial activity against Mycobacterium tuberculosis H37Rv with MIC = 1.56 μg·mL⁻¹ (5 μM). Propyl 3-{[4-(trifluoromethyl)phenyl]carbamoyl}pyrazine-2-carboxylate (18a) showed also high antimycobacterial activity against Mycobacterium tuberculosis H37Rv with MIC = 3.13 μg·mL⁻¹. In vitro cytotoxicity of the active compounds was investigated and no significant cytotoxic effect was observed. Based to structural similarity to known inhibitors of decaprenylphosphoryl-β-d-ribose oxidase, DprE1, we performed molecular docking of the prepared acids to DprE1. These in silico experiments indicate that modification of the linker connecting aromatic parts of molecule does not have any negative influence on the binding. Full article

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

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11 pages, 1573 KiB

Open AccessCommunication

Forbidden Coherence Transfer of ¹⁹F Nuclei to Quantitatively Measure the Dynamics of a CF₃-Containing Ligand in Receptor-Bound States

by Yuji Tokunaga¹, Koh Takeuchi¹ and Ichio Shimada^1,2,*

¹ Molecular Profiling Research Center for Drug Discovery, National Institute of Advanced Industrial Science and Technology (AIST), 2-3-26 Aomi, Koto-ku, Tokyo 135-0064, Japan

² Graduate School of Pharmaceutical Sciences, the University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan

Molecules 2017, 22(9), 1492; https://doi.org/10.3390/molecules22091492 - 7 Sep 2017

Cited by 4 | Viewed by 5680

Abstract

The dynamic property of a ligand in the receptor-bound state is an important metric to characterize the interactions in the ligand–receptor interface, and the development of an experimental strategy to quantify the amplitude of motions in the bound state is of importance to [...] Read more.

The dynamic property of a ligand in the receptor-bound state is an important metric to characterize the interactions in the ligand–receptor interface, and the development of an experimental strategy to quantify the amplitude of motions in the bound state is of importance to introduce the dynamic aspect into structure-guided drug development (SGDD). Fluorine modifications are frequently introduced at the hit-to-lead optimization stage to enhance the binding potency and other characteristics of a ligand. However, the effects of fluorine modifications are generally difficult to predict, owing to the pleiotropic nature of the interactions. In this study, we report an NMR-based approach to experimentally evaluate the local dynamics of trifluoromethyl (CF₃)-containing ligands in the receptor-bound states. For this purpose, the forbidden coherence transfer (FCT) analysis, which has been used to study the dynamics of methyl moieties in proteins, was extended to the ¹⁹F nuclei of CF₃-containing ligands. By applying this CF₃–FCT analysis to a model interaction system consisting of a ligand, AST-487, and a receptor, p38α, we successfully quantified the amplitude of the CF₃ dynamics in the p38α-bound state. The strategy would bring the CF₃-containing ligands within the scope of dynamic SGDD to improve the affinity and specificity for the drug-target receptors. Full article

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

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21 pages, 800 KiB

Open AccessReview

Ethnopharmacology and Therapeutic Value of Bridelia micrantha (Hochst.) Baill. in Tropical Africa: A Comprehensive Review

by Alfred Maroyi

Medicinal Plants and Economic Development (MPED) Research Centre, Department of Botany, University of Fort Hare, Private Bag X1314, Alice 5700, South Africa

Molecules 2017, 22(9), 1493; https://doi.org/10.3390/molecules22091493 - 8 Sep 2017

Cited by 25 | Viewed by 7906

Abstract

Bridelia micrantha is traditionally used in tropical Africa to treat a wide range of human and animal diseases. The aim of this study was to summarise the research that has been done on the ethnomedicinal uses, phytochemistry and pharmacological properties of B. micrantha [...] Read more.

Bridelia micrantha is traditionally used in tropical Africa to treat a wide range of human and animal diseases. The aim of this study was to summarise the research that has been done on the ethnomedicinal uses, phytochemistry and pharmacological properties of B. micrantha so as to understand its importance and potential value in primary healthcare systems. The literature search for information on ethnomedicinal uses and pharmacological activities of B. micrantha was undertaken using databases such as Web of Science, Scopus, Google Scholar, Science Direct, BioMed Central (BMC), PubMed and Springerlink. Other relevant literature sources included books, book chapters, websites, theses, conference papers and other scientific publications. This study showed that B. micrantha is used as herbal medicine in just over half (57.3%) of the countries in tropical Africa where it is indigenous. A total of 54 ethnomedicinal uses of B. micrantha have been recorded with a high degree of consensus on burns, wounds, conjunctivitis, painful eyes, constipation, gastric ulcers, cough, headache, rheumatism, painful joints, dysentery, ethnoveterinary medicine, malaria, sexually transmitted infections, stomach ache, tape worms and diarrhoea. Different plant parts, aqueous and organic extracts exhibited anthelmintic, antimicrobial, anticonvulsant and sedative, antidiabetic, antidiarrhoeal, antinociceptive, antioxidant, antiplasmodial, antischistosomal, hepatoprotective, insecticidal and β-lactamase inhibitory activities. Full article

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

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15 pages, 3471 KiB

Open AccessArticle

Simultaneous Determination of Seven Phenolic Acids in Rat Plasma Using UHPLC-ESI-MS/MS after Oral Administration of Echinacea purpurea Extract

by Yan Du¹, Zhibin Wang², Libo Wang¹, Mingjie Gao³, Liqian Wang³, Chunli Gan^1,*

and Chunjuan Yang^3,*

¹ Department of Medicinal Chemistry and Natural Medicine Chemistry, College of Pharmacy, Harbin Medical University, No. 157 Baojian Road, Nangang District, Harbin 150081, China

² Key Laboratory of Chinese Materia Medica (Ministry of Education), Heilongjiang University of Chinese Medicine, Harbin 150040, China

³ Department of Pharmaceutical Analysis and Analytical Chemistry, College of Pharmacy, Harbin Medical University, No. 157 Baojian Road, Nangang District, Harbin 150081, China

Molecules 2017, 22(9), 1494; https://doi.org/10.3390/molecules22091494 - 7 Sep 2017

Cited by 20 | Viewed by 6303

Abstract

A rapid and sensitive Ultra High Performance Liquid Chromatography Electrospray Ionization Tandem Mass Spectrometry (UHPLC-ESI-MS/MS) method was developed and validated to simultaneously determine the concentration of seven phenolic acids (syringic acid, ferulic acid, caffeic acid, vanillic acid, p-coumaric acid, 3,4-dihydroxybenzoic acid and [...] Read more.

A rapid and sensitive Ultra High Performance Liquid Chromatography Electrospray Ionization Tandem Mass Spectrometry (UHPLC-ESI-MS/MS) method was developed and validated to simultaneously determine the concentration of seven phenolic acids (syringic acid, ferulic acid, caffeic acid, vanillic acid, p-coumaric acid, 3,4-dihydroxybenzoic acid and 4-hydroxybenzoic acid) in rat plasma after oral administration of Echinacea purpurea extract. After mixing with the internal standard (IS), butylparaben, plasma samples were prepared by liquid–liquid extraction with ethyl acetate. The separation was performed using the Agilent Eclipse Plus C₁₈ column (1.8 μm, 2.1 mm × 50 mm) with a gradient system consisting of solution A (0.1% acetic acid in water) and solution B (methanol) at a flow rate of 0.3 mL/min. The detection was accomplished by a multiple reaction monitoring (MRM) mode with electrospray ionization (ESI). The method was validated in terms of linearity, precision, accuracy, extraction recovery, matrix effect and stability. This method was successfully applied to study the pharmacokinetic properties of the seven compounds after oral administration of Echinacea purpurea extract in rats. Full article

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12 pages, 4752 KiB

Open AccessArticle

The Small Glutathione Peroxidase Mimic 5P May Represent a New Strategy for the Treatment of Liver Cancer

by Juxin Yin^1,2

, Bingmei Wang¹, Xuejun Zhu¹, Xiaonan Qu¹, Yi Huang¹, Shaowu Lv^1,*, Ying Mu^1,2 and Guimin Luo¹

¹ Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, College of Life Science, Jilin University, Changchun 130000, China

² Research Center for Analytical Instrumentation, Institute of Cyber-Systems and Control, State Key Laboratory of Industrial Control Technology, Zhejiang University, Hangzhou 310000, China

Molecules 2017, 22(9), 1495; https://doi.org/10.3390/molecules22091495 - 8 Sep 2017

Cited by 9 | Viewed by 4983

Abstract

Glutathione peroxidase (GPx) is an antioxidant protein containing selenium. Owing to the limitations of native GPx, considerable efforts have been made to develop GPx mimics. Here, a short 5-mer peptides (5P) was synthesized and characterized using matrix-assisted laser desorption ionization time-of-flight mass spectrometry. [...] Read more.

Glutathione peroxidase (GPx) is an antioxidant protein containing selenium. Owing to the limitations of native GPx, considerable efforts have been made to develop GPx mimics. Here, a short 5-mer peptides (5P) was synthesized and characterized using matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Enzyme coupled assays were used to evaluate GPx activity. The cell viability and apoptosis of H22 cells were tested, and mice bearing H22 cell-derived tumors were used to determine the effects of 5P on tumor inhibition. In comparison with other enzyme models, 5P provided a suitable substrate with proper catalytic site positions, resulting in enhanced catalytic activity. In our mouse model, 5P showed excellent inhibition of tumor growth and improved immunity. In summary, our findings demonstrated the design and synthesis of the small 5P molecule, which inhibited tumor growth and improved immunity. Notably, 5P could inhibit tumor growth without affecting normal growth. Based on these advantages, the novel mimic may have several clinical applications. Full article

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

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12 pages, 1458 KiB

Open AccessArticle

Topological Characterization of Carbon Graphite and Crystal Cubic Carbon Structures

by Wei Gao^1,*, Muhammad Kamran Siddiqui²

, Muhammad Naeem²

and Najma Abdul Rehman²

¹ School of Information Science and Technology, Yunnan Normal University, Kunming 650500, China

² Department of Mathematics, COMSATS Institute of Information Technology, Sahiwal 57000, Pakistan

Molecules 2017, 22(9), 1496; https://doi.org/10.3390/molecules22091496 - 7 Sep 2017

Cited by 132 | Viewed by 5285

Abstract

Graph theory is used for modeling, designing, analysis and understanding chemical structures or chemical networks and their properties. The molecular graph is a graph consisting of atoms called vertices and the chemical bond between atoms called edges. In this article, we study the [...] Read more.

Graph theory is used for modeling, designing, analysis and understanding chemical structures or chemical networks and their properties. The molecular graph is a graph consisting of atoms called vertices and the chemical bond between atoms called edges. In this article, we study the chemical graphs of carbon graphite and crystal structure of cubic carbon. Moreover, we compute and give closed formulas of degree based additive topological indices, namely hyper-Zagreb index, first multiple and second multiple Zagreb indices, and first and second Zagreb polynomials. Full article

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3 pages, 171 KiB

Open AccessEditorial

Strait Gate: Special Issue on Advances in Silicon Chemistry

by Mitsuo Kira

Key Laboratory of Organosilicon Chemistry and Material Technology of Ministry of Education, Hangzhou Normal University, Hangzhou 311121, Zhejiang, China

Molecules 2017, 22(9), 1497; https://doi.org/10.3390/molecules22091497 - 7 Sep 2017

Viewed by 3402

Abstract

Manufacturing high-purity element silicon and organic polysilicones are two major silicon industries, supporting the basis of the modern electronic industry and our daily lives [...]
Full article

(This article belongs to the Special Issue Advances in Silicon Chemistry)

18 pages, 1940 KiB

Open AccessArticle

Anti-HIV Activities and Mechanism of 12-O-Tricosanoylphorbol-20-acetate, a Novel Phorbol Ester from Ostodes katharinae

by Huan Chen^1,2,†, Rong Zhang^3,†, Rong-Hua Luo¹, Liu-Meng Yang¹, Rui-Rui Wang¹, Xiao-Jiang Hao^3,* and Yong-Tang Zheng^1,4,*

¹ Key Laboratory of Bioactive Peptides of Yunnan Province/Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, Yunnan, China

² Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming 650204, Yunnan, China

³ State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, Yunnan, China

⁴ KIZ-SU Joint Laboratory of Animal Models and Drug Development, College of Pharmaceutical Sciences, Soochow University, Suzhou 215006, Jiangsu, China

^† These authors contributed equally to this work.

Molecules 2017, 22(9), 1498; https://doi.org/10.3390/molecules22091498 - 8 Sep 2017

Cited by 28 | Viewed by 5760

Abstract

APOBEC3G is a member of the human cytidine deaminase family that restricts Vif-deficient viruses by being packaged with progeny virions and inducing the G to A mutation during the synthesis of HIV-1 viral DNA when the progeny virus infects new cells. HIV-1 Vif [...] Read more.

APOBEC3G is a member of the human cytidine deaminase family that restricts Vif-deficient viruses by being packaged with progeny virions and inducing the G to A mutation during the synthesis of HIV-1 viral DNA when the progeny virus infects new cells. HIV-1 Vif protein resists the activity of A3G by mediating A3G degradation. Phorbol esters are plant-derived organic compounds belonging to the tigliane family of diterpenes and could activate the PKC pathway. In this study, we identified an inhibitor 12-O-tricosanoylphorbol-20-acetate (hop-8), a novel ester of phorbol which was isolated from Ostodes katharinae of the family Euphorbiaceae, that inhibited the replication of wild-type HIV-1 and HIV-2 strains and drug-resistant strains broadly both in C8166 cells and PBMCs with low cytotoxicity and the EC₅₀ values ranged from 0.106 μM to 7.987 μM. One of the main mechanisms of hop-8 is to stimulate A3G expressing in HIV-1 producing cells and upregulate the A3G level in progeny virions, which results in reducing the infectivity of the progeny virus. This novel mechanism of hop-8 inhibition of HIV replication might represents a promising approach for developing new therapeutics for HIV infection. Full article

(This article belongs to the Section Natural Products Chemistry)

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10 pages, 1114 KiB

Open AccessReview

Human Erythrocyte Acetylcholinesterase in Health and Disease

by Carlota Saldanha

Instituto de Bioquímica, Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Av. Professor Egas Moniz, 1649-028 Lisboa, Portugal

Molecules 2017, 22(9), 1499; https://doi.org/10.3390/molecules22091499 - 8 Sep 2017

Cited by 60 | Viewed by 8439

Abstract

The biochemical properties of erythrocyte or human red blood cell (RBC) membrane acetylcholinesterase (AChE) and its applications on laboratory class and on research are reviewed. Evidence of the biochemical and the pathophysiological properties like the association between the RBC AChE enzyme activity and [...] Read more.

The biochemical properties of erythrocyte or human red blood cell (RBC) membrane acetylcholinesterase (AChE) and its applications on laboratory class and on research are reviewed. Evidence of the biochemical and the pathophysiological properties like the association between the RBC AChE enzyme activity and the clinical and biophysical parameters implicated in several diseases are overviewed, and the achievement of RBC AChE as a biomarker and as a prognostic factor are presented. Beyond its function as an enzyme, a special focus is highlighted in this review for a new function of the RBC AChE, namely a component of the signal transduction pathway of nitric oxide. Full article

(This article belongs to the Special Issue The Cholinesterases—Structure, Mechanism, Function and Drug Design: The 25th Anniversary of the Solution of the Crystal Structure of Acetylcholinesterase by Joel L. Sussman and Israel Silman)

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13 pages, 716 KiB

Open AccessArticle

Effect of Vertical Shoot-Positioned, Scott-Henry, Geneva Double-Curtain, Arch-Cane, and Parral Training Systems on the Volatile Composition of Albariño Wines

by Mar Vilanova^1,*, Zlatina Genisheva², Miguel Tubio³, Katia Álvarez³, Jose Ramón Lissarrague⁴ and José Maria Oliveira²

¹ Misión Biológica de Galicia (CSIC), P.O. Box 28, 38080 Pontevedra, Spain

² CEB—Centre of Biological Engineering, University of Minho, 4710-057 Braga, Portugal

³ Martín Códax Winery, Vilariño, 36630 Cambados, Spain

⁴ Escuela Técnica Superior de Ingenieros Agrónomos, Department of Agricultural Production, Universidad Politécnica de Madrid, 28040 Madrid, Spain

Molecules 2017, 22(9), 1500; https://doi.org/10.3390/molecules22091500 - 8 Sep 2017

Cited by 17 | Viewed by 6305

Abstract

Viticultural practices influence both grape and wine quality. The influence of training systems on volatile composition was investigated for Albariño wine from Rías Baixas AOC in Northwest Spain. The odoriferous contribution of the compounds to the wine aroma was also studied. Volatile compounds [...] Read more.

Viticultural practices influence both grape and wine quality. The influence of training systems on volatile composition was investigated for Albariño wine from Rías Baixas AOC in Northwest Spain. The odoriferous contribution of the compounds to the wine aroma was also studied. Volatile compounds belonging to ten groups (alcohols, C₆-compounds, ethyl esters, acetates, terpenols, C₁₃-norisoprenoids, volatile phenols, volatile fatty acids, lactones and carbonyl compounds) were determined in Albariño wines from different training systems, Vertical Shoot-Positioned (VSP), Scott-Henry (SH), Geneva Double-Curtain (GDC), Arch-Cane (AC), and Parral (P) during 2010 and 2011 vintages. Wines from GDC showed the highest total volatile composition with the highest concentrations of alcohols, ethyl esters, fatty acids, and lactones families. However, the highest levels of terpenes and C₁₃-norisoprenoids were quantified in the SH system. A fruitier aroma was observed in Albariño wines from GDC when odor activity values were calculated. Full article

(This article belongs to the Collection Wine Chemistry)

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15 pages, 3268 KiB

Open AccessArticle

Wound Healing Potential of Chlorogenic Acid and Myricetin-3-O-β-Rhamnoside Isolated from Parrotia persica

by Sara E. Moghadam¹, Samad N. Ebrahimi²

, Peyman Salehi², Mahdi Moridi Farimani², Matthias Hamburger³

and Ehsan Jabbarzadeh^1,4,*

¹ Department of Chemical Engineering, University of South Carolina, Columbia, SC 29208, USA

² Department of Phytochemistry, Medicinal Plants and Drug Research Institute, Shahid Beheshti University, GC, Evin, Tehran 1983969411 , Iran

³ Division of Pharmaceutical Biology, University of Basel, Basel 4056, Switzerland

⁴ Biomedical Engineering Program, University of South Carolina, Columbia, SC 29208, USA

Molecules 2017, 22(9), 1501; https://doi.org/10.3390/molecules22091501 - 8 Sep 2017

Cited by 77 | Viewed by 7063

Abstract

Wound healing is a complex physiological process that is controlled by a well-orchestrated cascade of interdependent biochemical and cellular events, which has spurred the development of therapeutics that simultaneously target these active cellular constituents. We assessed the potential of Parrotia persica (Hamamelidaceae) in [...] Read more.

Wound healing is a complex physiological process that is controlled by a well-orchestrated cascade of interdependent biochemical and cellular events, which has spurred the development of therapeutics that simultaneously target these active cellular constituents. We assessed the potential of Parrotia persica (Hamamelidaceae) in wound repair by analyzing the regenerative effects of its two main phenolic compounds, myricetin-3-O-β-rhamnoside and chlorogenic acid. To accomplish this, we performed phytochemical profiling and characterized the chemical structure of pure compounds isolated from P. persica, followed by an analysis of the biological effects of myricetin-3-O-β-rhamnoside and chlorogenic acid on three cell types, including keratinocytes, fibroblasts, and endothelial cells. Myricetin-3-O-β-rhamnoside and chlorogenic acid exhibited complementary pro-healing properties. The percentage of keratinocyte wound closure as measured by a scratch assay was four fold faster in the presence of 10 µg/mL chlorogenic acid, as compared to the negative control. On the other hand, myricetin-3-O-β-rhamnoside at 10 µg/mL was more effective in promoting fibroblast migration, demonstrating a two-fold higher rate of closure compared to the negative control group. Both compounds enhanced the capillary-like tube formation of endothelial cells in an in vitro angiogenesis assay. Our results altogether delineate the potential to synergistically accelerate the fibroblastic and remodelling phases of wound repair by administering appropriate amounts of myricetin-3-O-β-rhamnoside and chlorogenic acid. Full article

(This article belongs to the Section Natural Products Chemistry)

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15 pages, 7797 KiB

Open AccessArticle

Senna singueana: Antioxidant, Hepatoprotective, Antiapoptotic Properties and Phytochemical Profiling of a Methanol Bark Extract

by Mansour Sobeh^1,*

, Mona F. Mahmoud²

, Rehab A. Hasan³, Haroan Cheng¹, Assem M. El-Shazly⁴ and Michael Wink^1,*

¹ Institute of Pharmacy and Molecular Biotechnology, Heidelberg University, Im Neuenheimer Feld 364, Heidelberg 69120, Germany

² Department of Pharmacology and Toxicology, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt

³ Department of Histology, Faculty of Medicine for Girls, Al-Azhar University, Cairo 11651, Egypt

⁴ Department of Pharmacognosy, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt

Molecules 2017, 22(9), 1502; https://doi.org/10.3390/molecules22091502 - 8 Sep 2017

Cited by 46 | Viewed by 8789

Abstract

Natural products are considered as an important source for the discovery of new drugs to treat aging-related degenerative diseases and liver injury. The present study profiled the chemical constituents of a methanol extract from Senna singueana bark using HPLC-PDA-ESI-MS/MS and 36 secondary metabolites [...] Read more.

