Molecules

Research

14 pages, 638 KiB

Open AccessArticle

Total Synthesis and Pharmacological Investigation of Cordyheptapeptide A

by Suresh Kumar^1,†, Rajiv Dahiya^2,*,†, Sukhbir Lal Khokra¹, Rita Mourya³, Suresh V. Chennupati⁴ and Sandeep Maharaj²

¹ Institute of Pharmaceutical Sciences, Kurukshetra University, Kurukshetra 136119, Haryana, India

² Laboratory of Peptide Research and Development, School of Pharmacy, Faculty of Medical Sciences, The University of the West Indies, St. Augustine, Trinidad & Tobago, West Indies

³ School of Pharmacy, College of Medicine and Health Sciences, University of Gondar, P.O. Box 196, Gondar 6200, Ethiopia

⁴ Department of Pharmacy, College of Medical and Health Sciences, Wollega University, P.O. Box 395, Nekemte, Ethiopia

^† These authors contributed equally to this work.

Molecules 2017, 22(6), 682; https://doi.org/10.3390/molecules22060682 - 27 May 2017

Cited by 15 | Viewed by 6072

Abstract

The present investigation reports the synthesis of a phenylalanine-rich N-methylated cyclopeptide, cordyheptapeptide A (8), previously isolated from the insect pathogenic fungus Cordyceps sp. BCC 1788, accomplished through the coupling of N-methylated tetrapeptide and tripeptide fragments followed by cyclization of [...] Read more.

The present investigation reports the synthesis of a phenylalanine-rich N-methylated cyclopeptide, cordyheptapeptide A (8), previously isolated from the insect pathogenic fungus Cordyceps sp. BCC 1788, accomplished through the coupling of N-methylated tetrapeptide and tripeptide fragments followed by cyclization of the linear heptapeptide unit. Structure elucidation of the newly synthesized cyclopolypeptide was performed by means of FT-IR, ¹H-NMR, ¹³C-NMR, and fast atom bombardment mass spectrometry (FABMS), and screened for its antibacterial, antidermatophytic, and cytotoxic potential. According to the antimicrobial activity results, the newly synthesized N-Methylated cyclopeptide exhibited potent antibacterial activity against Gram-negative bacteria Pseudomonas aeruginosa and Klebsiella pneumoniae and antifungal activity against dermatophytes Trichophyton mentagrophytes and Microsporum audouinii at a concentration of 6 μg/mL, in comparison to the reference drugs, gatifloxacin and griseofulvin. In addition, cyclopolypeptide 8 displayed suitable levels of cytotoxicity against Dalton’s lymphoma ascites (DLA) and Ehrlich’s ascites carcinoma (EAC) cell lines. Full article

(This article belongs to the Collection Bioactive Compounds)

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12 pages, 3637 KiB

Open AccessArticle

New Mild and Simple Approach to Isothiocyanates: A Class of Potent Anticancer Agents

by Bingling Luo^1,2,†, Jiankang Wang^1,2,†, Xiaobing Li¹, Wenhua Lu¹, Jing Yang¹, Yumin Hu¹, Peng Huang^1,2 and Shijun Wen^1,2,*

¹ Sun Yat-Sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine; Sun Yat-Sen University, 651 Dongfeng East Road, Guangzhou 510060, China

² School of Pharmaceutical Sciences, Sun Yat-sen University, 132 Waihuan East Road, Guangzhou 510006, China

^† The authors contributed equally to this work.

Molecules 2017, 22(6), 773; https://doi.org/10.3390/molecules22060773 - 1 Jun 2017

Cited by 21 | Viewed by 6180

Abstract

In our current work, acetyl chloride-mediated synthesis of phenethyl isothiocyanate (PEITC) derivatives proves to be convenient and provides the expected products at good to excellent yields. Biological evaluation and structure-activity relationship analysis found that the novel compound 7 showed the best anticancer activity [...] Read more.

In our current work, acetyl chloride-mediated synthesis of phenethyl isothiocyanate (PEITC) derivatives proves to be convenient and provides the expected products at good to excellent yields. Biological evaluation and structure-activity relationship analysis found that the novel compound 7 showed the best anticancer activity against human cancer cell line Panc1 and HGC27 compared with PEITC. Compounds 6 and 7 induced more apoptosis in pancreatic cancer cells but less toxicity in non-cancer cells. Further biological study demonstrated that 7 substantially increased intracellular reactive oxygen species (ROS) and depleted glutathione (GSH), leading to an oxidative stress to kill cancer cell. Full article

(This article belongs to the Special Issue Chemistry and Pharmacology of Modulators of Oxidative Stress)

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9 pages, 702 KiB

Open AccessArticle

Secondary Sulfonamides as Effective Lactoperoxidase Inhibitors

by Zeynep Köksal¹

, Ramazan Kalin^2,3, Yasemin Camadan⁴, Hande Usanmaz⁵, Züleyha Almaz⁶, İlhami Gülçin^2,*

, Taner Gokcen^7,8, Ahmet Ceyhan Gören⁷

and Hasan Ozdemir²

¹ Department of Chemistry, Faculty of Sciences, İstanbul Medeniyet University, 34730 İstanbul, Turkey

² Department of Chemistry, Faculty of Science, Ataturk University, 25240 Erzurum, Turkey

³ Department of Basic Science, Faculty of Science, Erzurum Technical University, 25240 Erzurum, Turkey

⁴ Pharmacy Services Program, Vocational School of Health Services, Artvin Coruh University, 08000 Artvin, Turkey

⁵ Department of Bioengineering, Faculty of Engineering and Architecture, Sinop University, 57000 Sinop, Turkey

⁶ Department of Molecular Biology and Genetics, Faculty of Sciences and Arts, Muş Alparslan University, 49250 Muş, Turkey

⁷ TUBITAK UME, Chemistry Group Laboratories, P.O. Box: 54, 41470 Gebze Kocaeli, Turkey

⁸ Department of Organic Chemistry, Faculty of Science, Istanbul Technical University, 34469 Istanbul, Turkey

Molecules 2017, 22(6), 793; https://doi.org/10.3390/molecules22060793 - 24 May 2017

Cited by 36 | Viewed by 6326

Abstract

Secondary sulfonamides (4a–8h) incorporating acetoxybenzamide, triacetoxybenzamide, hydroxybenzamide, and trihydroxybenzamide and possessing thiazole, pyrimidine, pyridine, isoxazole and thiadiazole groups were synthesized. Lactoperoxidase (LPO, E.C.1.11.1.7), as a natural antibacterial agent, is a peroxidase enzyme secreted from salivary, mammary, and other mucosal [...] Read more.

Secondary sulfonamides (4a–8h) incorporating acetoxybenzamide, triacetoxybenzamide, hydroxybenzamide, and trihydroxybenzamide and possessing thiazole, pyrimidine, pyridine, isoxazole and thiadiazole groups were synthesized. Lactoperoxidase (LPO, E.C.1.11.1.7), as a natural antibacterial agent, is a peroxidase enzyme secreted from salivary, mammary, and other mucosal glands. In the present study, the in vitro inhibitory effects of some secondary sulfonamide derivatives (4a–8h) were examined against LPO. The obtained results reveal that secondary sulfonamide derivatives (4a–8h) are effective LPO inhibitors. The K_i values of secondary sulfonamide derivatives (4a–8h) were found in the range of 1.096 × 10⁻³ to 1203.83 µM against LPO. However, the most effective inhibition was found for N-(sulfathiazole)-3,4,5-triacetoxybenzamide (6a), with K_i values of 1.096 × 10⁻³ ± 0.471 × 10⁻³ µM as non-competitive inhibition. Full article

(This article belongs to the Special Issue Sulfonamides)

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15 pages, 892 KiB

Open AccessArticle

Production of Recombinant Antimicrobial Polymeric Protein Beta Casein-E 50-52 and Its Antimicrobial Synergistic Effects Assessment with Thymol

by Shohreh Fahimirad¹, Hamid Abtahi^2,*, Seyed Hadi Razavi¹, Houshang Alizadeh¹ and Mansour Ghorbanpour³

¹ Agriculture and Natural Resources Biotechnology Department, University of Tehran, Karaj 31587-11167, Iran

² Molecular and Medicine Research Center, Arak University of Medical Sciences, Arak, Molecular and Medicine Research Center, Arak University of Medical Sciences, Arak 38181-76941, Iran

³ Department of Medicinal Plants, Faculty of Agriculture and Natural Resources, Arak University, Arak 3815688349, Iran

Molecules 2017, 22(6), 822; https://doi.org/10.3390/molecules22060822 - 31 May 2017

Cited by 36 | Viewed by 6451

Abstract

Accelerating emergence of antimicrobial resistance among food pathogens and consumers’ increasing demands for preservative-free foods are two contemporary challenging aspects within the food industry. Antimicrobial packaging and the use of natural preservatives are promising solutions. In the present study, we used beta-casein—one [...] Read more.

Accelerating emergence of antimicrobial resistance among food pathogens and consumers’ increasing demands for preservative-free foods are two contemporary challenging aspects within the food industry. Antimicrobial packaging and the use of natural preservatives are promising solutions. In the present study, we used beta-casein—one of the primary self-assembly proteins in milk with a high polymeric film production capability—as a fusion partner for the recombinant expression of E 50-52 antimicrobial peptide in Escherichia coli. The pET21a-BCN-E 50-52 construct was transformed to E. coli BL21 (DE3), and protein expression was induced under optimized conditions. Purified protein obtained from nickel affinity chromatography was refolded under optimized dialysis circumstances and concentrated to 1600 µg/mL fusion protein by ultrafiltration. Antimicrobial activities of recombinant BCN-E 50-52 performed against Escherichia coli, Salmonella typhimurium, Listeria monocytogenes, Staphylococcus aureus, Aspergillus flavus, and Candida albicans. Subsequently, the synergistic effects of BCN-E 50-52 and thymol were assayed. Results of checkerboard tests showed strong synergistic activity between two compounds. Time–kill and growth kinetic studies indicated a sharp reduction of cell viability during the first period of exposure, and SEM (scanning electron microscope) results validated the severe destructive effects of BCN E 50-52 and thymol in combination on bacterial cells. Full article

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

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14 pages, 3449 KiB

Open AccessArticle

Green Synthesis of Zinc Oxide Nanoparticles for Enhanced Adsorption of Lead Ions from Aqueous Solutions: Equilibrium, Kinetic and Thermodynamic Studies

by Susan Azizi¹, Mahnaz Mahdavi Shahri^2,* and Rosfarizan Mohamad^1,3,*

¹ Department of Bioprocess Technology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, UPM Serdang, Selangor 43400, Malaysia

² Department of Chemistry, Shiraz Branch, Islamic Azad University, Shiraz 74731-71987, Iran

³ Laboratory of Biopolymer and Derivatives, Institute of Tropical Forestry and Forest Products, Universiti Putra Malaysia, UPM Serdang, Selangor 43400, Malaysia

Molecules 2017, 22(6), 831; https://doi.org/10.3390/molecules22060831 - 8 Jun 2017

Cited by 128 | Viewed by 10855

Abstract

In the present study, ZnO nanoparticles (NPs) were synthesized in zerumbone solution by a green approach and appraised for their ability to absorb Pb(II) ions from aqueous solution. The formation of as-synthesized NPs was established by X-ray diffraction (XRD), Transmission Electron Microscopy (TEM), [...] Read more.

In the present study, ZnO nanoparticles (NPs) were synthesized in zerumbone solution by a green approach and appraised for their ability to absorb Pb(II) ions from aqueous solution. The formation of as-synthesized NPs was established by X-ray diffraction (XRD), Transmission Electron Microscopy (TEM), and UV–visible studies. The XRD and TEM analyses revealed high purity and wurtzite hexagonal structure of ZnO NPs with a mean size of 10.01 ± 2.6 nm. Batch experiments were performed to investigate the impact of process parameters viz. Pb(II) concentration, pH of solution, adsorbent mass, solution temperature, and contact time variations on the removal efficiency of Pb(II). The adsorption isotherm data provided that the adsorption process was mainly monolayer on ZnO NPs. The adsorption process follows pseudo-second-order reaction kinetic. The maximum removal efficiencies were 93% at pH 5. Thermodynamic parameters such as enthalpy change (ΔH⁰), free energy change (ΔG⁰), and entropy change (ΔS⁰) were calculated; the adsorption process was spontaneous and endothermic. The good efficiency of the as-synthesized NPs makes them attractive for applications in water treatment, for removal of heavy metals from aqueous system. Full article

(This article belongs to the Section Green Chemistry)

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12 pages, 3295 KiB

Open AccessArticle

Endophytic Bacteria Isolated from Panax ginseng Improves Ginsenoside Accumulation in Adventitious Ginseng Root Culture

by Xiaolin Song, Hao Wu, Zhenhao Yin, Meilan Lian^* and Chengri Yin^*

Key Laboratory of Natural Resources of Changbai Mountain and Functional Molecules, Ministry of Education, Yanbian University, Yanji 133002, China

Molecules 2017, 22(6), 837; https://doi.org/10.3390/molecules22060837 - 23 May 2017

Cited by 73 | Viewed by 8161

Abstract

Ginsenoside is the most important secondary metabolite of ginseng. Natural sources of wild ginseng have been overexploited. Although root culture could reduce the length of the growth cycle of ginseng, the number of ginsenosides is fewer and their contents are lower in adventitious [...] Read more.

Ginsenoside is the most important secondary metabolite of ginseng. Natural sources of wild ginseng have been overexploited. Although root culture could reduce the length of the growth cycle of ginseng, the number of ginsenosides is fewer and their contents are lower in adventitious roots of ginseng than that in ginseng cultivated in the field. In this study, we investigated the effects of endophytic bacterial elicitors on biomass and ginsenoside production in adventitious roots cultures of Panax ginseng. Endophyte LB 5-3 as an elicitor could increase biomass and ginsenoside accumulation in ginseng adventitious root culture. After 6 days elicitation with a 10.0 mL of strain LB 5-3, the content of total ginsenoside was 2.026 mg g⁻¹ which was four times more than that in unchallenged roots. The combination of methyl jasmonate and strain LB 5-3 had a negative effect on ginseng adventitious root growth and ginsenoside production. The genomic DNA of strain LB 5-3 was sequenced, and was found to be most closely related to Bacillus altitudinis (KX230132.1). The challenged ginseng adventitious root extracts exerted inhibitory effect against the HepG2 cells, which IC₅₀ value was 0.94 mg mL⁻¹. Full article

(This article belongs to the Special Issue Current Trends in Ginseng Research)

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14 pages, 1929 KiB

Open AccessArticle

Immunomodulatory Effect of Agave tequilana Evaluated on an Autoimmunity Like-SLE Model Induced in Balb/c Mice with Pristane

by Zúlima Jannette Gutiérrez Nava^1,2

, Antonio Ruperto Jiménez-Aparicio²

, Maribel Lucila Herrera-Ruiz² and Enrique Jiménez-Ferrer^2,*

¹ Centro de Desarrollo de Productos Bióticos (CEPROBI), Instituto Politécnico Nacional (IPN), Yautepec, Morelos C.P. 62731, Mexico

² Centro de Investigación Biomédica del Sur (CIBIS), Instituto Mexicano del Seguro Social (IMSS), Xochitepec, Morelos C.P. 62790, Mexico

Molecules 2017, 22(6), 848; https://doi.org/10.3390/molecules22060848 - 25 May 2017

Cited by 20 | Viewed by 4755

Abstract

In this work, the immunomodulatory activity of the acetone extract and the fructans obtained from Agave tequilana were evaluated, on the systemic autoimmunity type-SLE model generated by the administration of 2,6,10,14-tetramethylpentadecane (TMPD, also known as pristane) on Balb/c female mice. The systemic autoimmunity [...] Read more.

In this work, the immunomodulatory activity of the acetone extract and the fructans obtained from Agave tequilana were evaluated, on the systemic autoimmunity type-SLE model generated by the administration of 2,6,10,14-tetramethylpentadecane (TMPD, also known as pristane) on Balb/c female mice. The systemic autoimmunity type-SLE was observed seven months after the application of TMPD, in which the animals from the negative control group (animals with damage and without any other treatment) developed articular inflammation, proteinuria, an increment of the antinuclear antibody titters and tissue pro-inflammatory cytokines levels (IL-1β, IL-6, TNF-α e IFN-γ) as well as the anti-inflammatory cytokine IL-10. The administration of the different treatments and the extracts of A. tequilana, provoked the decrease of: articular inflammation, the development of proteinuria, ssDNA/dsDNA antinuclear antibody titters and cytokines IL-1β, IL-6, TNF-α, IFN-γ and IL-10. The phytochemical analysis of the acetone extract identified the presence of the following compounds: β-sitosterol glycoside; 3,7,11,15-tetramethyl-2-hexadecen-1-ol (phytol); octadecadienoic acid-2,3-dihydroxypropyl ester; stigmasta-3,5-dien-7-one; cycloartenone and cycloartenol. Therefore, A. tequilana contains active compounds with the capacity to modify the evolution of the systemic autoimmunity type-SLE on a murine model. Full article

(This article belongs to the Section Natural Products Chemistry)

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8 pages, 1186 KiB

Open AccessArticle

Phloroglucinols with Antioxidant Activities Isolated from Lysidice rhodostegia

by Xian-Fu Wu^1,2,*

, Li Li¹, Yong Li¹, Hai-Ning Lv¹, Yun-Bao Liu¹ and You-Cai Hu^1,*

¹ 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

² National Institutes for Food and Drug Control, Beijing 100050, China

Molecules 2017, 22(6), 855; https://doi.org/10.3390/molecules22060855 - 23 May 2017

Cited by 8 | Viewed by 3990

Abstract

Two new phloroglucinols, lysidisides X and Y (1 and 2), and two known compounds, 2-(2-methylbutyryl)phloroglucinol 1-O-β-d-glucopyranoside (3) and (E)-resveratrol 3-(6″-galloyl)-O-β-d-glucopyranoside (4), have been isolated from the roots [...] Read more.

Two new phloroglucinols, lysidisides X and Y (1 and 2), and two known compounds, 2-(2-methylbutyryl)phloroglucinol 1-O-β-d-glucopyranoside (3) and (E)-resveratrol 3-(6″-galloyl)-O-β-d-glucopyranoside (4), have been isolated from the roots of Lysidice rhodostegia. The structures of 1 and 2 were elucidated primarily by NMR experiments. Their absolute configurations were deduced via circular dichroism (CD) data and electronic circular dichroism (ECD) calculations. Compounds 1 and 2 exhibited significant antioxidative activities with IC₅₀ values of 12.0 and 11.8 µM, respectively. Full article

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8 pages, 716 KiB

Open AccessArticle

14,15-Secopregnane-Type Glycosides with 5α:9α-Peroxy and Δ^6,8(14)-diene Linkages from the Roots of Cynanchum stauntonii

by An-Jun Deng¹, Jin-Qian Yu^1,2, Zhi-Hong Li¹, Lin Ma¹, Zhi-Hui Zhang¹ and Hai-Lin Qin^1,*

¹ 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

² Shandong Analysis and Test Center, Shandong Academy of Sciences, Jinan 250014, Shandong, China

Molecules 2017, 22(6), 860; https://doi.org/10.3390/molecules22060860 - 23 May 2017

Cited by 5 | Viewed by 4008

Abstract

Three new 14,15-secopregnane-type glycosides, stauntosides UA, UA₁, and UA₂, were isolated from the roots of Cynanchum stauntonii. The three compounds share the first reported and same basic structural features of 3β-hydroxy-14:16,15:20,18:20-triepoxy-5α:9α-peroxy-14,15-secopregnane-6,8(14)-diene named as stauntogenin G as the aglycones. [...] Read more.

Three new 14,15-secopregnane-type glycosides, stauntosides UA, UA₁, and UA₂, were isolated from the roots of Cynanchum stauntonii. The three compounds share the first reported and same basic structural features of 3β-hydroxy-14:16,15:20,18:20-triepoxy-5α:9α-peroxy-14,15-secopregnane-6,8(14)-diene named as stauntogenin G as the aglycones. The structures of the new compounds were characterized on the basis of extensive spectroscopic analyses, mainly 1D and 2D NMR and MS methods and chemical analysis. The isolation and identification of the new compounds graced the structural diversity of pregnane-type steroids from C. stauntonii. Full article

(This article belongs to the Section Natural Products Chemistry)

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10 pages, 3010 KiB

Open AccessArticle

Daucosterol Inhibits the Proliferation, Migration, and Invasion of Hepatocellular Carcinoma Cells via Wnt/β-Catenin Signaling

by Junquan Zeng¹, Xing Liu², Xiaofei Li³, Yongliang Zheng⁴, Bin Liu⁴ and Youzhang Xiao^5,*

¹ Department of Hematology, Jinggangshan University, Ji’an 343009, China

² Molecular Biology Laboratory, Jinggangshan University, Ji’an 343009, China

³ Department of Nursing, The Central People’s Hospital of Ji’an City, Ji’an 343000, China

⁴ Department of Hematology, The Affiliated Hospital of Jinggangshan University, Ji’an 343000, China

⁵ Department of Pathology, Jinggangshan University, Ji’an 343009, China

Molecules 2017, 22(6), 862; https://doi.org/10.3390/molecules22060862 - 2 Jun 2017

Cited by 48 | Viewed by 6957

Abstract

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide. The purpose of this study was to determine the effects of daucosterol on HCC by investigating Wnt/β-catenin signaling. In this study, HepG2 and SMMC-7721 cells were treated with varying concentrations [...] Read more.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide. The purpose of this study was to determine the effects of daucosterol on HCC by investigating Wnt/β-catenin signaling. In this study, HepG2 and SMMC-7721 cells were treated with varying concentrations of daucosterol, and the corresponding inhibitory effects on HCC cells were examined via CCK-8 assays. Cell migration and invasion abilities were detected via transwell assays. β-Catenin and phospho (p)-β-catenin levels were analyzed via western blotting. Our results showed that daucosterol reduced the proliferation, migration, and invasion capacities of HCC cells in a concentration-dependent manner. In addition, daucosterol reduced the levels of β-catenin and p-β-catenin in HepG2 and SMMC-7721 cells. Furthermore, the Wnt signaling pathway inhibitor SB-216763 was used to treat HepG2 and SMMC-7721 cells with daucosterol. Our results showed that co-treatment with daucosterol and SB-216763 abolished the effects of daucosterol on cell inhibition ratios, cell migration, and cell invasion. These findings indicated that daucosterol inhibited cell migration and invasion in HCC cells via the Wnt/β-catenin signaling pathway. Therefore, our study highlights the use of daucosterol as a promising therapeutic strategy for HCC treatment. Full article

(This article belongs to the Special Issue Cancer Chemoprevention)

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19 pages, 2157 KiB

Open AccessArticle

Anti-Inflammatory Activity of a Polymeric Proanthocyanidin from Serjania schiedeana

by David Osvaldo Salinas-Sánchez^1,2, Enrique Jiménez-Ferrer¹

, Veronica Sánchez-Sánchez^1,3, Alejandro Zamilpa¹

, Manasés González-Cortazar¹, Jaime Tortoriello¹ and Maribel Herrera-Ruiz^1,*

¹ Biomedical Research Center of the South (IMSS), Argentina 1, Col. Centro, Xochitepec 62790, Morelos, Mexico

² Biodiversity and Conservation Research Center (UAEM), Av. Universidad 1001, Col. Chamilpa, Cuernavaca 62209, Morelos, Mexico

³ Faculty of Biological Sciences (FBC), UAEM, Av. Universidad 1001, Col. Chamilpa, Cuernavaca 62209, Morelos, Mexico

Molecules 2017, 22(6), 863; https://doi.org/10.3390/molecules22060863 - 26 May 2017

Cited by 25 | Viewed by 4462

Abstract

The ethyl acetate extract (SsAcOEt) from Serjania schiedeana, select fractions (F-6, F-12, F-13, F-14), and one isolated compound, were evaluated in 12-O-tetradecanoylphorbol 13-acetate (TPA) ear edema and kaolin/carrageenan (KC)-induced monoarthritis assays. SsEtOAc induced edema inhibition of 90% (2.0 mg/ear), fractions [...] Read more.