Natural products are considered as an important source for the discovery of new drugs to treat aging-related degenerative diseases and liver injury. The present study profiled the chemical constituents of a methanol extract from Senna singueana bark using HPLC-PDA-ESI-MS/MS and 36 secondary metabolites were identified. Proanthocyanidins dominated the extract. Monomers, dimers, trimers of (epi)catechin, (epi)gallocatechin, (epi)guibourtinidol, (ent)cassiaflavan, and (epi)afzelechin represented the major constituents. The extract demonstrated notable antioxidant activities in vitro: In DPPH (EC₅₀ of 20.8 µg/mL), FRAP (18.16 mM FeSO₄/mg extract) assays, and total phenolic content amounted 474 mg gallic acid equivalent (GAE)/g extract determined with the Folin-Ciocalteu method. Also, in an in vivo model, the extract increased the survival rate of Caenorhabditis elegans worms pretreated with the pro-oxidant juglone from 43 to 64%, decreased intracellular ROS inside the wild-type nematodes by 47.90%, and induced nuclear translocation of the transcription factor DAF-16 in the transgenic strain TJ356. Additionally, the extract showed a remarkable hepatoprotective activity against d-galactosamine (d-GalN) induced hepatic injury in rats. It significantly reduced elevated AST (aspartate aminotransferase), and total bilirubin. Moreover, the extract induced a strong cytoplasmic Bcl-2 expression indicating suppression of apoptosis. In conclusion, the bark extract of S. sengueana represents an interesting candidate for further research in antioxidants and liver protection. Full article

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

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16 pages, 13947 KiB

Open AccessArticle

FeCl₃∙6H₂O/TMSBr-Catalyzed Rapid Synthesis of Dihydropyrimidinones and Dihydropyrimidinethiones under Microwave Irradiation

by Fei Zhao^*

, Xiuwen Jia, Pinyi Li, Jingwei Zhao, Jun Huang, Honglian Li and Lin Li

Antibiotics Research and Re-Evaluation Key Laboratory of Sichuan Province, Sichuan Industrial Institute of Antibiotics, Chengdu University, 168 Hua Guan Road, Chengdu 610052, China

Molecules 2017, 22(9), 1503; https://doi.org/10.3390/molecules22091503 - 11 Sep 2017

Cited by 5 | Viewed by 5583

Abstract

An efficient and practical protocol has been developed to synthesize dihydropyrimidinones and dihydropyrimidinethiones through FeCl₃∙6H₂O/TMSBr-catalyzed three-component cyclocondensation under microwave irradiation. This approach features high yields, broad substrate scope, short reaction time, mild reaction conditions, operational simplicity and easy work-up, [...] Read more.

An efficient and practical protocol has been developed to synthesize dihydropyrimidinones and dihydropyrimidinethiones through FeCl₃∙6H₂O/TMSBr-catalyzed three-component cyclocondensation under microwave irradiation. This approach features high yields, broad substrate scope, short reaction time, mild reaction conditions, operational simplicity and easy work-up, thus affording a versatile method for the synthesis of dihydropyrimidinones and dihydropyrimidinethiones. Full article

(This article belongs to the Special Issue Catalytic Cascade Reactions)

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2 pages, 175 KiB

Open AccessEditorial

Special Issue: Asymmetric Synthesis 2017

by Rafael Chinchilla

Departamento de Química Orgánica, Facultad de Ciencias, and Instituto de Síntesis Orgánica (ISO), Universidad de Alicante, Aptdo. 99, 03080 Alicante, Spain

Molecules 2017, 22(9), 1504; https://doi.org/10.3390/molecules22091504 - 8 Sep 2017

Cited by 1 | Viewed by 4045

Abstract

The use of asymmetric synthetic methodologies plays a crucial role, nowadays, in the preparation of bioactive or other interesting compounds [...]
Full article

(This article belongs to the Special Issue Asymmetric Synthesis 2017)

13 pages, 4395 KiB

Open AccessArticle

Hair Regenerative Mechanisms of Red Ginseng Oil and Its Major Components in the Testosterone-Induced Delay of Anagen Entry in C57BL/6 Mice

by Van-Long Truong¹, Min Ji Bak^1,2, Changook Lee³, Mira Jun⁴ and Woo-Sik Jeong^1,*

¹ Department of Food and Life Sciences, College of BNIT, Inje University, Gimhae 50834, Korea

² Department of Chemical Biology, Susan Lehman Cullman Laboratory for Cancer Research, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA

³ Department of Pharmaceutics, College of Pharmacy, Inje University, Gimhae 50834, Korea

⁴ Department of Food Science and Nutrition, Dong-A University, Busan 49315, Korea

Molecules 2017, 22(9), 1505; https://doi.org/10.3390/molecules22091505 - 8 Sep 2017

Cited by 57 | Viewed by 13076

Abstract

Hair loss (alopecia) is a universal problem for numerous people in the world. The present study was conducted to investigate the effects of red ginseng oil (RGO) and its major components on hair re-growth using testosterone (TES)-induced delay of anagen entry in C57BL/6 [...] Read more.

Hair loss (alopecia) is a universal problem for numerous people in the world. The present study was conducted to investigate the effects of red ginseng oil (RGO) and its major components on hair re-growth using testosterone (TES)-induced delay of anagen entry in C57BL/6 mice and their mechanisms of action. Seven-week-old C57BL/6 mice were daily treated with TES for 1 h prior to topical application of 10% RGO, 1% linoleic acid (LA), 1% β-sitosterol (SITOS), or 1% bicyclo(10.1.0)tridec-1-ene (BICYCLO) once a day for 28 days. Hair regenerative capacity was significantly restored by treatment of RGO and its major compounds in the TES-treated mice. Histological analysis showed that RGO along with LA and SITOS but not BICYCLO promoted hair growth through early inducing anagen phase that was delayed by TES in mice. Treatment of mice with RGO, LA, or SITOS up-regulated Wnt/β-catenin and Shh/Gli pathways-mediated expression of genes such as β-catenin, Lef-1, Sonic hedgehog, Smoothened, Gli-1, Cyclin D1, and Cyclin E in the TES-treated mice. In addition, RGO and its major components reduced the protein level of TGF-β but enhanced the expression of anti-apoptotic protein Bcl-2. These results suggest that RGO is a potent novel therapeutic natural product for treatment of androgenic alopecia possibly through hair re-growth activity of its major components such as LA and SITOS. Full article

(This article belongs to the Special Issue Current Trends in Ginseng Research)

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16 pages, 8685 KiB

Open AccessArticle

New Tetra-Schiff Bases as Efficient Photostabilizers for Poly(vinyl chloride)

by Dina S. Ahmed¹, Gamal A. El-Hiti^2,*

, Ayad S. Hameed¹, Emad Yousif^3,*

and Ahmed Ahmed⁴

¹ Department of Chemistry, College of Science, Tikrit University, Tikrit 34001, Iraq

² Cornea Research Chair, Department of Optometry, College of Applied Medical Sciences, King Saud University, P.O. Box 10219, Riyadh 11433, Saudi Arabia

³ Department of Chemistry, College of Science, Al-Nahrain University, Baghdad 64021, Iraq

⁴ Polymer Research Unit, College of Science, Al-Mustansiriyah University, Baghdad 10052, Iraq

Molecules 2017, 22(9), 1506; https://doi.org/10.3390/molecules22091506 - 9 Sep 2017

Cited by 75 | Viewed by 6128

Abstract

Three new tetra-Schiff bases were synthesized and characterized to be used as photostabilizers for poly(vinyl chloride) (PVC) films. The photostability of PVC films (40 μm thickness) in the presence of Schiff bases (0.5 wt %) upon irradiation (300 h) with a UV light [...] Read more.

Three new tetra-Schiff bases were synthesized and characterized to be used as photostabilizers for poly(vinyl chloride) (PVC) films. The photostability of PVC films (40 μm thickness) in the presence of Schiff bases (0.5 wt %) upon irradiation (300 h) with a UV light (λ_max = 365 nm and light intensity = 6.43 × 10⁻⁹ ein∙dm⁻³∙s⁻¹) was examined using various spectroscopic measurements and surface morphology analysis. The changes in various functional groups’ indices, weight and viscosity average molecular weight of PVC films were monitored against irradiation time. The additives used showed photostability for PVC films, with Schiff base 1 being the most effective additive upon irradiation, followed by 2 and 3. The atomic force microscopy (AFM) images for the PVC surface containing Schiff base 1 after irradiation were found to be smooth, with a roughness factor (Rq) of 36.8, compared to 132.2 for the PVC (blank). Several possible mechanisms that explain PVC photostabilization upon irradiation in the presence of tetra-Schiff bases were proposed. Full article

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15 pages, 3761 KiB

Open AccessArticle

COX Inhibition Profile and Molecular Docking Studies of Some 2-(Trimethoxyphenyl)-Thiazoles

by Smaranda Dafina Oniga¹

, Liliana Pacureanu^2,*, Cristina Ioana Stoica¹, Mariana Doina Palage^1,*

, Alexandra Crăciun³

, Laurentiu Răzvan Rusu³, Elena-Luminita Crisan² and Cătălin Araniciu¹

¹ Faculty of Pharmacy, “Iuliu Hatieganu” University of Medicine and Pharmacy, 8 Victor Babes St, Cluj–Napoca 400012, Romania

² Institute of Chemistry Timisoara of Romanian Academy, 24 M. Viteazul Ave., Timisoara 300223, Romania

³ Faculty of Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, 8 Victor Babes St, Cluj–Napoca 400012, Romania

Molecules 2017, 22(9), 1507; https://doi.org/10.3390/molecules22091507 - 9 Sep 2017

Cited by 58 | Viewed by 9736

Abstract

Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used therapeutic agents that exhibit frequent and sometimes severe adverse effects, including gastrointestinal ulcerations and cardiovascular disorders. In an effort to obtain safer NSAIDs, we assessed the direct cyclooxygenase (COX) inhibition activity and we investigated the potential [...] Read more.

Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used therapeutic agents that exhibit frequent and sometimes severe adverse effects, including gastrointestinal ulcerations and cardiovascular disorders. In an effort to obtain safer NSAIDs, we assessed the direct cyclooxygenase (COX) inhibition activity and we investigated the potential COX binding mode of some previously reported 2-(trimethoxyphenyl)-thiazoles. The in vitro COX inhibition assays were performed against ovine COX-1 and human recombinant COX-2. Molecular docking studies were performed to explain the possible interactions between the inhibitors and both COX isoforms binding pockets. Four of the tested compounds proved to be good inhibitors of both COX isoforms, but only compound A3 showed a good COX-2 selectivity index, similar to meloxicam. The plausible binding mode of compound A3 revealed hydrogen bond interactions with binding site key residues including Arg120, Tyr355, Ser530, Met522 and Trp387, whereas hydrophobic contacts were detected with Leu352, Val349, Leu359, Phe518, Gly526, and Ala527. Computationally predicted pharmacokinetic profile revealed A3 as lead candidate. The present data prove that the investigated compounds inhibit COX and thus confirm the previously reported in vivo anti-inflammatory screening results suggesting that A3 is a suitable candidate for further development as a NSAID. Full article

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

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16 pages, 4699 KiB

Open AccessArticle

Early Embryogenesis of Brown Alga Fucus vesiculosus L. is Characterized by Significant Changes in Carbon and Energy Metabolism

by Elena Tarakhovskaya^1,*,†

, Valeriya Lemesheva¹, Tatiana Bilova¹

and Claudia Birkemeyer^2,†

¹ Department of Plant Physiology and Biochemistry, Faculty of Biology, St.-Petersburg State University, 199034 St.-Petersburg, Russia

² Faculty of Chemistry and Mineralogy, Leipzig University, 04103 Leipzig, Germany

^† These authors contributed equally to this work.

Molecules 2017, 22(9), 1509; https://doi.org/10.3390/molecules22091509 - 9 Sep 2017

Cited by 18 | Viewed by 7510

Abstract

Brown algae have an important role in marine environments. With respect to their broad distribution and importance for the environment and human use, brown algae of the order Fucales in particular became a model system for physiological and ecological studies. Thus, several fucoids [...] Read more.

Brown algae have an important role in marine environments. With respect to their broad distribution and importance for the environment and human use, brown algae of the order Fucales in particular became a model system for physiological and ecological studies. Thus, several fucoids have been extensively studied for their composition on the molecular level. However, research of fucoid physiology and biochemistry so far mostly focused on the adult algae, so a holistic view on the development of these organisms, including the crucial first life stages, is still missing. Therefore, we employed non-targeted metabolite profiling by gas chromatography coupled to mass spectrometry to create a non-biased picture of the early development of the fucoid alga Fucus vesiculosus. We found that embryogenic physiology was mainly dominated by a tight regulation of carbon and energy metabolism. The first dramatic changes of zygote metabolism started within 1 h after fertilization, while metabolism of 6–9 days old embryos appeared already close to that of an adult alga, indicated by the intensive production of secondary metabolites and accumulation of mannitol and citric acid. Given the comprehensive description and analysis we obtained in our experiments, our results exhibit an invaluable resource for the design of further experiments related to physiology of early algal development. Full article

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

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1 pages, 121 KiB

Open AccessEditorial

Molecules New Aims and Scope

by Derek J. McPhee

Editor-in-Chief, MDPI AG, St. Alban-Anlage 66, 4052 Basel, Switzerland

Molecules 2017, 22(9), 1510; https://doi.org/10.3390/molecules22091510 - 20 Sep 2017

Viewed by 4757

Abstract

As we approach the end of our 22nd year as the pioneering and preeminent Open Access journal in the field of organic chemistry and natural products, time has come to formally announce what has been the de facto reality of the journal for [...] Read more.

As we approach the end of our 22nd year as the pioneering and preeminent Open Access journal in the field of organic chemistry and natural products, time has come to formally announce what has been the de facto reality of the journal for the past few years, the expansion of the range of topics we cover.[...] Full article

14 pages, 1085 KiB

Open AccessArticle

Isaria fumosorosea KCh J2 Entomopathogenic Strain as an Effective Biocatalyst for Steroid Compound Transformations

by Ewa Kozłowska^*

, Monika Dymarska, Edyta Kostrzewa-Susłow and Tomasz Janeczko^*

Department of Chemistry, Wrocław University of Environmental and Life Sciences, Norwida 25, 50-375 Wrocław, Poland

Molecules 2017, 22(9), 1511; https://doi.org/10.3390/molecules22091511 - 9 Sep 2017

Cited by 17 | Viewed by 5895

Abstract

The catalytic activity of enzymes produced by an entomopathogenic filamentous fungus (Isaria fumosorosea KCh J2) towards selected steroid compounds (androstenedione, adrenosterone, progesterone, 17α-methyltestosterone and dehydroepiandrosterone) was investigated. All tested substrates were efficiently transformed. The structure of the substrate has a crucial impact [...] Read more.

The catalytic activity of enzymes produced by an entomopathogenic filamentous fungus (Isaria fumosorosea KCh J2) towards selected steroid compounds (androstenedione, adrenosterone, progesterone, 17α-methyltestosterone and dehydroepiandrosterone) was investigated. All tested substrates were efficiently transformed. The structure of the substrate has a crucial impact on regio- and stereoselectivity of hydroxylation since it affects binding to the active site of the enzyme. Androstenedione was hydroxylated in the 7α-position to give a key intermediate in the synthesis of the diuretic-7α-hydroxyandrost-4-ene-3,17-dione with 82% conversion. Adrenosterone and 17α-methyltestosterone were hydroxylated in the 6β-position. Hydroxylated derivatives such as 15β-hydroxy-17α-methyltestosterone and 6β,12β-dihydroxy-17α-methyltestosterone were also observed. In the culture of Isaria fumosorosea KCh J2, DHEA was effectively hydroxylated in the C-7 position and then oxidized to give 7-oxo-DHEA, 3β,7α- and 3β,7β-dihydroxy-17a-oxa-d-homo-androst-5-ene-17-one. We obtained 7β-OH-DHEA lactone with 82% yield during 3 days transformation of highly concentrated (5 g/L) DHEA. Full article

(This article belongs to the Section Bioorganic Chemistry)

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14 pages, 3426 KiB

Open AccessArticle

Development, Physicochemical Characterization and In Vitro Anti-Inflammatory Activity of Solid Dispersions of α,β Amyrin Isolated from Protium Oilresin

by Walter Ferreira Da Silva Júnior¹, Jonas Gabriel de Oliveira Pinheiro¹, Danielle Lima Bezerra De Menezes¹, Natan Emanuell de Sobral E Silva¹, Patrícia Danielle Oliveira De Almeida², Emerson Silva Lima²

, Valdir Florêncio Da Veiga Júnior^3,4

, Eduardo Pereira De Azevedo⁵ and Ádley Antonini Neves De Lima^1,*

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

² Department of Pharmacy, Laboratory of Biological Activity, Federal University of Amazonas, Manaus 69077-000, AM, Brazil

³ Department of Chemistry, Institute of Exact Sciences, Federal University of Amazonas, Manaus 69077-000, AM, Brazil

⁴ Military Institute of Engineering, Rio de Janeiro 22290-270, RJ, Brazil

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

Molecules 2017, 22(9), 1512; https://doi.org/10.3390/molecules22091512 - 9 Sep 2017

Cited by 12 | Viewed by 5568

Abstract

α,β Amyrin (ABAM) is a natural mixture of pentacyclic triterpenes that has shown a variety of pharmacological properties, including anti-inflammatory effect. ABAM is isolated from Burseraceae oilresins, especially from the Protium species, which is commonly found in the Brazilian Amazon. This work aimed [...] Read more.

α,β Amyrin (ABAM) is a natural mixture of pentacyclic triterpenes that has shown a variety of pharmacological properties, including anti-inflammatory effect. ABAM is isolated from Burseraceae oilresins, especially from the Protium species, which is commonly found in the Brazilian Amazon. This work aimed to develop solid dispersions (SD) of ABAM with the following hydrophilic polymers: polyvinylpyrrolidone (PVP-K30), polyethylene glycol (PEG-6000) and hydroxypropylmethylcellulose (HPMC). The SDs were prepared by physical mixture (PM), kneading (KND) and rotary evaporation (RE) methods. In order to verify any interaction between ABAM and the hydrophilic polymers, physicochemical characterization was performed by Fourier transform infrared (FTIR), scanning electron microscopy (SEM), powder X-ray diffraction (XRD), thermogravimetry (TG) and differential scanning calorimetry (DSC) analysis. Furthermore, an in vitro anti-inflammatory assay was performed with ABAM alone and as SDs with the hydrophilic polymers. The results from the characterization analysis show that the SDs were able to induce changes in the physicochemical properties of ABAM, which suggests interaction with the polymer matrix. In vitro anti-inflammatory assay showed that the SDs improved the anti-inflammatory activity of ABAM and showed no cytotoxicity. In conclusion, this study showed the potential use of SDs as an efficient tool for improving the stability and anti-inflammatory activity of ABAM without cytotoxicity. Full article

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16 pages, 9219 KiB

Open AccessArticle

Visible Light-Cured Glycol Chitosan Hydrogel Containing a Beta-Cyclodextrin-Curcumin Inclusion Complex Improves Wound Healing In Vivo

by Sun-Jung Yoon¹

, Hoon Hyun², Deok-Won Lee³ and Dae Hyeok Yang^4,*

¹ Department of Orthopedic Surgery, Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Jeonju 54907, Korea

² Department of Biomedical Sciences, Chonnam National University Medical School, Gwangju 61469, Korea

³ Department of Oral and Maxillofacial Surgery, Kyung Hee University Dental Hospital at Gangdong, Kyung Hee University, Seoul 05278, Korea

⁴ Institute of Cell and Tissue Engineering, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea

Molecules 2017, 22(9), 1513; https://doi.org/10.3390/molecules22091513 - 10 Sep 2017

Cited by 51 | Viewed by 9563

Abstract

Scarless wound healing is ideal for patients suffering from soft tissue defects. In this study, we prepared a novel wet dressing (β-CD-ic-CUR/GC) based on the visible light-cured glycol chitosan (GC) hydrogel and inclusion complex between beta-cyclodextrin (β-CD) and curcumin (CUR). We also evaluated [...] Read more.

Scarless wound healing is ideal for patients suffering from soft tissue defects. In this study, we prepared a novel wet dressing (β-CD-ic-CUR/GC) based on the visible light-cured glycol chitosan (GC) hydrogel and inclusion complex between beta-cyclodextrin (β-CD) and curcumin (CUR). We also evaluated its efficacy in the acceleration of wound healing as compared to that of CUR-loaded GC (CUR/GC). The conjugation of glycidyl methacrylate (GM) to GC for photo-curing was confirmed by ¹H-NMR measurement, and the photo-cured GC hydrogel was characterized by the analyses of rheology, swelling ratio, SEM and degradation rate. After visible light irradiation, the surface/cross-sectional morphologies and storage (G′)/loss (G′′) moduli revealed the formation of hydrogel with interconnected porosity. The dressing β-CD-ic-CUR/GC exhibited a controlled release of 90% CUR in a sustained manner for 30 days. On the other hand, CUR/GC showed CUR release of 16%. β-CD acted as an excipient in improving the water-solubility of CUR and affected the release behavior of CUR. The in vivo animal tests including measurement of the remaining unhealed wound area and histological analyses showed that β-CD-ic-CUR/GC may have potential as a wet dressing agent to enhance soft tissue recovery in open fractures. Full article

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

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9 pages, 667 KiB

Open AccessArticle

Four Prenylflavone Derivatives with Antiplasmodial Activities from the Stem of Tephrosia purpurea subsp. leptostachya

by Yoseph Atilaw¹, Lois Muiva-Mutisya¹, Albert Ndakala¹, Hoseah M. Akala²

, Redemptah Yeda², Yu J. Wu³, Paolo Coghi³, Vincent K. W. Wong³

, Máté Erdélyi^4,5,*

and Abiy Yenesew^1,*

¹ Department of Chemistry, University of Nairobi, Nairobi, P.O. Box 30197-00100, Kenya

² Global Emerging Infections Surveillance (GEIS) Program, United States Army Medical Research Unit-Kenya (USAMRU-K), Kenya Medical Research Institute (KEMRI)—Walter Reed Project, Kisumu and Nairobi, P.O. Box 54-40100, Kisumu, Kenya

³ State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, P.O. Box 999078, China

⁴ Department of Chemistry and Molecular Biology, University of Gothenburg, SE-40530 Gothenburg, Sweden

⁵ Swedish NMR Centre, University of Gothenburg, P.O. Box 465, SE-40530 Gothenburg, Sweden

Molecules 2017, 22(9), 1514; https://doi.org/10.3390/molecules22091514 - 10 Sep 2017

Cited by 13 | Viewed by 6434

Abstract

Four new flavones with modified prenyl groups, namely (E)-5-hydroxytephrostachin (1), purleptone (2), (E)-5-hydroxyanhydrotephrostachin (3), and terpurlepflavone (4), along with seven known compounds (5–11), were isolated from the [...] Read more.