The ethyl acetate extract (SsAcOEt) from Serjania schiedeana, select fractions (F-6, F-12, F-13, F-14), and one isolated compound, were evaluated in 12-O-tetradecanoylphorbol 13-acetate (TPA) ear edema and kaolin/carrageenan (KC)-induced monoarthritis assays. SsEtOAc induced edema inhibition of 90% (2.0 mg/ear), fractions showed activity within a range of 67–89%. Due to the fact F-14 showed the highest effect, it was separated, yielding a proanthocyanidin-type called epicatechin–(4β → 8)–epicatechin–(4β → 8, 2β → O → 7) epicatechin (ETP). This compound (2.0 mg/ear) provoked 72% of edema inhibition (ED50 = 0.25 mg/ear, Emax = 52.9%). After 9 days of treatment, joint inflammation was decreasing, and on the last day, SsEtOAc (400 mg/kg), F-14 and ETP (10 mg/kg), SsEtOAc (200 mg/kg), methotrexate (MTX) 1.0 mg/kg and meloxicam (MEL) 1.5 mg/kg, produced an inhibition articulate edema of 94, 62, 36, 21, 80, and 54%, respectively. In the joint, pro-inflammatory molecules were elevated in animals without treatment (vehicle group, VEH). Treatments from S. schiedeana induced a decrease in the concentration of interleukin (IL)-1β, IL-17, and IL-6, and SsEtOAc at a higher dose diminished tumor necrosis factor (TNF-α). IL-10 and IL-4 were fewer in the VEH group in comparison with healthy mice; the animals with treatments from S. schiedeana induced an increment in the levels of these cytokines in joint and spleen. Full article

(This article belongs to the Section Natural Products Chemistry)

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13 pages, 4354 KiB

Open AccessArticle

Encapsulation of the Antioxidant R-(+)-α-Lipoic Acid in Permethylated α- and β-Cyclodextrins: Thermal and X-ray Structural Characterization of the 1:1 Inclusion Complexes

by Mino R. Caira^*, Susan A. Bourne

and Buntubonke Mzondo

Centre for Supramolecular Chemistry Research, Department of Chemistry, University of Cape Town, Rondebosch 7701, South Africa

Molecules 2017, 22(6), 866; https://doi.org/10.3390/molecules22060866 - 23 May 2017

Cited by 9 | Viewed by 6474

Abstract

The naturally occurring compound α-lipoic acid (ALA) is implicated in manifold critical biological roles and its potent antioxidant properties and potential for treatment of various diseases have led to its widespread use as a dietary supplement. However, shortcomings of poor aqueous solubility and [...] Read more.

The naturally occurring compound α-lipoic acid (ALA) is implicated in manifold critical biological roles and its potent antioxidant properties and potential for treatment of various diseases have led to its widespread use as a dietary supplement. However, shortcomings of poor aqueous solubility and low thermal stability have hampered its development as a medicinal agent, prompting the use of cyclodextrins (CDs) to address these problems. The paucity of published structural data on the nature of the interactions between ALA and CDs motivated the present study, which describes the synthesis and X-ray structural elucidation of crystalline inclusion complexes between the biologically relevant R-(+)-α-lipoic acid (RALA) and the host molecules permethylated α-CD (TMA) and permethylated β-CD (TMB). Single crystal X-ray diffraction of TMA·RALA·6H₂O and TMB·RALA revealed significantly different orientations of the RALA molecule within the TMA and TMB cavities, but in both cases the guest molecule is fully encapsulated by the respective parent host molecules and residues of CD molecules of neighboring complex units. While pure RALA melted at 46–48 °C, combined thermal analysis techniques indicated that on heating the respective complexes, the release of RALA occurred at significantly higher onset temperatures, in the range 150–170 °C. Full article

(This article belongs to the Special Issue Cyclodextrin Chemistry)

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8 pages, 838 KiB

Open AccessArticle

On Forgotten Topological Indices of Some Dendrimers Structure

by Yasir Bashir¹, Adnan Aslam², Muhammad Kamran¹

, Muhammad Imran Qureshi³, Adnan Jahangir¹, Muhammad Rafiq¹, Nargis Bibi⁴

and Nazeer Muhammad^1,*

¹ Department of Mathematics, COMSATS Institute of Information Technology, Wah Cantt 47040, Pakistan

² Department of Natural Sciences and Humainities, University of Engineering and Technology, Lahore (RCET) 54890, Pakistan

³ Department of Mathematics, COMSATS Institute of Information Technology, Vehari 61100, Pakistan

⁴ Department of Computer Science, Fatima Jinnah Women University, Rawalpindi 46000, Pakistan

Molecules 2017, 22(6), 867; https://doi.org/10.3390/molecules22060867 - 24 May 2017

Cited by 55 | Viewed by 5635

Abstract

A series of previously conducted experiments pertaining to various chemicals and drugs uncover a natural linkage between the molecular structures and the bio-medical and pharmacological characteristics. The forgotten topological index computed for the molecular structures of various chemical compounds and drugs has proven [...] Read more.

A series of previously conducted experiments pertaining to various chemicals and drugs uncover a natural linkage between the molecular structures and the bio-medical and pharmacological characteristics. The forgotten topological index computed for the molecular structures of various chemical compounds and drugs has proven significant in medical and pharmaceutical fields by predicting biological features of new chemical compounds and drugs. A topological index can be considered as the transformation of chemical structure into a real number. Dendrimers are highly-branched star-shaped macromolecules with nanometer-scale dimensions. Dendrimers are defined by three components: a central core, an interior dendritic structure (the branches), and an exterior surface with functional surface groups. In this paper, we determine forgotten topological indices of poly(propyl) ether imine, porphyrin, and zinc–porphyrin dendrimers. Full article

(This article belongs to the Section Computational and Theoretical Chemistry)

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18 pages, 1697 KiB

Open AccessArticle

Design and Synthesis of Dendrimers with Facile Surface Group Functionalization, and an Evaluation of Their Bactericidal Efficacy

by Elizabeth Ladd^1,2,3, Amir Sheikhi^1,2,3, Na Li^1,3, Theo G.M. Van de Ven^1,2,3,* and Ashok Kakkar^1,3,*

¹ Department of Chemistry, McGill University, 801 Sherbrooke St. West, Montreal, QC H3A 0B8, Canada

² Pulp and Paper Research Centre, McGill University, 3420 rue University, Montreal, QC H3A 2A7, Canada

³ Centre for Self-Assembled Chemical Structures, McGill University, 801 Sherbrooke St. West, Montreal, QC H3A 0B8, Canada

Molecules 2017, 22(6), 868; https://doi.org/10.3390/molecules22060868 - 24 May 2017

Cited by 26 | Viewed by 7858

Abstract

We report a versatile divergent methodology to construct dendrimers from a tetrafunctional core, utilizing the robust copper(I) catalyzed alkyne-azide cycloaddition (CuAAC, “click”) reaction for both dendrimer synthesis and post-synthesis functionalization. Dendrimers of generations 1–3 with 8–32 protected or free OH and acetylene surface [...] Read more.

We report a versatile divergent methodology to construct dendrimers from a tetrafunctional core, utilizing the robust copper(I) catalyzed alkyne-azide cycloaddition (CuAAC, “click”) reaction for both dendrimer synthesis and post-synthesis functionalization. Dendrimers of generations 1–3 with 8–32 protected or free OH and acetylene surface groups, were synthesized using building blocks that included acetylene- or azide-terminated molecules with carboxylic acid or diol end groups, respectively. The acetylene surface groups were subsequently used to covalently link cationic amino groups. A preliminary evaluation indicated that the generation one dendrimer with terminal NH₃⁺ groups was the most effective bactericide, and it was more potent than several previously studied dendrimers. Our results suggest that size, functional end groups and hydrophilicity are important parameters to consider in designing efficient antimicrobial dendrimers. Full article

(This article belongs to the Special Issue Dendrimers: A Themed Issue in Honor of Professor Donald A. Tomalia on the Occasion of His 80th Birthday)

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19 pages, 2014 KiB

Open AccessArticle

In Silico Study and Bioprospection of the Antibacterial and Antioxidant Effects of Flavone and Its Hydroxylated Derivatives

by Camila De Albuquerque Montenegro^1,2,*, Gregório Fernandes Gonçalves¹, Abrahão Alves de Oliveira Filho³, Andressa Brito Lira¹, Thays Thyara Mendes Cassiano², Natanael Teles Ramos de Lima², José Maria Barbosa-Filho^1,4, Margareth De Fátima Formiga Melo Diniz^1,4 and Hilzeth Luna Freire Pessôa⁵

¹ Postgraduate Program in Natural Products and Synthetic Bioactive, Federal University of Paraiba, João Pessoa 58033-455, Paraíba, Brazil

² Department of Pharmacy, Center Biological Sciences and Health, State University of Paraiba, Campina Grande 58429-600, Paraíba, Brazil

³ Academic Biological Science Unit, Health Center and Rural Technology, Federal University of Campina Grande, Patos 58708-110, Paraíba, Brazil

⁴ Department of Pharmaceutical Sciences, Health Sciences Center, Federal University of Paraiba, João Pessoa 58059-900, Paraíba, Brazil

⁵ Department of Molecular Biology, Center of Exact Sciences and Nature, Federal University of Paraíba, João Pessoa 58051-090, Paraíba, Brazil

Molecules 2017, 22(6), 869; https://doi.org/10.3390/molecules22060869 - 24 May 2017

Cited by 16 | Viewed by 5733

Abstract

Flavonoid compounds are widely used as natural protective species, which can act as anti-inflammatory, antioxidant, anticoagulant, antihypertensive and antitumor agents. This study set out to investigate the probable pharmacological activities, along with the antibacterial and antioxidant effects, of flavone and its hydroxy derivatives: [...] Read more.

Flavonoid compounds are widely used as natural protective species, which can act as anti-inflammatory, antioxidant, anticoagulant, antihypertensive and antitumor agents. This study set out to investigate the probable pharmacological activities, along with the antibacterial and antioxidant effects, of flavone and its hydroxy derivatives: 3-hydroxyflavone, 5-hydroxyflavone and 6-hydroxyflavone. To do so, we investigated their pharmacological characteristics, using in silico tests that indicate likelihood of activity or inactivity, with the PASS online software, and the antimicrobial potential against Gram positive and Gram negative bacteria was also analyzed, including bacteria of clinical importance. We also tested for oxidant and antioxidant potential in these molecules in the presence of reactive oxygen species (ROS) and phenylhydrazine (Ph). The results revealed the following characteristics: pharmacological activities for the flavonoids as agonists of cell membrane integrity and as permeability inhibitors, as antagonists of anaphylatoxin receptors, as inhibitors of both kinase and peroxidase, and as having both antimutagenic capacity and vaso-protective potential. All of the flavonoids exhibited moderate antibacterial activity against Gram positive and Gram negative strains, with the flavones being bactericidal at 200 μg/mL for the strains of P. aeruginosa ATCC 8027, S. aureus ATCC 25619 and E. coli 104; the other flavonoids revealed bacteriostatic action. The substances did not promote erythrocyte oxidation and behaved as sequestrators and antioxidants of hydrogen peroxide (H₂O₂) and phenylhydrazine (Ph). It was concluded that the analyzed compounds have various pharmacological activities in accordance with the predictions of PASS online, as their antibacterial and antioxidant activities were confirmed. The study also helps to consolidate the use of computational chemistry in silico tools to guide new drug search and discovery protocols. Full article

(This article belongs to the Section Medicinal Chemistry)

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15 pages, 2997 KiB

Open AccessArticle

Preparation, Characterization, and Antioxidant Activity Evaluation of Liposomes Containing Water-Soluble Hydroxytyrosol from Olive

by Jiao-Jiao Yuan^1,2, Frank G.F. Qin^1,*, Jun-Ling Tu^1,* and Bing Li²

¹ School of Chemical Engineering and Energy Technology, Dongguan University of Technology, Dongguan 523808, China

² School of Food Science and Engineering, South China University of Technology, Guangzhou 510640, China

Molecules 2017, 22(6), 870; https://doi.org/10.3390/molecules22060870 - 24 May 2017

Cited by 36 | Viewed by 6867

Abstract

Due to the multiple hydroxyl groups in its structure, hydroxytyrosol (HT) is very sensitive to air and light and has very strong instability and hydrophilicity that affect its biological activity. This study attempted to prepare liposomes containing water-soluble HT to improve the bioavailability [...] Read more.

Due to the multiple hydroxyl groups in its structure, hydroxytyrosol (HT) is very sensitive to air and light and has very strong instability and hydrophilicity that affect its biological activity. This study attempted to prepare liposomes containing water-soluble HT to improve the bioavailability and biocompatibility of the target drug. The preparation process factors (temperature, mass ratio of phospholipid (PL) and cholesterol (CH), Tween-80 volume, HT mass) were studied and response surface methodology (RSM) was applied to optimize the conditions. The results demonstrated that by using a temperature of 63 °C, mass ratio of PL and CH 4.5:1, HT mass 5 mg and Tween-80 volume of 6 mL, HT liposomes with an encapsulation efficiency (EE) of 45.08% were prepared. It was found that the particle sizes of the HT liposomes were well distributed in the range of 100–400 nm. Compared to free HT, prepared HT liposomes had better stability and a distinct slow release effect in vitro. Besides, HT liposomes presented better DPPH radical scavenging activity than free HT, which could be due to the fact that HT was encapsulated fully inside the liposomes. In addition, the encapsulation mechanism of HT was evaluated. In summary, the results indicated that HT liposome could enhance the antioxidant activity and was a promising formulation for prolonging the biological activity time of the target drug. Full article

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18 pages, 7032 KiB

Open AccessArticle

Biosynthesis of ZnO Nanoparticles by a New Pichia kudriavzevii Yeast Strain and Evaluation of Their Antimicrobial and Antioxidant Activities

by Amin Boroumand Moghaddam^1,2, Mona Moniri^1,2, Susan Azizi^1,*

, Raha Abdul Rahim³, Arbakariya Bin Ariff^1,4, Wan Zuhainis Saad^5,6, Farideh Namvar⁷, Mohammad Navaderi^8,*

and Rosfarizan Mohamad^1,6,*

¹ Department of Bioprocess Technology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia

² Young Research and Elite Club, Sabzevar Branch, Islamic Azad University, Sabzevar, Iran

³ Department of Cell and Molecular Biology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia

⁴ Bioprocessing and Biomanufacturing Research Centre, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia

⁵ Department of Microbiology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia

⁶ Institute of Tropical Forestry and Forest Products, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia

⁷ Department of Medicine, Mashhad Branch, Islamic Azad University, Mashhad, Iran

⁸ Young Research and Elite Club, Parand Branch, Islamic Azad University, Parand, Iran

Molecules 2017, 22(6), 872; https://doi.org/10.3390/molecules22060872 - 24 May 2017

Cited by 187 | Viewed by 10214

Abstract

The potential ability of a new yeast strain, Pichia kudriavzevii, in the synthesis of zinc oxide nanoparticles (ZnO-NPs) through a green method was explored in this study. The effect of reaction time (12, 24 and 36 h) on the structure of the [...] Read more.

The potential ability of a new yeast strain, Pichia kudriavzevii, in the synthesis of zinc oxide nanoparticles (ZnO-NPs) through a green method was explored in this study. The effect of reaction time (12, 24 and 36 h) on the structure of the resulting ZnO nanoparticles was investigated. From the XRD and TEM results, the ZnO-NPs with a hexagonal wurtzite structure and a particle crystal size of ~10–61 nm was formed at different reaction times. Combing XRD, TEM, and PL results, it was revealed that the sample prepared at intermediate duration (24 h) has the most favorable nanosized structure with the lowest defect concentration. The biomedical properties of ZnO-NPs as free radical scavenging activity, cytotoxicity and antibacterial agents were characterized. Biosynthesized ZnO-NPs showed strong DPPH free radical scavenging and a dose dependent toxicity with non-toxic effects on Vero cells for concentrations below 190 µg/mL. Desirable bactericidal activity was shown by the ZnO-NPs on Gram-positive bacteria (Bacillus subtilis, Staphylococcus epidermidis and Staphylococcus aurous) and Gram-negative bacteria (Escherichia coli and Serratia marcescens). A maximum inhibition zone of ~19 mm was observed for Staphylococcus epidermidis at a concentration of 100 µg/mL for sample prepared at 24 h. The results from this study reveal that ZnO-NPs possesses potential for many medical and industrial applications. Full article

(This article belongs to the Section Green Chemistry)

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12 pages, 1837 KiB

Open AccessArticle

Impact of Maturity of Malay Cherry (Lepisanthes alata) Leaves on the Inhibitory Activity of Starch Hydrolases

by Yan Zhang¹

, Yuyang Gui¹ and Dejian Huang^1,2,*

¹ Food Science and Technology Programme, c/o Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore 117543, Singapore

² National University of Singapore (Suzhou) Research Institute, 377 Lin Quan Street, Suzhou Industrial Park, Suzhou 215123, Jiangsu, China

Molecules 2017, 22(6), 873; https://doi.org/10.3390/molecules22060873 - 24 May 2017

Cited by 2 | Viewed by 4658

Abstract

Aqueous extracts of young (7-day-old) Malay cherry (Lepisanthes alata) leaves were incorporated into wheat and rice flours to evaluate their inhibitory activities against α-amylase and α-glucosidase. HPLC-ESI/MS² results showed that the active components in young leaves were proanthocyanidins with lower [...] Read more.

Aqueous extracts of young (7-day-old) Malay cherry (Lepisanthes alata) leaves were incorporated into wheat and rice flours to evaluate their inhibitory activities against α-amylase and α-glucosidase. HPLC-ESI/MS² results showed that the active components in young leaves were proanthocyanidins with lower mean degrees of polymerisation (≤10). The IC₅₀ of the aqueous extracts of young leaves were 2.50 ± 0.03 and 12.91 ± 0.29 µg/mL, against α-amylase and α-glucosidase, which make them less active compared to the mature leaves. In contrast, total proanthocyanidins in aqueous extracts decreased as the leaves matured, indicating that the compounds in the mature leaves have much higher activity. However, there was no significant difference in the digestibility of wheat noodles incorporated with the aqueous extracts from either young or mature leaves. Interestingly, with regard to rice noodles, their digestibility was mostly reduced by incorporating aqueous extracts of young leaves compared to using mature leaves. Full article

(This article belongs to the Collection Bioactive Compounds)

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12 pages, 1253 KiB

Open AccessArticle

Isolation of Monoterpene Dihydrochalcones from Piper montealegreanum Yuncker (Piperaceae)

by Harley Da Silva Alves^1,*, Wilma Raianny Vieira da Rocha¹, Raimundo Braz-Filho^2,3 and Maria Célia de Oliveira Chaves⁴

¹ Department of Pharmacy/Post-Graduation Program in Pharmaceutical Sciences, State University of Paraíba, 58429-500 Campina Grande-PB, Brazil

² Chemical Science Laboratory, CCT, State University of Fluminense North Darcy Ribeiro, 28013-600 Campo dos Goytacazes-RJ, Brazil

³ Department of Chemistry, DEQUIM-ICE-Federal University Rural of Rio de Janeiro, CEP 23894-374 Seropédica-RJ, Brazil

⁴ Research Institute for Drugs and Medicines, Federal University of Paraíba, CEP 58051-900 João Pessoa-PB, Brazil

Molecules 2017, 22(6), 874; https://doi.org/10.3390/molecules22060874 - 9 Jun 2017

Cited by 5 | Viewed by 4709

Abstract

Four new compounds were isolated from the branches of Piper montealegreanum Yuncker, a shrub found in the Amazon rainforest, including two new dihydrochalcones named claricine (1) and maisine (2), a cinnamic acid derivative 3 and a phenylalkanoid 4, [...] Read more.

Four new compounds were isolated from the branches of Piper montealegreanum Yuncker, a shrub found in the Amazon rainforest, including two new dihydrochalcones named claricine (1) and maisine (2), a cinnamic acid derivative 3 and a phenylalkanoid 4, along with a porphyrin identified as the known compound phaeophytin a (5). The structures were established using spectroscopic experiments, including 1D and 2D NMR and HRESIMS experiments, performed on the two monoterpene dihydrochalcones and their monoacetyl derivatives. The structural diversity of these substances is very important for the Piper genus chemotaxonomy. Full article

(This article belongs to the Section Natural Products Chemistry)

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12 pages, 1209 KiB

Open AccessArticle

Structure Modification of an Active Azo-Compound as a Route to New Antimicrobial Compounds

by Simona Concilio^1,*, Lucia Sessa²

, Anna Maria Petrone^2,3, Amalia Porta²

, Rosita Diana⁴, Pio Iannelli² and Stefano Piotto²

¹ Department of Industrial Engineering, University of Salerno, Via Giovanni Paolo II 132, 84084 Fisciano, Italy

² Department of Pharmacy, University of Salerno, Via Giovanni Paolo II 132, 84084 Fisciano, Italy

³ PhD Program in Drug Discovery and Development, University of Salerno, Via Giovanni Paolo II 132, 84084 Fisciano, Italy

⁴ Department of Chemical Science, University of Napoli “Federico II”, Cupa Nuova Cintia 21, 80126 Napoli, Italy

Molecules 2017, 22(6), 875; https://doi.org/10.3390/molecules22060875 - 25 May 2017

Cited by 47 | Viewed by 7431

Abstract

Some novel (phenyl-diazenyl)phenols 3a–g were designed and synthesized to be evaluated for their antimicrobial activity. A previously synthesized molecule, active against bacteria and fungi, was used as lead for modifications and optimization of the structure, by introduction/removal or displacement of hydroxyl [...] Read more.

Some novel (phenyl-diazenyl)phenols 3a–g were designed and synthesized to be evaluated for their antimicrobial activity. A previously synthesized molecule, active against bacteria and fungi, was used as lead for modifications and optimization of the structure, by introduction/removal or displacement of hydroxyl groups on the azobenzene rings. The aim of this work was to evaluate the consequent changes of the antimicrobial activity and to validate the hypothesis that, for these compounds, a plausible mechanism could involve an interaction with protein receptors, rather than an interaction with membrane. All newly synthesized compounds were analyzed by ¹H-NMR, DSC thermal analysis and UV-Vis spectroscopy. The in vitro minimal inhibitory concentrations (MIC) of each compound was determined against Gram-positive and Gram-negative bacteria and Candida albicans. Compounds 3b and 3g showed the highest activity against S. aureus and C. albicans, with remarkable MIC values of 10 µg/mL and 3 µg/mL, respectively. Structure-activity relationship studies were capable to rationalize the effect of different substitutions on the phenyl ring of the azobenzene on antimicrobial activity. Full article

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

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14 pages, 2952 KiB

Open AccessArticle

Identification of Anthocyanin Composition and Functional Analysis of an Anthocyanin Activator in Solanum nigrum Fruits

by Shaoli Wang^1,†

, Zhaohui Chu^1,†

, Mingxing Ren², Ru Jia¹, Changbao Zhao¹, Dan Fei³, Hao Su¹, Xiaoqi Fan¹, Xiaotian Zhang¹, Yang Li¹, Yingzi Wang⁴ and Xinhua Ding^1,*

¹ State Key Laboratory of Crop Biology, Shandong Provincial Key Laboratory for Biology of Vegetable Diseases and Insect Pests, Shandong Agricultural University, Taian 271018, Shandong, China

² Shaoxing Entry-Exit Inspection and Quarantine Bureau, Shaoxing 312000, Zhejiang, China

³ Anhui Biothun Biotechnology Company, Hefei 230088, Anhui, China

⁴ Institute of Plant Protection, Yantai Academy of Agricultural Science, Yantai 265500, Shandong, China

^† These authors contributed equally to this work.

Molecules 2017, 22(6), 876; https://doi.org/10.3390/molecules22060876 - 25 May 2017

Cited by 32 | Viewed by 8281

Abstract

Solanum nigrum fruits have been conventionally used in beverages due to their nutritional substances such as minerals, vitamins, amino acids, proteins, sugars, polyphenols, and anthocyanins. The characterization of components and regulatory mechanism of anthocyanins in S. nigrum fruits have rarely been reported. In [...] Read more.

Solanum nigrum fruits have been conventionally used in beverages due to their nutritional substances such as minerals, vitamins, amino acids, proteins, sugars, polyphenols, and anthocyanins. The characterization of components and regulatory mechanism of anthocyanins in S. nigrum fruits have rarely been reported. In this study, we determined that the peel and flesh of S. nigrum fruits shared similar HPLC profiles but different contents and total antioxidant activities for anthocyanins. After an efficient purification method, mainly including extraction with pH 1.0 distilled water and then desorption with pH 1.0 95% ethanol after a DM-130 resin adsorption step to obtain more pure anthocyanin extracts, the purity of anthocyanins extracted from S. nigrum fruits reached 56.1%. Moreover, eight anthocyanins from S. nigrum fruit were identified with HPLC-MS/MS for the first time. A typical R2R3-MYB transcription factor gene, SnMYB, was also cloned for the first time by rapid amplification of cDNA ends (RACE)-PCR from S. nigrum. Moreover, the contents of anthocyanins were shown to correlate well (r = 0.93) with the expression levels of SnMYB gene during the fruit’s developmental stages. Most significantly, SnMYB gene successfully produced high anthocyanin content (1.03 mg/g) when SnMYB gene was transiently expressed in tobacco leaves. Taken together, S. nigrum fruits are a promising resource for anthocyanin extraction, and SnMYB gene is an activator that positively regulates anthocyanin biosynthesis in S. nigrum. Full article

(This article belongs to the Collection Bioactive Compounds)

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14 pages, 707 KiB

Open AccessArticle

Design, Synthesis, and Biological Activities of Novel Pyrazole Oxime Compounds Containing a Substituted Pyridyl Moiety

by Cuili Chen^1,2, Jia Chen³, Haiying Gu^1,2,*, Ning Bao² and Hong Dai^3,*

¹ College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou 215123, China

² School of Public Health, Nantong University, Nantong 226019, China

³ College of Chemistry and Chemical Engineering, Nantong University, Nantong 226019, China

Molecules 2017, 22(6), 878; https://doi.org/10.3390/molecules22060878 - 25 May 2017

Cited by 9 | Viewed by 4570

Abstract

In this paper, in order to find novel biologically active pyrazole oximes, a series of pyrazole oxime compounds bearing a substituted pyridyl unit were prepared. Bioassays showed that some target compounds were found to have good acaricidal activity against Tetranychus cinnabarinus at a [...] Read more.

In this paper, in order to find novel biologically active pyrazole oximes, a series of pyrazole oxime compounds bearing a substituted pyridyl unit were prepared. Bioassays showed that some target compounds were found to have good acaricidal activity against Tetranychus cinnabarinus at a concentration of 500 μg/mL, compound 9q especially displayed potent acaricidal activity against T. cinnabarinus when the concentration was reduced to 100 μg/mL. Interestingly, most target compounds possessed excellent insecticidal activities against Oriental armyworm at 500 μg/mL. Moreover, some compounds were active against Aphis medicaginis and Nilaparvata lugens at 500 μg/mL. Additionally, compounds 9b, 9g, 9l, 9p, 9q, 9r, 9s, 9t, 9u, and 9v displayed significant antiproliferative activities against HepG2 cells with IC₅₀ values of 1.53–17.27 μM, better than that of the control 5-fluorouracil (IC₅₀ = 35.67 μM). Full article

(This article belongs to the Section Organic Chemistry)

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11 pages, 2682 KiB

Open AccessArticle

Floral Scent Chemistry of Luculia yunnanensis (Rubiaceae), a Species Endemic to China with Sweetly Fragrant Flowers

by Yuying Li¹

, Youming Wan¹, Zhenghai Sun², Taiqiang Li¹, Xiongfang Liu¹, Hong Ma^1,*, Xiuxian Liu¹, Rui He¹, Yan Ma¹ and Zhenghong Li^1,*

¹ Research Institute of Resource Insects, Chinese Academy of Forestry, Kunming 650224, China

² School of Gardening, Southwest Forestry University, Kunming 650224, China

Molecules 2017, 22(6), 879; https://doi.org/10.3390/molecules22060879 - 25 May 2017

Cited by 20 | Viewed by 5297

Abstract

Luculia plants are famed ornamentals with sweetly fragrant flowers. Luculia yunnanensis Hu is an endemic plant from Yunnan Province, China. Headspace-solid phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS) was used to identify the volatile organic compounds (VOCs) of the different flower development stages of L. [...] Read more.

Luculia plants are famed ornamentals with sweetly fragrant flowers. Luculia yunnanensis Hu is an endemic plant from Yunnan Province, China. Headspace-solid phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS) was used to identify the volatile organic compounds (VOCs) of the different flower development stages of L. yunnanensis for the evaluation of floral volatile polymorphism. The results showed that a total of 40 compounds were identified at four different stages. The main aroma-active compounds were 3-carene, α-cubebene, α-copaene, δ-cadinene, and isoledene. Floral scent emission had the tendency to ascend first and descend in succession, reaching its peak level at the initial-flowering stage. The richest diversity of floral volatiles was detected at the full-flowering stage. Principal component analysis (PCA) indicated that the composition and its relative content of floral scent differed at the whole flower development stage. In comparison with the other two species of Luculia (L. pinceana and L. gratissima), the composition and its relative content of floral scent were also different among the tree species. Full article

(This article belongs to the Section Natural Products Chemistry)

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15 pages, 2467 KiB

Open AccessArticle

Yeast Extract Stimulates Ginsenoside Production in Hairy Root Cultures of American Ginseng Cultivated in Shake Flasks and Nutrient Sprinkle Bioreactors

by Ewa Kochan^1,*, Piotr Szymczyk¹

, Łukasz Kuźma²

, Anna Lipert³

and Grażyna Szymańska¹

¹ Pharmaceutical Biotechnology Department, Medical University of Lodz, Muszyńskiego 1, Lodz 90-151, Poland

² Department of Biology and Pharmaceutical Botany, Medical University of Lodz, Muszyńskiego l, Lodz 90-151, Poland

³ Department of Sports Medicine, Medical University of Lodz, Pomorska 251, Lodz 92-213, Poland

Molecules 2017, 22(6), 880; https://doi.org/10.3390/molecules22060880 - 26 May 2017

Cited by 50 | Viewed by 8688

Abstract

One of the most effective strategies to enhance metabolite biosynthesis and accumulation in biotechnological systems is the use of elicitation processes. This study assesses the influence of different concentrations of yeast extract (YE) on ginsenoside biosynthesis in Panax quinquefolium (American ginseng) hairy roots [...] Read more.

One of the most effective strategies to enhance metabolite biosynthesis and accumulation in biotechnological systems is the use of elicitation processes. This study assesses the influence of different concentrations of yeast extract (YE) on ginsenoside biosynthesis in Panax quinquefolium (American ginseng) hairy roots cultivated in shake flasks and in a nutrient sprinkle bioreactor after 3 and 7 days of elicitation. The saponin content was determined using HPLC. The maximum yield (20 mg g⁻¹ d.w.) of the sum of six examined ginsenosides (Rb1, Rb2, Rc, Rd, Re and Rg1) in hairy roots cultivated in shake flasks was achieved after application of YE at 50 mg L⁻¹ concentration and 3 day exposure time. The ginsenoside level was 1.57 times higher than that attained in control medium. The same conditions of elicitation (3 day time of exposure and 50 mg L⁻¹ of YE) also favourably influenced the biosynthesis of studied saponins in bioreactor cultures. The total ginsenoside content was 32.25 mg g⁻¹ d.w. and was higher than that achieved in control medium and in shake flasks cultures. Obtained results indicated that yeast extract can be used to increase ginsenoside production in hairy root cultures of P. quinquefolium. Full article

(This article belongs to the Special Issue Current Trends in Ginseng Research)

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12 pages, 3426 KiB

Open AccessArticle

Identification of Non-Electrophilic Nrf2 Activators from Approved Drugs

by Qing-Ye Zhang^1,*,†, Xin-Yi Chu^1,†, Ling-Han Jiang¹

, Meng-Yuan Liu¹, Zhi-Ling Mei² and Hong-Yu Zhang^1,*

¹ Hubei Key Laboratory of Agricultural Bioinformatics, College of Informatics, Huazhong Agricultural University, Wuhan 430070, China

² Shanghai Thinkgene Biotech Co., LTD., Shanghai 200000, China

^† The first two authors contributed equally.

Molecules 2017, 22(6), 883; https://doi.org/10.3390/molecules22060883 - 26 May 2017

Cited by 25 | Viewed by 5774

Abstract

Oxidative damage can lead to a wide range of diseases. Nrf2 is an important transcription factor that regulates many of the cytoprotective enzymes involved in the oxidative stress response. Therefore, targeting the regulation of Nrf2 activation is one logical and effective strategy to [...] Read more.

Oxidative damage can lead to a wide range of diseases. Nrf2 is an important transcription factor that regulates many of the cytoprotective enzymes involved in the oxidative stress response. Therefore, targeting the regulation of Nrf2 activation is one logical and effective strategy to prevent or lower the risk of oxidative stress-related diseases. Until now, most research has focused on electrophilic indirect Nrf2 activators, but the risk of ‘off-target’ effects may be associated with these activators. To find novel small non-electrophilic modulators of Nrf2, we started from chemical agents derived from a connectivity map (cMap) and identified 22 non-electrophilic potential Nrf2-activating drugs through a drug repositioning tactic. By determining the expression changes of antioxidant genes in MCF7 cells that were treated with the potential Nrf2 activators using quantitative real-time polymerase chain reaction RT-PCR (real-time polymerase chain reaction) (qRT-PCR), astemizole was found to have a greater scale of upregulating antioxidant genes NQO1, HO-1, and GCLM than the positive control d,l-sulforaphane, although the testing concentration was lower than that of the control. Astemizole is a good potential redox regulator and deserves more pharmacodynamic experimentation to test and verify its feasibility for use as an Nrf2 activator. Full article

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15 pages, 2406 KiB

Open AccessArticle

In Vitro Antioxidant Activity of Idebenone Derivative-Loaded Solid Lipid Nanoparticles

by Lucia Montenegro^*

, Maria N. Modica, Loredana Salerno, Anna Maria Panico, Lucia Crascì

, Giovanni Puglisi and Giuseppe Romeo

Department of Drug Sciences, University of Catania, V. le A. Doria 6, 95125 Catania, Italy

Molecules 2017, 22(6), 887; https://doi.org/10.3390/molecules22060887 - 27 May 2017

Cited by 14 | Viewed by 6140

Abstract

Idebenone (IDE) has been proposed for the treatment of neurodegenerative diseases involving mitochondria dysfunctions. Unfortunately, to date, IDE therapeutic treatments have not been as successful as expected. To improve IDE efficacy, in this work we describe a two-step approach: (1) synthesis of IDE [...] Read more.

Idebenone (IDE) has been proposed for the treatment of neurodegenerative diseases involving mitochondria dysfunctions. Unfortunately, to date, IDE therapeutic treatments have not been as successful as expected. To improve IDE efficacy, in this work we describe a two-step approach: (1) synthesis of IDE ester derivatives by covalent linking IDE to other two antioxidants, trolox (IDETRL) and lipoic acid (IDELIP), to obtain a synergic effect; (2) loading of IDE, IDETRL, or IDELIP into solid lipid nanoparticles (SLN) to improve IDE and its esters’ water solubility while increasing and prolonging their antioxidant activity. IDE and its derivatives loaded SLN showed good physico-chemical and technological properties (spherical shape, mean particle sizes 23–25 nm, single peak in the size distribution, ζ potential values −1.76/−2.89 mV, and good stability at room temperature). In vitro antioxidant activity of these SLN was evaluated in comparison with free drugs by means of oxygen radical absorbance capacity (ORAC) test. IDETRL and IDELIP showed a greater antioxidant activity than IDE and encapsulation of IDE and its derivatives into SLN was able to prolong their antioxidant activity. These results suggest that loading IDETRL and IDELIP into SLN could be a useful strategy to improve IDE efficacy. Full article

(This article belongs to the Section Medicinal Chemistry)

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11 pages, 1356 KiB

Open AccessArticle

Effect of Selected Mercapto Flavor Compounds on Acrylamide Elimination in a Model System

by Zhiyong Xiong^1,2, Bing Li^1,3,*, Lin Li^1,3,4,*, Liting Wan¹, Xiaolong Peng¹ and Yongpo Yin¹

¹ School of Food Sciences and Engineering, South China University of Technology, Guangzhou 510640, China

² School of Chemical Engineering and Materials Science, Beijing Institute of Technology Zhuhai, Zhuhai 519088, China

³ Guangdong Province Key Laboratory for Green Processing of Natural Products and Product Safety, Guangzhou 510640, China

⁴ School of Chemical Engineering and Energy Technology, Dongguan University of Technology, Dongguan 523808, China

Molecules 2017, 22(6), 888; https://doi.org/10.3390/molecules22060888 - 31 May 2017

Cited by 7 | Viewed by 5262

Abstract

The effect of four mercapto flavor compounds (1,2-ethanedithiol, 1-butanethiol, 2-methyl-3-furanthiol, and 2-furanmethanethiol) on acrylamide elimination were investigated in model systems. The obtained results showed that mercaptans assayed were effective in elimination arylamide in a model system. Their reactivities for decreasing acrylamide content depended [...] Read more.

The effect of four mercapto flavor compounds (1,2-ethanedithiol, 1-butanethiol, 2-methyl-3-furanthiol, and 2-furanmethanethiol) on acrylamide elimination were investigated in model systems. The obtained results showed that mercaptans assayed were effective in elimination arylamide in a model system. Their reactivities for decreasing acrylamide content depended on mercaptan’s molecular structure and acrylamide disappearance decreased in the following order: 1,2-ethanedithiol > 2-methyl-3-furanthiol > 1-butanethiol > 2-furanmethanethiol. Mercaptans were added to acrylamide to produce the corresponding 3-(alkylthio) propionamides. This reaction was irreversible and only trace amounts of acrylamide were formed by thermal heating of 3-(alkylthio) propanamide. Although a large amount disappeared, only part of the acrylamide conversed into 3-(alkylthio) propionamides. All of these results constitute a fundamental proof of the complexity of the reactions involved in the removal of free acrylamide in foods. This implies mercapto flavor/aroma may directly or indirectly reduce the level of acrylamide in food processing. This study could be regarded as a pioneer contribution on acrylamide elimination in a model system by the addition of mercapto flavor compounds. Full article

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

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13 pages, 1718 KiB

Open AccessArticle

Comprehensive Characterization for Ginsenosides Biosynthesis in Ginseng Root by Integration Analysis of Chemical and Transcriptome

by Jing-Jing Zhang^1,2,†

, He Su^2,3,†, Lei Zhang^4,†, Bao-Sheng Liao², Shui-Ming Xiao², Lin-Lin Dong², Zhi-Gang Hu¹, Ping Wang¹, Xi-Wen Li², Zhi-Hai Huang³, Zhi-Ming Gao⁵, Lian-Juan Zhang², Liang Shen², Rui-Yang Cheng², Jiang Xu^2,* and Shi-Lin Chen^2,*

¹ College of Pharmacy, Hubei University of Chinese Medicine, Wuhan 430065, China

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

³ Guangdong Provincial Hospital of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, and China Academy of Chinese Medical Sciences Guangdong Branch, China Academy of Chinese Medical Sciences, Guangzhou 510006, China

⁴ Data Center, China Academy of Chinese Medicinal Sciences, Beijing 100700, China

⁵ The Engineering Technology Research Center for Chinese Medicine, Henan Agricultural University, Zhengzhou 450002, China

^† These authors contributed equally to this work.

Molecules 2017, 22(6), 889; https://doi.org/10.3390/molecules22060889 - 31 May 2017

Cited by 32 | Viewed by 8062

Abstract

Herbgenomics provides a global platform to explore the genetics and biology of herbs on the genome level. Panax ginseng C.A. Meyer is an important medicinal plant with numerous pharmaceutical effects. Previous reports mainly discussed the transcriptome of ginseng at the organ level. However, [...] Read more.

Herbgenomics provides a global platform to explore the genetics and biology of herbs on the genome level. Panax ginseng C.A. Meyer is an important medicinal plant with numerous pharmaceutical effects. Previous reports mainly discussed the transcriptome of ginseng at the organ level. However, based on mass spectrometry imaging analyses, the ginsenosides varied among different tissues. In this work, ginseng root was separated into three tissues—periderm, cortex and stele—each for five duplicates. The chemical analysis and transcriptome analysis were conducted simultaneously. Gene-encoding enzymes involved in ginsenosides biosynthesis and modification were studied based on gene and molecule data. Eight widely-used ginsenosides were distributed unevenly in ginseng roots. A total of 182,881 unigenes were assembled with an N50 contig size of 1374 bp. About 21,000 of these unigenes were positively correlated with the content of ginsenosides. Additionally, we identified 192 transcripts encoding enzymes involved in two triterpenoid biosynthesis pathways and 290 transcripts encoding UDP-glycosyltransferases (UGTs). Of these UGTs, 195 UGTs (67.2%) were more highly expressed in the periderm, and that seven UGTs and one UGT were specifically expressed in the periderm and stele, respectively. This genetic resource will help to improve the interpretation on complex mechanisms of ginsenosides biosynthesis, accumulation, and transportation. Full article

(This article belongs to the Special Issue Isoprenoid Biosynthesis)

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14 pages, 1298 KiB

Open AccessArticle

Structural Characterization of Lignin in Fruits and Stalks of Chinese Quince

by Hui-Shuang Yin, Hua-Min Liu^* and Yu-Lan Liu

Department of Oil Engineering, College of Food Science and Technology, Henan University of Technology, Zhengzhou 450001, China

Molecules 2017, 22(6), 890; https://doi.org/10.3390/molecules22060890 - 27 May 2017

Cited by 28 | Viewed by 6000

Abstract

Chinese quince (Chaenomeles sinensis) is used in food and pharmaceutical products, but it is seldom eaten as a raw fruit due to its astringent, woody flesh. The structural characterization of lignin fractions from Chinese quince was very important to investigate the [...] Read more.

Chinese quince (Chaenomeles sinensis) is used in food and pharmaceutical products, but it is seldom eaten as a raw fruit due to its astringent, woody flesh. The structural characterization of lignin fractions from Chinese quince was very important to investigate the structure-activity relationships of lignin. In this investigation, to characterize the structure of lignin in Chinese quince fruits, the milled wood lignin sample was isolated from the fruits (FMWL) and the chemical structure of FMWL was investigated by sugar analysis, FT-IR, GPC, pyrolysis-GC/MS analysis, UV spectra analysis, thermogravimetric analysis (TGA), and advanced NMR spectroscopic techniques. In addition, the lignin fraction from the stalk of Chinese quince (SMWL) was also prepared for comparison to obtained more information of lignin structure in the fruits. The results showed that the two lignin fractions isolated from fruit and stalk of Chinese quince exhibited different structural features. The two MWL samples were mainly composed of β-O-4 ether bonds, β-5 and β-β′ carbon-carbon linkages in the lignin structural units. Compared to the SMWL, the FMWL fraction had the higher S/G ratio and more carbohydrates linkages. The predominant carbohydrates associated with FMWL and SMWL fractions were glucans-type hemicelluloses and xylan-type hemicelluloses, respectively. Understanding the structure of lignin could give insight into the properties of the lignin and enable the food processing industry to separate lignin more efficiently. Full article

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13 pages, 3806 KiB

Open AccessFeature PaperArticle

Identification of Novel Vacuolin-1 Analogues as Autophagy Inhibitors by Virtual Drug Screening and Chemical Synthesis

by Chang Chen^1,†, Yingying Lu^2,3,†, Ho Ming Siu^3,†, Jintao Guan^2,3, LongChao Zhu^2,3, Shuang Zhang¹, Jianbo Yue^2,3,* and Liangren Zhang^1,*

¹ State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China

² City University of Hong Kong Shen Zhen Research Institute, Shenzhen 518057, China

³ Department of Biomedical Sciences, City University of Hong Kong, Hong Kong, China

^† Equal contribution.