Four new flavones with modified prenyl groups, namely (E)-5-hydroxytephrostachin (1), purleptone (2), (E)-5-hydroxyanhydrotephrostachin (3), and terpurlepflavone (4), along with seven known compounds (5–11), were isolated from the CH₂Cl₂/MeOH (1:1) extract of the stem of Tephrosia purpurea subsp. leptostachya, a widely used medicinal plant. Their structures were elucidated on the basis of NMR spectroscopic and mass spectrometric evidence. Some of the isolated compounds showed antiplasmodial activity against the chloroquine-sensitive D6 strains of Plasmodium falciparum, with (E)-5-hydroxytephrostachin (1) being the most active, IC₅₀ 1.7 ± 0.1 μM, with relatively low cytotoxicity, IC₅₀ > 21 μM, against four cell-lines. Full article

(This article belongs to the Collection Natural Products as Leads or Drugs against Neglected Tropical Diseases)

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13 pages, 1319 KiB

Open AccessArticle

Alterations in Pharmacokinetics of Gemcitabine and Erlotinib by Concurrent Administration of Hyangsayukgunja-Tang, a Gastroprotective Herbal Medicine

by Tae Hwan Kim^1,†

, Soyoung Shin^2,†

, Sarah Kim¹

, Jürgen B. Bulitta¹

, Kwon-Yeon Weon³, Sang Hoon Joo³, Eunsook Ma³, Sun Dong Yoo⁴, Gi-Young Park⁵, Dong Rak Kwon⁵, Seok Won Jeong³, Da Young Lee³ and Beom Soo Shin^4,*

¹ Center for Pharmacometrics and Systems Pharmacology, Department of Pharmaceutics, College of Pharmacy, University of Florida, Orlando, FL 32827, USA

² College of Pharmacy, Wonkwang University, Iksan, Jeonbuk 54538, Korea

³ College of Pharmacy, Catholic University of Daegu, 13-13 Hayang-ro, Hayang-eup, Gyeongsan-si, Gyeongbuk 38430, Korea

⁴ School of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi-do 16419, Korea

⁵ Department of Rehabilitation Medicine, School of Medicine, Catholic University of Daegu, Daegu 42472, Korea

^† Tae Hwan Kim and Soyoung Shin contributed equally to this work.

Molecules 2017, 22(9), 1515; https://doi.org/10.3390/molecules22091515 - 10 Sep 2017

Cited by 5 | Viewed by 6401

Abstract

Gemcitabine and erlotinib are the chemotherapeutic agents used in the treatment of various cancers and their combination is being accepted as a first-line treatment of advanced pancreatic cancer. Hyangsayukgunja-tang (HYT) is a traditional oriental medicine used in various digestive disorders and potentially helpful [...] Read more.

Gemcitabine and erlotinib are the chemotherapeutic agents used in the treatment of various cancers and their combination is being accepted as a first-line treatment of advanced pancreatic cancer. Hyangsayukgunja-tang (HYT) is a traditional oriental medicine used in various digestive disorders and potentially helpful to treat gastrointestinal adverse effects related to chemotherapy. The present study was aimed to evaluate the effect of HYT on the pharmacokinetics of gemcitabine and erlotinib given simultaneously in rats. Rats were pretreated with HYT at an oral dose of 1200 mg/kg/day once daily for a single day or 14 consecutive days. Immediately after pretreatment with HYT, gemcitabine and erlotinib were administered by intravenous injection (10 mg/kg) and oral administration (20 mg/kg), respectively. The effects of HYT on pharmacokinetics of the two drugs were estimated by non-compartmental analysis and pharmacokinetic modeling. The pharmacokinetics of gemcitabine and erlotinib were not altered by single dose HYT pretreatment. However, the plasma levels of OSI-420 and OSI-413, active metabolites of erlotinib, were significantly decreased in the multiple dose HYT pretreatment group. The pharmacokinetic model estimated increased systemic clearances of OSI-420 and OSI-413 by multiple doses of HYT. These data suggest that HYT may affect the elimination of OSI-420 and OSI-413. Full article

(This article belongs to the Special Issue Herbal Remedies Meet Modern Day Medicine: Challenges and Opportunities)

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14 pages, 2364 KiB

Open AccessArticle

Ginsenoside Rg3 Prevents Oxidative Stress-Induced Astrocytic Senescence and Ameliorates Senescence Paracrine Effects on Glioblastoma

by Jingang Hou¹, Sunchang Kim^1,2,*, Changkeun Sung³ and Chulhee Choi⁴

¹ Intelligent Synthetic Biology Center, Daejeon 34141, Korea

² Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Korea

³ Department of Food Science and Technology, College of Agriculture and Biotechnology, Chungnam National University, Daejeon 34141, Korea

⁴ Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Korea

Molecules 2017, 22(9), 1516; https://doi.org/10.3390/molecules22091516 - 10 Sep 2017

Cited by 34 | Viewed by 7345

Abstract

Senescent astrocytes in aging brain express senescence-associated secretory phenotype (SASP) and link with increased brain aging and its related diseases. In order to determine whether ginsenosides ameliorate the astrocytic senescence in vitro, human astrocytic CRT cells and primary rat astrocytes were used in [...] Read more.

Senescent astrocytes in aging brain express senescence-associated secretory phenotype (SASP) and link with increased brain aging and its related diseases. In order to determine whether ginsenosides ameliorate the astrocytic senescence in vitro, human astrocytic CRT cells and primary rat astrocytes were used in the present study. Ginsenosides Rg1, Re, Rb1 and Rg3 (5 μg/mL) could effectively prevent the astrocytic senescence induced by H₂O₂ exposure. However, these ginsenosides did not reverse the astrocytic senescence. Importantly, senescent astrocytes herein produce SASP. The expression of major components of SASP, IL-6 and IL-8, are greatly increased in senescent astrocytes. Ginsenoside Rg3 (10 μg/mL) effectively suppressed the expressions of IL-6 and IL-8, which is associated with regulations of NF-κB and p38MAPK activation. In addition, after incubation with Rg3, conditioned medium from senescent astrocytic CRT cells significantly decreased the ability to promote the proliferation of astrocytoma U373-MG, U87-MG and U251-MG cells compared with non-treated senescent samples. Similar patterns were confirmed in chemotherapy-induced glioblastoma senescent cells. The present study explored a potential candidate for amelioration of astrocytic senescence and SASP in brain aging, which provided a basis for developing strategies to reduce the dark side of senescence in normal or pathological aging process. Full article

(This article belongs to the Special Issue Neuroprotective Agents)

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10 pages, 374 KiB

Open AccessArticle

The Application of Quantitative ¹H-NMR for the Determination of Orlistat in Tablets

by Shanshan Sun, Mengxia Jin, Xia Zhou, Jinghua Ni, Xiangju Jin, Hongyue Liu and Yinghong Wang^*

State Key Laboratory for Bioactive Substances and Functions of Natural Medicines and Beijing Key Laboratory of New Drug Mechanisms and Pharmacological Evaluation Study, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, No.1 Xiannongtan Street, Beijing 100050, China

Molecules 2017, 22(9), 1517; https://doi.org/10.3390/molecules22091517 - 10 Sep 2017

Cited by 49 | Viewed by 8137

Abstract

A quantitative nuclear magnetic resonance (qNMR) method to measure the content of Orlistat in tablets was studied and found to be efficient, accurate, reliable, and simple. In this paper, phloroglucinolanhydrous and dimethylsulfoxide-d₆ (DMSO-d₆) served as the internal standard [...] Read more.

A quantitative nuclear magnetic resonance (qNMR) method to measure the content of Orlistat in tablets was studied and found to be efficient, accurate, reliable, and simple. In this paper, phloroglucinolanhydrous and dimethylsulfoxide-d₆ (DMSO-d₆) served as the internal standard and solvent, respectively. The qNMR methodology, including the linearity, range, the limit of detection (LOD) and quantification (LOQ), stability, precision, and accuracy, was validated seriatim, and the results were very favorable. The content determination results of three batches of Orlistat in tablets were almost identical upon comparing the qNMR method and the high-performance liquid chromatography (HPLC) method. The recommended method authentically compensated the deficiencies of the current HPLC method for determining Orlistat content, and proved to be a method complementary to traditional analysis for the purity measurement of Orlistat in some pharmaceutical preparations. Full article

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13 pages, 5220 KiB

Open AccessReview

State of Panax ginseng Research: A Global Analysis

by Wanqi Xu¹

, Hyung-Kyoon Choi² and Linfang Huang^1,*

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

² College of Pharmacy, Chung-Ang University, Seoul 156-756, Korea

Molecules 2017, 22(9), 1518; https://doi.org/10.3390/molecules22091518 - 11 Sep 2017

Cited by 68 | Viewed by 10222

Abstract

This article aims to understand the global and longitudinal trends of research on Panax ginseng. We used bibliometrics to analyze 3974 papers collected from the Web of Science^TM Core Collection database during 1959–2016. The number of publications showed a steady growth [...] Read more.

This article aims to understand the global and longitudinal trends of research on Panax ginseng. We used bibliometrics to analyze 3974 papers collected from the Web of Science^TM Core Collection database during 1959–2016. The number of publications showed a steady growth before 2000 and exponentially increased in stage III (2000–2016, about 86% of the papers were published). Research on P. ginseng was conducted in 64 countries, mainly in Asia; in particular, 41% and 28% of the publications were from South Korea and China, respectively. The institutions from South Korea and China had high publication output and close cooperation and provided the majority of financial support. All top 10 authors and four of the top 20 journals in terms of number of publications originated from South Korea. The leading research subjects were pharmacology (39%), plant science (26%), and integrative complementary medicine (19%). The hotspot of P. ginseng research transformed from basic science to application, and multidisciplinary sciences will play a substantial role in the future. This study provides a comprehensive analysis to elucidate the global distribution, collaboration patterns, and research trends in the P. ginseng domain. Full article

(This article belongs to the Special Issue Current Trends in Ginseng Research)

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9 pages, 3524 KiB

Open AccessCommunication

Synthesis of Bisimidazole Derivatives for Selective Sensing of Fluoride Ion

by Liang Zhang^*

and Fang Liu

School of Material Science and Engineering, Yancheng Institute of Technology, Yancheng 224051, Jiangsu, China

Molecules 2017, 22(9), 1519; https://doi.org/10.3390/molecules22091519 - 11 Sep 2017

Cited by 12 | Viewed by 5067

Abstract

Rapid and efficient analysis of fluoride ion is crucial to providing key information for fluoride ion hazard assessment and pollution management. In this study, we synthesized one symmetrical structure called 1,4-bis(4,5-diphenyl-1H-imidazol-2-yl)benzene (1a) and two asymmetrical structures, namely 2-(4-(4,5-diphenyl-1H [...] Read more.

Rapid and efficient analysis of fluoride ion is crucial to providing key information for fluoride ion hazard assessment and pollution management. In this study, we synthesized one symmetrical structure called 1,4-bis(4,5-diphenyl-1H-imidazol-2-yl)benzene (1a) and two asymmetrical structures, namely 2-(4-(4,5-diphenyl-1H-imidazol-2-yl)phenyl)-1H-phenanthro(9,10-d)imidazole (1b) and 2-(4-(4,5-diphenyl-1H-imidazol-2-yl)phenyl)-1H-imidazo(4,5-f)(1,10)phenanthroline (1c), which served as an efficient anion sensor for fluoride ion over a wide range of other anions (Cl⁻, Br⁻, I⁻, NO₃⁻, ClO₄⁻, HSO₄⁻, BF₄⁻, and PF₆⁻) owing to imidazole group in the main backbone. The absorption intensity of compound 1a at λ_max 358 nm slightly decreased; however, a new band at λ_max 414 nm appeared upon the addition of fluoride ion, while no evident change occurred upon the addition of eight other anions. The photoluminescence intensity of compound 1a at λ_max 426 nm was nearly quenched and fluorescence emission spectra were broadened when fluoride ion was added into dimethyl sulfoxide (DMSO) solution of compound 1a. Compared with the optical behaviors of the DMSO solution of compound 1a in the presence of Bu₄N⁺F⁻, compounds 1b and 1c exhibited considerable sensitivity to fluoride ion due to the increase in coplanarity. Furthermore, compared with the fluorescence emission behaviors of the DMSO solutions of compounds 1a and 1b in the presence of Bu₄N⁺F⁻, compound 1c exhibited the most significant sensitivity to fluoride ion due to the charge transfer enhancement. Consequently, the detection limits of compounds 1a–1c increased from 5.47 × 10⁻⁶ M to 4.21 × 10⁻⁶ M to 9.12 × 10⁻⁷ M. Furthermore, the largest red shift (75 nm) of the DMSO solution compound 1c in the presence of fluoride ion can be observed. Our results suggest that the increase in coplanarity and the introduction of electron-withdrawing groups to the imidazole backbone can improve the performance in detecting fluoride ion. Full article

(This article belongs to the Section Photochemistry)

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20 pages, 1404 KiB

Open AccessArticle

Bioactivity In Vitro of Quercetin Glycoside Obtained in Beauveria bassiana Culture and Its Interaction with Liposome Membranes

by Paulina Strugała^1,*, Tomasz Tronina²

, Ewa Huszcza² and Janina Gabrielska¹

¹ Department of Physics and Biophysics, Wrocław University of Environmental and Life Sciences, Norwida 25, 50-375 Wrocław, Poland

² Department of Chemistry, Wrocław University of Environmental and Life Sciences, Norwida 25, 50-375 Wrocław, Poland

Molecules 2017, 22(9), 1520; https://doi.org/10.3390/molecules22091520 - 11 Sep 2017

Cited by 40 | Viewed by 6451

Abstract

Quercetin (Q) was used as substrate for regioselective glycosylation at the C-7 position catalyzed by Beauveria bassiana AM278 strain. As a result the glycoside quercetin 7-O-β-d-(4″-O-methyl)glucopyranoside (Q 7-MeGlu) was formed. The goal of the studies was to [...] Read more.

Quercetin (Q) was used as substrate for regioselective glycosylation at the C-7 position catalyzed by Beauveria bassiana AM278 strain. As a result the glycoside quercetin 7-O-β-d-(4″-O-methyl)glucopyranoside (Q 7-MeGlu) was formed. The goal of the studies was to determine the anti-oxidative (liposome membrane protection against free radicals IC₅₀^{Q 7-MeGlu} = 5.47 and IC₅₀^Q = 4.49 µM) and anti-inflammatory (COX-1 and COX-2 enzymes activity inhibition) properties of Q 7-MeGlu as compared to Q. Every attempt was made to clarify the antioxidant activity of these molecules, which are able to interact with egg phosphatidylcholine liposomes, using a fluorometric method (by applying the probes MC540, TMA-DPH and DPH). The results indicated that Q 7-MeGlu and Q are responsible for increasing the packing order, mainly in the hydrophilic but also in hydrophobic regions of the membrane (Q > Q 7-MeGlu). These observations, confirmed by a ¹H-NMR method, are key to understanding their antioxidant activity which is probably caused by the stabilizing effect on the lipid membranes. The results showed that Q 7-MeGlu and Q have ability to quench the human serum albumin (HSA) intrinsic fluorescence through a static quenching mechanism. The results of thermodynamic parameters indicated that the process of formation complexes between studied molecules and HSA was spontaneous and caused through Van der Waals interactions and hydrogen bonding. Full article

(This article belongs to the Special Issue Phospholipids: Structure and Function)

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3 pages, 177 KiB

Open AccessEditorial

Special Issue: Intramolecular Hydrogen Bonding 2017

by Steve Scheiner

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

Molecules 2017, 22(9), 1521; https://doi.org/10.3390/molecules22091521 - 11 Sep 2017

Cited by 15 | Viewed by 4934

Abstract

Even after more than a century of study [1–6], scrutiny, and detailed examination, the H-bond continues [7–12] to evoke a level of fascination that surpasses many other phenomena [...]
Full article

(This article belongs to the Special Issue Intramolecular Hydrogen Bonding 2017)

24 pages, 3968 KiB

Open AccessReview

Triarylborane-Based Materials for OLED Applications

by Gulsen Turkoglu^1,*, M. Emin Cinar¹ and Turan Ozturk^1,2,*

¹ Department of Chemistry, Istanbul Technical University, Maslak, Istanbul 34469, Turkey

² Chemistry Group Laboratories, TUBITAK-UME P.O. Box 54, Gebze, Kocaeli 41471, Turkey

Molecules 2017, 22(9), 1522; https://doi.org/10.3390/molecules22091522 - 13 Sep 2017

Cited by 104 | Viewed by 14734

Abstract

Multidisciplinary research on organic fluorescent molecules has been attracting great interest owing to their potential applications in biomedical and material sciences. In recent years, electron deficient systems have been increasingly incorporated into fluorescent materials. Triarylboranes with the empty p orbital of their boron [...] Read more.

Multidisciplinary research on organic fluorescent molecules has been attracting great interest owing to their potential applications in biomedical and material sciences. In recent years, electron deficient systems have been increasingly incorporated into fluorescent materials. Triarylboranes with the empty p orbital of their boron centres are electron deficient and can be used as strong electron acceptors in conjugated organic fluorescent materials. Moreover, their applications in optoelectronic devices, energy harvesting materials and anion sensing, due to their natural Lewis acidity and remarkable solid-state fluorescence properties, have also been investigated. Furthermore, fluorescent triarylborane-based materials have been commonly utilized as emitters and electron transporters in organic light emitting diode (OLED) applications. In this review, triarylborane-based small molecules and polymers will be surveyed, covering their structure-property relationships, intramolecular charge transfer properties and solid-state fluorescence quantum yields as functional emissive materials in OLEDs. Also, the importance of the boron atom in triarylborane compounds is emphasized to address the key issues of both fluorescent emitters and their host materials for the construction of high-performance OLEDs. Full article

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11 pages, 3501 KiB

Open AccessArticle

Transesterification Synthesis of Chloramphenicol Esters with the Lipase from Bacillus amyloliquefaciens

by Fengying Dong¹, Lingmeng Li¹, Lin Lin², Dannong He², Jingwen Chen³, Wei Wei^1,* and Dongzhi Wei^1,*

¹ State Key Laboratory of Bioreactor Engineering, Newworld Institute of Biotechnology, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, China

² Research Laboratory for Functional Nanomaterial, National Engineering Research Center for Nanotechnology, Shanghai 200241, China

³ Department of Pathology, Microbiology and Immunology, School of medicine, University of South Carolina, 6311 Garners Ferry Rd., Columbia, SC 29209, USA

Molecules 2017, 22(9), 1523; https://doi.org/10.3390/molecules22091523 - 19 Sep 2017

Cited by 11 | Viewed by 7014

Abstract

This work presents a synthetic route to produce chloramphenicol esters by taking advantage the high enantio- and regio-selectivity of lipases. A series of chloramphenicol esters were synthesized using chloramphenicol, acyl donors of different carbon chain length and lipase Lip_BA (lipase cloned from [...] Read more.

This work presents a synthetic route to produce chloramphenicol esters by taking advantage the high enantio- and regio-selectivity of lipases. A series of chloramphenicol esters were synthesized using chloramphenicol, acyl donors of different carbon chain length and lipase Lip_BA (lipase cloned from Bacillus amyloliquefaciens). Among acyl donors with different carbon chain lengths, vinyl propionate was found to be the best. The influences of different organic solvents, reaction temperature, reaction time, enzyme loading and water content on the synthesis of the chloramphenicol esters were studied. The synthesis of chloramphenicol propionate (0.25 M) with 4.0 g L⁻¹ of Lip_BA loading gave a conversion of ~98% and a purity of ~99% within 8 h at 50 °C in 1,4-dioxane as solvent. The optimum mole ratio of vinyl propionate to chloramphenicol was increased to 5:1. This is the first report of B. amyloliquefaciens lipase being used in chloramphenicol ester synthesis and a detailed study of the synthesis of chloramphenicol propionate using this reaction. The high enzyme activity and selectivity make lipase Lip_BA an attractive catalyst for green chemical synthesis of molecules with complex structures. Full article

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

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14 pages, 1873 KiB

Open AccessCommunication

Development of a Matrix Solid-Phase Dispersion Extraction Combined with UPLC/Q-TOF-MS for Determination of Phenolics and Terpenoids from the Euphorbia fischeriana

by Wenjing Li, Yu Lin, Yuchun Wang and Bo Hong^*

College of Pharmacy, Qiqihar Medical University, Qiqihar 161006, Heilongjiang, China

Molecules 2017, 22(9), 1524; https://doi.org/10.3390/molecules22091524 - 11 Sep 2017

Cited by 15 | Viewed by 4461

Abstract

A method based on a simplified extraction by matrix solid phase dispersion (MSPD) followed by ultra-performance liquid chromatography coupled with the quadrupole time-of-flight tandem mass spectrometry (UPLC/Q-TOF-MS) determination is validated for analysis of two phenolics and three terpenoids in Euphorbia fischeriana. The [...] Read more.

A method based on a simplified extraction by matrix solid phase dispersion (MSPD) followed by ultra-performance liquid chromatography coupled with the quadrupole time-of-flight tandem mass spectrometry (UPLC/Q-TOF-MS) determination is validated for analysis of two phenolics and three terpenoids in Euphorbia fischeriana. The optimized experimental parameters of MSPD including dispersing sorbent (silica gel), ratio of sample to dispersing sorbent (1:2), elution solvent (water–ethanol: 30–70) and volume of the elution solvent (10 mL) were examined and set down. The highest extraction yields of chromatogram information and the five compounds were obtained under the optimized conditions. A total of 25 constituents have been identified and five components have been quantified from Euphorbia fischeriana. A linear relationship (r² ≥ 0.9964) between the concentrations and the peak areas of the mixed standard substances were revealed. The average recovery was between 92.4% and 103.2% with RSD values less than 3.45% (n = 5). The extraction yields of two phenolics and three terpenoids obtained by the MSPD were higher than those of traditional reflux and sonication extraction with reduced requirement on sample, solvent and time. In addition, the optimized method will be applied for analyzing terpenoids in other Chinese herbal medicine samples. Full article

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12 pages, 6265 KiB

Open AccessArticle

Arenobufagin Induces Apoptotic Cell Death in Human Non-Small-Cell Lung Cancer Cells via the Noxa-Related Pathway

by Liang Ma, Yindi Zhu, Sheng Fang, Hongyan Long, Xiang Liu^* and Zi Liu^*

Department of Chemical Biology and Pharmaceutical Engineering, School of Chemistry and Chemical Engineering, Anhui University of Technology, Ma’anshan 243002, Anhui, China

Molecules 2017, 22(9), 1525; https://doi.org/10.3390/molecules22091525 - 11 Sep 2017

Cited by 29 | Viewed by 5595

Abstract

Arenobufagin, an active component isolated from the traditional Chinese medicine Chan Su, exhibits anticancer influences in several human malignancies. However, the effects and action mechanisms of arenobufagin on non-small-cell lung cancer (NSCLC) are still unknown. In this study, we reported that arenobufagin acted [...] Read more.