Molecules 2017, 22(6), 891; https://doi.org/10.3390/molecules22060891 - 27 May 2017

Cited by 19 | Viewed by 6159

Abstract

Autophagy is a fundamental cellular degradation process which is essential for cell homeostasis, and dysfunctional autophagy has been associated with a variety of human diseases, such as cancer. Several autophagy chemical modulators have been applied in a number of preclinical or clinical trials [...] Read more.

Autophagy is a fundamental cellular degradation process which is essential for cell homeostasis, and dysfunctional autophagy has been associated with a variety of human diseases, such as cancer. Several autophagy chemical modulators have been applied in a number of preclinical or clinical trials against these autophagy related diseases, especially cancer. Small molecule vacuolin-1 potently and reversibly inhibits both endosomal-lysosomal trafficking and autophagosome-lysosome fusion, yet the molecular mechanisms underlying vacuolin-1 mediated autophagy inhibition remain unknown. Here, we first performed the virtual drug screening and identified 14 vacuolin-1 analogues as autophagy inhibitors. Based on these virtual screening results, we further designed and synthesized 17 vacuolin-1 analogues, and found that 13 of them are autophagy inhibitors and a couple of them are as potent as vacuolin-1. In summary, these studies expanded the pool of useful autophagy inhibitors and reveal the structural-activity relationship of vacuolin-1 analogues, which is useful for future development of vacuolin-1 analogues with high potency and for identification of the molecular targets of vacuolin-1. Full article

(This article belongs to the Section Medicinal Chemistry)

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19 pages, 2743 KiB

Open AccessArticle

The Cytotoxicity of the Ajoene Analogue BisPMB in WHCO1 Oesophageal Cancer Cells Is Mediated by CHOP/GADD153

by Vuyolwethu Siyo¹, Georgia Schäfer^1,2, Roger Hunter³, Andriy Grafov⁴

, Iryna Grafova⁴, Martin Nieger⁴, Arieh A. Katz^1,2, M. Iqbal Parker^1,2,5 and Catherine H. Kaschula^6,*

¹ Department of Integrative Biomedical Sciences, University of Cape Town, Cape Town 7925, South Africa

² Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town 7925, South Africa

³ Department of Chemistry, University of Cape Town, Cape Town 7700, South Africa,

⁴ Department of Chemistry, University of Helsinki, 00014 Helsinki, Finland

⁵ International Centre for Genetic Engineering and Biotechnology, Cape Town 7925, South Africa

⁶ Department of Chemistry and Polymer Science, Stellenbosch University, 7600 Stellenbosch, South Africa

Molecules 2017, 22(6), 892; https://doi.org/10.3390/molecules22060892 - 28 May 2017

Cited by 27 | Viewed by 5777

Abstract

Garlic is a food and medicinal plant that has been used in folk medicine since ancient times for its beneficial health effects, which include protection against cancer. Crushed garlic cloves contain an array of small sulfur-rich compounds such as ajoene. Ajoene is able [...] Read more.

Garlic is a food and medicinal plant that has been used in folk medicine since ancient times for its beneficial health effects, which include protection against cancer. Crushed garlic cloves contain an array of small sulfur-rich compounds such as ajoene. Ajoene is able to interfere with biological processes and is cytotoxic to cancer cells in the low micromolar range. BisPMB is a synthetic ajoene analogue that has been shown in our laboratory to have superior cytotoxicity to ajoene. In the current study we have performed a DNA microarray analysis of bisPMB-treated WHCO1 oesophageal cancer cells to identify pathways and processes that are affected by bisPMB. The most significantly enriched biological pathways as assessed by gene ontology, KEGG and ingenuity pathway analysis were those involving protein processing in the endoplasmic reticulum (ER) and the unfolded protein response. In support of these pathways, bisPMB was found to inhibit global protein synthesis and lead to increased levels of ubiquitinated proteins. BisPMB also induced alternate splicing of the transcription factor XBP-1; increased the expression of the ER stress sensor GRP78 and induced expression of the ER stress marker CHOP/GADD153. CHOP expression was found to be central to the cytotoxicity of bisPMB as its silencing with siRNA rendered the cells resistant to bisPMB. The MAPK proteins, JNK and ERK1/2 were activated following bisPMB treatment. However JNK activation was not critical in the cytotoxicity of bisPMB, and ERK1/2 activation was found to play a pro-survival role. Overall the ajoene analogue bisPMB appears to induce cytotoxicity in WHCO1 cells by activating the unfolded protein response through CHOP/GADD153. Full article

(This article belongs to the Special Issue The Chemistry of Alliums)

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11 pages, 2372 KiB

Open AccessCommunication

Synthesis and Free Radical Scavenging Activity of New Hydroxybenzylidene Hydrazines

by Frantisek Sersen^1,*,†, Fridrich Gregan^2,†, Peter Kotora³, Jarmila Kmetova², Juraj Filo¹, Dusan Loos⁴ and Juraj Gregan^5,6,*

¹ Institute of Chemistry, Faculty of Natural Sciences, Comenius University in Bratislava, Ilkovicova 6, 842 15 Bratislava, Slovakia

² Department of Chemistry, Faculty of Natural Sciences, Matej Bell University, Tajovskeho 40, 974 01 Banska Bystrica, Slovakia

³ Institute of Process Engineering, Faculty of Mechanical Engineering, Slovak University of Technology in Bratislava, Namestie slobody 17, 812 31 Bratislava, Slovakia

⁴ Department of Organic Chemistry, Faculty of Natural Sciences, Comenius University in Bratislava, Ilkovicova 6, 842 15 Bratislava, Slovakia

⁵ Department of Genetics, Faculty of Natural Sciences, Comenius University in Bratislava, Ilkovicova 6, 842 15 Bratislava, Slovakia

⁶ Department of Chromosome Biology, Max F. Perutz Laboratories, University of Vienna, Dr. Bohr-Gasse 9, 1030 Vienna, Austria

^† These authors contributed equally to this work.

Molecules 2017, 22(6), 894; https://doi.org/10.3390/molecules22060894 - 29 May 2017

Cited by 6 | Viewed by 4085

Abstract

Hydroxybenzylidene hydrazines exhibit a wide spectrum of biological activities. Here, we report synthesis and free radical scavenging activity of nine new N-(hydroxybenzylidene)-N′-[2,6-dinitro-4-(trifluoromethyl)]phenylhydrazines. The chemical structures of these compounds were confirmed by 1H-NMR, 13C-NMR, 19F-NMR, IR spectroscopy, LC-MS, and elemental analysis. The prepared compounds [...] Read more.

Hydroxybenzylidene hydrazines exhibit a wide spectrum of biological activities. Here, we report synthesis and free radical scavenging activity of nine new N-(hydroxybenzylidene)-N′-[2,6-dinitro-4-(trifluoromethyl)]phenylhydrazines. The chemical structures of these compounds were confirmed by 1H-NMR, 13C-NMR, 19F-NMR, IR spectroscopy, LC-MS, and elemental analysis. The prepared compounds were tested for their activity to scavenge 2,2-diphenyl-1-picrylhydrazyl (DPPH), galvinoxyl radical (GOR), and 2,2′-azino-bis(3-ethylbenzothiazoline)-6-sulphonic acid (ABTS) radicals. The free radical scavenging activity expressed as SC50 values of these compounds varied in a wide range, from a strong to no radical scavenging effect. The most effective radical scavengers were hydroxybenzylidene hydrazines containing three hydroxyl groups in the benzylidene part of their molecules. The prepared compounds were also tested for their activity to inhibit photosynthetic electron transport in spinach chloroplasts. IC50 values of these compounds varied in wide range, from an intermediate to no inhibitory effect.
Full article

(This article belongs to the Section Medicinal Chemistry)

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13 pages, 6990 KiB

Open AccessArticle

Genealogy of Conjugated Acyclic Polyenes

by Haruo Hosoya

Department of Information Sciences, Faculty of Science, Ochanomizu University (Emeritus) Otsuka 2-1-1, Bunkyo-ku, Tokyo 112-8610, Japan

Molecules 2017, 22(6), 896; https://doi.org/10.3390/molecules22060896 - 29 May 2017

Cited by 4 | Viewed by 5423

Abstract

Based on the total π-electron energies E_πs of Hückel Molecular Orbital (HMO) method for all the possible isomers of conjugated acyclic polyenes (C₂_nH₂_n₊₂) up to n = 7, the structure–stability relation of the possible [...] Read more.

Based on the total π-electron energies E_πs of Hückel Molecular Orbital (HMO) method for all the possible isomers of conjugated acyclic polyenes (C₂_nH₂_n₊₂) up to n = 7, the structure–stability relation of the possible isomers was analyzed. It was shown that the mean length of conjugation L can roughly predict the ordering of stability among isomers, while the Z-index, or Hosoya-index, can almost perfectly reproduce their stability. Further, the genealogy of the conjugated acyclic polyene family was obtained by drawing systematic diagrams connecting these isomers of different n, and governed by several simple rules. Namely, the stability change of a given isomer in the genealogy connecting n and n + 1 polyenes can be classified into three different modes of vinyl addition (elongation, inner and outer branching) and horn growing, i.e., substitution of –HC=CH– moiety with –HC(=CH₂)–C(=CH₂)H–. By using the Z-index, we can extend this type of discussion to polyene radicals and even to “cross-conjugated” cyclic polyenes containing only one odd-membered cycle, such as radialene and fulvene. Full article

(This article belongs to the Special Issue Cutting-Edge Organic Chemistry in Japan)

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14 pages, 1654 KiB

Open AccessArticle

Synthesis of Gallic Acid Analogs as Histamine and Pro-Inflammatory Cytokine Inhibitors for Treatment of Mast Cell-Mediated Allergic Inflammation

by Xiang Fei¹, In-Gyu Je², Tae-Yong Shin³, Sang-Hyun Kim^2,* and Seung-Yong Seo^1,*

¹ College of Pharmacy and Gachon Institute of Pharmaceutical Sciences, Gachon University, Incheon 21936, Korea

² Department of Pharmacology, School of Medicine, Kyungpook National University, Daegu 41944, Korea

³ College of Pharmacy, Woosuk University, Jeonbuk 565-701, Korea

Molecules 2017, 22(6), 898; https://doi.org/10.3390/molecules22060898 - 29 May 2017

Cited by 16 | Viewed by 9001

Abstract

Gallic acid (3,4,5-trihydroxybenzoic acid), is a natural product found in various foods and herbs that are well known as powerful antioxidants. Our previous report demonstrated that it inhibits mast cell-derived inflammatory allergic reactions by blocking histamine release and pro-inflammatory cytokine expression. In this [...] Read more.

Gallic acid (3,4,5-trihydroxybenzoic acid), is a natural product found in various foods and herbs that are well known as powerful antioxidants. Our previous report demonstrated that it inhibits mast cell-derived inflammatory allergic reactions by blocking histamine release and pro-inflammatory cytokine expression. In this report, various amide analogs of gallic acid have been synthesized by introducing different amines through carbodiimide-mediated amide coupling and Pd/C-catalyzed hydrogenation. These compounds showed a modest to high inhibitory effect on histamine release and pro-inflammatory cytokine expression. Among them, the amide bearing (S)-phenylglycine methyl ester 3d was found to be more active than natural gallic acid. Further optimization yielded several (S)- and (R)-phenylglycine analogs that inhibited histamine release in vitro. Our findings suggest that some gallamides could be used as a treatment for allergic inflammatory diseases. Full article

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

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18 pages, 638 KiB

Open AccessArticle

Influence of Freeze Concentration Technique on Aromatic and Phenolic Compounds, Color Attributes, and Sensory Properties of Cabernet Sauvignon Wine

by Yan-Yan Wu¹, Kai Xing², Xiao-Xu Zhang¹, Hui Wang², Yong Wang², Fang Wang² and Jing-Ming Li^1,*

¹ Center for Viticulture and Enology, College of Food Science and Nutritional Engineering, China Agricultural University, P.O. Box 301, Beijing 100083, China

² Sino-French Joint Venture Dynasty Winery Ltd., Tianjin 300402, China

Molecules 2017, 22(6), 899; https://doi.org/10.3390/molecules22060899 - 2 Jun 2017

Cited by 23 | Viewed by 6311

Abstract

Red wines produced in the Xinjiang region of China possess poor color density, and lack fruity notes and elegance. The freeze concentration technique, as a well-established concentration method for liquid food systems, was applied to the Cabernet Sauvignon (Vitis vinifera L.) wine-making [...] Read more.

Red wines produced in the Xinjiang region of China possess poor color density, and lack fruity notes and elegance. The freeze concentration technique, as a well-established concentration method for liquid food systems, was applied to the Cabernet Sauvignon (Vitis vinifera L.) wine-making process, aiming to investigate its effect on wine quality improvement. Results showed that the freeze concentration treatment did not significantly alter the physicochemical properties of the wine, except for an increase of glycerol and alcoholic content. This technique increased ester contents, as well as decreasing the amount of volatile acids. Higher alcohol contents were also increased, but within an acceptable content range. All taken into consideration, the freeze concentration treated wine showed better fragrance characters according to sensory evaluation. The non-anthocyanin composition was altered by this application, however, the difference disappeared after the aging process. Fortunately, sensory evaluation showed that the treated wine possessed better mouthfeel properties. Anthocyanin contents were enhanced, and effectively stabilized the fresh wine color attributes, resulting in an improvement in appearance of the treated wine. All results considered, it can be concluded that freeze concentration treatment could be a good choice to improve wine quality. Full article

(This article belongs to the Collection Wine Chemistry)

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11 pages, 3799 KiB

Open AccessArticle

Antinociceptive Effect of the Essential Oil from Croton conduplicatus Kunth (Euphorbiaceae)

by Raimundo Gonçalves De Oliveira Júnior¹

, Christiane Adrielly Alves Ferraz¹, Juliane Cabral Silva¹, Ana Paula De Oliveira¹, Tâmara Coimbra Diniz¹, Mariana Gama E Silva¹, Lucindo José Quintans Júnior²

, Ana Valéria Vieira De Souza³, Uiliane Soares Dos Santos³, Izabel Cristina Casanova Turatti⁴, Norberto Peporine Lopes⁴, Vitor Prates Lorenzo⁵ and Jackson Roberto Guedes da Silva Almeida^1,*

¹ Center for Studies and Research of Medicinal Plants, Federal University of San Francisco Valley, 56306-385 Petrolina-PE, Brazil

² Departament of Physiology, Federal University of Sergipe, 49100-000 Aracaju-SE, Brazil

³ Embrapa-Semiárido, 56302-970 Petrolina-PE, Brazil

⁴ Faculty of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, 14040-903 Ribeirão Preto-SP, Brazil

⁵ Federal Institute of Education, Science and Technology Sertão Pernambucano, 56300-000 Petrolina-PE, Brazil

Molecules 2017, 22(6), 900; https://doi.org/10.3390/molecules22060900 - 30 May 2017

Cited by 22 | Viewed by 5836

Abstract

Medicinal plants have been widely used in the treatment of chronic pain. In this study, we describe the antinociceptive effect of the essential oil from Croton conduplicatus (the EO 25, 50, and 100 mg/kg, i.p.), a medicinal plant native to Brazil. Antinociceptive activity [...] Read more.

Medicinal plants have been widely used in the treatment of chronic pain. In this study, we describe the antinociceptive effect of the essential oil from Croton conduplicatus (the EO 25, 50, and 100 mg/kg, i.p.), a medicinal plant native to Brazil. Antinociceptive activity was investigated by measuring the nociception induced by acetic acid, formalin, hot plate and carrageenan. A docking study was performed with the major constituents of the EO (E-caryophyllene, caryophyllene oxide, and camphor). The EO reduced nociceptive behavior at all doses tested in the acetic acid-induced nociception test (p < 0.05). The same was observed in both phases (neurogenic and inflammatory) of the formalin test. When the hot-plate test was conducted, the EO (50 mg/kg) extended the latency time after 60 min of treatment. The EO also reduced leukocyte migration at all doses, suggesting that its antinociceptive effect involves both central and peripheral mechanisms. Pretreatment with glibenclamide and atropine reversed the antinociceptive effect of the EO on the formalin test, suggesting the involvement of K_ATP channels and muscarinic receptors. The docking study revealed a satisfactory interaction profile between the major components of the EO and the different muscarinic receptor subtypes (M2, M3, and M4). These results corroborate the medicinal use of C. conduplicatus in folk medicine. Full article

(This article belongs to the Special Issue Essential Oils: Chemistry and Bioactivity)

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9 pages, 1036 KiB

Open AccessArticle

Expression of Genes Related to Phenylpropanoid Biosynthesis in Different Organs of Ixeris dentata var. albiflora

by Sang-Hoon Lee^1,2, Yun-Ji Park³, Sang Un Park³

, Sang-Won Lee¹, Seong-Cheol Kim¹, Chan-Sik Jung¹, Jae-Ki Jang¹, Yoonkang Hur²

and Yeon Bok Kim^1,*

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

² Department of Biology, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon 34134, Korea

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

Molecules 2017, 22(6), 901; https://doi.org/10.3390/molecules22060901 - 30 May 2017

Cited by 12 | Viewed by 5429

Abstract

Members of the genus Ixeris have long been used in traditional medicines as stomachics, sedatives, and diuretics. Phenylalanine ammonia-lyase (PAL), cinnamate-4-hydroxylase (C4H), 4-coumarate: coenzyme-A (CoA) ligase (4CL), chalcone synthase (CHS), and dihydroflavonol 4-reductase (DFR) are important enzymes in the phenylpropanoid pathway. In this [...] Read more.

Members of the genus Ixeris have long been used in traditional medicines as stomachics, sedatives, and diuretics. Phenylalanine ammonia-lyase (PAL), cinnamate-4-hydroxylase (C4H), 4-coumarate: coenzyme-A (CoA) ligase (4CL), chalcone synthase (CHS), and dihydroflavonol 4-reductase (DFR) are important enzymes in the phenylpropanoid pathway. In this study, we analyzed seven genes from Ixeris dentata var. albiflora that are involved in phenylpropanoid biosynthesis, using an Illumina/Solexa HiSeq 2000 platform. The amino acid sequence alignments for IdPALs, IdC4H, Id4CLs, IdCHS, and IdDFR showed high identity to sequences from other plants. We also investigated transcript levels using quantitative real-time PCR, and analyzed the accumulation of phenylpropanoids in different organs of I. dentata var. albiflora using high-performance liquid chromatography. The transcript levels of IdC4H, Id4CL1, IdCHS, and IdDFR were highest in the leaf. The catechin, chlorogenic acid, ferulic acid, and quercetin contents were also highest in the leaf. We suggest that expression of IdC4H, Id4CL1, IdCHS, and IdDFR is associated with the accumulation of phenylpropanoids. Our results may provide baseline information for elucidating the mechanism of phenylpropanoid biosynthesis in different organs of I. dentata var. albiflora. Full article

(This article belongs to the Section Natural Products Chemistry)

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14 pages, 2212 KiB

Open AccessArticle

Characterization of Metabolite Profile in Phyllanthus niruri and Correlation with Bioactivity Elucidated by Nuclear Magnetic Resonance Based Metabolomics

by Ahmed Mediani¹

, Faridah Abas^1,2,*, M. Maulidiani², Alfi Khatib^2,3, Chin Ping Tan⁴, Intan Safinar Ismail^2,5

, Khozirah Shaari^2,5 and Amin Ismail⁵

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

² Department of Pharmaceutical Chemistry, Faculty of Pharmacy, International Islamic University Malaysia, 25200 Kuantan, Pahang, Malaysia

³ Department of Food Technology, Faculty of Food Science and Technology, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia

⁴ Department of Chemistry, Faculty of Science, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia

⁵ Department of Nutrition and Dietetics, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia

Molecules 2017, 22(6), 902; https://doi.org/10.3390/molecules22060902 - 30 May 2017

Cited by 29 | Viewed by 7710

Abstract

Phyllanthus niruri is an important medicinal plant. To standardize the extract and guarantee its maximum benefit, processing methods optimization ought to be amenable and beneficial. Herein, three dried P. niruri samples, air (AD), freeze (FD) and oven (OD), extracted with various ethanol to [...] Read more.

Phyllanthus niruri is an important medicinal plant. To standardize the extract and guarantee its maximum benefit, processing methods optimization ought to be amenable and beneficial. Herein, three dried P. niruri samples, air (AD), freeze (FD) and oven (OD), extracted with various ethanol to water ratios (0%, 50%, 70%, 80% and 100%) were evaluated for their metabolite changes using proton nuclear magnetic resonance (¹H-NMR)-based metabolomics approach. The amino acids analysis showed that FD P. niruri exhibited higher content of most amino acids compared to the other dried samples. Based on principal component analysis (PCA), the FD P. niruri extracted with 80% ethanol contained higher amounts of hypophyllanthin and phenolic compounds based on the loading plot. The partial least-square (PLS) results showed that the phytochemicals, including hypophyllanthin, catechin, epicatechin, rutin, quercetin and chlorogenic, caffeic, malic and gallic acids were correlated with antioxidant and α-glucosidase inhibitory activities, which were higher in the FD material extracted with 80% ethanol. This report optimized the effect of drying and ethanol ratios and these findings demonstrate that NMR-based metabolomics was an applicable approach. The FD P. niruri extracted with 80% ethanol can be used as afunctional food ingredient for nutraceutical or in medicinal preparation. Full article

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14 pages, 3024 KiB

Open AccessArticle

Combined Treatment with Hyaluronic Acid and Mesalamine Protects Rats from Inflammatory Bowel Disease Induced by Intracolonic Administration of Trinitrobenzenesulfonic Acid

by Chih-Tung Chiu¹, Sheng-Nan Kuo¹, Shao-Wen Hung² and Cheng-Yao Yang^2,*

¹ Holy Stone Healthcare Co., Ltd., Taipei 11493, Taiwan

² Division of Animal Resource, Animal Technology Laboratories, Agricultural Technology Research Institute, Hsinchu City 30093, Taiwan

Molecules 2017, 22(6), 904; https://doi.org/10.3390/molecules22060904 - 30 May 2017

Cited by 22 | Viewed by 8324

Abstract

Drugs such as mesalamine (5-ASA) are currently recommended for the treatment of inflammatory bowel disease (IBD). To reduce the frequency of their administration and improve their therapeutic effect, this study investigated the adhesion efficacy, wound healing promotion, and decrease in inflammation in ulcers [...] Read more.

Drugs such as mesalamine (5-ASA) are currently recommended for the treatment of inflammatory bowel disease (IBD). To reduce the frequency of their administration and improve their therapeutic effect, this study investigated the adhesion efficacy, wound healing promotion, and decrease in inflammation in ulcers in the colonic tissue of rats with colitis after combined treatment with hyaluronic acid (HA) and 5-ASA (IBD98-M). HA-fluoresceinamine (FL) conjugates successfully adhered to the mucosal layer and were conjugated in the vascular tissue. In addition, macroscopic and microscopic observations indicated that colonic injuries reduced significantly after treatment with IBD98-M. Compared with PBS and 5-ASA treatment alone, treatment with IBD98-M more effectively reduced bowel inflammation and promoted colonic mucosal healing in TNBS-induced colitis. IBD98-M treatment also reduced myeloperoxidase activity and the expression levels of cyclooxygenase 2 and tumor necrosis factor-αin the colitis tissue. In conclusion, IBD98-M treatment strongly promoted wound healing in colonic injuries and significantly inhibited MPO activity in the inflamed colon tissue of rats. Combined treatment with HA and 5-ASA can accelerate wound healing and reduce inflammatory reaction in rat colitis. Full article

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

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16 pages, 3812 KiB

Open AccessArticle

Effect of Montmorillonite Nanogel Composite Fillers on the Protection Performance of Epoxy Coatings on Steel Pipelines

by Ayman M. Atta^1,2,*, Ashraf M. El-Saeed², Hamad A. Al-Lohedan¹

and Mohamed Wahby³

¹ Chemistry Department, College of Science, King Saud University, Riyadh 11451, Saudi Arabia

² Petroleum Application Department, Egyptian Petroleum Research Institute, Nasr City, Cairo 11727, Egypt

³ Arki for advanced construction chemicals Co. Ltd., Riyadh 11451, Saudi Arabia

Molecules 2017, 22(6), 905; https://doi.org/10.3390/molecules22060905 - 2 Jun 2017

Cited by 24 | Viewed by 5035

Abstract

Montmorillonite (MMT) clay mineral is widely used as filler for several organic coatings. Its activity is increased by exfoliation via chemical modification to produce nanomaterials. In the present work, the modification of MMT to form nanogel composites is proposed to increase the dispersion [...] Read more.

Montmorillonite (MMT) clay mineral is widely used as filler for several organic coatings. Its activity is increased by exfoliation via chemical modification to produce nanomaterials. In the present work, the modification of MMT to form nanogel composites is proposed to increase the dispersion of MMT into epoxy matrices used to fill cracks and holes produced by the curing exotherms of epoxy resins. The dispersion of MMT in epoxy improved both the mechanical and anti-corrosion performance of epoxy coatings in aggressive marine environments. In this respect, the MMT surfaces were chemically modified with different types of 2-acrylamido-2-methyl propane sulfonic acid (AMPS) nanogels using a surfactant-free dispersion polymerization technique. The effect of the chemical structure, nanogel content and the interaction with MMT surfaces on the surface morphology, surface charges and dispersion in the epoxy matrix were investigated for use as nano-filler for epoxy coatings. The modified MMT nanogel epoxy composites showed excellent resistance to mechanical damage and salt spray resistance up to 1000 h. The interaction of MMT nanogel composites with the epoxy matrix and good response of AMPS nanogel to sea water improve their ability to act as self-healing materials for epoxy coatings for steel. Full article

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15 pages, 1189 KiB

Open AccessArticle

Alternative Access to Functionalized 2,8-Ethanonoradamantane Derivatives

by Pelayo Camps^1,*

, Tània Gómez¹, Ane Otermin¹ and Mercè Font-Bardia^2,3

¹ Laboratori de Química Farmacèutica (Unitat Associada al CSIC), Facultat de Farmàcia i Ciències de la Alimentació and Institut de Biomedicina (IBUB), Universitat de Barcelona, Av. Joan XXIII 27-31, Barcelona 08028, Spain

² Departament de Mineralogia, Petrologia i Geologia Aplicada, Universitat de Barcelona, Martí Franquès s/n, Barcelona 08028, Spain

³ Unitat de Difracció de RX, Centres Científics i Tecnològics de la Universitat de Barcelona (CCiTUB), Solé i Sabarís 1-3, Barcelona 08028, Spain

Molecules 2017, 22(6), 906; https://doi.org/10.3390/molecules22060906 - 31 May 2017

Cited by 1 | Viewed by 4082

Abstract

7a-(Methoxycarbonyl)-N-methyl-1,3a,5,6,7,7a-hexahydro-4H-1,4,6-(epiethane[1,1,2]triyl)indene-4,9-dicarboximide has been prepared through a modification of a previous synthetic sequence, in which the benzyloxymethyl hydroxyl protecting group has been replaced by methoxymethyl, to avoid the apparent formation of a benzyl ester derivative as a side product. The [...] Read more.

7a-(Methoxycarbonyl)-N-methyl-1,3a,5,6,7,7a-hexahydro-4H-1,4,6-(epiethane[1,1,2]triyl)indene-4,9-dicarboximide has been prepared through a modification of a previous synthetic sequence, in which the benzyloxymethyl hydroxyl protecting group has been replaced by methoxymethyl, to avoid the apparent formation of a benzyl ester derivative as a side product. The overall yield of the new synthetic sequence is comparable to the previous one. Two advantages of the new procedure are: (a) no benzyl ester was formed and (b) a stereoisomeric mixture of syn- and anti-alcohols at the beginning of the synthetic sequence could be separated and the rest of the synthesis could be carried out with the main syn-stereoisomer instead of the corresponding stereoisomeric mixture as it was the case in the previous process. Additionally, several functional 2,8-ethanonoradamantane derivatives have been prepared. Full article

(This article belongs to the Section Organic Chemistry)

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10 pages, 2248 KiB

Open AccessArticle

Five New Limonoids from Peels of Satsuma Orange (Citrus reticulata)

by Takashi Kikuchi, Yasuaki Ueno, Yoshino Hamada, Chika Furukawa, Takako Fujimoto, Takeshi Yamada

and Reiko Tanaka^*

Faculty of Pharmaceutical Sciences, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1142, Japan

Molecules 2017, 22(6), 907; https://doi.org/10.3390/molecules22060907 - 31 May 2017

Cited by 13 | Viewed by 4811

Abstract

Five new: 21,23-dihydro-21-hydroxy-23-oxonomilin (1), 21,23-dihydro-23-methoxy-21-oxonomilin (2), 21,23-dihydro-21-hydroxy-23-oxonomilinic acid methyl ester (3), 21,23-dihydro-23-methoxy-21-oxolimonin (4), and 21,23-dihydro-21-oxolimonin (5), and seven known limonoids were isolated from peels of satsuma orange (Citrus reticulata). The isolated [...] Read more.

Five new: 21,23-dihydro-21-hydroxy-23-oxonomilin (1), 21,23-dihydro-23-methoxy-21-oxonomilin (2), 21,23-dihydro-21-hydroxy-23-oxonomilinic acid methyl ester (3), 21,23-dihydro-23-methoxy-21-oxolimonin (4), and 21,23-dihydro-21-oxolimonin (5), and seven known limonoids were isolated from peels of satsuma orange (Citrus reticulata). The isolated compounds were evaluated for their inhibitory effects on macrophage activation by an inhibitory assay of nitric oxide (NO) production. Among them, compound (2) exhibited NO inhibitory activity without cytotoxicity. Full article

(This article belongs to the Section Natural Products Chemistry)

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15 pages, 3545 KiB

Open AccessArticle

Synthesis, Characterization and Protonation Behavior of Quinoxaline-Fused Porphycenes

by Daiki Kuzuhara^*,†

, Mika Sakaguchi, Wataru Furukawa, Takuya Okabe, Naoki Aratani and Hiroko Yamada^*

¹ Graduate School of Materials Science, Nara Institute of Science and Technology, 8916-5 Takayama-cho, Ikoma 630-0192, Japan

^† Current address: Faculty of Science and Engineering, Iwate University, 4-3-5 Ueda, Morioka 020-8551, Japan.

Molecules 2017, 22(6), 908; https://doi.org/10.3390/molecules22060908 - 31 May 2017

Cited by 17 | Viewed by 6244

Abstract

9,10-Quinoxaline-fused porphycenes 1a-H₂ and 1b-H₂ were synthesized by intramolecular McMurry coupling. As a result of the annulation of the quinoxaline moiety on the porphycene skeleton, 1a-H₂ and 1b-H₂ display absorption and fluorescence in the near infra-red (NIR) region. Additionally, [...] Read more.

9,10-Quinoxaline-fused porphycenes 1a-H₂ and 1b-H₂ were synthesized by intramolecular McMurry coupling. As a result of the annulation of the quinoxaline moiety on the porphycene skeleton, 1a-H₂ and 1b-H₂ display absorption and fluorescence in the near infra-red (NIR) region. Additionally, the quinoxaline moieties of 1a-H₂ and 1b-H₂ act as electron-withdrawing groups, introducing lower reduction potentials than for pristine porphycene. The protonation occurred at the nitrogen atoms in the cavity of freebase porphycenes and at the quinoxaline moieties for their nickel complexes to give diprotonic species. Full article

(This article belongs to the Special Issue Porphyrins and Phthalocyanines: Synthesis, Properties and Applications)

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10 pages, 2150 KiB

Open AccessArticle

Genotypic Variation in Wheat Flour Lysophospholipids

by Lei Liu^1,*, Qi Guo^1,2, Zhonghu He^2,3,*, Xianchun Xia², Daniel L. E. Waters¹, Carolyn A. Raymond¹ and Graham J. King¹

¹ Southern Cross Plant Science, Southern Cross University, Lismore, NSW 2480, Australia

² Institute of Crop Science, Chinese Academy of Agricultural Sciences, Beijing 100081, China

³ CIMMYT China Office, Chinese Academy of Agricultural Sciences, Beijing 100081, China

Molecules 2017, 22(6), 909; https://doi.org/10.3390/molecules22060909 - 31 May 2017

Cited by 6 | Viewed by 4886

Abstract

Lysophospholipids (LPLs) are the most abundant polar lipids in wheat endosperm and naturally complex with amylose, affecting starch physicochemical properties. We analyzed LPLs in wheat flour from 58 cultivars which differ by grain hardness using liquid chromatography mass spectrometry (LCMS). There were significant [...] Read more.

Lysophospholipids (LPLs) are the most abundant polar lipids in wheat endosperm and naturally complex with amylose, affecting starch physicochemical properties. We analyzed LPLs in wheat flour from 58 cultivars which differ by grain hardness using liquid chromatography mass spectrometry (LCMS). There were significant differences in LPL content between cultivars, demonstrating that genotype rather than environment contributes most to the total variance in wheat endosperm LPLs. Polar lipids such as LPLs may play a role in grain hardness through their interaction with puroindoline proteins, however, no strong correlation between kernel hardness and LPLs was detected. This may reflect the location of LPLs within the starch granule as opposed to the puroindoline proteins outside starch granules. LPLs may have an indirect relationship with kernel hardness as they could share the same origin as polar lipids that interact with puroindoline on the starch granule surface. Full article

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16 pages, 1924 KiB

Open AccessArticle

Himatanthus drasticus Leaves: Chemical Characterization and Evaluation of Their Antimicrobial, Antibiofilm, Antiproliferative Activities

by Cristiane Santos Silva e Silva Figueiredo¹, Joice Castelo Branco Santos¹, José Artur de Aguiar Castro Junior¹, Vinícius Galvão Wakui², João F. S. Rodrigues¹, Mariana Oliveira Arruda^1,3, Andrea De Souza Monteiro¹, Valério Monteiro-Neto^1,3

, Maria Rosa Quaresma Bomfim¹, Lucília Kato², Luís Cláudio Nascimento da Silva^1,*,*,†

and Marcos Augusto Grigolin Grisotto^1,4,*,*,†

¹ Programa de Pós-graduação em Biologia Parasitária, Universidade Ceuma, São Luís 65075120, Brazil

² Laboratório de Produtos Naturais e Síntese, Instituto de Química, Universidade Federal de Goiás, Goiânia 74001-970, Brazil

³ Centro de Ciências Biológicas e da Saúde, Universidade Federal do Maranhão, São Luís 65065545, Brazil

⁴ Instituto Florence de Ensino Superior, São Luís 65020470, Brazil

^* Correspondence: luisclaudionsilva@yahoo.com.br; marcos.grisotto@gmail.com; Tel.: +55-98-984-087-71

^† These two authors contribute equally to this work.

Molecules 2017, 22(6), 910; https://doi.org/10.3390/molecules22060910 - 31 May 2017

Cited by 9 | Viewed by 6358

Abstract

Plant-derived products have played a fundamental role in the development of new therapeutic agents. This study aimed to analyze antimicrobial, antibiofilm, cytotoxicity and antiproliferative potentials of the extract and fractions from leaves of Himatanthus drasticus, a plant from the Apocynaceae family. After [...] Read more.

Plant-derived products have played a fundamental role in the development of new therapeutic agents. This study aimed to analyze antimicrobial, antibiofilm, cytotoxicity and antiproliferative potentials of the extract and fractions from leaves of Himatanthus drasticus, a plant from the Apocynaceae family. After harvesting, H. drasticus leaves were macerated and a hydroalcoholic extract (HDHE) and fractions were prepared. Antimicrobial tests, such as agar-diffusion, Minimum Inhibitory Concentration (MIC) and Minimal Bactericidal Concentration (MBC) were carried out against several bacterial species. Staphylococcus aureus, Pseudomonas aeruginosa, Listeria monocytogenes and Klebsiella pneumoniae were inhibited by at least one extract or fraction in the agar-diffusion assay (inhibition halos from 12 mm to 30 mm). However, the lowest MIC value was found for HDHE against K. pneumoniae. In addition, HDHE and its fractions were able to inhibit biofilm formation at sub-inhibitory concentrations (780 µg/mL and 1.56 µg/mL). As the best activities were found for HDHE, we selected it for further assays. HDHE was able to increase ciprofloxacin (CIP) activity against K. pneumoniae, displaying synergistic (initial concentration CIP + HDHE: 2 µg/mL + 600 µg/mL and 2.5 µg/mL + 500 µg/mL) and additive effects (CIP + HDHE: 3 µg/mL + 400 µg/mL). This action seems to be associated with the alteration in bacterial membrane permeability induced by HDHE (as seen by propidium iodide labeling). This extract was non-toxic for red blood cell or human peripheral blood mononuclear cells (PBMCs). Additionally, it inhibited the lipopolysaccharide-induced proliferation of PBMCs. The following compounds were detected in HDHE using HPLC-ESI-MS analysis: plumieride, plumericin or isoplumericin, rutin, quercetin and derivatives, and chlorogenic acid. Based on these results we suggest that compounds from H. drasticus have antimicrobial and antibiofilm activities against K. pneumoniae and display low cytotoxicity and anti-proliferative action in PBMC stimulated with lipopolysaccharide. Full article

(This article belongs to the Special Issue Frontiers in Antimicrobial Drug Discovery and Design)

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17 pages, 1299 KiB

Open AccessArticle

Rapid Screening and Identification of Diterpenoids in Tinospora sinensis Based on High-Performance Liquid Chromatography Coupled with Linear Ion Trap-Orbitrap Mass Spectrometry

by Lu-Lu Xu¹, Feng-Xia Guo¹, Sen-Sen Chi¹, Zi-Jian Wang², Yan-Yan Jiang¹, Bin Liu^1,*,* and Jia-Yu Zhang^2,*,*

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

² Beijing Research Institution of Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China

^* Correspondence: liubinyn67@163.com (B.L.)

Molecules 2017, 22(6), 912; https://doi.org/10.3390/molecules22060912 - 31 May 2017

Cited by 21 | Viewed by 8312

Abstract

Diterpenoids are considered the major active compounds in Tinospora sinensis in virtue of their special structures and activities. Herein, an analytical method was developed for rapid screening and identification of diterpenoids in T. sinensis using high-performmance liquid chromatography coupled with linear ion trap-Orbitrap [...] Read more.

Diterpenoids are considered the major active compounds in Tinospora sinensis in virtue of their special structures and activities. Herein, an analytical method was developed for rapid screening and identification of diterpenoids in T. sinensis using high-performmance liquid chromatography coupled with linear ion trap-Orbitrap mass spectrometry (HPLC-LTQ-Orbitrap) in negative ion mode. Two diterpenoid reference standards were first analyzed to obtain their characteristic ESI-MS/MS fragmentation patterns. Then, based on the extracted ion chromatogram (EIC) data-mining method and characteristic fragmentation pathways analysis, diterpenoids in T. sinensis were rapidly screened and identified. After that, an important parameter, Clog P, was adopted to discriminate between the isomers of diterpenoids. As a result, 63 diterpenoids were characterized from the extract of T. sinensis, including 10 diterpenoids and 53 diterpenoid glycosides. Among them, 15 compounds were tentatively identified as new compounds. Finally, target isolation of one diterpenoid glycoside named tinosineside A was performed based on the obtained results, which further confirmed the deduced fragmentation patterns and identified diterpenoid profile in T. sinensis. The results demonstrated that the established method could be a rapid, effective analytical tool for screening and characterization of diterpenoids in the complex systems of natural medicines. Full article

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19 pages, 6621 KiB

Open AccessArticle

Synthesis and Evaluation of Novel 2-Pyrrolidone-Fused (2-Oxoindolin-3-ylidene)methylpyrrole Derivatives as Potential Multi-Target Tyrosine Kinase Receptor Inhibitors

by Ting-Hsuan Yang¹, Chun-I Lee², Wen-Hsin Huang² and An-Rong Lee^1,2,*

¹ Graduate Institute of Medical Sciences, National Defense Medical Center, No. 161, Section 6, Mingchuan East Road, Taipei 11490, Taiwan

² School of Pharmacy, National Defense Medical Center, No. 161, Section 6, Mingchuan East Road, Taipei 11490, Taiwan

Molecules 2017, 22(6), 913; https://doi.org/10.3390/molecules22060913 - 31 May 2017

Cited by 26 | Viewed by 7830

Abstract

Signaling pathways of VEGFs and PDGFs are crucial in tumor angiogenesis, which is essential in solid tumor progression and metastasis. This study reports our strategy for designing and synthesizing a series of novel 2-pyrrolidone-fused (2-oxoindolin-3-ylidene)methylpyrrole derivatives as potential multi-target tyrosine kinase receptor inhibitors. [...] Read more.

Signaling pathways of VEGFs and PDGFs are crucial in tumor angiogenesis, which is essential in solid tumor progression and metastasis. This study reports our strategy for designing and synthesizing a series of novel 2-pyrrolidone-fused (2-oxoindolin-3-ylidene)methylpyrrole derivatives as potential multi-target tyrosine kinase receptor inhibitors. The target compounds were obtained by condensation of 5-substituted oxindoles with N-substituted 2-pyrrolidone aldehyde 7 in satisfactory yields. Of these, 11 and 12 had the highest potency and, compared to sunitinib, showed: (1) significant increase in anti-proliferation of various cancer cells with a favorable selective index (SI); (2) higher inhibitory potency against both VEGFR-2 and PDGFRβ. The molecular modeling results showed that, in terms of VEGFR-2 binding, the synthesized products had a similar binding mode to sunitinib but with tighter interaction. Full article

(This article belongs to the Special Issue Kinase Inhibitors)

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10 pages, 1515 KiB

Open AccessArticle

Some Physical Properties of Protein Moiety of Alkali-Extracted Tea Polysaccharide Conjugates Were Shielded by Its Polysaccharide

by Xiaoqiang Chen^1,*

, Wei Song², Jin Zhao³, Zhifa Zhang⁴ and Yuntian Zhang¹

¹ College of Bioengineering and Food, Hubei University of Technology, Wuhan 430068, China

² Department of Food Science and Engineering, MIITKey Laboratory of Critical Materials Technology for New Energy Conversion and Storage, School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin 150090, China

³ College of Life Science, China Jiliang University, Hangzhou 310018, China

⁴ Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China

Molecules 2017, 22(6), 914; https://doi.org/10.3390/molecules22060914 - 31 May 2017

Cited by 31 | Viewed by 5643

Abstract

Polysaccharide conjugates were alkali-extracted from green tea (TPC-A). Although it contained 11.80% covalently binding proteins, TPC-A could not bind to the Coomassie Brilliant Blue dyes G250 and R250. TPC-A had no expected characteristic absorption peak of protein in the UV-vis spectrum scanning in [...] Read more.

Polysaccharide conjugates were alkali-extracted from green tea (TPC-A). Although it contained 11.80% covalently binding proteins, TPC-A could not bind to the Coomassie Brilliant Blue dyes G250 and R250. TPC-A had no expected characteristic absorption peak of protein in the UV-vis spectrum scanning in the range of 200–700 nm. The UV-vis wavelength of 280 nm was not suitable to detect the presence of the protein portion of TPC-A. The zeta potential of TPC-A merely presented the negative charge properties of polysaccharides instead of the acid–base property of its protein section across the entire pH range. Furthermore, TPC-A was more stable when the pH of solution exceeded 4.0. In addition, no precipitation or haze was generated in the TPC-A/(−)-epigallocatechin gallate (EGCG) mixtures during 12 h storage. TPC-A has emulsifying activity, which indicated that its protein moiety formed hydrophobic groups. Thus, it was proposed that some physical properties of TPC-A protein were shielded by its olysaccharide, since the protein moiety was wrapped by its polysaccharide chains. Full article

(This article belongs to the Collection Bioactive Compounds)

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15 pages, 1655 KiB

Open AccessArticle

UHPLC-TQ-MS Coupled with Multivariate Statistical Analysis to Characterize Nucleosides, Nucleobases and Amino Acids in Angelicae Sinensis Radix Obtained by Different Drying Methods

by Shaoqing Zhu, Sheng Guo^*, Jin-ao Duan^*, Dawei Qian, Hui Yan, Xiuxiu Sha and Zhenhua Zhu

Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China

Molecules 2017, 22(6), 918; https://doi.org/10.3390/molecules22060918 - 1 Jun 2017

Cited by 28 | Viewed by 5513

Abstract

To explore the nutrients in roots of Angelica sinensis (Angelicae Sinensis Radix, ASR), a medicinal and edible plant, and evaluate its nutritional value, a rapid and reliable UHPLC-TQ-MS method was established and used to determine the potential nutritional compounds, including nucleosides, nucleobases and [...] Read more.