Arenobufagin, an active component isolated from the traditional Chinese medicine Chan Su, exhibits anticancer influences in several human malignancies. However, the effects and action mechanisms of arenobufagin on non-small-cell lung cancer (NSCLC) are still unknown. In this study, we reported that arenobufagin acted through activation of Noxa-related pathways and promoted apoptotic cell death in human NSCLC cells. Our results revealed that arenobufagin-induced apoptosis was caspase-dependent, as evidenced by the fact that caspase-9, caspase-3 and poly (ADP-ribose) polymerase (PARP) were cleaved, and pretreatment with a pan-caspase inhibitor Z-VAD-FMK inhibited the pro-apoptosis effect of arenobufagin. Mechanistically, we further found that arenobufagin rapidly upregulated the expression of the pro-apoptosis protein Noxa, and abrogated the anti-apoptosis protein Mcl-1, a major binding partner of Noxa in the cell. More importantly, the knockdown of Noxa greatly blocked arenobufagin-induced cell death, highlighting the contribution of this protein in the anti-NSCLC effects of arenobufagin. Interestingly, arenobufagin also increased the expression of p53, a direct transcriptional activator for the upregulation of the Noxa protein. Taken together, our results suggest that arenobufagin is a potential anti-NSCLC agent that triggers apoptotic cell death in NSCLC cells through interfering with the Noxa-related pathway. Full article

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

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12 pages, 2495 KiB

Open AccessArticle

Evaluation of the Molecular Structural Parameters of Normal Rice Starch and Their Relationships with Its Thermal and Digestion Properties

by Lingshang Lin^1,2, Qing Zhang^1,2, Long Zhang^1,2 and Cunxu Wei^1,2,*

¹ Key Laboratory of Crop Genetics and Physiology of Jiangsu Province/Key Laboratory of Plant Functional Genomics of the Ministry of Education, Yangzhou University, Yangzhou 225009, China

² Co-Innovation Center for Modern Production Technology of Grain Crops of Jiangsu Province/Joint International Research Laboratory of Agriculture & Agri-Product Safety of the Ministry of Education, Yangzhou University, Yangzhou 225009, China

Molecules 2017, 22(9), 1526; https://doi.org/10.3390/molecules22091526 - 12 Sep 2017

Cited by 45 | Viewed by 6273

Abstract

The molecular structural parameters of six normal rice starches with different amylose contents were investigated through their iodine absorption spectra and gel permeation chromatography of fully branched and debranched starches. The thermal and digestion properties of starches were also determined and their relationships [...] Read more.

The molecular structural parameters of six normal rice starches with different amylose contents were investigated through their iodine absorption spectra and gel permeation chromatography of fully branched and debranched starches. The thermal and digestion properties of starches were also determined and their relationships with molecular structural parameters were analyzed. Results showed that the molecular structural parameters of maximum absorption wavelength, blue value (BV), optical density 620 nm/550 nm (OD 620/550), amylose, intermediate component, and amylopectin, including its short branch-chains, long branch-chains, and branching degree, had high correlation in different determining methods. The intermediate component of starch was significantly positively related to amylose and negatively related to amylopectin, and the amylopectin branching degree was significantly positively related to amylopectin content and negatively related to amylose content. The gelatinization temperatures and enthalpy of native starch were significantly positively related to BV, OD 620/550, and amylose content and negatively related to amylopectin short branch-chains. The gelatinization temperatures and enthalpy of retrograded starch were significantly negatively related to amylopectin branching degree. The digestions of gelatinized and retrograded starches were significantly negatively related to the BV, OD 620/550, amylose, and intermediate component and positively related to amylopectin and its short branch-chains and branching degree. Full article

(This article belongs to the Special Issue Polysaccharide-based Materials)

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15 pages, 1706 KiB

Open AccessArticle

Antibiofilm Activity and Mechanism of Action of the Disinfectant Chloramine T on Candida spp., and Its Toxicity against Human Cells

by Gabriela Lacet Silva Ferreira¹, Pedro Luiz Rosalen², Larissa Rangel Peixoto¹, Ana Luiza Alves de Lima Pérez¹, Fabíola Galbiatti de Carvalho Carlo¹, Lúcio Roberto Cançado Castellano¹, Jefferson Muniz de Lima¹, Irlan Almeida Freires³, Edeltrudes De Oliveira Lima¹ and Ricardo Dias de Castro^1,*

¹ Graduate Program in Dentistry, School of Dentistry, Universidade Federal da Paraíba (UFPB), João Pessoa PB 58051900, Brazil

² Department of Physiological Sciences, Piracicaba Dental School, University of Campinas (UNICAMP), Piracicaba SP 13414903, Brazil

³ Department of Oral Biology, University of Florida College of Dentistry, Gainesville, FL 32610, USA

Molecules 2017, 22(9), 1527; https://doi.org/10.3390/molecules22091527 - 17 Sep 2017

Cited by 15 | Viewed by 6304

Abstract

We evaluated the antifungal and anti-biofilm activity, mechanism of action and cytotoxicity of chloramine T trihydrate (CAT) against Candida spp. The Minimum Inhibitory and Fungicidal Concentrations (MIC/MFC) of CAT were determined. Changes in CAT-treated C. albicans growth kinetics and micromorphology were evaluated, as [...] Read more.

We evaluated the antifungal and anti-biofilm activity, mechanism of action and cytotoxicity of chloramine T trihydrate (CAT) against Candida spp. The Minimum Inhibitory and Fungicidal Concentrations (MIC/MFC) of CAT were determined. Changes in CAT-treated C. albicans growth kinetics and micromorphology were evaluated, as well as the mechanism of action, and its effects on biofilm. Cytotoxicity was assessed by the hemolysis method. The data were analyzed by inferential statistics (p ≤ 0.05). CAT showed antifungal activity against all strains, with MIC values ranging between 1.38 and 5.54 mmol/L (MIC_75%: 2.77 mmol/L). CAT demonstrated an immediate and sustained action on C. albicans growth kinetics, particularly at 2 × MIC. This compound likely acts on the cell wall and membrane permeability simultaneously and was found to cause changes in C. albicans micromorphology. Tha antibiofilm activity of CAT was similar to that of sodium hypochlorite (p > 0.05) against mature biofilms. CAT was more effective than NaOCl in reducing mature biofilm upon 1-min exposure at 2 × MIC (24 h) and 4 × MIC (48 h) (p < 0.05). Toxicological analysis revealed that CAT had hemolytic activity between 61 and 67.7% as compared to 100% by NaOCl. CAT has antifungal and anti-biofilm properties, probably acting on both cell wall and membrane permeability, and showed low toxicity in vitro. Full article

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

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13 pages, 2307 KiB

Open AccessArticle

Complete Chloroplast Genome of Pinus massoniana (Pinaceae): Gene Rearrangements, Loss of ndh Genes, and Short Inverted Repeats Contraction, Expansion

by ZhouXian Ni¹

, YouJu Ye¹, Tiandao Bai^1,2, Meng Xu¹ and Li-An Xu^1,*

¹ Co-Innovation Center for Sustainable Forestry in Southern China, Nanjing Forestry University, Nanjing 210037, China

² Forestry College, Guangxi University, Nanning 530004, China

Molecules 2017, 22(9), 1528; https://doi.org/10.3390/molecules22091528 - 11 Sep 2017

Cited by 37 | Viewed by 6070

Abstract

The chloroplast genome (CPG) of Pinus massoniana belonging to the genus Pinus (Pinaceae), which is a primary source of turpentine, was sequenced and analyzed in terms of gene rearrangements, ndh genes loss, and the contraction and expansion of short inverted repeats (IRs). P. [...] Read more.

The chloroplast genome (CPG) of Pinus massoniana belonging to the genus Pinus (Pinaceae), which is a primary source of turpentine, was sequenced and analyzed in terms of gene rearrangements, ndh genes loss, and the contraction and expansion of short inverted repeats (IRs). P. massoniana CPG has a typical quadripartite structure that includes large single copy (LSC) (65,563 bp), small single copy (SSC) (53,230 bp) and two IRs (IRa and IRb, 485 bp). The 108 unique genes were identified, including 73 protein-coding genes, 31 tRNAs, and 4 rRNAs. Most of the 81 simple sequence repeats (SSRs) identified in CPG were mononucleotides motifs of A/T types and located in non-coding regions. Comparisons with related species revealed an inversion (21,556 bp) in the LSC region; P. massoniana CPG lacks all 11 intact ndh genes (four ndh genes lost completely; the five remained truncated as pseudogenes; and the other two ndh genes remain as pseudogenes because of short insertions or deletions). A pair of short IRs was found instead of large IRs, and size variations among pine species were observed, which resulted from short insertions or deletions and non-synchronized variations between “IRa” and “IRb”. The results of phylogenetic analyses based on whole CPG sequences of 16 conifers indicated that the whole CPG sequences could be used as a powerful tool in phylogenetic analyses. Full article

(This article belongs to the Section Molecular Diversity)

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13 pages, 6934 KiB

Open AccessArticle

The Effects of Resveratrol on Inflammation and Oxidative Stress in a Rat Model of Chronic Obstructive Pulmonary Disease

by Xiao-Li Wang^1,2

, Ting Li¹, Ji-Hong Li², Shu-Ying Miao¹ and Xian-Zhong Xiao^1,*

¹ Department of Pathophysiology, Xiangya School of Medicine, Central South University, Changsha 410000, Hunan, China

² Department of Pathology, Medical College of Jishou University, Jishou 416000, Hunan, China

Molecules 2017, 22(9), 1529; https://doi.org/10.3390/molecules22091529 - 12 Sep 2017

Cited by 133 | Viewed by 10717

Abstract

Oxidative stress and inflammation are hypothesized to contribute to the pathogenesis of chronic obstructive pulmonary disease (COPD). Resveratrol (trans-3,5,4′-trihydroxystilbene) is known for its antioxidant and anti-inflammatory properties. The study aimed to investigate the effects of resveratrol in a rat model with COPD on [...] Read more.

Oxidative stress and inflammation are hypothesized to contribute to the pathogenesis of chronic obstructive pulmonary disease (COPD). Resveratrol (trans-3,5,4′-trihydroxystilbene) is known for its antioxidant and anti-inflammatory properties. The study aimed to investigate the effects of resveratrol in a rat model with COPD on the regulation of oxidative stress and inflammation via the activation of Sirtuin1 (SIRTl) and proliferator-activated receptor-γ coactivator-1α (PGC-1α). Thirty Wistar rats were randomly divided into three groups: control group, COPD group and resveratrol intervention group. The COPD model was established by instilling with lipopolysaccharide (LPS) and challenging with cigarette smoke (CS). The levels of interleukin-6 (IL-6) and interleukin-8 (IL-8) in serum were measured. The levels of malondialdehyde (MDA) and the activity of superoxide dismutase (SOD) were measured. The expression levels of SIRT1 and PGC-1α in the lung tissues were examined by immunohistochemistry as well as real-time reverse transcriptase polymerase chain reaction (real-time RT-PCR) and western blotting analysis. After the treatment with resveratrol (50 mg/kg), compared with the COPD group, alleviation of inflammation and reconstruction in the small airways of the lungs were seen. Resveratrol might be correlated not only with the lower level of MDA and the higher activity of SOD, but also with the upregulation of SIRT1 and PGC-1α expression. Resveratrol treatment decreased serum levels of IL-6 and IL-8. Our findings indicate that resveratrol had a therapeutic effect in our rat COPD model, which is related to the inhibition of oxidative stress and inflammatory response. The mechanism may be related to the activation and upgrading of the SIRT1/PGC-1α signaling pathways. Thus resveratrol might be a therapeutic modality in COPD. Full article

(This article belongs to the Special Issue Improvements for Resveratrol Efficacy)

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11 pages, 1790 KiB

Open AccessArticle

Determination of the Main Nucleosides and Nucleobases in Natural and Cultured Ophiocordyceps xuefengensis

by Juan Zou^1,2, Ling Wu¹, Zheng-Mi He¹, Ping Zhang¹ and Zuo-Hong Chen^1,*

¹ College of Life Science, Hunan Normal University, Changsha 410081, China

² Key Laboratory of Research and Utilization of Ethnomedicinal Plant Resources of Hunan Province, College of Biological and Food Engineering, Huaihua University, Huaihua 418000, China

Molecules 2017, 22(9), 1530; https://doi.org/10.3390/molecules22091530 - 11 Sep 2017

Cited by 19 | Viewed by 4594

Abstract

Ophiocordyceps xuefengensis, a recently described species of Ophiocordyceps that is associated with the larvae of Phassus nodus (Hepialidae) in the living root or trunk of the medicinal plant Clerodendrum cyrtophyllum, is the largest known Cordyceps species and is recognized as a [...] Read more.

Ophiocordyceps xuefengensis, a recently described species of Ophiocordyceps that is associated with the larvae of Phassus nodus (Hepialidae) in the living root or trunk of the medicinal plant Clerodendrum cyrtophyllum, is the largest known Cordyceps species and is recognized as a desirable alternative for natural Ophiocordyceps sinensis. This study investigated the main nucleosides and nucleobases in natural and cultured Ophiocordyceps xuefengensis. The contents of the nucleosides and nucleobases in the natural and cultured samples were determined by reverse phase HPLC. The highest concentration of adenosine was found in the natural fruit body and the cultured stroma, with almost no adenosine in the cadaver of Phassus nodus. The contents of adenine, guanosine, uridine and uracil in the cultured mycelium were significantly higher than those in the natural sample. Inosine was only detected in the natural samples. Thymidine and 2-deoxyadenosine were only found in the cadaver of Phassus nodus. Cordycepin was not detected in the five samples examined. These results suggested that the cultured mycelium and cultured stroma of Ophiocordyceps xuefengensis might be a promising substitute for natural O. xuefengensis. Full article

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12 pages, 1216 KiB

Open AccessArticle

An Efficient, Eco-friendly and Sustainable One-Pot Synthesis of 3,4-Dihydropyrimidin-2(1H)-ones Directly from Alcohols Catalyzed by Heteropolyanion-Based Ionic Liquids

by Renzhong Fu

, Yang Yang^*

, Xudong Ma, Yu Sun, Jin Li, Hang Gao, Huaxing Hu, Xiaojun Zeng and Jun Yi^*

Jiangsu Laboratory of Advanced Functional Material, School of Chemistry and Materials Engineering, Changshu Institute of Technology, Changshu 215500, China

Molecules 2017, 22(9), 1531; https://doi.org/10.3390/molecules22091531 - 11 Sep 2017

Cited by 19 | Viewed by 7540

Abstract

Efficient, eco-friendly and sustainable access to 3,4-dihydropyrimidin-2(1H)-ones directly from alcohols under microwave and solvent-free conditions has been reported. The practical protocol involves heteropolyanion-based catalyzed oxidation of alcohols to aldehydes with NaNO₃ as the oxidant followed by cyclocondensation with dicarbonyl compounds [...] Read more.

Efficient, eco-friendly and sustainable access to 3,4-dihydropyrimidin-2(1H)-ones directly from alcohols under microwave and solvent-free conditions has been reported. The practical protocol involves heteropolyanion-based catalyzed oxidation of alcohols to aldehydes with NaNO₃ as the oxidant followed by cyclocondensation with dicarbonyl compounds and urea or thiourea in a two-step, one-pot manner. Compatibility with different functional groups, good to excellent yields and reusable catalysts are the main highlights. The utilization of alcohols instead of aldehydes is a valid and green alternative to the classical Biginelli reaction. Full article

(This article belongs to the Special Issue Catalytic Cascade Reactions)

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9 pages, 1356 KiB

Open AccessArticle

Optimization and Comparison of Synthetic Procedures for a Group of Triazinyl-Substituted Benzene-Sulfonamide Conjugates with Amino Acids

by Dominika Krajčiová¹, Daniel Pecher^1,2

, Vladimír Garaj³ 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, Slovakia

² Toxicological and Antidoping Center, Faculty of Pharmacy, Comenius University in Bratislava, Odbojárov 10, SK-832 32 Bratislava, Slovakia

³ Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Comenius University in Bratislava, Odbojárov 10, SK-832 32 Bratislava, Slovakia

Molecules 2017, 22(9), 1533; https://doi.org/10.3390/molecules22091533 - 13 Sep 2017

Cited by 6 | Viewed by 5647

Abstract

Sulfonamides incorporating 1,3,5-triazine moieties can selectively and potently inhibit carbonic anhydrase transmembrane isoforms IX, XII, and XIV over cytosolic isoforms I and II. In the present work, a highly effective synthetic procedure was proposed for this group of potent cancerostatic drugs and compared [...] Read more.

Sulfonamides incorporating 1,3,5-triazine moieties can selectively and potently inhibit carbonic anhydrase transmembrane isoforms IX, XII, and XIV over cytosolic isoforms I and II. In the present work, a highly effective synthetic procedure was proposed for this group of potent cancerostatic drugs and compared with previously used methods. The synthesis of triazinyl-substituted benzene-sulfonamide conjugates with amino acids can be easily carried out using sodium carbonate-based water solution as a synthetic medium instead of N,N-Diisopropylethylamine/Dimethylformamide. The benefits of this synthetic procedure include: (i) high selectivity of the creation of disubstituted conjugates; (ii) several times higher yield (≥95%) than that achieved previously; (iii) elimination of organic solvents by the use of an environmental friendly water medium (green chemistry); (iv) simple and fast isolation of the product. The synthesis and resulting products were evaluated using TLC, IR, NMR, and MS methods. The present work demonstrates a significant advantage in providing shortened routes to target structures. Full article

(This article belongs to the Special Issue Sulfonamides)

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13 pages, 12100 KiB

Open AccessCommunication

The Anti-Proliferation Activity and Mechanism of Action of K₁₂[V₁₈O₄₂(H₂O)]∙6H₂O on Breast Cancer Cell Lines

by Wen Qi, Boyu Zhang, Yanfei Qi^*, Shuanli Guo, Rui Tian, Jiaheng Sun and Mingming Zhao

School of Public Health, Jilin University, Changchun 130021, Jilin, China

Molecules 2017, 22(9), 1535; https://doi.org/10.3390/molecules22091535 - 12 Sep 2017

Cited by 25 | Viewed by 5493

Abstract

Polyoxometalates (POMs) are inorganic clusters that possess potential anti-bacterial, anti-viral, and anti-tumor activities. Herein, the in vitro anti-proliferation activities of K₁₂[V₁₈O₄₂(H₂O)]∙6H₂O (V₁₈) have been investigated on the MCF-7 and MDA-MB-231 [...] Read more.

Polyoxometalates (POMs) are inorganic clusters that possess potential anti-bacterial, anti-viral, and anti-tumor activities. Herein, the in vitro anti-proliferation activities of K₁₂[V₁₈O₄₂(H₂O)]∙6H₂O (V₁₈) have been investigated on the MCF-7 and MDA-MB-231 cell lines. The results indicated that V₁₈ could inhibit the proliferation of MCF-7 (IC₅₀, 11.95 μM at 48 h) in a dose-dependent manner compared to the positive control, 5-fluorouracil (5-Fu, p < 0.05). The anti-proliferation activity of V₁₈ might be mediated by arrest of the MCF-7 cells in the G₂/M phase and induction of apoptosis and necrosis. Moreover, V₁₈ can effectively quench the fluorescence of ctDNA. The binding mode between them may be groove or outside stacking binding. V₁₈ can also effectively quench the intrinsic fluorescence of bovine serum albumin (BSA) and human serum albumin (HSA) via static quenching, and changed the conformation of BSA and HSA. Full article

(This article belongs to the Special Issue Metal Based Drugs: Opportunities and Challenges)

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16 pages, 5223 KiB

Open AccessArticle

Skin Penetration Enhancement by Natural Oils for Dihydroquercetin Delivery

by Vytis Čižinauskas^1,*, Nicolas Elie²

, Alain Brunelle²

and Vitalis Briedis¹

¹ Department of Clinical Pharmacy, Lithuanian University of Health Sciences, Sukilėlių pr. 13, Kaunas 50166, Lithuania

² Institut de Chimie des Substances Naturelles, CNRS UPR 2301, University Paris-Sud, Université Paris-Saclay, Avenue de la Terrasse, Gif-sur-Yvette 91198, France

Molecules 2017, 22(9), 1536; https://doi.org/10.3390/molecules22091536 - 12 Sep 2017

Cited by 28 | Viewed by 14534

Abstract

Natural oils are commonly used in topical pharmaceutical formulations as emulsifiers, stabilizers or solubility enhancers. They are presented as safe and inert components, mainly used for formulation purposes. It is confirmed that natural oils can affect the skin penetration of various substances. Fatty [...] Read more.

Natural oils are commonly used in topical pharmaceutical formulations as emulsifiers, stabilizers or solubility enhancers. They are presented as safe and inert components, mainly used for formulation purposes. It is confirmed that natural oils can affect the skin penetration of various substances. Fatty acids are mainly responsible for this effect. Current understanding lacks reliable scientific data on penetration of natural oils into the skin and their skin penetration enhancement potential. In the current study, fatty acid content analysis was used to determine the principal fatty acids in soybean, olive, avocado, sea-buckthorn pulp, raspberry seed and coconut oils. Time of flight secondary ion mass spectrometry bioimaging was used to determine the distribution of these fatty acids in human skin ex vivo after application of the oils. Skin penetration enhancement ratios were determined for a perspective antioxidant compound dihydroquercetin. The results demonstrated skin penetration of fatty acids from all oils tested. Only soybean and olive oils significantly increased the skin distribution of dihydroquercetin and can be used as skin penetration enhancers. However, no correlation can be determined between the fatty acids’ composition and skin penetration enhancement using currently available methodological approaches. This indicates that potential chemical penetration enhancement should be evaluated during formulation of topically applied products containing natural oils. Full article

(This article belongs to the Section Natural Products Chemistry)

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7 pages, 763 KiB

Open AccessArticle

Effects of Sleep Quality on Melatonin Levels and Inflammatory Response after Major Abdominal Surgery in an Intensive Care Unit

by Necdet Fatih Yaşar^1,*

, Bartu Badak¹, Ağgül Canik², Sema Şanal Baş³, Sema Uslu², Setenay Öner⁴ and Ersin Ateş¹

¹ Department of General Surgery, Medical School, Eskisehir Osmangazi University, Eskisehir 26480, Turkey

² Department of Biochemistry, Medical School, Eskisehir Osmangazi University, Eskisehir 26480, Turkey

³ Department of Anesthesiology and Reanimation, Medical School, Eskisehir Osmangazi University, Eskisehir 26480, Turkey

⁴ Department of Biostatistics, Medical School, Eskisehir Osmangazi University, Eskisehir 26480, Turkey

Molecules 2017, 22(9), 1537; https://doi.org/10.3390/molecules22091537 - 12 Sep 2017

Cited by 15 | Viewed by 5504

Abstract

Disruption of nocturnal sleep in an intensive care unit may remarkably affect production of melatonin, which is also known to have anti-inflammatory properties. In the present study, we aimed to investigate the effect of sleep quality on melatonin levels and inflammation after surgery. [...] Read more.

Disruption of nocturnal sleep in an intensive care unit may remarkably affect production of melatonin, which is also known to have anti-inflammatory properties. In the present study, we aimed to investigate the effect of sleep quality on melatonin levels and inflammation after surgery. Thus, we compared the patients, who were screened in the side-rooms where the lights were dimmed and noise levels were reduced, with the patients who received usual care. Preoperative and postoperative urine 6-sulphatoxymelatonin, serum interleukin-1 (IL-1), interleukin-6 (IL-6), and c-reactive protein (CRP) levels were measured and data on sleep quality was collected using the Richards–Campbell Sleep Questionnaire. Postoperative CRP and IL-6 levels were greater in the control group than in the experimental group, whereas postoperative 24 h melatonin levels were greater than preoperative levels and the difference was steeper in the experimental group in concordance with sleep quality scores. Thus, the regulation of light and noise in ICUs may help the recovery after major surgeries in patients, potentially by increasing melatonin production, which has anti-inflammatory properties. 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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15 pages, 1101 KiB

Open AccessArticle

Synthesis and Antifungal Activity of Novel 3-Caren-5-One Oxime Esters

by Min Huang, Wen-Gui Duan^*, Gui-Shan Lin^*, Kun Li and Qiong Hu

School of Chemistry and Chemical Engineering, Guangxi University, Nanning 530004, Guangxi, China

Molecules 2017, 22(9), 1538; https://doi.org/10.3390/molecules22091538 - 12 Sep 2017

Cited by 15 | Viewed by 5775

Abstract

A series of novel 3-caren-5-one oxime esters were designed and synthesized by multi-step reactions in an attempt to develop potent antifungal agents. Two E-Z stereoisomers of the intermediate 3-caren-5-one oxime were separated by column chromatography for the first time. The structures [...] Read more.

A series of novel 3-caren-5-one oxime esters were designed and synthesized by multi-step reactions in an attempt to develop potent antifungal agents. Two E-Z stereoisomers of the intermediate 3-caren-5-one oxime were separated by column chromatography for the first time. The structures of all the intermediates and target compounds were confirmed by UV-Vis, FTIR, NMR, ESI-MS, and elemental analysis. The antifungal activity of the target compounds was preliminarily evaluated by the in vitro method against Fusarium oxysporum f. sp. cucumerinum, Physalospora piricola, Alternaria solani, Cercospora arachidicola, Gibberella zeae, Rhizoeotnia solani, Bipolaris maydis, and Colleterichum orbicalare at 50 µg/mL. The target compounds exhibited best antifungal activity against P. piricola, in which compounds (Z)-4r (R = β-pyridyl), (Z)-4q (R = α-thienyl), (E)-4f′ (R = p-F Ph), (Z)-4i (R = m-Me Ph), (Z)-4j (R = p-Me Ph), and (Z)-4p (R = α-furyl) had inhibition rates of 97.1%, 87.4%, 87.4%, 85.0%, 81.9%, and 77.7%, respectively, showing better antifungal activity than that of the commercial fungicide chlorothanil. Also, compound (Z)-4r (R = β-pyridyl) displayed remarkable antifungal activity against all the tested fungi, with inhibition rates of 76.7%, 82.7%, 97.1%, 66.3%, 74.7%, 93.9%, 76.7% and 93.3%, respectively, showing better or comparable antifungal activity than that of the commercial fungicide chlorothanil. Besides, the E-Z isomers of the target oxime esters were found to show obvious differences in antifungal activity. These results provide an encouraging framework that could lead to the development of potent novel antifungal agents. Full article

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

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18 pages, 4338 KiB

Open AccessReview

Cardiovascular Activity of the Chemical Constituents of Essential Oils

by Tadeu Uggere De Andrade¹, Girlandia Alexandre Brasil¹, Denise Coutinho Endringer¹, Flávio Rogério Da Nóbrega² and Damião Pergentino De Sousa^2,*

¹ Departamento de Farmácia, Universidade de Vila Velha, Vila Velha ES 29102-770, Brazil

² Departamento de Ciências Farmacêuticas, Universidade Federal da Paraíba, João Pessoa PB 58051-970, Brazil

Molecules 2017, 22(9), 1539; https://doi.org/10.3390/molecules22091539 - 17 Sep 2017

Cited by 30 | Viewed by 8869

Abstract

Cardiovascular diseases are a leading cause of death in developed and developing countries and decrease the quality of life, which has enormous social and economic consequences for the population. Recent studies on essential oils have attracted attention and encouraged continued research of this [...] Read more.

Cardiovascular diseases are a leading cause of death in developed and developing countries and decrease the quality of life, which has enormous social and economic consequences for the population. Recent studies on essential oils have attracted attention and encouraged continued research of this group of natural products because of their effects on the cardiovascular system. The pharmacological data indicate a therapeutic potential for essential oils for use in the treatment of cardiovascular diseases. Therefore, this review reports the current studies of essential oils chemical constituents with cardiovascular activity, including a description of their mechanisms of action. Full article

(This article belongs to the Collection Bioactive Compounds)

12 pages, 1039 KiB

Open AccessArticle

A Facile Oxidative Opening of the C-Ring in Luotonin A and Derivatives

by Amra Ibric¹, Kathrin Dutter¹, Brigitte Marian² and Norbert Haider^1,*

¹ Department of Pharmaceutical Chemistry, University of Vienna, Althanstraße 14, A-1090 Vienna, Austria

² Institute of Cancer Research, Medical University of Vienna, Borschkegasse 8a, A-1090 Vienna, Austria

Molecules 2017, 22(9), 1540; https://doi.org/10.3390/molecules22091540 - 12 Sep 2017

Cited by 6 | Viewed by 4844

Abstract

An oxidative ring opening reaction of the central ring C in the alkaloid Luotonin A and two of its derivatives was found to occur upon heating with an excess amine and potassium carbonate in dimethylsulfoxide (DMSO) solution in the presence of air oxygen. [...] Read more.

An oxidative ring opening reaction of the central ring C in the alkaloid Luotonin A and two of its derivatives was found to occur upon heating with an excess amine and potassium carbonate in dimethylsulfoxide (DMSO) solution in the presence of air oxygen. The structure of the novel amide-type products was elucidated and a possible mechanism for this reaction is proposed. Four of the new compounds show moderate in vitro anticancer activity towards human colon adenocarcinoma cells. Full article

(This article belongs to the Collection Heterocyclic Compounds)

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15 pages, 1216 KiB

Open AccessFeature PaperArticle

Development of Novel Nrf2/ARE Inducers Bearing Pyrazino[2,1-a]isoquinolin Scaffold with Potent In Vitro Efficacy and Enhanced Physicochemical Properties

by Hongbin Dai¹, Qiong Jiao², Tian Liu², Qidong You^2,* and Zhengyu Jiang^2,*

¹ Jiangsu Hengrui Medicine Company, Kunlunshan Road, Lianyungang Eco & Tech Development Zone, Lianyungang 222047, China

² State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China

Molecules 2017, 22(9), 1541; https://doi.org/10.3390/molecules22091541 - 13 Sep 2017

Cited by 2 | Viewed by 4220

Abstract

Pyrazino[2,1-a]isoquinolin analogues were reported as potent activators of Nrf2/ARE signaling both in vitro and in vivo by our group. In this study, we simplified the ring system to investigate the functions of various parts of the pyrazino[2,1-a]isoquinolin scaffold. We [...] Read more.

Pyrazino[2,1-a]isoquinolin analogues were reported as potent activators of Nrf2/ARE signaling both in vitro and in vivo by our group. In this study, we simplified the ring system to investigate the functions of various parts of the pyrazino[2,1-a]isoquinolin scaffold. We proved that the tetrahydroisoquinoline was not essential for activity and the pyrido[1,2-a]pyrazin analogues 3b and 3g retained the cellular Nrf2/ARE activation activity. Besides, this simplification significantly enhanced water solubility and membrane permeability, indicating that these compounds are more favourable for the further development of therapeutic agents around Nrf2 activation. Full article

(This article belongs to the Section Medicinal Chemistry)

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20 pages, 6449 KiB

Open AccessArticle

Exogenous Melatonin Alleviates Alkaline Stress in Malus hupehensis Rehd. by Regulating the Biosynthesis of Polyamines

by Xiaoqing Gong, Shuting Shi, Fangfang Dou, Yi Song and Fengwang Ma^*

State Key Laboratory of Crop Stress Biology for Arid Areas, College of Horticulture, Northwest A & F University, Yangling 712100, Shaanxi, China

Molecules 2017, 22(9), 1542; https://doi.org/10.3390/molecules22091542 - 13 Sep 2017

Cited by 99 | Viewed by 7271

Abstract

Since melatonin was identified in plants decades ago, much attention has been devoted to discovering its role in plant science. There is still a great deal to learn about the functional importance of melatonin, as well as its functional mode. In this paper, [...] Read more.

Since melatonin was identified in plants decades ago, much attention has been devoted to discovering its role in plant science. There is still a great deal to learn about the functional importance of melatonin, as well as its functional mode. In this paper, we examine the role of melatonin treatment in the response of Malus hupehensis Rehd. to alkaline conditions. Stressed seedlings showed chlorosis and suppressed growth. However, this phenotype was ameliorated when 5 µM melatonin was added to the irrigation solution. This supplementation was also associated with a reduction in cell membrane damage and maintenance of a normal root system architecture. Fewer reactive oxygen species (ROS) were accumulated due to the enhanced scavenging activity of antioxidant enzymes superoxide dismutase, peroxidase, and catalase. In addition, alkaline-stressed seedlings that received the melatonin supplement accumulated more polyamines compared with untreated seedlings. Transcript levels of six genes involved in polyamine synthesis, including SAMDC1, -3, and -4, and SPDS1, -3, and -5, -6, were upregulated in response to melatonin application. All of these results demonstrate that melatonin has a positive function in plant tolerance to alkaline stress because it regulates enzyme activity and the biosynthesis of polyamines. 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, 2719 KiB

Open AccessArticle

An NMR-Based Metabolomic Approach to Unravel the Preventive Effect of Water-Soluble Extract from Dendrobium officinale Kimura & Migo on Streptozotocin-Induced Diabetes in Mice

by Hong Zheng¹

, Linlin Pan¹, Pengtao Xu¹, Jianjun Zhu², Ruohan Wang¹, Wenzong Zhu³, Yongsheng Hu¹ and Hongchang Gao^1,*

¹ Institute of Metabonomics & Medical NMR, School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou 325035, China

² Wenzhou Academy of Agricultural Sciences, Wenzhou 325006, China

³ Department of Neurology Rehabilitation, Wenzhou Chinese Medicine Hospital, Wenzhou 325000, China

Molecules 2017, 22(9), 1543; https://doi.org/10.3390/molecules22091543 - 15 Sep 2017

Cited by 27 | Viewed by 6060

Abstract

Dendrobium officinale Kimura & Migo (D. officinale) is a precious herbal medicine. In this study, we investigated metabolic mechanism underlying the effect of D. officinale water extract (DOWE) on diabetes prevention in mice after streptozotocin (STZ) exposure using NMR-based metabolomics. Interestingly, [...] Read more.

Dendrobium officinale Kimura & Migo (D. officinale) is a precious herbal medicine. In this study, we investigated metabolic mechanism underlying the effect of D. officinale water extract (DOWE) on diabetes prevention in mice after streptozotocin (STZ) exposure using NMR-based metabolomics. Interestingly, we found a decrease in blood glucose and an increase in liver glycogen in mice pretreated with DOWE after STZ exposure. The DOWE pretreatment significantly increased citrate and glutamine in the serum as well as creatine, alanine, leucine, isoleucine, valine, glutamine, glutathione and taurine in the liver of STZ-treated mice. Furthermore, serum glucose was significantly negatively correlated with citrate, pyruvate, alanine, isoleucine, histidine and glutamine in the serum as well as alanine and taurine in the liver. These findings suggest that the effect of DOWE on diabetes prevention may be linked to increases in liver glycogen and taurine as well as the up-regulation of energy and amino acid metabolism. Full article

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

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26 pages, 5870 KiB

Open AccessArticle

Concept for Recycling Waste Biomass from the Sugar Industry for Chemical and Biotechnological Purposes

by Magdalena Modelska¹, Joanna Berlowska^2,*

, Dorota Kregiel²

, Weronika Cieciura², Hubert Antolak², Jolanta Tomaszewska¹, Michał Binczarski¹, Elzbieta Szubiakiewicz¹ and Izabela A. Witonska^1,*

¹ Institute of General and Ecological Chemistry, Faculty of Chemistry, Lodz University of Technology, Zeromskiego 116, 90-924 Lodz, Poland

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

Molecules 2017, 22(9), 1544; https://doi.org/10.3390/molecules22091544 - 13 Sep 2017

Cited by 29 | Viewed by 7140

Abstract

The objective of this study was to develop a method for the thermally-assisted acidic hydrolysis of waste biomass from the sugar industry (sugar beet pulp and leaves) for chemical and biotechnological purposes. The distillates, containing furfural, can be catalytically reduced directly into furfurayl [...] Read more.

The objective of this study was to develop a method for the thermally-assisted acidic hydrolysis of waste biomass from the sugar industry (sugar beet pulp and leaves) for chemical and biotechnological purposes. The distillates, containing furfural, can be catalytically reduced directly into furfurayl alcohol or tetrahydrofurfuryl alcohol. The sugars present in the hydrolysates can be converted by lactic bacteria into lactic acid, which, by catalytic reduction, leads to propylene glycol. The sugars may also be utilized by microorganisms in the process of cell proliferation, and the biomass obtained used as a protein supplement in animal feed. Our study also considered the effects of the mode and length of preservation (fresh, ensilage, and drying) on the yields of furfural and monosaccharides. The yield of furfural in the distillates was measured using gas chromatography with flame ionization detector (GC-FID). The content of monosaccharides in the hydrolysates was measured spectrophotometrically using enzymatic kits. Biomass preserved under all tested conditions produced high yields of furfural, comparable to those for fresh material. Long-term storage of ensiled waste biomass did not result in loss of furfural productivity. However, there were significant reductions in the amounts of monosaccharides in the hydrolysates. Full article

(This article belongs to the Section Green Chemistry)

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12 pages, 1963 KiB

Open AccessArticle

Valorization of By-Products from Commercial Fish Species: Extraction and Chemical Properties of Skin Gelatins

by Sérgio C. Sousa¹, José A. Vázquez^2,*

, Ricardo I. Pérez-Martín³

, Ana P. Carvalho^4,*

and Ana M. Gomes¹

¹ CBQF—Centro de Biotecnologia e Química Fina—Laboratório Associado, Escola Superior de Biotecnologia, Universidade Católica Portuguesa/Porto, Rua Arquiteto Lobão Vital, Apartado 2511, 4202-401 Porto, Portugal

² Grupo de Reciclado y Valorización de Materiales Residuales (REVAL), Instituto de Investigacións Mariñas (IIM-CSIC) r/Eduardo Cabello, 6. Vigo-36208 Galicia, Spain

³ Grupo de Bioquímica de Alimentos, Instituto de Investigacións Mariñas (IIM-CSIC) r/Eduardo Cabello, 6. Vigo-36208 Galicia, Spain

⁴ REQUIMTE/LAQV, Instituto Superior de Engenharia do Porto, Porto Polytechnic Institute, Rua Dr. António Bernardino de Almeida 431, 4294-015 Porto, Portugal

Molecules 2017, 22(9), 1545; https://doi.org/10.3390/molecules22091545 - 14 Sep 2017

Cited by 47 | Viewed by 7361

Abstract

Fish skins constitute an important fraction of the enormous amount of wastes produced by the fish processing industry, part of which may be valorized through the extraction of gelatins. This research exploited the extraction and characterization of gelatins from the skin of three [...] Read more.

Fish skins constitute an important fraction of the enormous amount of wastes produced by the fish processing industry, part of which may be valorized through the extraction of gelatins. This research exploited the extraction and characterization of gelatins from the skin of three seawater fish species, namely yellowfin tuna (Thunnus albacares), blue shark (Prionace glauca), and greenland halibut (Reinhardtius hippoglossoides). Characterization included chemical composition, rheology, structure, texture, and molecular weight, whereas extraction studies intended to reduce costly steps during extraction process (reagents concentration, water consumption, and time of processing), while maintaining extraction efficiency. Chemical and physical characterization of the obtained gelatins revealed that the species from which the gelatin was extracted, as well as the heat treatment used, were key parameters in order to obtain a final product with specific properties. Therefore, the extraction conditions selected during gelatin production will drive its utilization into markets with well-defined specifications, where the necessity of unique products is being claimed. Such achievements are of utmost importance to the food industry, by paving the way to the introduction in the market of gelatins with distinct rheological and textural properties, which enables them to enlarge their range of applications. Full article

(This article belongs to the Section Green Chemistry)

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16 pages, 3311 KiB

Open AccessArticle

Methylisoindigo and Its Bromo-Derivatives Are Selective Tyrosine Kinase Inhibitors, Repressing Cellular Stat3 Activity, and Target CD133+ Cancer Stem Cells in PDAC

by Jana Tegethoff^1,†, Roland Bischoff^2,†, Sawsan Saleh¹, Biljana Blagojevic¹, Karl-Heinz Merz² and Xinlai Cheng^1,*

¹ Department of Pharmacy and Molecular Biotechnology, Division of Pharmaceutical Biology, University of Heidelberg, Im Neuenheimer Feld 364, D-69120 Heidelberg, Germany

² Department of Chemistry, Division of Food Chemistry and Toxicology, University of Kaiserslautern, Erwin-Schrödinger-Strasse 52, D-67663 Kaiserslautern, Germany

^† These authors contributed equally to this work.

Molecules 2017, 22(9), 1546; https://doi.org/10.3390/molecules22091546 - 13 Sep 2017

Cited by 7 | Viewed by 6292

Abstract

Indirubin is an active component of the herbal ingredient ‘Danggui Longhui wan’, which was used for the treatment of inflammation and chronic myeloid leukemia in China. The recent study showed its derivative methylisoindigo (also known as meisoindigo) preferentially targeting cancer stem cells (CSCs) [...] Read more.

Indirubin is an active component of the herbal ingredient ‘Danggui Longhui wan’, which was used for the treatment of inflammation and chronic myeloid leukemia in China. The recent study showed its derivative methylisoindigo (also known as meisoindigo) preferentially targeting cancer stem cells (CSCs) in interference with AMPK and LKB1, the cellular metabolic sensors. In this study, we screened the effect of meisoindigo on a panel of 300 protein kinases and found that it selectively inhibited Stat3-associated tyrosine kinases and further confirmed its activity in cell based assays. To gain a deeper insight into the structure–activity relationship we produced 7 bromo-derivatives exhausting the accessible positions on the bisindole backbone except for in the 4-position due to the space limitation. We compared their anti-proliferative effects on tumor cells. We found that 6-bromomeisoindigo showed improved toxicity in company with increased Stat3 inhibition. Moreover, we detected that 6-bromomeisoindigo induced apoptosis of 95% of CD133+ pancreatic cancer cells. Considering that CD133 is a common marker highly expressed in a range of CSCs, our results imply the potential application of 6-bromomeisoindigo for the treatment of CSCs in different types of cancers. Full article

(This article belongs to the Special Issue Kinase Inhibitors)

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8 pages, 1466 KiB

Open AccessArticle

Cytotoxic Polyketides with an Oxygen-Bridged Cyclooctadiene Core Skeleton from the Mangrove Endophytic Fungus Phomosis sp. A818

by Wei Zhang^1,2

, Baobing Zhao³

, Liangcheng Du^2,* and Yuemao Shen^3,*

¹ Shandong Provincial Key Laboratory of Synthetic Biology, CAS Key Laboratory of Biofuels, Qingdao Institute of Bioenergy and Bioprocess Technology, Qingdao 266101, China

² Department of Chemistry, University of Nebraska-Lincoln, Lincoln, NE 68588-0304, USA

³ Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, Jinan 250012, China

Molecules 2017, 22(9), 1547; https://doi.org/10.3390/molecules22091547 - 14 Sep 2017

Cited by 3 | Viewed by 4376

Abstract

Plant endophytic microorganisms represent a largely untapped resource for new bioactive natural products. Eight polyketide natural products were isolated from a mangrove endophytic fungus Phomosis sp. A818. The structural elucidation of these compounds revealed that they share a distinct feature in their chemical [...] Read more.