To explore the nutrients in roots of Angelica sinensis (Angelicae Sinensis Radix, ASR), a medicinal and edible plant, and evaluate its nutritional value, a rapid and reliable UHPLC-TQ-MS method was established and used to determine the potential nutritional compounds, including nucleosides, nucleobases and amino acids, in 50 batches of ASR samples obtained using two drying methods. The results showed that ASR is a healthy food rich in nucleosides, nucleobases and amino acids, especially arginine. The total average content of nucleosides and nucleobases in all ASR samples was 3.94 mg/g, while that of amino acids reached as high as 61.79 mg/g. Principle component analysis showed that chemical profile differences exist between the two groups of ASR samples prepared using different drying methods, and the contents of nutritional compounds in samples dried with the tempering-intermittent drying processing method (TIDM) were generally higher than those dried using the traditional solar processing method. The above results suggest that ASR should be considered an ideal healthy food and TIDM could be a suitable drying method for ASR when taking nucleosides, nucleobases and amino acids as the major consideration for their known human health benefits. Full article

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13 pages, 3267 KiB

Open AccessFeature PaperArticle

Stable ABTS Immobilized in the MIL-100(Fe) Metal-Organic Framework as an Efficient Mediator for Laccase-Catalyzed Decolorization

by Youxun Liu^1,2,†, Yuanyuan Geng^1,†, Mingyang Yan¹ and Juan Huang^1,*

¹ School of Basic Medical Sciences, Xinxiang Medical University, Jinsui Avenue 601, Xinxiang 453003, Henan, China

² Henan Collaborative Innovation Center of Molecular Diagnostics and Laboratory Medicine, Jinsui Avenue 601, Xinxiang 453003, Henan, China

^† These authors contributed equally to this work.

Molecules 2017, 22(6), 920; https://doi.org/10.3390/molecules22060920 - 2 Jun 2017

Cited by 31 | Viewed by 6347

Abstract

The successful encapsulation of 2,2′-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS), a well-known laccase mediator, within a mesoporous metal-organic framework sample (i.e., MIL-100(Fe)) was achieved using a one-pot hydrothermal synthetic method. The as-prepared ABTS@MIL-100(Fe) was characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier transform infrared [...] Read more.

The successful encapsulation of 2,2′-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS), a well-known laccase mediator, within a mesoporous metal-organic framework sample (i.e., MIL-100(Fe)) was achieved using a one-pot hydrothermal synthetic method. The as-prepared ABTS@MIL-100(Fe) was characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier transform infrared (FT-IR) spectroscopy, nitrogen sorption, and cyclic voltammetry (CV). Our ABTS@MIL-100(Fe)-based electrode exhibited an excellent electrochemical response, indicating that MIL-100(Fe) provides an appropriate microenvironment for the immobilization and electroactivity of ABTS molecules. ABTS@MIL-100(Fe) was then evaluated as an immobilized laccase mediator for dye removal using indigo carmine (IC) as a model dye. Through the application of laccase in combination with a free (ABTS) or immobilized (ABTS@MIL-100(Fe)) mediator, decolorization yields of 95% and 94%, respectively, were obtained for IC after 50 min. In addition, following seven reuse cycles of ABTS@MIL-100(Fe) for dye treatment, a decolorization yield of 74% was obtained. Dye decolorization occurred through the breakdown of the chromophoric group by the Laccase/ABTS@MIL-100(Fe) system, and a catalytic mechanism was proposed. We therefore expect that the stability, reusability, and validity of ABTS@MIL-100(Fe) as a laccase mediator potentially render it a promising tool for dye removal, in addition to reducing the high running costs and potential toxicity associated with synthetic mediators. Full article

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12 pages, 603 KiB

Open AccessArticle

New Pinane Derivatives Found in Essential Oils of Calocedrus decurrens

by Gabriel Garcia¹, Loïc Tissandié², Jean-Jacques Filippi² and Félix Tomi^1,*

¹ Université de Corse-CNRS, UMR 6134 SPE, Équipe Chimie et Biomasse, Route des Sanguinaires, Site de Vignola, 20000 Ajaccio, France

² Institut de Chimie de Nice, Université de Nice-Sophia Antipolis, UMR 7272 CNRS, Parc Valrose, 06108 Nice CEDEX 2, France

Molecules 2017, 22(6), 921; https://doi.org/10.3390/molecules22060921 - 2 Jun 2017

Cited by 6 | Viewed by 5068

Abstract

The main objective of this study was to determine the chemical composition of essential oils (EOs) obtained from leaf, old branches, and young branches of a coniferous species Calocedrus decurrens acclimated to Corsica. The analytical investigation was conducted by GC(RI), GC-MS, pc-GC, and [...] Read more.

The main objective of this study was to determine the chemical composition of essential oils (EOs) obtained from leaf, old branches, and young branches of a coniferous species Calocedrus decurrens acclimated to Corsica. The analytical investigation was conducted by GC(RI), GC-MS, pc-GC, and NMR. C. decurrens leaf, old branches, and young branches EOs contained α-pinene (11.2; 56.6; 22.3%), myrcene (13.4; 8.4; 9.7%), Δ-3-carene (31.3; 5.2; 11.1%), limonene (6.4; 5.1; 5.5%), terpinolene (6.9; 1.5; 3.2%), and pin-2-en-8-ol (4.2; 4.5; 10.4%) as major components, respectively. Special attention was paid to purifying and identifying four unusual pinane derivatives: pin-2-en-8-ol, pin-2-en-8-yl Acetate, pin-2-en-8-al, and methyl pin-2-en-8-oate. The last two are reported for the first time. Full article

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

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10 pages, 981 KiB

Open AccessArticle

Characterization of Aliphatic Polyesters Synthesized via Enzymatic Ring-Opening Polymerization in Ionic Liquids

by Urszula Piotrowska^1,2,*

, Marcin Sobczak^1,2 and Ewa Oledzka¹

¹ Department of Biomaterials Chemistry, Chair of Inorganic and Analytical Chemistry, Faculty of Pharmacy with the Laboratory Medicine Division, Medical University of Warsaw, 1 Banacha Street, Warsaw 02-097, Poland

² Department of Organic Chemistry and Biochemistry, Faculty of Materials Science and Design, Kazimierz Pulaski University of Technology and Humanities in Radom, 27 Chrobrego Street, Radom 26-600, Poland

Molecules 2017, 22(6), 923; https://doi.org/10.3390/molecules22060923 - 2 Jun 2017

Cited by 8 | Viewed by 4252

Abstract

To evaluate the effects of ionic liquids (ILs) on the microstructural features of aliphatic polyesters for biomedical applications, a series of copolymers were synthesized by lipase ring opening polymerization of rac-lactide (rac-LA) and ε-caprolactone (CL). The chemical structures of resulting [...] Read more.

To evaluate the effects of ionic liquids (ILs) on the microstructural features of aliphatic polyesters for biomedical applications, a series of copolymers were synthesized by lipase ring opening polymerization of rac-lactide (rac-LA) and ε-caprolactone (CL). The chemical structures of resulting polymers were characterized by ¹H- and ¹³C-NMR and the average molecular weight (M_n) and dispersity index were characterized by gel permeation chromatography. The structure of the copolymers confirms the presence of linear polymer chains with end-functional hydroxyl groups allowing covalent coupling of the therapeutic agents. Chain microstructure of copolymers indicates the presence of both random and block copolymers depending on the synthesis conditions. Moreover, it was found that CL is the most active co-monomer during copolymerization which enhances the polymerizability of rac-LA and allows to obtain higher M_n of the copolymers. The results demonstrate that ILs could be promising solvents in synthesis of aliphatic esters for biomedical applications. Full article

(This article belongs to the Section Organic Chemistry)

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13 pages, 1366 KiB

Open AccessArticle

Phytochemical Quantification and the In Vitro Acetylcholinesterase Inhibitory Activity of Phellodendron chinense and Its Components

by Yu Jin Kim^1,2,†, Hye-Sun Lim^1,†, Yoonju Kim¹, Jun Lee^1,3

, Bu-Yeo Kim¹ and Soo-Jin Jeong^1,3,*

¹ Herbal Medicine Research Division, Korea Institute of Oriental Medicine, Daejeon 34054, Korea

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

³ Korean Medicine of Life Science, University of Science & Technology, Daejeon 34113, Korea

^† These authors contributed equally to this work.

Molecules 2017, 22(6), 925; https://doi.org/10.3390/molecules22060925 - 2 Jun 2017

Cited by 22 | Viewed by 5319

Abstract

The dried bark of Phellodendron chinense has been used as a traditional herbal medicine to remove damp heat, relieve consumptive fever, and cure dysentery and diarrhea. In the present study, we performed quantitative analyses of the two components of P. chinense, phellodendrine [...] Read more.

The dried bark of Phellodendron chinense has been used as a traditional herbal medicine to remove damp heat, relieve consumptive fever, and cure dysentery and diarrhea. In the present study, we performed quantitative analyses of the two components of P. chinense, phellodendrine and berberine, using high-performance liquid chromatography. A 70% ethanol extract of P. chinense was prepared and the two components were separated on a C-18 analytical column using a gradient solvent system of acetonitrile and 0.1% (v/v) aqueous trifluoroacetic acid. The ultraviolet wavelength used for detection was 200 nm for phellodendrine and 226 nm for berberine. The analytical method established here showed high linearity (correlation coefficient, ≥0.9991). The amount of phellodendrine and berberine used was 22.255 ± 0.123 mg/g and 269.651 ± 1.257 mg/g, respectively. Moreover, we performed an in vitro acetylcholinesterase (AChE) activity assay and an amyloid-β aggregation test to examine the biological properties of phellodendrine and berberine as therapeutic drugs for Alzheimer’s disease. Phellodendrine and berberine inhibited AChE activity in a dose-dependent manner (IC₅₀ = 36.51 and 0.44 μM, respectively). In contrast, neither phellodendrine nor berberine had an effect on amyloid-β aggregation. The P. chinense extract and phellodendrine, but not berberine, exhibited antioxidant activity by increasing radical scavenging activity. Moreover, P. chinense demonstrated a neuroprotective effect in hydrogen peroxide-treated HT22 hippocampal cells. Overall, our findings suggest that P. chinense has potential as an anti-Alzheimer’s agent via the suppression of the enzymatic activity of acetylcholinesterase and the stimulation of antioxidant activity. Full article

(This article belongs to the Section Medicinal Chemistry)

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14 pages, 1185 KiB

Open AccessArticle

Cu Nanoparticles in Hydrogels of Chitosan-PVA Affects the Characteristics of Post-Harvest and Bioactive Compounds of Jalapeño Pepper

by Zeus H. Pinedo-Guerrero¹, Alma Delia Hernández-Fuentes²

, Hortensia Ortega-Ortiz³, Adalberto Benavides-Mendoza¹, Gregorio Cadenas-Pliego³ and And Antonio Juárez-Maldonado^4,*

¹ Departamento de Horticultura, Universidad Autónoma Agraria Antonio Narro, 25315 Saltillo, Coahuila, Mexico

² Instituto de Ciencias Agropecuarias, Universidad Autónoma del Estado de Hidalgo, Tulancingo, 43600 Hidalgo, Mexico

³ Centro de Investigación en Química Aplicada, 25294 Saltillo, Coahuila, Mexico

⁴ Departamento de Botánica, Universidad Autónoma Agraria Antonio Narro, 25315 Saltillo, Coahuila, Mexico

Molecules 2017, 22(6), 926; https://doi.org/10.3390/molecules22060926 - 2 Jun 2017

Cited by 59 | Viewed by 6611

Abstract

Peppers are consumed all over the world due to the flavor, aroma, and color that they add to food. Additionally, they play a role in human health, as they contain a high concentration of bioactive compounds and antioxidants. The treatments used were an [...] Read more.

Peppers are consumed all over the world due to the flavor, aroma, and color that they add to food. Additionally, they play a role in human health, as they contain a high concentration of bioactive compounds and antioxidants. The treatments used were an absolute control, Cs-PVA, and four treatments with 0.02, 0.2, 2, and 10 mg (nCu) g⁻¹ (Cs-PVA). The application of Cu nanoparticles in chitosan-PVA hydrogels increases the content of capsaicin by up to 51% compared to the control. This application also increases the content of antioxidants ABTS [2,2′-azino-bis (3-ethylbenzothiazolin-6-sulfonic acid)] and DPPH (2,2-diphenyl-1-picrylhydrazyl), total phenols and flavonoids (4%, 6.6%, 5.9%, and 12.7%, respectively) in jalapeño pepper fruits stored for 15 days at room temperature; under refrigeration, it increases DPPH antioxidants, total phenols, and flavonoids (23.9%, 1.54%, and 17.2%, respectively). The application of Cu nanoparticles in chitosan-PVA hydrogels, even when applied to the substrate, not only has an effect on the development of the jalapeño pepper crop, but also modifies the post-harvest characteristics of the jalapeño pepper fruits. Full article

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

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13 pages, 775 KiB

Open AccessArticle

Simultaneous Quantification of Multiple Representative Components in the Xian-Ling-Gu-Bao Capsule by Ultra-Performance Liquid Chromatography Coupled with Quadrupole Time-of-Flight Tandem Mass Spectrometry

by Zhi-Hong Yao^1,2,*,†

, Zi-Fei Qin^1,2,3,†

, Hong Cheng¹, Xiao-Meng Wu¹, Yi Dai^1,2,*, Xin-Luan Wang⁴, Ling Qin⁴, Wen-Cai Ye^1,2,3 and Xin-Sheng Yao^1,2,3

¹ College of Pharmacy, Jinan University, Guangzhou 510632, China

² Guangdong Provincial Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou 510632, China

³ G Integrated Chinese and Western Medicine Postdoctoral Research Station, Jinan University, Guangzhou 510632, China

⁴ Musculoskeletal Research Laboratory, Department of Orthopedics and Traumatology, the Chinese University of Hong Kong, Satin, N.T. Hong Kong SAR, China

^† These authors contributed equally to this work.

Molecules 2017, 22(6), 927; https://doi.org/10.3390/molecules22060927 - 2 Jun 2017

Cited by 14 | Viewed by 5477

Abstract

Xian-Ling-Gu-Bao capsule (XLGB), a famous traditional Chinese medicine prescription, is extensively used for the treatment of osteoporosis in China. However, few studies on the holistic quality control of XLGB have been reported. In this study, a reliable method using 18 representative components in [...] Read more.

Xian-Ling-Gu-Bao capsule (XLGB), a famous traditional Chinese medicine prescription, is extensively used for the treatment of osteoporosis in China. However, few studies on the holistic quality control of XLGB have been reported. In this study, a reliable method using 18 representative components in XLGB was successfully established and applied to evaluate 34 batches of XLGB samples by ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF-MS). The choice of quantitative markers mostly followed four principles, i.e., absorbed components in plasma, bioactive compounds with in vitro anti-osteoporosis activity, those derived from multiple individual medicinal herbs in XLGB with multiple representative structure types, and quantitative chemical markers in the Chinese Pharmacopoeia. The results showed chemical consistency was good except for individual batches. Multivariate statistical analysis indicated that asperosaponin VI from Radix Dipsaci, epimedin C, magnoflorine, and icariin from Herba Epimedii as well as timosaponin BII from Rhizoma Anemarrhenae varied significantly in multiple samples, which hinted an assay for these four components should be completed during all of the manufacturing processes. Taken together, this study provided a feasible method for holistic quality control of XLGB by multiple chemical markers, which could play a vital role in guaranteeing the safety, effectiveness, and controllability of administering the capsules as a medication in clinics. Full article

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10 pages, 1869 KiB

Open AccessArticle

Variability in the Content of Trans-Resveratrol, Trans-ε-Viniferin and R2-Viniferin in Grape Cane of Seven Vitis vinifera L. Varieties during a Three-Year Study

by Jan Tříska^1,*, Naděžda Vrchotová¹, Josef Balík², Ivo Soural² and Radek Sotolář²

¹ Global Change Research Institute, Academy of Sciences of the Czech Republic, v. v. i., Lipová 9, České Budějovice 37005, Czech Republic

² Faculty of Horticulture, Mendel University in Brno, Valtická 337, Lednice 69144, Czech Republic

Molecules 2017, 22(6), 928; https://doi.org/10.3390/molecules22060928 - 3 Jun 2017

Cited by 17 | Viewed by 5226

Abstract

Grape canes are a waste product from viticulture that show potential as an industrially extractable source of stilbenes, which are valuable for medical and other purposes. In this work, grape canes collected in three consecutive years (2014–2016) at six different places in South [...] Read more.

Grape canes are a waste product from viticulture that show potential as an industrially extractable source of stilbenes, which are valuable for medical and other purposes. In this work, grape canes collected in three consecutive years (2014–2016) at six different places in South Moravia, Czech Republic were extracted, and the contents of trans-resveratrol, trans-ε-viniferin, and r2-viniferin were determined by high-performance liquid chromatography. The study included three blue grape varieties of Vitis vinifera L. (Cabernet Moravia, Blaufränkisch, and Piwi variety Laurot) and four white grape varieties (Chardonnay, Green Veltliner, Piwi variety Hibernal, and Piwi variety Malverina). From the viewpoint of producing extracts with high stilbenes content, the Hibernal variety is clearly the best. The mean amounts of the stilbenes for this variety at all localities and for all three years were 4.99 g/kg for trans-resveratrol, 3.24 g/kg for trans-ε-viniferin, and 1.73 g/kg for r2-viniferin. The influence of vintage, locality, and variety on the amounts of stilbenes was studied using PCA analysis. In contrast to expectations, there was no strong impact of locality on stilbenes content. The differences were varietal for most varieties, regardless of the area of cultivation. Laurot and Hibernal varieties did differ significantly in that respect, however, as they exhibited clear dependence on location. Full article

(This article belongs to the Collection Bioactive Compounds)

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14 pages, 2378 KiB

Open AccessArticle

Curcumin Inhibits LIN-28A through the Activation of miRNA-98 in the Lung Cancer Cell Line A549

by Wei-Lun Liu^1,2,3

, Jia-Ming Chang⁴, Inn-Wen Chong^5,6

, Yi-Li Hung^2,7, Yung-Hsiang Chen^8,9

, Wen-Tsung Huang¹⁰, Hsuan-Fu Kuo¹¹, Chong-Chao Hsieh¹² and Po-Len Liu^5,*

¹ Department of Intensive Care Medicine, Chi Mei Medical Center, Liouying, Tainan 73657, Taiwan

² School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei 24205, Taiwan

³ Graduate Institute of Medical Sciences, College of Health Sciences, Chang Jung Christian University, Tainan 71101, Taiwan

⁴ Department of pharmacology, Institute for Drug Evaluation Platform, Development Center for Biotechnology, New Taipei 22180, Taiwan

⁵ Department of Respiratory Therapy, College of Medicine, Kaohsiung Medical University, Kaohsiung 80756, Taiwan

⁶ Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 80756, Taiwan

⁷ Department of Pediatrics, Cathay General Hospital, Taipei 10630, Taiwan

⁸ Graduate Institute of Integrated Medicine, College of Chinese Medicine, China Medical University, Taichung 40407, Taiwan

⁹ Department of Psychology, College of Medical and Health Science, Asia University, Taichung 41354, Taiwan

¹⁰ Division of Hemato-oncology, Department of Internal Medicine, Chi Mei Medical Center, Liouying, Tainan 73657, Taiwan

¹¹ Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80145, Taiwan

¹² Division of Cardiovascular Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung 80756, Taiwan

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Molecules 2017, 22(6), 929; https://doi.org/10.3390/molecules22060929 - 3 Jun 2017

Cited by 58 | Viewed by 7324

Abstract

Metastasis is common in lung cancer and is associated with poor clinical outcomes and increased mortality. Curcumin is a natural anti-cancer agent that inhibits the metastasis of various cancers by modulating the expression of micro (mi) RNAs such as miR-98, which acts as [...] Read more.

Metastasis is common in lung cancer and is associated with poor clinical outcomes and increased mortality. Curcumin is a natural anti-cancer agent that inhibits the metastasis of various cancers by modulating the expression of micro (mi) RNAs such as miR-98, which acts as a tumor suppressor. This study investigated the effect of curcumin on miR-98 expression and in vitro cell line growth and invasiveness in lung cancer. Curcumin treatment enhanced the expression of miR-98 and reduced that of the miR-98 target gene LIN28A as well as matrix metalloproteinase (MMP) 2 and MMP9 in vitro and in vivo. MiR-98 overexpression suppressed lung cancer cell migration and invasion by inhibiting LIN28A-induced MMP2 and MMP9 expression. Meanwhile, LIN28A level was downregulated by overexpression of miR-98 mimic. Induction of miR-98 by curcumin treatment suppressed MMP2 and MMP9 by targeting LIN28A. These findings provide insight into the mechanisms by which curcumin suppresses lung cancer cell line growth in vitro and in vivo and invasiveness in vitro. Full article

(This article belongs to the Special Issue Curcumin an Example of Pleiotropic Agents—Design, Synthesis and Biological Evaluation of Curcumin Analogues or Curcumin Derivatives)

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11 pages, 973 KiB

Open AccessArticle

Laurus nobilis: Composition of Essential Oil and Its Biological Activities

by Lucia Caputo¹

, Filomena Nazzaro²

, Lucéia Fatima Souza^1,3, Luigi Aliberti¹, Laura De Martino¹

, Florinda Fratianni²

, Raffaele Coppola⁴

and Vincenzo De Feo^1,*

¹ Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132, 84084 Fisciano (Salerno), Italy

² Istituto di Scienze dell’Alimentazione, Consiglio Nazionale delle Ricerche (ISA-CNR), Via Roma 64, 83100 Avellino, Italy

³ Post-Doctoral by National Counsel of Technological and Scientific Development (CNPq/Brazil), 70000-000 Brasília, Brazil

⁴ Dipartimento di Agricoltura, Ambiente e Alimenti-Università del Molise, Via de Sanctis snc, 86100 Campobasso, Italy

Molecules 2017, 22(6), 930; https://doi.org/10.3390/molecules22060930 - 3 Jun 2017

Cited by 148 | Viewed by 15838

Abstract

Laurus nobilis is native to the southern Mediterranean region and cultivated mainly in Europe and the USA as an ornamental and medicinal plant. The chemical composition of the essential oil (EO) from leaves of L. nobilis, collected in Southern Italy, was studied by [...] Read more.

Laurus nobilis is native to the southern Mediterranean region and cultivated mainly in Europe and the USA as an ornamental and medicinal plant. The chemical composition of the essential oil (EO) from leaves of L. nobilis, collected in Southern Italy, was studied by GC and GC-MS. In all, 55 compounds were identified, accounting for 91.6% of the total oil. 1,8-Cineole (31.9%), sabinene (12.2%), and linalool (10.2%) were the main components. Antimicrobial and antifungal activities of EO and 1,8-cineole were determined in vitro. The cytotoxicity of the EO was evaluated against SH-SY5Y cell line, as well as the influence of the EO on the expression of adenylate cyclase 1 (ADCY1), suggesting possible oil effects on the Central Nervous System. Full article

(This article belongs to the Special Issue Essential Oils: Chemistry and Bioactivity)

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15 pages, 2196 KiB

Open AccessArticle

Optimization of Ultrasonic-assisted Extraction of Fatty Acids in Seeds of Brucea Javanica (L.) Merr. from Different Sources and Simultaneous Analysis Using High-Performance Liquid Chromatography with Charged Aerosol Detection

by Zhuona Wu^1,2, Ling Li¹, Ning Li³, Tong Zhang^1,2,*, Yiqiong Pu¹, Xitong Zhang⁴, Yue Zhang^1,2 and Bing Wang^1,2,*

¹ Experiment Center for Teaching and Learning, Shanghai University of Traditional Chinese Medicine, No. 1200, Cailun Road, Pudong New District, Shanghai 201203, China

² School of Pharmacy, Shanghai University of Traditional Chinese Medicine, No. 1200, Cailun Road, Pudong New District, Shanghai 201203, China

³ Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, No. 1200, Cailun Road, Pudong New District, Shanghai 201203, China

⁴ Shanghai Xiangshan Hospital of Traditional Chinese Medicine, No. 528, Middle Fuxing Road, Huangpu District, Shanghai 200020, China

Molecules 2017, 22(6), 931; https://doi.org/10.3390/molecules22060931 - 4 Jun 2017

Cited by 8 | Viewed by 5538

Abstract

Our research aimed to optimize the oil extraction process and determine the fatty acids in Brucea javanica (L.) Merr. seeds. The extraction technology was optimized using response surface methodology. A Box-Behnken design was employed to investigate the effects of three independent variables on [...] Read more.