Plant endophytic microorganisms represent a largely untapped resource for new bioactive natural products. Eight polyketide natural products were isolated from a mangrove endophytic fungus Phomosis sp. A818. The structural elucidation of these compounds revealed that they share a distinct feature in their chemical structures, an oxygen-bridged cyclooctadiene core skeleton. The study on their structure–activity relationship showed that the α,β-unsaturated δ-lactone moiety, as exemplified in compounds 1 and 2, was critical to the cytotoxic activity of these compounds. In addition, compound 4 might be a potential agonist of AMPK (5′-adenosine monophosphate-activated protein kinase). Full article

(This article belongs to the Special Issue Special Issue in Honor of Professor Thomas James Simpson on the Occasion of His 70th Birthday)

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27 pages, 3258 KiB

Open AccessArticle

Development of a Non-Hydroxamate Dual Matrix Metalloproteinase (MMP)-7/-13 Inhibitor

by Thomas Fischer and Rainer Riedl^*

Center for Organic and Medicinal Chemistry, Institute of Chemistry and Biotechnology, Zurich University of Applied Sciences ZHAW, Einsiedlerstrasse 31, 8820 Wädenswil, Switzerland

Molecules 2017, 22(9), 1548; https://doi.org/10.3390/molecules22091548 - 14 Sep 2017

Cited by 10 | Viewed by 8517

Abstract

Matrix metalloproteinase 7 (MMP-7) is a member of the MMP superfamily and is able to degrade extracellular matrix proteins such as casein, gelatin, fibronectin and proteoglycan. MMP-7 is a validated target for the development of small molecule drugs against cancer. MMP-13 is within [...] Read more.

Matrix metalloproteinase 7 (MMP-7) is a member of the MMP superfamily and is able to degrade extracellular matrix proteins such as casein, gelatin, fibronectin and proteoglycan. MMP-7 is a validated target for the development of small molecule drugs against cancer. MMP-13 is within the enzyme class the most efficient contributor to type II collagen degeneration and is a validated target in arthritis and cancer. We have developed the dual MMP-7/-13 inhibitor ZHAWOC6941 with IC₅₀-values of 2.2 μM (MMP-7) and 1.2 μM (MMP-13) that is selective over a broad range of MMP isoforms. It spares MMP-1, -2, -3, -8, -9, -12 and -14, making it a valuable modulator for targeted polypharmacology approaches. Full article

(This article belongs to the Special Issue Metalloenzyme Inhibitors and Activators)

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13 pages, 3770 KiB

Open AccessReview

Understanding of MYB Transcription Factors Involved in Glucosinolate Biosynthesis in Brassicaceae

by Mi-Suk Seo and Jung Sun Kim^*

Genomics Division, Department of Agricultural Bio-Resources, National Institute of Agricultural Sciences, Rural Development Administration, Wansan-gu, Jeonju 54874, Korea

Molecules 2017, 22(9), 1549; https://doi.org/10.3390/molecules22091549 - 14 Sep 2017

Cited by 73 | Viewed by 11244

Abstract

Glucosinolates (GSLs) are widely known secondary metabolites that have anticarcinogenic and antioxidative activities in humans and defense roles in plants of the Brassicaceae family. Some R2R3-type MYB (myeloblastosis) transcription factors (TFs) control GSL biosynthesis in Arabidopsis. However, studies on the MYB TFs [...] Read more.

Glucosinolates (GSLs) are widely known secondary metabolites that have anticarcinogenic and antioxidative activities in humans and defense roles in plants of the Brassicaceae family. Some R2R3-type MYB (myeloblastosis) transcription factors (TFs) control GSL biosynthesis in Arabidopsis. However, studies on the MYB TFs involved in GSL biosynthesis in Brassica species are limited because of the complexity of the genome, which includes an increased number of paralog genes as a result of genome duplication. The recent completion of the genome sequencing of the Brassica species permits the identification of MYB TFs involved in GSL biosynthesis by comparative genome analysis with A. thaliana. In this review, we describe various findings on the regulation of GSL biosynthesis in Brassicaceae. Furthermore, we identify 63 orthologous copies corresponding to five MYB TFs from Arabidopsis, except MYB76 in Brassica species. Fifty-five MYB TFs from the Brassica species possess a conserved amino acid sequence in their R2R3 MYB DNA-binding domain, and share close evolutionary relationships. Our analysis will provide useful information on the 55 MYB TFs involved in the regulation of GSL biosynthesis in Brassica species, which have a polyploid genome. Full article

(This article belongs to the Special Issue Metallopeptides)

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11 pages, 399 KiB

Open AccessReview

Acetylcholinesterase and Nicotinic Acetylcholine Receptors in Schistosomes and Other Parasitic Helminths

by Hong You^1,*, Chang Liu^1,2, Xiaofeng Du¹ and Donald P. McManus^1,*

¹ Molecular Parasitology Laboratory, Infectious Diseases Division, QIMR Berghofer Medical Research Institute, Brisbane, Queensland 4006, Australia

² Parasitology Laboratory, School of Animal Medicine, Northeast Agricultural University, Harbin 150030, China

Molecules 2017, 22(9), 1550; https://doi.org/10.3390/molecules22091550 - 14 Sep 2017

Cited by 18 | Viewed by 8218

Abstract

Schistosomiasis, which is caused by helminth trematode blood flukes of the genus Schistosoma, is a serious health and economic problem in tropical areas, and the second most prevalent parasitic disease after malaria. Currently, there is no effective vaccine available and treatment is [...] Read more.

Schistosomiasis, which is caused by helminth trematode blood flukes of the genus Schistosoma, is a serious health and economic problem in tropical areas, and the second most prevalent parasitic disease after malaria. Currently, there is no effective vaccine available and treatment is entirely dependent on a single drug, praziquantel (PZQ), raising a significant potential public health threat due to the emergence of PZQ drug resistance. It is thus urgent and necessary to explore novel therapeutic targets for the treatment of schistosomiasis. Previous studies demonstrated that acetylcholinesterase (AChE) and nicotinic acetylcholine receptors (nAChRs) play important roles in the schistosome nervous system and ion channels, both of which are targeted by a number of currently approved and marketed anthelminthic drugs. To improve understanding of the functions of the cholinergic system in schistosomes, this article reviews previous studies on AChE and nAChRs in schistosomes and other helminths and discusses their potential as suitable targets for vaccine development and drug design against schistosomiasis. Full article

(This article belongs to the Special Issue The Cholinesterases—Structure, Mechanism, Function and Drug Design: The 25th Anniversary of the Solution of the Crystal Structure of Acetylcholinesterase by Joel L. Sussman and Israel Silman)

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22 pages, 2912 KiB

Open AccessArticle

Development, Optimization and In Vitro/In Vivo Characterization of Collagen-Dextran Spongious Wound Dressings Loaded with Flufenamic Acid

by Mihaela Violeta Ghica¹, Mădălina Georgiana Albu Kaya^2,*, Cristina-Elena Dinu-Pîrvu¹, Dumitru Lupuleasa³ and Denisa Ioana Udeanu⁴

¹ Department of Physical and Colloidal Chemistry, Faculty of Pharmacy, University of Medicine and Pharmacy ”Carol Davila”, Bucharest 020956, Romania

² Department of Collagen Research, Division of Leather and Footwear Research Institute, National Research & Development Institute for Textiles and Leather, Bucharest 031215, Romania

³ Department of Pharmaceutical Technology and Biopharmacy, Faculty of Pharmacy, University of Medicine and Pharmacy ”Carol Davila”, Bucharest 020956, Romania

⁴ Department of Clinical Laboratory and Food Safety, Faculty of Pharmacy, University of Medicine and Pharmacy ”Carol Davila”, Bucharest 020956, Romania

Molecules 2017, 22(9), 1552; https://doi.org/10.3390/molecules22091552 - 15 Sep 2017

Cited by 49 | Viewed by 7401

Abstract

The aim of this study was the development and optimization of some topical collagen-dextran sponges with flufenamic acid, designed to be potential dressings for burn wounds healing. The sponges were obtained by lyophilization of hydrogels based on type I fibrillar collagen gel extracted [...] Read more.

The aim of this study was the development and optimization of some topical collagen-dextran sponges with flufenamic acid, designed to be potential dressings for burn wounds healing. The sponges were obtained by lyophilization of hydrogels based on type I fibrillar collagen gel extracted from calf hide, dextran and flufenamic acid, crosslinked and un-crosslinked, and designed according to a 3-factor, 3-level Box-Behnken experimental design. The sponges showed good fluid uptake ability quantified by a high swelling ratio. The flufenamic acid release profiles from sponges presented two stages—burst effect resulting in a rapid inflammation reduction, and gradual delivery ensuring the anti-inflammatory effect over a longer burn healing period. The resistance to enzymatic degradation was monitored through a weight loss parameter. The optimization of the sponge formulations was performed based on an experimental design technique combined with response surface methodology, followed by the Taguchi approach to select those formulations that are the least affected by the noise factors. The treatment of experimentally induced burns on animals with selected sponges accelerated the wound healing process and promoted a faster regeneration of the affected epithelial tissues compared to the control group. The results generated by the complex sponge characterization indicate that these formulations could be successfully used for burn dressing applications. Full article

(This article belongs to the Special Issue Natural Polymers and Biopolymers)

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21 pages, 4868 KiB

Open AccessArticle

Cytotoxic Evaluation of (2S)-5,7-Dihydroxy-6-prenylflavanone Derivatives Loaded PLGA Nanoparticles against MiaPaCa-2 Cells

by Berenice Andrade-Carrera¹, Beatriz Clares^2,3

, Véronique Noé⁴, Mireia Mallandrich^3,5

, Ana C. Calpena^3,5

, María Luisa García^3,5 and María Luisa Garduño-Ramírez^1,*

¹ Centro de Investigaciones Químicas, Instituto de Investigación en Ciencias Básicas y Aplicadas, Universidad Autónoma del Estado de Morelos, Avenida Universidad 1001, Col. Chamilpa, Cuernavaca, Morelos 62209, Mexico

² Department of Pharmacy and Pharmaceutical Technology, School of Pharmacy, Campus of Cartuja s/n, University of Granada, 18071 Granada, Spain

³ Nanoscience and Nanotechnology Institute (IN2UB), University of Barcelona, 27-31 Joan XXIII Avenue, 08028 Barcelona, Spain

⁴ Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Science, University of Barcelona, 27-31 Joan XXIII Avenue, 08028 Barcelona, Spain

⁵ Department of Pharmacy, Pharmaceutical Technology and Physical Chemistry, School of Pharmacy and Food Sciences, University of Barcelona, 27-31 Joan XXIII Avenue, 08028 Barcelona, Spain

Molecules 2017, 22(9), 1553; https://doi.org/10.3390/molecules22091553 - 15 Sep 2017

Cited by 18 | Viewed by 6563

Abstract

The search for new alternatives for the prevention and treatment of cancer is extremely important to minimize human mortality. Natural products are an alternative to chemical drugs, since they are a source of many potential compounds with anticancer properties. In the present study, [...] Read more.

The search for new alternatives for the prevention and treatment of cancer is extremely important to minimize human mortality. Natural products are an alternative to chemical drugs, since they are a source of many potential compounds with anticancer properties. In the present study, the (2S)-5,7-dihydroxy-6-prenylflavanone (semi-systematic name), also called (2S)-5,7-dihydroxy-6-(3-methyl-2-buten-1-yl)-2-phenyl-2,3-dihydro-4H-1-Benzopyran-4-one (CAS Name registered) (1) was isolated from Eysenhardtia platycarpa leaves. This flavanone 1 was considered as the lead compound to generate new cytotoxic derivatives 1a, 1b, 1c and 1d. These compounds 1, 1a, 1b, 1c, and 1d were then loaded in nanosized drug delivery systems such as polymeric nanoparticles (NPs). Small homogeneous spherical shaped NPs were obtained. Cytotoxic activity of free compounds 1, 1a, 1b, 1c, and 1d and encapsulated in polymeric NPs (NPs1, NPs1a, NPs1b, NPs1c and NPs1d) were evaluated against the pancreatic cancer cell line MiaPaCa-2. The obtained results demonstrated that NPs1a and NPs1b exhibited optimal cytotoxicity, and an even higher improvement of the cytotoxic efficacy was exhibited with the encapsulation of 1a. Based on these results, NPs1a were proposed as promising anticancer agent candidates. Full article

(This article belongs to the Special Issue Synthesis and Modification of Natural Product)

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15 pages, 2432 KiB

Open AccessArticle

Comparison of Two Components of Propolis: Caffeic Acid (CA) and Caffeic Acid Phenethyl Ester (CAPE) Induce Apoptosis and Cell Cycle Arrest of Breast Cancer Cells MDA-MB-231

by Agata Kabała-Dzik^1,*

, Anna Rzepecka-Stojko², Robert Kubina¹

, Żaneta Jastrzębska-Stojko³, Rafał Stojko⁴, Robert Dariusz Wojtyczka⁵

and Jerzy Stojko⁶

¹ Department of Pathology, School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia in Katowice, Ostrogórska 30, Sosnowiec 41-200, Poland

² Department of Pharmaceutical Chemistry, School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia in Katowice, Jagiellońska 4, Sosnowiec 41-200, Poland

³ Department of Anesthesiology and Intensive Care, Prof. K. Gibiński University Clinical Center, Medical University of Silesia in Katowice, Ceglana 35, Katowice 40-514, Poland

⁴ Department of Women Health, School of Health Sciences, Medical University of Silesia in Katowice, Medyków 12, Katowice 40-752, Poland

⁵ Department and Institute of Microbiology and Virology, School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia in Katowice, Jagiellońska 4, Sosnowiec 41-200, Poland

⁶ Department of Toxicology and Bioanalysis, School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia in Katowice, Jagiellońska 4, Sosnowiec 41-200, Poland

Molecules 2017, 22(9), 1554; https://doi.org/10.3390/molecules22091554 - 15 Sep 2017

Cited by 75 | Viewed by 9632

Abstract

Studies show that caffeic acid (CA) and caffeic acid phenethyl ester (CAPE) are compounds with potent chemopreventive effects. Breast cancer is a common form of aggressive cancer among women worldwide. This study shows a comparison of CA and CAPE activity on triple-negative human [...] Read more.

Studies show that caffeic acid (CA) and caffeic acid phenethyl ester (CAPE) are compounds with potent chemopreventive effects. Breast cancer is a common form of aggressive cancer among women worldwide. This study shows a comparison of CA and CAPE activity on triple-negative human caucasian breast adenocarcinoma line cells (MDA-MB-231). MDA-MB-231 cells were treated by CA and CAPE with doses of from 10 to 100 µM, for periods of 24 h and 48 h. Cytotoxicity MTT tests, apoptosis by Annexin V, and cell cycle with Dead Cell Assays were performed. Cytotoxic activity was greater for CAPE compared to CA (both incubation times, same dosage). IC₅₀ values for CAPE were 27.84 µM (24 h) and 15.83 µM (48 h) and for CA > 10,000 µM (24 h) and > 1000 µM (48 h). Polyphenols induced apoptosis, while CAPE (dose dependently), induced a higher apoptotic effect. CAPE also induced cell cycle arrest in S phase (time and dose dependently), CA did it only for 50 and 100 µM. A dose dependent decline was seen for the G0/G1 phase (CAPE, 48 h), as well as elimination of phase G2/M by 100 µM of CAPE (only mild effect for CA). Comparing CA and CAPE activity on MDA-MB-231, CAPE clearly showed better activity for the same dosages and experiment times. Full article

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

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11 pages, 1547 KiB

Open AccessArticle

Synthesis, In Vitro α-Glucosidase Inhibitory Activity and Molecular Docking Studies of Novel Benzothiazole-Triazole Derivatives

by Zipeng Gong^1,2,3, Yaping Peng⁴, Jie Qiu⁴, Anbai Cao⁴, Guangcheng Wang^4,* and Zhiyun Peng^4,*

¹ Provincial Key Laboratory of Pharmaceutics in Guizhou Province, Guizhou Medical University, Beijing Road, Guiyang 550004, China

² School of Pharmacy, Guizhou Medical University, 4 Beijing Road, Guiyang 550004, China

³ National Engineering Research Center of Miao’s Medicines, 4 Beijing Road, Guiyang 550004, China

⁴ College of Chemistry and Chemical Engineering, Hunan Engineering Laboratory for Analyse and Drugs Development of Ethnomedicine in Wuling Mountains, Jishou University, Jishou 416000, China

Molecules 2017, 22(9), 1555; https://doi.org/10.3390/molecules22091555 - 15 Sep 2017

Cited by 53 | Viewed by 7687

Abstract

Benzothiazole-triazole derivatives 6a–6s have been synthesized and characterized by ¹HNMR and ¹³C-NMR. All synthetic compounds were screened for their in vitro α-glucosidase inhibitory activity by using Baker’s yeast α-glucosidase enzyme. The majority of compounds exhibited a varying degree of α-glucosidase inhibitory [...] Read more.

Benzothiazole-triazole derivatives 6a–6s have been synthesized and characterized by ¹HNMR and ¹³C-NMR. All synthetic compounds were screened for their in vitro α-glucosidase inhibitory activity by using Baker’s yeast α-glucosidase enzyme. The majority of compounds exhibited a varying degree of α-glucosidase inhibitory activity with IC50 values between 20.7 and 61.1 μM when compared with standard acarbose (IC₅₀ = 817.38 μM). Among the series, compound 6s (IC₅₀ = 20.7 μM) bearing a chlorine group at the 5-position of the benzothiazole ring and a tertbutyl group at the para position of the phenyl ring, was found to be the most active compound. Preliminary structure-activity relationships were established. Molecular docking studies were performed to predict the binding interaction of the compounds in the binding pocket of the enzyme. Full article

(This article belongs to the Section Medicinal Chemistry)

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10 pages, 3874 KiB

Open AccessArticle

The Influence of Accelerated UV-A and Q-SUN Irradiation on the Antimicrobial Properties of Coatings Containing ZnO Nanoparticles

by Małgorzata Mizielińska^*

, Łukasz Łopusiewicz

, Monika Mężyńska and Artur Bartkowiak

Center of Bioimmobilisation and Innovative Packaging Materials, Faculty of Food Sciences and Fisheries, West Pomeranian University of Technology Szczecin, Janickiego 35, Szczecin 71-270, Poland

Molecules 2017, 22(9), 1556; https://doi.org/10.3390/molecules22091556 - 17 Sep 2017

Cited by 25 | Viewed by 7042

Abstract

The influence of accelerated UV-A and Q-SUN irradiation on the antimicrobial properties of coatings containing ZnO nanoparticles was investigated using a polyethylene (PE) film covering. The results of the study showed that Methyl Hydroxypropyl Celluloses (MHPC) coatings did not influence the growth of [...] Read more.

The influence of accelerated UV-A and Q-SUN irradiation on the antimicrobial properties of coatings containing ZnO nanoparticles was investigated using a polyethylene (PE) film covering. The results of the study showed that Methyl Hydroxypropyl Celluloses (MHPC) coatings did not influence the growth of S. aureus, B. cereus, E. coli, P. aeruginosa or C. albicans cells. MHPC coatings containing ZnO nanoparticles inhibited the growth of bacterial strains and reduced the number of C. albicans strains. Accelerated Q-SUN and UV-A irradiation had no influence on the antimicrobial effect of nano ZnO coatings against S. aureus, B. cereus and E. coli. Q-SUN irradiation decreased the activity of MHPC coatings containing nanoparticles against P. aeruginosa and C. albicans. An FT-IR analysis clearly showed that ZnO nanoparticles shielded the MHPC coating during Q-SUN irradiation. Full article

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

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17 pages, 4027 KiB

Open AccessReview

Probing Gas Adsorption in Zeolites by Variable-Temperature IR Spectroscopy: An Overview of Current Research

by Edoardo Garrone¹, Montserrat R. Delgado²

, Barbara Bonelli¹ and Carlos O. Arean^2,*

¹ Politecnico di Torino, The Department of Applied Science And Technology and INSTM Unit of Torino-Politecnico, Corso Duca degli Abruzzi 24, 10129 Turin, Italy

² Department of Chemistry, University of the Balearic Islands, E-07122 Palma, Spain

Molecules 2017, 22(9), 1557; https://doi.org/10.3390/molecules22091557 - 15 Sep 2017

Cited by 10 | Viewed by 7139

Abstract

The current state of the art in the application of variable-temperature IR (VTIR) spectroscopy to the study of (i) adsorption sites in zeolites, including dual cation sites; (ii) the structure of adsorption complexes and (iii) gas-solid interaction energy is reviewed. The main focus [...] Read more.

The current state of the art in the application of variable-temperature IR (VTIR) spectroscopy to the study of (i) adsorption sites in zeolites, including dual cation sites; (ii) the structure of adsorption complexes and (iii) gas-solid interaction energy is reviewed. The main focus is placed on the potential use of zeolites for gas separation, purification and transport, but possible extension to the field of heterogeneous catalysis is also envisaged. A critical comparison with classical IR spectroscopy and adsorption calorimetry shows that the main merits of VTIR spectroscopy are (i) its ability to provide simultaneously the spectroscopic signature of the adsorption complex and the standard enthalpy change involved in the adsorption process; and (ii) the enhanced potential of VTIR to be site specific in favorable cases. 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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7 pages, 1643 KiB

Open AccessArticle

A New Erythrinan Alkaloid Glycoside from the Seeds of Erythrina crista-galli

by Qing-Wei Tan^1,2,*, Jian-Cheng Ni¹

, Pei-Hua Fang¹ and Qi-Jian Chen^1,2,*

¹ Key Laboratory of Bio-Pesticide and Chemistry-Biology, Ministry of Education, Fujian Agriculture and Forestry University, Fuzhou 350002, Fujian, China

² Key Laboratory of Plant Virology of Fujian Province, Institute of Plant Virology, Fujian Agriculture and Forestry University, Fuzhou 350002, Fujian, China

Molecules 2017, 22(9), 1558; https://doi.org/10.3390/molecules22091558 - 16 Sep 2017

Cited by 15 | Viewed by 6206

Abstract

A new Erythrina alkaloid glycoside, named erythraline-11β-O-glucopyranoside, was isolated from the seeds of Erythrina crista-galli L., together with five known Erythrina alkaloids and an indole alkaloid. The structure of the new alkaloid glycoside was elucidated by spectroscopic methods, and all of [...] Read more.

A new Erythrina alkaloid glycoside, named erythraline-11β-O-glucopyranoside, was isolated from the seeds of Erythrina crista-galli L., together with five known Erythrina alkaloids and an indole alkaloid. The structure of the new alkaloid glycoside was elucidated by spectroscopic methods, and all of the compounds were evaluated for their antiviral activity against tobacco mosaic virus. Full article

(This article belongs to the Section Natural Products Chemistry)

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14 pages, 5312 KiB

Open AccessArticle

Identification of Novel Bisbenzimidazole Derivatives as Anticancer Vacuolar (H⁺)-ATPase Inhibitors

by Renukadevi Patil¹, Arpita Kulshrestha², Anjali Tikoo², Sara Fleetwood², Gajendra Katara², Bala Kolli², William Seibel³, Alice Gilman-Sachs², Shivaputra A. Patil^1,* and Kenneth D. Beaman^2,*

¹ Pharmaceutical Sciences Department, College of Pharmacy, Rosalind Franklin University of Medicine and Science, North Chicago, IL 60064, USA

² Department of Microbiology and Immunology, Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, IL 60064, USA

³ Division of Oncology, Cincinnati Children’s Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA

Molecules 2017, 22(9), 1559; https://doi.org/10.3390/molecules22091559 - 16 Sep 2017

Cited by 10 | Viewed by 6922

Abstract

The vacuolar (H⁺)-ATPases (V-ATPases) are a family of ATP-driven proton pumps and they have been associated with cancer invasion, metastasis, and drug resistance. Despite the clear involvement of V-ATPases in cancer, the therapeutic use of V-ATPase-targeting small molecules has not reached [...] Read more.

The vacuolar (H⁺)-ATPases (V-ATPases) are a family of ATP-driven proton pumps and they have been associated with cancer invasion, metastasis, and drug resistance. Despite the clear involvement of V-ATPases in cancer, the therapeutic use of V-ATPase-targeting small molecules has not reached human clinical trials to date. Thus, V-ATPases are emerging as important targets for the identification of potential novel therapeutic agents. We identified a bisbenzimidazole derivative (V) as an initial hit from a similarity search using four known V-ATPase inhibitors (I–IV). Based on the initial hit (V), we designed and synthesized a focused set of novel bisbenzimidazole analogs (2a–e). All newly prepared compounds have been screened for selected human breast cancer (MDA-MB-468, MDA-MB-231, and MCF7) and ovarian cancer (A2780, Cis-A2780, and PA-1) cell lines, along with the normal breast epithelial cell line, MCF10A. The bisbenzimidazole derivative (2e) is active against all cell lines tested. Remarkably, it demonstrated high cytotoxicity against the triple-negative breast cancer (TNBC) cell line, MDA-MB-468 (IC₅₀ = 0.04 ± 0.02 μM). Additionally, it has been shown to inhibit the V-ATPase pump that is mainly responsible for acidification. To the best of our knowledge the bisbenzimidazole pharmacophore has been identified as the first V-ATPase inhibitor in its class. These results strongly suggest that the compound 2e could be further developed as a potential anticancer V-ATPase inhibitor for breast cancer treatment. 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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13 pages, 402 KiB

Open AccessArticle

Chemical Composition, Antibacterial Activity, and Synergistic Effects with Conventional Antibiotics and Nitric Oxide Production Inhibitory Activity of Essential Oil from Geophila repens (L.) I.M. Johnst

by Huijuanzi Rao, Pengxiang Lai and Yang Gao^*

Marine College, Shandong University, Weihai 264209, China

Molecules 2017, 22(9), 1561; https://doi.org/10.3390/molecules22091561 - 17 Sep 2017

Cited by 28 | Viewed by 6507

Abstract

Geophila repens (L.) I.M. Johnst, a perennial herb, belongs to the Rubiaceae family. In this study, we identified the chemical composition of the Geophila repens essential oil (GR-EO) for the first time. Totally, seventy-seven compounds were identified according to GC and GC-MS, which [...] Read more.

Geophila repens (L.) I.M. Johnst, a perennial herb, belongs to the Rubiaceae family. In this study, we identified the chemical composition of the Geophila repens essential oil (GR-EO) for the first time. Totally, seventy-seven compounds were identified according to GC and GC-MS, which represent 98.0% of the oil. And the major components of GR-EO were β-caryophyllene (23.3%), β-elemene (8.0%), farnesyl butanoate (7.4%), myrcene (3.5%), and trans-nerolidol (3.3%). Then we evaluated the antibacterial activities of GR-EO and the synergistic effects of GR-EO in combination with commercial antibiotics using the microdilution and Checkerboard method. The results demonstrated that GR-EO possessed an excellent broad spectrum antibacterial activity, especially against Pseudomonas aeruginosa and Bacillus subtilis. It also showed that the combined application of GR-EO with antibiotics led to synergistic effects in most cases. And the most prominent synergistic effect was noticed when GR-EO was in combination with Streptomycin and tested against Escherichia coli (fractional inhibitory concentration indices (FICI) of 0.13). Additionally, the results of a Griess assay revealed that GR-EO exhibited a potent inhibitory effect on NO production in lipopolysaccharide (LPS)-activated RAW 264.7 (murine macrophage) cells. In conclusion, the combination of GR-EO and the commercial antibiotics has significant potential for the development of new antimicrobial treatment and reduction of drug resistance. Full article

(This article belongs to the Special Issue Essential Oils as Antimicrobial and Anti-infectious Agents)

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15 pages, 2582 KiB

Open AccessArticle

Indexing Natural Products for Their Potential Anti-Diabetic Activity: Filtering and Mapping Discriminative Physicochemical Properties

by Mouhammad Zeidan^1,†, Mahmoud Rayan^2,†, Nuha Zeidan^3,†, Mizied Falah^4,5,† and Anwar Rayan^2,6,*

¹ Molecular Genetics and Virology Laboratory, QRC-Qasemi Research Center, Al-Qasemi Academic College, P.O. Box 124, Baka EL-Garbiah 30100, Israel

² Institute of Applied Research-Galilee Society, P.O. Box 437, Shefa-Amr 20200, Israel

³ Clalit Health Service, Diet and Nutrition Unit, P.O. Box 789, Arara 30026, Israel

⁴ Eliachar Research Laboratory, Galilee Medical Center, P.O. Box 21, Nahariya 22100, Israel

⁵ Faculty of Medicine in the Galilee, Bar-Ilan University, Ramat Gan 52900, Israel

⁶ Drug Discovery Informatics Laboratory, QRC-Qasemi Research Center, Al-Qasemi Academic College, P.O. Box 124, Baka EL-Garbiah 30100, Israel

Molecules 2017, 22(9), 1563; https://doi.org/10.3390/molecules22091563 - 17 Sep 2017

Cited by 20 | Viewed by 6581

Abstract

Diabetes mellitus (DM) poses a major health problem, for which there is an unmet need to develop novel drugs. The application of in silico techniques and optimization algorithms is instrumental to achieving this goal. A set of 97 approved anti-diabetic drugs, representing the [...] Read more.

Diabetes mellitus (DM) poses a major health problem, for which there is an unmet need to develop novel drugs. The application of in silico techniques and optimization algorithms is instrumental to achieving this goal. A set of 97 approved anti-diabetic drugs, representing the active domain, and a set of 2892 natural products, representing the inactive domain, were used to construct predictive models and to index anti-diabetic bioactivity. Our recently-developed approach of ‘iterative stochastic elimination’ was utilized. This article describes a highly discriminative and robust model, with an area under the curve above 0.96. Using the indexing model and a mix ratio of 1:1000 (active/inactive), 65% of the anti-diabetic drugs in the sample were captured in the top 1% of the screened compounds, compared to 1% in the random model. Some of the natural products that scored highly as potential anti-diabetic drug candidates are disclosed. One of those natural products is caffeine, which is noted in the scientific literature as having the capability to decrease blood glucose levels. The other nine phytochemicals await evaluation in a wet lab for their anti-diabetic activity. The indexing model proposed herein is useful for the virtual screening of large chemical databases and for the construction of anti-diabetes focused libraries. Full article

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20 pages, 12400 KiB

Open AccessFeature PaperArticle

Brush Polymer of Donor-Accepter Dyads via Adduct Formation between Lewis Base Polymer Donor and All Carbon Lewis Acid Acceptor

by Yang Wang^1,2, Miao Hong³, Travis S. Bailey⁴ and Eugene Y.-X. Chen^1,*

¹ Department of Chemistry, Colorado State University, Fort Collins, CO 80523-1872, USA

² School of Fundamental Sciences, China Medical University, Shenyang 110122, China

³ State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China

⁴ Department of Chemical and Biological Engineering, Colorado State University, Fort Collins, CO 80523-1370, USA

Molecules 2017, 22(9), 1564; https://doi.org/10.3390/molecules22091564 - 18 Sep 2017

Cited by 6 | Viewed by 6518

Abstract

A synthetic method that taps into the facile Lewis base (LB)→Lewis acid (LA) adduct forming reaction between the semiconducting polymeric LB and all carbon LA C₆₀ for the construction of covalently linked donor-acceptor dyads and brush polymer of dyads is reported. The [...] Read more.

A synthetic method that taps into the facile Lewis base (LB)→Lewis acid (LA) adduct forming reaction between the semiconducting polymeric LB and all carbon LA C₆₀ for the construction of covalently linked donor-acceptor dyads and brush polymer of dyads is reported. The polymeric LB is built on poly(3-hexylthiophene) (P3HT) macromers containing either an alkyl or vinyl imidazolium end group that can be readily converted into the N-heterocyclic carbene (NHC) LB site, while the brush polymer architecture is conveniently constructed via radical polymerization of the macromer P3HT with the vinyl imidazolium chain end. Simply mixing of such donor polymeric LB with C₆₀ rapidly creates linked P3HT-C₆₀ dyads and brush polymer of dyads in which C₆₀ is covalently linked to the NHC junction connecting the vinyl polymer main chain and the brush P3HT side chains. Thermal behaviors, electronic absorption and emission properties of the resulting P3HT-C₆₀ dyads and brush polymer of dyads have been investigated. The results show that a change of the topology of the P3HT-C₆₀ dyad from linear to brush architecture enhances the crystallinity and T_m of the P3HT domain and, along with other findings, they indicate that the brush polymer architecture of donor-acceptor domains provides a promising approach to improve performances of polymer-based solar cells. Full article

(This article belongs to the Special Issue Lewis Pair Polymerization for New Reactivity and Structure in Polymer Synthesis)

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18 pages, 1464 KiB

Open AccessArticle

The Native Fruit Geoffroea decorticans from Arid Northern Chile: Phenolic Composition, Antioxidant Activities and In Vitro Inhibition of Pro-Inflammatory and Metabolic Syndrome-Associated Enzymes

by Felipe Jiménez-Aspee^1,*

, Cristina Theoduloz^2,*, Maria Del Pilar C. Soriano³, Maider Ugalde-Arbizu³, Maria Rosa Alberto⁴, Iris Catiana Zampini⁴, Maria Inés Isla⁴, Mario J. Simirgiotis⁵

and Guillermo Schmeda-Hirschmann³

¹ Departamento de Ciencias Básicas Biomédicas, Facultad de Ciencias de la Salud, Universidad de Talca, Talca 3460000, Chile

² Laboratorio de Cultivo Celular, Facultad de Ciencias de la Salud, Universidad de Talca, Talca 3460000, Chile

³ Laboratorio de Química de Productos Naturales, Instituto de Química de Recursos Naturales, Universidad de Talca, Talca 3460000, Chile

⁴ Laboratorio de Investigación de Productos Naturales (LIPRON), Instituto de Química del NOA (INQUINOA, CONICET), Universidad Nacional de Tucumán, San Miguel de Tucumán, Tucumán 4000, Argentina

⁵ Laboratorio de Productos Naturales, Instituto de Farmacia, Facultad de Ciencias, Universidad Austral de Chile, Valdivia 5090000, Chile

Molecules 2017, 22(9), 1565; https://doi.org/10.3390/molecules22091565 - 18 Sep 2017

Cited by 32 | Viewed by 7025

Abstract

The native tree Geoffroea decorticans (chañar) grows in the arid lands of northern Chile. It has been used as a food plant since prehistoric times. Phenolic-enriched extracts (PEEs) of Chilean chañar fruits were assessed for their chemical composition, antioxidant properties and inhibition of [...] Read more.

The native tree Geoffroea decorticans (chañar) grows in the arid lands of northern Chile. It has been used as a food plant since prehistoric times. Phenolic-enriched extracts (PEEs) of Chilean chañar fruits were assessed for their chemical composition, antioxidant properties and inhibition of pro-inflammatory and metabolic syndrome-associated enzymes. Phenolic profiles were determined by HPLC-DAD-MS/MS. The PEEs of G. decorticans showed a strong effect towards the enzymes COX-1/COX-2, with inhibition percentages ranging from inactive to 92.1% and inactive to 76.0% at 50 µg PEE/mL, respectively. The IC₅₀ values of the PEEs towards lipoxygenase and phospholipase A2 inhibitory activity were between 43.6–96.8 and 98.9–156.0 μg PEE/mL, respectively. Samples inhibited α-glucosidase (IC₅₀ 0.8–7.3 μg PEE/mL) and lipase (9.9 to >100 μg PEE/mL). However, samples did not inhibit α-amylase. The HPLC-DAD-MS analysis of the PEEs allowed the tentative identification of 53 compounds, mainly flavonol glycosides and procyanidins. The procyanidin content of the Chilean G. decorticans pulp was positively correlated with the antioxidant activity and the inhibition of the enzyme α-glucosidase. These results indicate that the Chilean chañar fruit contains bioactive polyphenols with functional properties. Full article

(This article belongs to the Section Natural Products Chemistry)

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9 pages, 1053 KiB

Open AccessArticle

Anti-Inflammatory and Anti-Oxidative Activities of Phenolic Compounds from Alnus sibirica Stems Fermented by Lactobacillus plantarum subsp. argentoratensis

by Thi Tam Le, Jun Yin and MinWon Lee^*

Laboratory of Pharmacognosy and Natural Product based Medicine, College of Pharmacy, Chung-Ang University, Seoul 156-756, Korea

Molecules 2017, 22(9), 1566; https://doi.org/10.3390/molecules22091566 - 18 Sep 2017

Cited by 13 | Viewed by 5961

Abstract

Fermentation of Alnus sibirica (AS) stems using Lactobacillus plantarum subsp. argentoratensis was conducted and three compounds isolated from the Alnus species were identified for the first time, 7-(3,4-dihydroxyphenyl)-1-(4-hydroxyphenyl)-heptan-3-one, 1-(3,4-dihydroxyphenyl)-7-(4-hydroxyphenyl)-heptan-3-one and 4-(3,4-dihydroxyphenyl)-butan-2-one, along with 14 known compounds. The anti-oxidative and anti-inflammatory abilities of AS [...] Read more.

Fermentation of Alnus sibirica (AS) stems using Lactobacillus plantarum subsp. argentoratensis was conducted and three compounds isolated from the Alnus species were identified for the first time, 7-(3,4-dihydroxyphenyl)-1-(4-hydroxyphenyl)-heptan-3-one, 1-(3,4-dihydroxyphenyl)-7-(4-hydroxyphenyl)-heptan-3-one and 4-(3,4-dihydroxyphenyl)-butan-2-one, along with 14 known compounds. The anti-oxidative and anti-inflammatory abilities of AS and fermented AS (FAS) as well as the isolated phenolic compounds from FAS were investigated. FAS showed stronger anti-oxidative and anti-inflammatory activities than non-fermented AS. Full article

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

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17 pages, 2485 KiB

Open AccessArticle

Stable Carbon Isotope Composition of the Lipids in Natural Ophiocordyceps sinensis from Major Habitats in China and Its Substitutes

by Lian-Xian Guo^1,2, Xiao-Ming Xu², Yue-Hui Hong², Yan Li^2,* and Jiang-Hai Wang^2,*

¹ Dongguan Key Laboratory of Environmental Medicine, School of Public Health, Guangdong Medical University, Dongguan 523808, China

² Guangdong Provincial Key Laboratory of Marine Resources and Coastal Engineering/South China Sea Bioresource Exploitation and Utilization Collaborative Innovation Center, School of Marine Sciences, Sun Yat-Sen University, Guangzhou 510006, China

Molecules 2017, 22(9), 1567; https://doi.org/10.3390/molecules22091567 - 18 Sep 2017

Cited by 11 | Viewed by 5391

Abstract

Ophiocordyceps sinensis is one rare medicinal fungus produced in the Qinghai-Tibetan Plateau. Its quality and price varies hugely with different habitat, and its numerous substitutes have sprung up in functional food markets. This paper aims to discriminate the geographic origin of wild O. [...] Read more.

Ophiocordyceps sinensis is one rare medicinal fungus produced in the Qinghai-Tibetan Plateau. Its quality and price varies hugely with different habitat, and its numerous substitutes have sprung up in functional food markets. This paper aims to discriminate the geographic origin of wild O. sinensis and its substitutes via element analyzer–isotope ratio mass spectrometry and gas chromatography–isotope ratio mass spectrometry. The δ¹³C values of major fatty acids in the lipids of O. sinensis are characterized unanimously by the variation relation C_18:0 < C_18:2 ≈ C_16:0 < C_18:1, while their fluctuation intervals are notably different between those of neutral and polar lipids. The comparative analysis of the δ¹³C ratios of major fatty acids in lipids of O. sinensis suggests that the δ¹³C patterns may be sensitive potential indicators to discriminate its geographical origin. The δ¹³C values of individual major fatty acids of lipids from the cultivated stromata of Cordyceps militaris (SCM), the fermented mycelia of Hirsurella sinensis (FM_H) and Paecilomyces epiali (FM_P) range from −31.2‰ to −29.7‰, −16.9‰ to −14.3‰, and −26.5‰ to −23.9‰, respectively. Their δ¹³C pattern of individual major fatty acids may be used as a potential indicator to discriminate the products of natural O. sinensis and its substitutes. Full article

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8 pages, 667 KiB

Open AccessArticle

Nematicidal Activity of 3-Acyltetramic Acid Analogues Against Pine Wood Nematode, Bursaphelenchus xylophilus

by Hyo-Rim Lee^1,2, Sung-Chan Lee¹, Ji-Eun Lee¹, Seon-Mi Seo^1,2, Yong-Chul Jeong³, Chan-Sik Jung⁴, Mark G. Moloney^3,* and Il-Kwon Park^1,2,*

¹ Department of Forest Sciences, College of Agriculture and Life Sciences, Seoul National University, Seoul 08826, Korea

² Research Institute of Agriculture and Life Science, College of Agriculture and Life Sciences, Seoul National University, Seoul 08826, Korea

³ Chemistry Research Laboratory, University of Oxford, Oxford OS1 3TA, UK

⁴ Division of Forest Insect Pests and Diseases, National Institute of Forest Science, Seoul 02455, Korea

Molecules 2017, 22(9), 1568; https://doi.org/10.3390/molecules22091568 - 18 Sep 2017

Cited by 8 | Viewed by 5127

Abstract

Among 98 3-acyltetramic acid analogues, compounds 1c, 2c, 2f and 2g, showed >90% nematicidal activity against the pine wood nematode Bursaphelenchus xylophilus at a 10 μg/mL concentration. The nematicidal activities of compounds 1d, 1h, and 2k were a [...] Read more.

Among 98 3-acyltetramic acid analogues, compounds 1c, 2c, 2f and 2g, showed >90% nematicidal activity against the pine wood nematode Bursaphelenchus xylophilus at a 10 μg/mL concentration. The nematicidal activities of compounds 1d, 1h, and 2k were a little lower at 88.0%, 85.8%, and 57.2% at a 10 μg/mL concentration, respectively. The nematicidal activity of emamection benzoate, widely used in Korea for the prevention of pine wilt disease, was 32.3% at a 10 μg/mL concentration. Other 3-acyltetramic acid analogues showed less than 30% nematicidal activity. A structure-activity relationship study indicated that the chain length of the C-acyl substituent was very important for high nematicidal activity. All active compounds had C₁₃H₂₇ or C₁₁H₂₃ acyl substituents, in two closely related groups with the common physicochemical properties of a polar surface area 57.6A², PSA (polar surface area) 7.8–8.6% and ClogP (calculated partition coefficient) 5.1–5.9 and a polar surface area 75–84A², PSA 11.1–11.6% and ClogP 4.7–5.1, respectively. Our study indicates that active 3-acyltetramic acid analogues could have potential as lead compounds for developing novel pine wood nematode control agents. Full article

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13 pages, 5292 KiB

Open AccessArticle

Spiropyran-Isoquinoline Dyad as a Dual Chemosensor for Co(II) and In(III) Detection

by Yong-Min Kho and Eun Ju Shin^*

Department of Chemistry, Sunchon National University, Suncheon, Jeonnam 57922, Korea

Molecules 2017, 22(9), 1569; https://doi.org/10.3390/molecules22091569 - 19 Sep 2017

Cited by 26 | Viewed by 6623

Abstract

Spiropyran derivatives have been studied as light-regulated chemosensors for a variety of metal cations and anions, but there is little research on chemosensors that simultaneously detect multiple metal cations. In this study, a spiropyran derivative with isoquinoline, SP-IQ, was prepared and it [...] Read more.