Our research aimed to optimize the oil extraction process and determine the fatty acids in Brucea javanica (L.) Merr. seeds. The extraction technology was optimized using response surface methodology. A Box-Behnken design was employed to investigate the effects of three independent variables on an ultrasonic-assisted extraction technique, namely, sonication time (X₁: 20–40 min), liquid–solid ratio (X₂: 16:1 mL/g–24:1 mL/g), and ethanol concentration (X₃: 90%–100%). The optimum conditions of sonication time, liquid–solid ratio, and ethanol concentration were 40 min, 24:1 mL/g, and 100%, respectively. The content of fatty acids and the oil yield were 14.64 mg/g and 16.87%, respectively, which match well with the predicted models. The optimum number of extraction times was eventually identified as two. A new rapid method for the qualitative and quantitative analysis of the fatty acids of B. javanica (L.) Merr. seed oil using HPLC with a charged aerosol detector was described. The fatty acid contents of 14 batches of B. javanica (L.) Merr. seed oil were determined, and the relevance and difference were analyzed by fingerprint analysis. The fingerprint has five common peaks, and the similarity was greater than 0.991. HPLC analysis represents a specialized and rational approach for the quality identification and comprehensive evaluation of B. javanica (L.) Merr. seed oils. 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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13 pages, 3734 KiB

Open AccessArticle

In Vitro Study of the Metabolic Characteristics of Eight Isoquinoline Alkaloids from Natural Plants in Rat Gut Microbiota

by Chi-Yu He, Jie Fu, Jia-Wen Shou

, Zhen-Xiong Zhao, Long Ren, Yan Wang^* and Jian-Dong Jiang^*

¹ State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences/Peking Union Medical College, Beijing 100050, China

^† These authors contributed equally to this work.

Molecules 2017, 22(6), 932; https://doi.org/10.3390/molecules22060932 - 4 Jun 2017

Cited by 25 | Viewed by 6005

Abstract

Gut microbiota is populated with an immense number of microorganisms, which can be regulated by dietary components and drugs to markedly affect the nutritional and health status of the host. Eight medicinal isoquinoline alkaloids from natural plants were cultured anaerobically with rat gut [...] Read more.

Gut microbiota is populated with an immense number of microorganisms, which can be regulated by dietary components and drugs to markedly affect the nutritional and health status of the host. Eight medicinal isoquinoline alkaloids from natural plants were cultured anaerobically with rat gut microbiota and an LC/MSⁿ-IT-TOF technique was used to identify the resulting metabolites. Palmatine, tetrahydropalmatine, dauricine, and tetrandrine containing nitro-hexatomic isoquinoline rings could be easily transformed by the intestinal flora in vitro and a total of nine demethylated metabolites were detected. However, sinomenine, homoharringtonine, harringtonine, and galanthamine, which all contained benzazepine, could not undergo demethylation. Computer-assisted docking was used to analyze the binding between these compounds and sterol 14α-demethylase. The computational results demonstrated that hydrophobic interactions were the main driving force for binding, but the steric hindrance produced by the benzazepine structure resulted in a weak interaction between the hit compounds and the enzyme. This work illustrated that gut microbiota were important in the metabolism of isoquinoline alkaloids. Full article

(This article belongs to the Section Medicinal Chemistry)

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12 pages, 1875 KiB

Open AccessArticle

Determination and Pharmacokinetic Study of Three Diterpenes in Rat Plasma by UHPLC-ESI-MS/MS after Oral Administration of Rosmarinus officinalis L. Extract

by Liqian Wang^1,†, Chunli Gan^2,†

, Zhibin Wang³, Lu Liu¹, Mingjie Gao¹, Qian Li¹ and Chunjuan Yang^1,*

¹ Department of Pharmaceutical Analysis and Analytical Chemistry, College of Pharmacy, Harbin Medical University, No. 157 Baojian Road, Nangang District, Harbin 150081, Heilongjiang, China

² Department of Medicinal Chemistry and Natural Medicine Chemistry, College of Pharmacy, Harbin Medical University, No. 157 Baojian Road, Nangang District, Harbin 150081, Heilongjiang, China

³ Key Laboratory of Chinese Materia Medica (Ministry of Education), Heilongjiang University of Chinese Medicine, Harbin 150040, Heilongjiang, China

^† These authors contributed equally to this work.

Molecules 2017, 22(6), 934; https://doi.org/10.3390/molecules22060934 - 4 Jun 2017

Cited by 19 | Viewed by 5660

Abstract

Rosmarinus officinalis L. is commonly used as a spice and flavoring agent. Diterpenes are the main active compounds of R. officinalis. An Ultra High Performance Liquid Chromatography-Tandem Mass Spectrometry (UHPLC-ESI-MS/MS) method was developed for the determination of carnosol, rosmanol, and carnosic acid [...] Read more.

Rosmarinus officinalis L. is commonly used as a spice and flavoring agent. Diterpenes are the main active compounds of R. officinalis. An Ultra High Performance Liquid Chromatography-Tandem Mass Spectrometry (UHPLC-ESI-MS/MS) method was developed for the determination of carnosol, rosmanol, and carnosic acid isolated from R. officinalis in rat plasma, and applied to a pharmacokinetic study after oral administration of R. officinalis extract. Sample preparation involved a liquid-liquid extraction of the analytes with ethyl acetate. Butylparaben was employed as an internal standard (I.S.). Chromatographic separation was carried out on a C₁₈ column (ACQUITY UPLC^® HSS T3, 1.8 μm, 2.1 mm × 100 mm) with a gradient system consisting of the mobile phase solution A (0.1% formic acid in water) and solution B (acetonitrile) at the flow rate of 0.3 mL/min. The quantification was obtained using multiple reaction monitoring (MRM) mode with electrospray ionization (ESI). The UHPLC-MS/MS assay was validated for linearity, accuracy, precision, extraction recovery, matrix effect and stability. This study described a simple, sensitive and validated UHPLC-MS/MS method for the simultaneous determination of three diterpene compounds in rat plasma after oral administration of R. officinalis extract, and investigated on their pharmacokinetic studies as well. Full article

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10 pages, 866 KiB

Open AccessArticle

Anti-Inflammatory Phenolic Acid Esters from the Roots and Rhizomes of Notopterygium incisium and Their Permeability in the Human Caco-2 Monolayer Cell Model

by Xiu-Wen Wu¹, Wei Wei¹, Xiu-Wei Yang^1,*, You-Bo Zhang¹, Wei Xu¹, Yan-Fang Yang¹, Guo-Yue Zhong², Hong-Ning Liu² and Shi-Lin Yang^2,3

¹ State Key Laboratory of Natural and Biomimetic Drugs, Department of Natural Medicines, School of Pharmaceutical Sciences, Peking University Health Science Center, Peking University, No. 38, Xueyuan Road, Haidian District, Beijing 100191, China

² School of Chinese Materia Medica, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, China

³ State Key Laboratory of Innovative Drug and Efficient Energy-Saving Pharmaceutical Equipment, Jiangxi University of Traditional Chinese Medicine, Nanchang 330006, China

Molecules 2017, 22(6), 935; https://doi.org/10.3390/molecules22060935 - 4 Jun 2017

Cited by 33 | Viewed by 6898

Abstract

A new ferulic acid ester named 4-methyl-3-trans-hexenylferulate (1), together with eight known phenolic acid esters (2–9), was isolated from the methanolic extract of the roots and rhizomes of Notopterygium incisium. Their structures were elucidated [...] Read more.

A new ferulic acid ester named 4-methyl-3-trans-hexenylferulate (1), together with eight known phenolic acid esters (2–9), was isolated from the methanolic extract of the roots and rhizomes of Notopterygium incisium. Their structures were elucidated by extensive spectroscopic techniques, including 2D NMR spectroscopy and mass spectrometry. 4-Methoxyphenethyl ferulate (8) NMR data is reported here for the first time. The uptake and transepithelial transport of the isolated compounds 1–9 were investigated in the human intestinal Caco-2 cell monolayer model. Compounds 2 and 6 were assigned for the well-absorbed compounds, compound 8 was assigned for the moderately absorbed compound, and compounds 1, 3, 4, 5, 7, and 9 were assigned for the poorly absorbed compounds. Moreover, all of the isolated compounds were assayed for the inhibitory effects against nitric oxide (NO) production in the lipopolysaccharide-activated RAW264.7 macrophages model and L-N⁶-(1-iminoethyl)-lysine (L-NIL) was used as a positive control. Compounds 1, 5, 8, and 9 exhibited potent inhibitory activity on NO production with the half maximal inhibitory concentration (IC₅₀) values of 1.01, 4.63, 2.47, and 2.73 μM, respectively, which were more effective than L-NIL with IC₅₀ values of 9.37 μM. These findings not only enriched the types of anti-inflammatory compounds in N. incisum but also provided some useful information for predicting their oral bioavailability and their suitability as drug leads or promising anti-inflammatory agents. Full article

(This article belongs to the Collection Bioactive Compounds)

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9 pages, 1400 KiB

Open AccessArticle

New Benzenoid Derivatives and Other Constituents from Lawsonia inermis with Inhibitory Activity against NO Production

by Chang-Syun Yang^1,†

, Jih-Jung Chen^2,3,†

, Hui-Chi Huang¹

, Guan-Jhong Huang^1,†, Sheng-Yang Wang^4,5, Ping-Jyun Sung⁶

, Ming-Jen Cheng⁷, Ming-Der Wu⁷ and Yueh-Hsiung Kuo^1,8,*

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

² Faculty of Pharmacy, School of Pharmaceutical Sciences, National Yang-Ming University, Taipei 112, Taiwan

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

⁴ Department of Forestry, National Chung-Hsing University, Taichung 402, Taiwan

⁵ Agricultural Biotechnology Research Center, Academia Sinica, Taipei 115, Taiwan

⁶ National Museum of Marine Biology and Aquarium, Pingtung 944, Taiwan

⁷ Food Industry Research and Development Institute, Hsinchu 300, Taiwan

⁸ Department of Biotechnology, Asia University, Taichung 413, Taiwan

^† These authors contributed equally to this work.

Molecules 2017, 22(6), 936; https://doi.org/10.3390/molecules22060936 - 5 Jun 2017

Cited by 7 | Viewed by 4121

Abstract

Three new benzenoid derivatives, lawsoinermone (1), inermidioic acid (2), and inermic acid (3) have been isolated from the aerial part of Lawsonia inermis, together with 11 known compounds (4–14). The structures of [...] Read more.

Three new benzenoid derivatives, lawsoinermone (1), inermidioic acid (2), and inermic acid (3) have been isolated from the aerial part of Lawsonia inermis, together with 11 known compounds (4–14). The structures of three new compounds were determined through spectroscopic and MS analyses. Compounds 1, 4–6, 13 and 14 were evaluated for inhibition of nitric oxide production in LPS-stimulated product of nitrite in RAW 264.7 cells with IC₅₀ values of 6.12, 16.43, 18.98, 9.30, 9.30 and 14.90 μg/mL, respectively. Full article

(This article belongs to the Section Natural Products Chemistry)

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16 pages, 7110 KiB

Open AccessArticle

Levo-Corydalmine Alleviates Neuropathic Cancer Pain Induced by Tumor Compression via the CCL2/CCR2 Pathway

by Yahui Hu¹, Nandani Darshika Kodithuwakku², Lin Zhou¹, Chengyuan Li¹, Dan Han¹, Weirong Fang¹, Jihua Liu^3,* and Yunman Li^1,*

¹ State Key Laboratory of Natural Medicines, Department of Physiology, China Pharmaceutical University, Nanjing 210009, China

² Institute of Indigenous Medicine, University of Colombo, Rajagiriya 11600, Sri Lanka

³ State Key Laboratory of Natural Medicines, School of Traditional Chinese Medicine, China Pharmaceutical University, Nanjing 210009, China

Molecules 2017, 22(6), 937; https://doi.org/10.3390/molecules22060937 - 6 Jun 2017

Cited by 22 | Viewed by 6415

Abstract

Background: Tumor compression-induced pain (TCIP) is a complex pathological cancer pain. Spinal glial cells play a critical role in maintenance of cancer pain by releasing proinflammatory cytokines and chemokines. In this study, we verified the role of levo-corydalmine (l-CDL) [...] Read more.

Background: Tumor compression-induced pain (TCIP) is a complex pathological cancer pain. Spinal glial cells play a critical role in maintenance of cancer pain by releasing proinflammatory cytokines and chemokines. In this study, we verified the role of levo-corydalmine (l-CDL) on TCIP. Methods: Spontaneous pain, paw withdrawal threshold and latency were assessed using TCIP mouse model. Immunofluorescence was used to identify the reactions of glia. RT-PCR and western blot or ELISA were used to determine mRNA or protein expression of tumor necrosis factor-α (TNF-α), interlukin-1β (IL-1β), CC chemokine ligand 2 (CCL2) and chemotactic cytokine receptor 2 (CCR2) in vivo and in vitro. Results: l-CDL significantly attenuated TCIP hypersensitivity, accompanying with downregulation of TNF-α and IL-1β expression levels and declined astrocytes and microglial activation. It also significantly decreased the expression of the mRNA and protein level for CCL2 and CCR2. Further, l-CDL could suppress TNF-α-induced astrocytes activation and IL-1β expression through downregulating the CCL2/CCR2. Besides, CCL2-induced BV-microglia activation and inflammatory factors secretion were suppressed by l-CDL via CCR2. Conclusions: Suppression of CCL2/CCR2 by l-CDL may contribute to alleviate TCIP, offering an alternative medication for TCIP. Full article

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

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14 pages, 1503 KiB

Open AccessArticle

Investigation of the Maillard Reaction between Polysaccharides and Proteins from Longan Pulp and the Improvement in Activities

by Miao-Miao Han¹, Yang Yi^1,*, Hong-Xun Wang¹ and Fei Huang²

¹ College of Food Science & Engineering, Wuhan Polytechnic University, Wuhan 430023, China

² Sericultural & Agri-food Research Institute, Guangdong Academy of Agricultural Sciences, Key Laboratory of Functional Foods, Ministry of Agriculture, Guangdong Key Laboratory of Agricultural Products Processing, Guangzhou 510610, China

Molecules 2017, 22(6), 938; https://doi.org/10.3390/molecules22060938 - 5 Jun 2017

Cited by 55 | Viewed by 7619

Abstract

The purpose of this study was to investigate the Maillard reaction between polysaccharides and proteins from longan pulp and the effects of reaction on their in vitro activities. The polysaccharide-protein mixtures of fresh longan pulp (LPPMs) were co-prepared by an alkali extraction–acid precipitation [...] Read more.

The purpose of this study was to investigate the Maillard reaction between polysaccharides and proteins from longan pulp and the effects of reaction on their in vitro activities. The polysaccharide-protein mixtures of fresh longan pulp (LPPMs) were co-prepared by an alkali extraction–acid precipitation method. They were then dry-heated under controlled conditions for monitoring the characterization of the Maillard reaction by the measurement of the free amino group content, ultraviolet-visible spectrum, Fourier transform infrared spectrum and molecular weight distribution. All the physicochemical analyses indicated the development of the Maillard reaction between polysaccharides and proteins. The in vitro activity evaluation indicated that the Maillard reaction could effectively enhance the antioxidant, antitumor and immunostimulating activities of LPPMs. The enhancement of 1,1-diphenyl-2-picrylhydrazyl radical scavenging activity and ferric reducing antioxidant power displayed both a positive correlation with the reaction time (p < 0.05). LPPMs dry-heated for three days obtained relatively strong inhibitory activity against HepG2 cells and SGC7901 cells, as well as strong immunostimulating effects on the nitric oxide production and tumor necrosis factor α secretion of macrophages. Maillard-type intermacromolecular interaction is suggested to be an effective and controllable method for improving the functional activities of polysaccharides and proteins from longan pulp. Full article

(This article belongs to the Special Issue Protein-Carbohydrate Interactions)

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11 pages, 826 KiB

Open AccessArticle

Pharmacokinetics and Tissue Distribution Kinetics of Puerarin in Rats Using Indirect Competitive ELISA

by Hui Kong^1,†, Xueqian Wang^1,†, Rongfeng Shi¹, Yan Zhao¹

, Jinjun Cheng¹, Xin Yan², Xiaoman Liu¹, Yongzhi Wang², Meiling Zhang², Qingguo Wang¹ and Huihua Qu^3,*

¹ School of Chinese Medicine, Beijing Key Laboratory, Beijing University of Chinese Medicine, Beijing 100029, China

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

³ Beijing Institute of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China

^† Hui Kong and Xueqian Wang contributed equally to this work.

Molecules 2017, 22(6), 939; https://doi.org/10.3390/molecules22060939 - 5 Jun 2017

Cited by 26 | Viewed by 6049

Abstract

Puerarin (PUE) is a compound isolated from the roots of Pueraria lobata. We studied the pharmacokinetics and tissue distribution kinetics of PUE in Sprague-Dawley rats following intraperitoneal administration of three concentrations. Indirect competitive ELISA based on an anti-PUE monoclonal antibody was used [...] Read more.

Puerarin (PUE) is a compound isolated from the roots of Pueraria lobata. We studied the pharmacokinetics and tissue distribution kinetics of PUE in Sprague-Dawley rats following intraperitoneal administration of three concentrations. Indirect competitive ELISA based on an anti-PUE monoclonal antibody was used to determine the concentration of PUE in the blood, heart, liver, spleen, lung, kidney, hippocampus, cerebral cortex, and striatum. The plasma and tissue distribution kinetic characteristics following a single injection of PUE (20, 40 and 80 mg/kg) were calculated using a non-compartment model. In the high-dose (80 mg/kg) and medium-dose (40 mg/kg) groups, the kinetic profile of PUE in blood and kidney samples showed two absorption peaks, while that of the other tissues showed only one peak. In the low-dose (20 mg/kg) group, there was only one peak, irrespective of the sample type. Pharmacokinetic parameters, such as the area under the curve, C_max, and T_max varied according to the administered dose. AUC and C_max values increased dose-dependently. PUE was widely distributed in areas of the brain such as the hippocampus, cerebral cortex, and striatum, providing a foundation for guiding the use of PUE in the treatment of cerebral ischaemic stroke and neurodegenerative diseases. Full article

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12 pages, 1454 KiB

Open AccessArticle

Sesquiterpene Variation in West Australian Sandalwood (Santalum spicatum)

by Jessie Moniodis^1,2,3,*, Christopher G. Jones¹, Michael Renton^1,4, Julie A. Plummer¹, E. Liz Barbour¹, Emilio L. Ghisalberti² and Joerg Bohlmann³

¹ School of Biological Sciences (M084), University of Western Australia, 35 Stirling Hwy, Crawley, WA 6009, Australia

² School of Chemistry and Biochemistry (M310), University of Western Australia, 35 Stirling Hwy, Crawley, WA 6009, Australia

³ Michael Smith Laboratories, University of British Columbia, 2185 East Mall, Vancouver, BC V6T1Z4, Canada

⁴ School of Agriculture and Environment, University of Western Australia, 35 Stirling Hwy, Crawley, WA 6009, Australia

Molecules 2017, 22(6), 940; https://doi.org/10.3390/molecules22060940 - 6 Jun 2017

Cited by 16 | Viewed by 7594

Abstract

West Australian sandalwood (Santalum spicatum) has long been exploited for its fragrant, sesquiterpene-rich heartwood; however sandalwood fragrance qualities vary substantially, which is of interest to the sandalwood industry. We investigated metabolite profiles of trees from the arid northern and southeastern and [...] Read more.

West Australian sandalwood (Santalum spicatum) has long been exploited for its fragrant, sesquiterpene-rich heartwood; however sandalwood fragrance qualities vary substantially, which is of interest to the sandalwood industry. We investigated metabolite profiles of trees from the arid northern and southeastern and semi-arid southwestern regions of West Australia for patterns in composition and co-occurrence of sesquiterpenes. Total sesquiterpene content was similar across the entire sample collection; however sesquiterpene composition was highly variable. Northern populations contained the highest levels of desirable fragrance compounds, α- and β-santalol, as did individuals from the southwest. Southeastern populations were higher in E,E-farnesol, an undesired allergenic constituent, and low in santalols. These trees generally also contained higher levels of α-bisabolol. E,E-farnesol co-occurred with dendrolasin. Contrasting α-santalol and E,E-farnesol chemotypes revealed potential for future genetic tree improvement. Although chemical variation was evident both within and among regions, variation was generally lower within regions. Our results showed distinct patterns in chemical diversity of S. spicatum across its natural distribution, consistent with earlier investigations into sandalwood population genetics. These results are relevant for plantation tree improvement and conservation efforts. Full article

(This article belongs to the Special Issue Isoprenoid Biosynthesis)

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9 pages, 1145 KiB

Open AccessArticle

Tryptophan Levels during Grape Ripening: Effects of Cultural Practices

by Ana Ruiz-Rodríguez¹, Ceferino A. Carrera¹, Widiastuti Setyaningsih^1,2

, Gerardo F. Barbero¹

, Marta Ferreiro-González¹

, Miguel Palma^1,* and Carmelo G. Barroso¹

¹ Department of Analytical Chemistry, IVAGRO, Faculty of Sciences, University of Cadiz, Puerto Real 11510, Spain

² Department of Food and Agricultural Product Technology, Faculty of Agricultural Technology, Gadjah Mada University, Jalan Flora, Bulaksumur 55281, Yogyakarta, Indonesia

Molecules 2017, 22(6), 941; https://doi.org/10.3390/molecules22060941 - 6 Jun 2017

Cited by 5 | Viewed by 4058

Abstract

Some cultural practices that are carried out during the grape ripening period are associated with vine stress, including leaf removal, grape bunch removal, and vegetable cover crops. Additionally, several nitrogen and sulfur supplements have also been used directly on leaves during the last [...] Read more.