Spiropyran derivatives have been studied as light-regulated chemosensors for a variety of metal cations and anions, but there is little research on chemosensors that simultaneously detect multiple metal cations. In this study, a spiropyran derivative with isoquinoline, SP-IQ, was prepared and it functions investigated as a light-regulated sensor for both Co²⁺ and In³⁺ cations. A colorless nonfluorescent SP-IQ converts to a pink-colored fluorescent MC-IQ by UV irradiation or standing in the dark, and MC-IQ returns to SP-IQ with visible light. Upon UV irradiation with the Co²⁺ cation for 7 min, the stronger absorption at 540 nm and the similar fluorescence intensity at 640 nm are observed, compared to when no metal cation is added, due to the formation of a Co²⁺ complex with pink color and pink fluorescence. When placed in the dark with the In³⁺ cation for 7 h, the colorless solution of SP-IQ changes to the In³⁺ complex with yellow color and pink fluorescence, which shows strong absorption at 410 nm and strong fluorescence at 640 nm. Selective detection of the Co²⁺ cation with UV irradiation and the In³⁺ cation in the dark could be possible with SP-IQ by both absorption and fluorescence spectroscopy or by the naked eye. Full article

(This article belongs to the Special Issue Advances in Spiro Compounds)

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15 pages, 3564 KiB

Open AccessArticle

Preventing Surgical Site Infections Using a Natural, Biodegradable, Antibacterial Coating on Surgical Sutures

by Jochen Reinbold¹, Ann-Kristin Uhde¹, Ingrid Müller², Tobias Weindl³, Jürgen Geis-Gerstorfer⁴, Christian Schlensak¹, Hans-Peter Wendel¹ and Stefanie Krajewski^1,*

¹ Department of Thoracic, Cardiac and Vascular Surgery, University Hospital Tuebingen, 72076 Tuebingen, Germany

² Department of Pharmaceutical Engineering, Albstadt-Sigmaringen University, 72488 Sigmaringen, Germany

³ Aimecs® GmbH, 84347 Pfarrkirchen, Germany

⁴ Section Medical Materials Science & Technology, University Hospital Tuebingen, 72076 Tuebingen, Germany

Molecules 2017, 22(9), 1570; https://doi.org/10.3390/molecules22091570 - 19 Sep 2017

Cited by 49 | Viewed by 10281

Abstract

Surgical site infections (SSIs) are one of the most common nosocomial infections, which can result in serious complications after surgical interventions. Foreign materials such as implants or surgical sutures are optimal surfaces for the adherence of bacteria and subsequent colonization and biofilm formation. [...] Read more.

Surgical site infections (SSIs) are one of the most common nosocomial infections, which can result in serious complications after surgical interventions. Foreign materials such as implants or surgical sutures are optimal surfaces for the adherence of bacteria and subsequent colonization and biofilm formation. Due to a significant increase in antibiotic-resistant bacterial strains, naturally occurring agents exhibiting antibacterial properties have great potential in prophylactic therapies. The aim of this study was to develop a coating for surgical sutures consisting of the antibacterial substance totarol, a naturally occurring diterpenoid isolated from Podocarpus totara in combination with poly(lactide-co-glycolide acid) (PLGA) as a biodegradable drug delivery system. Hence, non-absorbable monofilament and multifilament sutures were coated with solutions containing different amounts and ratios of totarol and PLGA, resulting in a smooth, crystalline coating. Using an agar diffusion test (ADT), it became evident that the PLGA/totarol-coated sutures inhibited the growth of Staphylococcus aureus over a period of 15 days. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay showed that the coated sutures were not cytotoxic to murine fibroblasts. Overall, the data indicates that our innovative, biodegradable suture coating has the potential to reduce the risk of SSIs and postoperative biofilm-formation on suture material without adverse effects on tissue. Full article

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

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21 pages, 37028 KiB

Open AccessArticle

Chemoinformatic Database Building and in Silico Hit-Identification of Potential Multi-Targeting Bioactive Compounds Extracted from Mushroom Species

by Annalisa Maruca

, Federica Moraca, Roberta Rocca, Fulvia Molisani, Francesca Alcaro, Maria Concetta Gidaro, Stefano Alcaro^*, Giosuè Costa

and Francesco Ortuso

Laboratorio di Chimica Farmaceutica, Dipartimento di Scienze della Salute, Università “Magna Græcia” di Catanzaro, Viale Europa, 88100 Catanzaro, Italy

Molecules 2017, 22(9), 1571; https://doi.org/10.3390/molecules22091571 - 19 Sep 2017

Cited by 28 | Viewed by 9536

Abstract

Mushrooms are widely-consumed fungi which contain natural compounds that can be used both for their nutritive and medicinal properties, i.e., taking advantage of their antimicrobial, antiviral, antitumor, anti-allergic, immunomodulation, anti-inflammatory, anti-atherogenic, hypoglycemic, hepatoprotective and antioxidant effects. Currently, scientific interest in natural compounds extracted [...] Read more.

Mushrooms are widely-consumed fungi which contain natural compounds that can be used both for their nutritive and medicinal properties, i.e., taking advantage of their antimicrobial, antiviral, antitumor, anti-allergic, immunomodulation, anti-inflammatory, anti-atherogenic, hypoglycemic, hepatoprotective and antioxidant effects. Currently, scientific interest in natural compounds extracted from the fungal species is increasing because these compounds are also known to have pharmacological/biological activity. Unfortunately, however, their mechanisms of action are often unknown, not well understood or have not been investigated in their entirety. Given the poly-pharmacological properties of bioactive fungal compounds, it was decided to carry out a multi-targeted approach to predict possible interactions occurring among bioactive natural fungal extracts and several macromolecular targets that are therapeutically interesting, i.e., proteins, enzymes and nucleic acids. A chemical database of compounds extracted from both edible and no-edible mushrooms was created. This database was virtually screened against 43 macromolecular targets downloaded from the Protein Data Bank website. The aim of this work is to provide a molecular description of the main interactions involving ligand/multi-target recognition in order to understand the polypharmacological profile of the most interesting fungal extracts and to suggest a design strategy of new multi-target agents. Full article

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

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17 pages, 2828 KiB

Open AccessFeature PaperArticle

Studying the Structural Significance of Galectin Design by Playing a Modular Puzzle: Homodimer Generation from Human Tandem-Repeat-Type (Heterodimeric) Galectin-8 by Domain Shuffling

by Anna-Kristin Ludwig¹, Malwina Michalak², Nadya Shilova³, Sabine André¹, Herbert Kaltner¹, Nicolai V. Bovin^3,*, Jürgen Kopitz^2,* and Hans-Joachim Gabius^1,*

¹ Institut für Physiologische Chemie, Tierärztliche Fakultät, Ludwig-Maximilians-Universität, Veterinärstraße 13, 80539 München, Germany

² Abteilung für Angewandte Tumorbiologie, Pathologisches Institut, Klinikum der Ruprecht-Karls-Universität, Im Neuenheimer Feld 224, 69120 Heidelberg, Germany

³ Shemyakin & Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, ul Miklukho-Maklaya 16/10, Moscow 117997, Russia

Molecules 2017, 22(9), 1572; https://doi.org/10.3390/molecules22091572 - 19 Sep 2017

Cited by 13 | Viewed by 5213

Abstract

Tissue lectins are emerging (patho)physiological effectors with broad significance. The capacity of adhesion/growth-regulatory galectins to form functional complexes with distinct cellular glycoconjugates is based on molecular selection of matching partners. Engineering of variants by changing the topological display of carbohydrate recognition domains (CRDs) [...] Read more.

Tissue lectins are emerging (patho)physiological effectors with broad significance. The capacity of adhesion/growth-regulatory galectins to form functional complexes with distinct cellular glycoconjugates is based on molecular selection of matching partners. Engineering of variants by changing the topological display of carbohydrate recognition domains (CRDs) provides tools to understand the inherent specificity of the functional pairing. We here illustrate its practical implementation in the case of human tandem-repeat-type galectin-8 (Gal-8). It is termed Gal-8 (NC) due to presence of two different CRDs at the N- and C-terminal positions. Gal-8N exhibits exceptionally high affinity for 3′-sialylated/sulfated β-galactosides. This protein is turned into a new homodimer, i.e., Gal-8 (NN), by engineering. The product maintained activity for lactose-inhibitable binding of glycans and glycoproteins. Preferential association with 3′-sialylated/sulfated (and 6-sulfated) β-galactosides was seen by glycan-array analysis when compared to the wild-type protein, which also strongly bound to ABH-type epitopes. Agglutination of erythrocytes documented functional bivalency. This result substantiates the potential for comparative functional studies between the variant and natural Gal-8 (NC)/Gal-8N. Full article

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15 pages, 1033 KiB

Open AccessArticle

Sulfadiazine Salicylaldehyde-Based Schiff Bases: Synthesis, Antimicrobial Activity and Cytotoxicity

by Martin Krátký^1,*, Magdaléna Dzurková², Jiří Janoušek³

, Klára Konečná⁴

, František Trejtnar³, Jiřina Stolaříková⁵ and Jarmila Vinšová¹

¹ Department of Organic and Bioorganic Chemistry, Faculty of Pharmacy in Hradec Králové, Charles University, Akademika Heyrovského 1203, 500 05 Hradec Králové, Czech Republic

² Department of Chemistry, Faculty of Science, J. E. Purkinje University, České mládeže 8, 400 96 Ústí nad Labem, Czech Republic

³ Department of Pharmacology and Toxicology, Faculty of Pharmacy, Charles University, Akademika Heyrovského 1203, 500 05 Hradec Králové, Czech Republic

⁴ Department of Biological and Medical Sciences, Faculty of Pharmacy, Charles University, Akademika Heyrovského 1203, 500 05 Hradec Králové, Czech Republic

⁵ Laboratory for Mycobacterial Diagnostics and Tuberculosis, Regional Institute of Public Health in Ostrava, Partyzánské námĕstí 7, 702 00 Ostrava, Czech Republic

Molecules 2017, 22(9), 1573; https://doi.org/10.3390/molecules22091573 - 19 Sep 2017

Cited by 85 | Viewed by 11792

Abstract

The resistance among microbes has brought an urgent need for new drugs. Thus, we synthesized a series of Schiff bases derived from the sulfa drug sulfadiazine and various salicylaldehydes. The resulting 4-[(2-hydroxybenzylidene)amino]-N-(pyrimidin-2-yl)benzene-sulfonamides were characterized and evaluated against Gram-positive and Gram-negative bacteria, [...] Read more.

The resistance among microbes has brought an urgent need for new drugs. Thus, we synthesized a series of Schiff bases derived from the sulfa drug sulfadiazine and various salicylaldehydes. The resulting 4-[(2-hydroxybenzylidene)amino]-N-(pyrimidin-2-yl)benzene-sulfonamides were characterized and evaluated against Gram-positive and Gram-negative bacteria, yeasts, moulds, Mycobacterium tuberculosis, nontuberculous mycobacteria (M. kansasii, M. avium) and their cytotoxicity was determined. Among bacteria, the genus Staphylococcus, including methicillin-resistant S. aureus, showed the highest susceptibility, with minimum inhibitory concentration values from 7.81 µM. The growth of Candida sp. and Trichophyton interdigitale was inhibited at concentrations starting from 1.95 µM. 4-[(2,5-Dihydroxybenzylidene)amino]-N-(pyrimidin-2-yl)-benzenesulfonamide was identified as the most selective Schiff base for these strains with no apparent cytotoxicity and a selectivity index higher than 16. With respect to M. tuberculosis and M. kansasii that were inhibited within the range of 8 to 250 µM, unsubstituted 4-[(2-hydroxy-benzylidene)amino]-N-(pyrimidin-2-yl)benzenesulfonamide meets the selectivity requirement. In general, dihalogenation of the salicylic moiety improved the antibacterial and antifungal activity but also increased the cytotoxicity, especially with an increasing atomic mass. Some derivatives offer more advantageous properties than the parent sulfadiazine, thus constituting promising hits for further antimicrobial drug development. Full article

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

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6 pages, 1461 KiB

Open AccessFeature PaperPerspective

Covalent Organic Frameworks—Organic Chemistry Beyond the Molecule

by Christian S. Diercks^1,2,3,*, Markus J. Kalmutzki^1,2,3 and Omar M. Yaghi^1,2,3,*

¹ Department of Chemistry, University of California, Berkeley, CA 94720, USA

² Materials Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA

³ Kavli Energy NanoSciences Institute, University of California, Berkeley, CA 94720, USA

Molecules 2017, 22(9), 1575; https://doi.org/10.3390/molecules22091575 - 19 Sep 2017

Cited by 40 | Viewed by 11323

Abstract

The synthesis of organic molecules has at its core, purity, definitiveness of structure, and the ability to access specific atoms through chemical reactions. When considering extended organic structures, covalent organic frameworks (COFs) stand out as a true extension of molecular organic chemistry to [...] Read more.

The synthesis of organic molecules has at its core, purity, definitiveness of structure, and the ability to access specific atoms through chemical reactions. When considering extended organic structures, covalent organic frameworks (COFs) stand out as a true extension of molecular organic chemistry to the solid state, because these three fundamental attributes of molecular organic chemistry are preserved. The fact that COFs are porous provides confined space within which molecules can be further modified and controlled. Full article

(This article belongs to the Special Issue Covalent Organic Frameworks and Related Porous Organic Materials)

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11 pages, 2698 KiB

Open AccessArticle

Quantitative Structure–Activity Relationship Modeling of Kinase Selectivity Profiles

by Sandeepkumar Kothiwale¹, Corina Borza², Ambra Pozzi^2,3 and Jens Meiler^1,*

¹ Department of Chemistry, Center for Structural Biology, Institute of Chemical Biology Vanderbilt University, Nashville, TN 37232, USA

² Department of Medicine, Division of Nephrology, Vanderbilt University, Nashville, TN 37232, USA

³ Department of Medicine, Veterans Affairs Hospital, Nashville, TN 37232, USA

Molecules 2017, 22(9), 1576; https://doi.org/10.3390/molecules22091576 - 19 Sep 2017

Cited by 10 | Viewed by 6215

Abstract

The discovery of selective inhibitors of biological target proteins is the primary goal of many drug discovery campaigns. However, this goal has proven elusive, especially for inhibitors targeting the well-conserved orthosteric adenosine triphosphate (ATP) binding pocket of kinase enzymes. The human kinome is [...] Read more.

The discovery of selective inhibitors of biological target proteins is the primary goal of many drug discovery campaigns. However, this goal has proven elusive, especially for inhibitors targeting the well-conserved orthosteric adenosine triphosphate (ATP) binding pocket of kinase enzymes. The human kinome is large and it is rather difficult to profile early lead compounds against around 500 targets to gain an upfront knowledge on selectivity. Further, selectivity can change drastically during derivatization of an initial lead compound. Here, we have introduced a computational model to support the profiling of compounds early in the drug discovery pipeline. On the basis of the extensive profiled activity of 70 kinase inhibitors against 379 kinases, including 81 tyrosine kinases, we developed a quantitative structure–activity relation (QSAR) model using artificial neural networks, to predict the activity of these kinase inhibitors against the panel of 379 kinases. The model’s performance in predicting activity ranges from 0.6 to 0.8 depending on the kinase, from the area under the curve (AUC) of the receiver operating characteristics (ROC). The profiler is available online at http://www.meilerlab.org/index.php/servers/show?s_id=23. Full article

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18 pages, 2935 KiB

Open AccessArticle

Improving the Efficiency of New Automatic Dishwashing Detergent Formulation by Addition of Thermostable Lipase, Protease and Amylase

by Ashwini Naganthran^1,2, Malihe Masomian^1,2, Raja Noor Zaliha Raja Abd. Rahman^1,2,*

, Mohd Shukuri Mohamad Ali^1,3 and Hisham Mohd Nooh^1,4

¹ Enzyme and Microbial Technology Research Center, Universiti Putra Malaysia, Serdang, Selangor 43400, Malaysia

² Department of Microbiology, Faculty of Biotechnology and Biomolecular Science, Universiti Putra Malaysia, Serdang, Selangor 43400, Malaysia

³ Department of Biochemistry, Faculty of Biotechnology and Biomolecular Science, Universiti Putra Malaysia, Serdang, Selangor 43400, Malaysia

⁴ Laboratory of Molecular Biomedicine, Institute of Bioscience, Universiti Putra Malaysia, Serdang, Selangor 43400, Malaysia

Molecules 2017, 22(9), 1577; https://doi.org/10.3390/molecules22091577 - 19 Sep 2017

Cited by 43 | Viewed by 12269

Abstract

The use of T1 lipase in automatic dishwashing detergent (ADD) is well established, but efficiency in hard water is very low. A new enzymatic environmentally-friendly dishwashing was formulated to be efficient in both soft and hard water. Thermostable enzymes such as T1 lipase [...] Read more.

The use of T1 lipase in automatic dishwashing detergent (ADD) is well established, but efficiency in hard water is very low. A new enzymatic environmentally-friendly dishwashing was formulated to be efficient in both soft and hard water. Thermostable enzymes such as T1 lipase from Geobacillus strain T1, Rand protease from Bacillus subtilis strain Rand, and Maltogenic amylase from Geobacillus sp. SK70 were produced and evaluated for an automatic dishwashing detergent formulation. The components of the new ADD were optimized for compatibility with these three enzymes. In compatibility tests of the enzymes with different components, several criteria were considered. The enzymes were mostly stable in non-ionic surfactants, especially polyhydric alcohols, Glucopon UP 600, and in a mixture of sodium carbonate and glycine (30:70) buffer at a pH of 9.25. Sodium polyacrylate and sodium citrate were used in the ADD formulation as a dispersing agent and a builder, respectively. Dishwashing performance of the formulated ADDs was evaluated in terms of percent of soil removed using the Leenert‘s Improved Detergency Tester. The results showed that the combination of different hydrolysis enzymes could improve the washing efficiency of formulated ADD compared to the commercial ADD “Finish” at 40 and 50 C. Full article

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

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16 pages, 4578 KiB

Open AccessFeature PaperArticle

Cytotoxic and Apoptotic Activities of Prunus spinosa Trigno Ecotype Extract on Human Cancer Cells

by Stefania Meschini^1,*, Evelin Pellegrini¹, Maria Condello¹, Giovanni Occhionero², Sebastiano Delfine³

, Giancarlo Condello⁴

and Franco Mastrodonato²

¹ National Center for Drug Research and Evaluation, Italian National Institute of Health, Rome 00161, Italy

² Italian Society of Biointegrated Medicine, Bagnoli del Trigno, Isernia 86091, Italy

³ Department of Agriculture, Environment and Food Science, University of Molise, Campobasso 86100, Italy

⁴ Department of Movement, Human and Health Sciences, University of Rome Foro Italico, Rome 00135, Italy

Molecules 2017, 22(9), 1578; https://doi.org/10.3390/molecules22091578 - 20 Sep 2017

Cited by 28 | Viewed by 7577

Abstract

The aim of this work was to demonstrate that a natural compound, not-toxic to normal cells, has cytotoxic and sensitizing effects on carcinoma cells, with the final goal of combining it with chemotherapeutic drugs to reduce the overall dose. Prunus spinosa Trigno ecotype [...] Read more.

The aim of this work was to demonstrate that a natural compound, not-toxic to normal cells, has cytotoxic and sensitizing effects on carcinoma cells, with the final goal of combining it with chemotherapeutic drugs to reduce the overall dose. Prunus spinosa Trigno ecotype (PsT) drupe extract with a nutraceutical activator complex (NAC) made of amino acids, vitamins and mineral salt blends, has shown in vitro anticancer activity. The cytotoxic effect of (PsT + NAC)^® has been evaluated on human cancer cells, with an initial screening with colorectal, uterine cervical, and bronchoalveolar cells, and a subsequent focus on colon carcinoma cells HCT116 and SW480. The viability reduction of HCT116 and SW480 after treatment with (PsT 10 mg/mL + NAC)^® was about 40% (p < 0.05), compared to control cells. The cell’s survival reduction was ineffective when the drug vehicle (NAC) was replaced with a phosphate buffer saline (PBS) or physiological solution (PS). The flow cytometry evaluation of cancer cells’ mitochondrial membrane potential showed an increase of 20% depolarized mitochondria. Cell cycle analysis showed a sub G1 (Gap 1 phase) peak appearance (HCT116: 35.1%; SW480: 11.6%), indicating apoptotic cell death induction that was confirmed by Annexin V assay (HCT116: 86%; SW480: 96%). Normal cells were not altered by (PsT + NAC)^® treatments. Full article

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

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16 pages, 4414 KiB

Open AccessArticle

The Effect of Copper Addition on the Activity and Stability of Iron-Based CO₂ Hydrogenation Catalysts

by Matthew J. Bradley¹, Ramagopal Ananth², Heather D. Willauer^3,*, Jeffrey W. Baldwin⁴, Dennis R. Hardy⁵ and Frederick W. Williams²

¹ ASEE Postdoctoral Research Associate, Naval Research Laboratory, Materials Science and Technology Division, Washington, DC 20375, USA

² Naval Research Laboratory, Chemistry Division, Washington, DC 20375, USA

³ Naval Research Laboratory, Materials Science and Technology Division, Washington, DC 20375, USA

⁴ Naval Research Laboratory, Acoustics Division, Washington, DC 20375, USA

⁵ NOVA Research Inc., 1900 Elkin Street, Alexandria, VA 22308, USA

Molecules 2017, 22(9), 1579; https://doi.org/10.3390/molecules22091579 - 20 Sep 2017

Cited by 28 | Viewed by 6387

Abstract

Iron-based CO₂ catalysts have shown promise as a viable route to the production of olefins from CO₂ and H₂ gas. However, these catalysts can suffer from low conversion and high methane selectivity, as well as being particularly vulnerable to water [...] Read more.

Iron-based CO₂ catalysts have shown promise as a viable route to the production of olefins from CO₂ and H₂ gas. However, these catalysts can suffer from low conversion and high methane selectivity, as well as being particularly vulnerable to water produced during the reaction. In an effort to improve both the activity and durability of iron-based catalysts on an alumina support, copper (10–30%) has been added to the catalyst matrix. In this paper, the effects of copper addition on the catalyst activity and morphology are examined. The addition of 10% copper significantly increases the CO₂ conversion, and decreases methane and carbon monoxide selectivity, without significantly altering the crystallinity and structure of the catalyst itself. The FeCu/K catalysts form an inverse spinel crystal phase that is independent of copper content and a metallic phase that increases in abundance with copper loading (>10% Cu). At higher loadings, copper separates from the iron oxide phase and produces metallic copper as shown by SEM-EDS. An addition of copper appears to increase the rate of the Fischer–Tropsch reaction step, as shown by modeling of the chemical kinetics and the inter- and intra-particle transport of mass and energy. Full article

(This article belongs to the Special Issue Hydrofunctionalization and Hydrogenation with Earth Abundant Metals)

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Molecules, Volume 22, Issue 9 (September 2017) – 186 articles

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