Some cultural practices that are carried out during the grape ripening period are associated with vine stress, including leaf removal, grape bunch removal, and vegetable cover crops. Additionally, several nitrogen and sulfur supplements have also been used directly on leaves during the last stage of the ripening period. In the work described here, five different cultural practices and the reference were applied in three replicates in the same vineyard. The evolution of tryptophan levels was evaluated from just after grape veraison until the harvest date. In some cases, certain specific treatments were also evaluated after the regular harvest date. The cultural techniques that involved the application of nitrogen led to higher levels of tryptophan at the harvest day when compared to other cultural techniques. It was also found that the application of nitrogen without sulfur had a faster effect on the level of tryptophan. It was established that a period of around 20 days is needed for the grapes to show clear differences in tryptophan levels after the application of nitrogen. Full article

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11 pages, 1724 KiB

Open AccessArticle

Evaluation of the Cardiotoxicity of Evodiamine In Vitro and In Vivo

by Weifeng Yang^2,†, Lina Ma^1,†, Sidi Li¹, Kaiyu Cui³, Lei Lei⁴ and Zuguang Ye^1,*

¹ Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China

² Experimental Research Center, China Academy of Chinese Medical Sciences, Beijing 100700, China

³ Pharmacy Faculty, Hubei University of Chinese Medicine, Wuhan 430065, China

⁴ Institute of Information on TCM, China Academy of Chinese Medical Sciences, Beijing 100700, China

^† These authors contributed equally to this work.

Molecules 2017, 22(6), 943; https://doi.org/10.3390/molecules22060943 - 9 Jun 2017

Cited by 55 | Viewed by 6924

Abstract

Evodiamine is a bioactive alkaloid that is specified as a biomarker for the quality assessment of Evodia rutaecarpa (E. rutaecarpa) and for traditional Chinese medicines containing this plant. We previously reported that quantitative structure–activity modeling indicated that evodiamine may cause cardiotoxicity. [...] Read more.

Evodiamine is a bioactive alkaloid that is specified as a biomarker for the quality assessment of Evodia rutaecarpa (E. rutaecarpa) and for traditional Chinese medicines containing this plant. We previously reported that quantitative structure–activity modeling indicated that evodiamine may cause cardiotoxicity. However, previous investigations have indicated that evodiamine has beneficial effects in patients with cardiovascular diseases and there are no previous in vitro or in vivo reports of evodiamine-induced cardiotoxicity. The present study investigated the effects of evodiamine on primary cultured neonatal rat cardiomyocytes in vitro, and on zebrafish in vivo. Cell viability was reduced in vitro, where evodiamine had a 24 h 50% inhibitory concentration of 28.44 µg/mL. Cells exposed to evodiamine also showed increased lactate dehydrogenase release and maleic dialdehyde levels, and reduced superoxide dismutase activity. In vivo, evodiamine had a 10% lethal concentration of 354 ng/mL and induced cardiac malfunction, as evidenced by changes in heart rate and circulation, and pericardial malformations. This study indicated that evodiamine could cause cardiovascular side effects involving oxidative stress. These findings suggest that cardiac function should be monitored in patients receiving preparations containing evodiamine. Full article

(This article belongs to the Collection Herbal Medicine Research)

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17 pages, 3199 KiB

Open AccessArticle

Pattern Evolution during Double Liquid-Vapor Phase Transitions under Weightlessness

by Ana Oprisan^1,*

, Yves Garrabos^2,3, Carole Lecoutre^2,3 and Daniel Beysens⁴

¹ Department of Physics and Astronomy, College of Charleston, Charleston, SC 29424, USA

² ESEME,Institut de Chimie de la Matiere Condensee de Bordeaux, CNRS, Univ. Bordeaux, ICMCB, UPR 9048, F-33600 Pessac, France

³ Service des Basses Temperatures, CEA-Grenoble et Universite Joseph Fourier, 38054 Grenoble, France

⁴ Physique et Mecanique des Milieux Heterogenes, UMR 7636 CNRS-ESPCI-Universite Pierre et Marie Curie-Universite Paris Diderot, 10 rue Vauquelin, 75005 Paris, France

Molecules 2017, 22(6), 947; https://doi.org/10.3390/molecules22060947 - 9 Jun 2017

Cited by 8 | Viewed by 4474

Abstract

Phase transition in fluids is ubiquitous in nature and has important applications in areas such as the food industry for volatile oils’ extraction or in nuclear plants for heat transfer. Fundamentals are hampered by gravity effects on Earth. We used direct imaging to [...] Read more.

Phase transition in fluids is ubiquitous in nature and has important applications in areas such as the food industry for volatile oils’ extraction or in nuclear plants for heat transfer. Fundamentals are hampered by gravity effects on Earth. We used direct imaging to record snapshots of phase separation that takes place in sulfur hexafluoride, SF₆, under weightlessness conditions on the International Space Station (ISS). The system was already at liquid-vapor equilibrium slightly below the critical temperature and further cooled down by a 0.2-mK temperature quench that produced a new phase separation. Both full view and microscopic views of the direct observation cell were analyzed to determine the evolution of the radii distributions. We found that radii distributions could be well approximated by a lognormal function. The fraction of small radii droplets declined while the fraction of large radii droplets increased over time. Phase separation at the center of the sample cell was visualized using a 12× microscope objective, which corresponds to a depth of focus of about 5

μ

m. We found that the mean radii of liquid droplets exhibit a

t^{1 / 3}

evolution, in agreement with growth driven by Brownian coalescence. It was also found that the mean radii of the vapor bubbles inside the liquid majority phase exhibit a

t^{1 / 2}

evolution, which suggest a possible directional motion of vapor bubbles due to the influence of weak remaining gravitational field and/or a composition Marangoni force. Full article

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

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10 pages, 1036 KiB

Open AccessArticle

Two New β-Dihydroagarofuran Sesquiterpenes from Celastrus orbiculatus Thunb and Their Anti-Proliferative Activity

by Jingjing Zhou¹, Na Han¹, Guanghui Lv¹, Lina Jia², Zhihui Liu¹ and Jun Yin^1,*

¹ Department of Pharmacognosy and Utilization Key Laboratory of Northeast Plant Materials, School of Traditional Chinese Medicine, Shenyang Pharmaceutical University, Shenyang 110016, China

² School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang 110016, China

Molecules 2017, 22(6), 948; https://doi.org/10.3390/molecules22060948 - 9 Jun 2017

Cited by 16 | Viewed by 4003

Abstract

Two new β-dihydroagarofuran-type sesquiterpenes (1–2) were isolated and identified from the fruit of Celastrus orbiculatus Thunb, together with seventeen known compounds (3–19). The structures of the isolated new compounds were elucidated based on extensive spectroscopic [...] Read more.

Two new β-dihydroagarofuran-type sesquiterpenes (1–2) were isolated and identified from the fruit of Celastrus orbiculatus Thunb, together with seventeen known compounds (3–19). The structures of the isolated new compounds were elucidated based on extensive spectroscopic analyses. The cytotoxic activities of the 19 sesquiterpenes on three cell lines, human acute promyelocytic leukemia HL-60, human leukemic K562, and human colon cancer HCT-116 cells, were evaluated in vitro. Compound 4 exhibited potent cytotoxic activity against HL-60, K562, and HCT116 cell lines with IC₅₀ values of 3.61 μΜ, 17.13 μΜ and 10.15 μΜ, respectively, and the other compounds displayed moderate activity. Full article

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15 pages, 1756 KiB

Open AccessArticle

Anti-Inflammatory and Antioxidant Properties of Peptides Released from β-Lactoglobulin by High Hydrostatic Pressure-Assisted Enzymatic Hydrolysis

by Fatemeh Bamdad¹, Seonghee Bark¹, Chul Hee Kwon¹, Joo-Won Suh^2,* and Hoon Sunwoo^1,*

¹ Centre for Pharmacy & Health Research, Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, 11361-87 Ave, Edmonton, AB T6G 2E1, Canada

² Center for Nutraceutical and Pharmaceutical Materials, Myongji University, Yongin, Gyeonggi 449-728, Korea

Molecules 2017, 22(6), 949; https://doi.org/10.3390/molecules22060949 - 7 Jun 2017

Cited by 69 | Viewed by 7118

Abstract

Background: β-lactoglobulin hydrolysates (BLGH) have shown antioxidant, antihypertensive, antimicrobial, and opioid activity. In the current study, an innovative combination of high hydrostatic pressure and enzymatic hydrolysis (HHP–EH) was used to increase the yield of short bioactive peptides, and evaluate the anti-inflammatory and antioxidant [...] Read more.

Background: β-lactoglobulin hydrolysates (BLGH) have shown antioxidant, antihypertensive, antimicrobial, and opioid activity. In the current study, an innovative combination of high hydrostatic pressure and enzymatic hydrolysis (HHP–EH) was used to increase the yield of short bioactive peptides, and evaluate the anti-inflammatory and antioxidant properties of the BLGH produced by the HHP–EH process. Method: BLG was enzymatically hydrolyzed by different proteases at an enzyme-to-substrate ratio of 1:100 under HHP (100 MPa) and compared with hydrolysates obtained under atmospheric pressure (AP-EH at 0.1 MPa). The degree of hydrolysis (DH), molecular weight distribution, and the antioxidant and anti-inflammatory properties of hydrolysates in chemical and cellular models were evaluated. Results: BLGH obtained under HHP–EH showed higher DH than the hydrolysates obtained under AP-EH. Free radical scavenging and the reducing capacity were also significantly stronger in HHP-BLGH compared to AP-BLGH. The BLGH produced by alcalase (Alc) (BLG-Alc) showed significantly higher antioxidant properties among the six enzymes examined in this study. The anti-inflammatory properties of BLG-HHP-Alc were observed in lipopolysaccharide-stimulated macrophage cells by a lower level of nitric oxide production and the suppression of the synthesis of pro-inflammatory cytokines. Peptide sequencing revealed that 38% of the amino acids in BLG-HHP-Alc are hydrophobic and aromatic residues, which contribute to its anti-inflammatory properties. Conclusions: Enzymatic hydrolysis of BLG under HHP produces a higher yield of short bioactive peptides with potential antioxidant and anti-inflammatory effects. Full article

(This article belongs to the Special Issue Natural Products and Chronic Diseases)

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13 pages, 5727 KiB

Open AccessArticle

Nanocrystalline TiO₂ Composite Films for the Photodegradation of Formaldehyde and Oxytetracycline under Visible Light Irradiation

by Min Wei¹, Xue-Lei Peng², Qi-Sheng Liu¹, Fang Li¹ and Ming-Ming Yao^1,*

¹ Key Laboratory of Interfacial Reaction & Sensing Analysis in Universities of Shandong, School of Chemistry and Chemical Engineering, University of Jinan, Jinan 250022, China

² Jinan Institute of Product Quality Inspections, Jinan 250022, China

Molecules 2017, 22(6), 950; https://doi.org/10.3390/molecules22060950 - 14 Jun 2017

Cited by 13 | Viewed by 4991

Abstract

In order to effectively photodegradate organic pollutants, ZnO composite and Co-B codoped TiO₂ films were successfully deposited on glass substrates via a modified sol-gel method and a controllable dip-coating technique. Combining with UV–Vis diffuse reflectance spectroscopy (DRS) and photoluminescence spectra (PL) analyses, [...] Read more.

In order to effectively photodegradate organic pollutants, ZnO composite and Co-B codoped TiO₂ films were successfully deposited on glass substrates via a modified sol-gel method and a controllable dip-coating technique. Combining with UV–Vis diffuse reflectance spectroscopy (DRS) and photoluminescence spectra (PL) analyses, the multi-modification could not only extend the optical response of TiO₂ to visible light region but also decrease the recombination rate of electron-hole pairs. XRD results revealed that the multi-modified TiO₂ film had an anatase-brookite biphase heterostructure. FE-SEM results indicated that the multi-modified TiO₂ film without cracks was composed of smaller round-like nanoparticles compared to pure TiO₂. BET surface area results showed that the specific surface area of pure TiO₂ and the multi-modified TiO₂ sample was 47.8 and 115.8 m²/g, respectively. By degradation of formaldehyde and oxytetracycline, experimental results showed that the multi-modified TiO₂ film had excellent photodegradation performance under visible light irradiation. Full article

(This article belongs to the Special Issue Nanocrystals: Synthesis, Characterization and Applications)

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13 pages, 7865 KiB

Open AccessArticle

Anti-Inflammatory Activities and Liver Protection of Alisol F and 25-Anhydroalisol F through the Inhibition of MAPK, STAT3, and NF-κB Activation In Vitro and In Vivo

by Xiaoxu Bi, Pu Wang, Qingjuan Ma, Li Han^*, Xingbo Wang, Yu Mu, Peipei Guan, Xiaodan Qu, Zhanyou Wang and Xueshi Huang^*

College of Life and Health Sciences, Northeastern University, Shenyang 110819, China

Molecules 2017, 22(6), 951; https://doi.org/10.3390/molecules22060951 - 8 Jun 2017

Cited by 31 | Viewed by 5415

Abstract

Alisol F and 25-anhydroalisol F isolated from Alisma orientale, were proved to exhibit anti-inflammatory potential in our previous work. In the current study, the anti-inflammatory effects and action mechanisms of alisol F and 25-anhydroalisol F were investigated in vitro. Moreover, the pharmacological [...] Read more.

Alisol F and 25-anhydroalisol F isolated from Alisma orientale, were proved to exhibit anti-inflammatory potential in our previous work. In the current study, the anti-inflammatory effects and action mechanisms of alisol F and 25-anhydroalisol F were investigated in vitro. Moreover, the pharmacological effects of alisol F in lipopolysaccharide (LPS)/d-galactosamine (d-gal)-induced acute liver-injured mice were evaluated. The results demonstrated that alisol F and 25-anhydroalisol F could suppress LPS-induced production of nitric oxide (NO), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and interleukin-1β (IL-1β), as well as inhibit the mRNA and protein levels of inducible nitric oxide (iNOS) and cyclooxygenase-2 (COX-2). In addition, we investigated the role of alisol F and 25-anhydroalisol F in mediating mitogen-activated protein kinases (MAPKs), signal transducers, and activators of transcription 3 (STAT3) and nuclear factor κB (NF-κB) pathways involved in the inflammation process of LPS-stimulated RAW 264.7 cells. The phosphorylation of ERK, JNK, p38, and STAT3, and the NF-κB signaling pathway, were obviously suppressed in alisol F and 25-anhydroalisol F treated cells. Results obtained from in vitro experiments suggested alisol F obviously improved liver pathological injury by inhibiting the production of TNF-α, IL-1β, and IL-6, and significantly decreasing the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in LPS/d-gal-induced mice. Furthermore, the reduction of phosphorylation of ERK and JNK, as well as suppression of the NF-κB signaling pathway, were also observed in liver tissues of the alisol F-treated mice model. Alisol F and 25-anhydroalisol F may serve as potential leads for development of anti-inflammatory agents for acute liver failure treatment. Full article

(This article belongs to the Section Medicinal Chemistry)

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12 pages, 5853 KiB

Open AccessArticle

Lipophilicity Studies on Thiosemicarbazide Derivatives

by Agata Paneth^1,*

, Anna Hawrył², Tomasz Plech¹

, Mirosław Hawrył², Ryszard Świeboda², Dominika Janowska¹, Monika Wujec¹ and Piotr Paneth³

¹ Department of Organic Chemistry, Medical University, Chodźki 4a, 20-093 Lublin, Poland

² Department of Inorganic Chemistry, Medical University, Chodźki 4a, 20-093 Lublin, Poland

³ Institute of Applied Radiation Chemistry, Lodz University of Technology, Żeromskiego 116, 90-924 Łódź, Poland

Molecules 2017, 22(6), 952; https://doi.org/10.3390/molecules22060952 - 8 Jun 2017

Cited by 10 | Viewed by 4058

Abstract

The lipophilicity of two series of thiosemicarbazide derivatives was assessed by the RP-HPLC method with the RP-18 chromatographic column and the methanol–water mixture as the mobile phase. Distribution coefficients logP_HPLC were compared to calculated values generated by commonly used AClogP software and [...] Read more.

The lipophilicity of two series of thiosemicarbazide derivatives was assessed by the RP-HPLC method with the RP-18 chromatographic column and the methanol–water mixture as the mobile phase. Distribution coefficients logP_HPLC were compared to calculated values generated by commonly used AClogP software and quantum chemical calculations. The reliability of the predictions was evaluated using the correlation matrix and PCA. For 4-benzoylthiosemicarbazides, a high correlation between theoretical and experimental logP parameters was obtained using the XlogP3 algorithm, while for 4-aryl/(cyclohexyl)thiosemicarbazides, the XlogP2 parameter was strongly correlated with the experimentally obtained logP. Full article

(This article belongs to the Section Medicinal Chemistry)

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13 pages, 4079 KiB

Open AccessArticle

Atom Efficient Preparation of Zinc Selenates for the Synthesis of Selenol Esters under “On Water” Conditions

by Luca Sancineto¹, Jaqueline Pinto Vargas², Bonifacio Monti¹, Massimiliano Arca³, Vito Lippolis³, Gelson Perin⁴, Eder Joao Lenardao^4,* and Claudio Santi^1,*

¹ Catalysis and Organic Green Chemistry Group, Department of Pharmaceutical Sciences, University of Perugia, Via del Liceo 1, 06100 Perugia, Italy

² Universidade Federal do Pampa—Unipampa, Av. Pedro Anunciação, 111, Caçapava do Sul-RS 96570-000, Brazil

³ Dipartimento di Scienze Chimiche e Geologiche, Università degli Studi di Cagliari, S.S. 554 bivio per Sestu, 09042 Monserrato, Cagliari, Italy

⁴ Laboratório de Síntese Orgânica Limpa-LASOL-CCQFA, Universidade Federal de Pelotas-UFPel, P.O. Box 354, Pelotas-RS 96010-900, Brazil

Molecules 2017, 22(6), 953; https://doi.org/10.3390/molecules22060953 - 8 Jun 2017

Cited by 17 | Viewed by 6111

Abstract

We describe here an atom efficient procedure to prepare selenol esters in good to excellent yields by reacting [(PhSe)₂Zn] or [(PhSe)₂Zn]TMEDA with acyl chlorides under “on water” conditions. The method is applicable to a series of aromatic and aliphatic [...] Read more.

We describe here an atom efficient procedure to prepare selenol esters in good to excellent yields by reacting [(PhSe)₂Zn] or [(PhSe)₂Zn]TMEDA with acyl chlorides under “on water” conditions. The method is applicable to a series of aromatic and aliphatic acyl chlorides and tolerates the presence of other functionalities in the starting material. Full article

(This article belongs to the Special Issue Celebrating Two Centuries of Research in Selenium Chemistry: State of the Art and New Prospectives)

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13 pages, 2294 KiB

Open AccessArticle

Rapid Complexation of Aptamers by Their Specific Antidotes

by Heidi Stoll^1,†, Heidrun Steinle^1,†, Nadja Wilhelm¹, Ludmilla Hann¹, Silju-John Kunnakattu¹, Miwako Narita², Christian Schlensak¹, Hans P. Wendel¹ and Meltem Avci-Adali^1,*

¹ Department of Thoracic and Cardiovascular Surgery, University Hospital Tuebingen, 72076 Tuebingen, Germany

² Laboratory of Hematology and Oncology, Graduate School of Health Sciences, Niigata University, Niigata 951-8518, Japan

^† These authors contributed equally to this work.

Molecules 2017, 22(6), 954; https://doi.org/10.3390/molecules22060954 - 8 Jun 2017

Cited by 11 | Viewed by 5907

Abstract

Nucleic acid ligands, aptamers, harbor the unique characteristics of small molecules and antibodies. The specificity and high affinity of aptamers enable their binding to different targets, such as small molecules, proteins, or cells. Chemical modifications of aptamers allow increased bioavailability. A further great [...] Read more.

Nucleic acid ligands, aptamers, harbor the unique characteristics of small molecules and antibodies. The specificity and high affinity of aptamers enable their binding to different targets, such as small molecules, proteins, or cells. Chemical modifications of aptamers allow increased bioavailability. A further great benefit of aptamers is the antidote (AD)-mediated controllability of their effect. In this study, the AD-mediated complexation and neutralization of the thrombin binding aptamer NU172 and Toll-like receptor 9 (TLR9) binding R10-60 aptamer were determined. Thereby, the required time for the generation of aptamer/AD-complexes was analyzed at 37 °C in human serum using gel electrophoresis. Afterwards, the blocking of aptamers’ effects was analyzed by determining the activated clotting time (ACT) in the case of the NU172 aptamer, or the expression of immune activation related genes IFN-1β, IL-6, CXCL-10, and IL-1β in the case of the R10-60 aptamer. Gel electrophoresis analyses demonstrated the rapid complexation of the NU172 and R10-60 aptamers by complementary AD binding after just 2 min of incubation in human serum. A rapid neutralization of anticoagulant activity of NU172 was also demonstrated in fresh human whole blood 5 min after addition of AD. Furthermore, the TLR9-mediated activation of PMDC05 cells was interrupted after the addition of the R10-60 AD. Using these two different aptamers, the rapid antagonizability of the aptamers was demonstrated in different environments; whole blood containing numerous proteins, cells, and different small molecules, serum, or cell culture media. Thus, nucleic acid ADs are promising molecules, which offer several possibilities for different in vivo applications, such as antagonizing aptamer-based drugs, immobilization, or delivery of oligonucleotides to defined locations. Full article

(This article belongs to the Collection Nanomedicine)

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17 pages, 9828 KiB

Open AccessArticle

From Intermolecular Interactions to Texture in Polycrystalline Surfaces of 1,ω-alkanediols (ω = 10–13)

by Gilgamesh Luis-Raya^1,2, Màrius Ramírez-Cardona^1,*

, Gabriel Luna-Bárcenas^3,*

, Martín A. Hernández-Landaverde³, Adair Jiménez-Nieto³, Jose Luis García-Rivas⁴, Beatriz Liliana España-Sánchez³ and Isaac C. Sanchez⁵

¹ Área Académica de Ciencias de la Tierra y Materiales, Universidad Autónoma del Estado de Hidalgo, Ciudad del Conocimiento, Col. Carboneras, Mineral de la Reforma, 42184 Hidalgo, Mexico

² Universidad Politécnica de Pachuca, Carretera Pachuca-Cd. Sahagún km 20 Ex-Hacienda de Santa Bárbara, Zempoala, 43830 Hidalgo, Mexico

³ Centro de Investigación y Estudios Avanzados, Unidad Querétaro, Querétaro, 76200 Querétaro, Mexico

⁴ División de Estudios de Posgrado e Investigación, Instituto Tecnológico de Toluca, Av. Tecnológico s/n Colonia Agrícola Bella Vista, 52149 Metepec, México

⁵ Department of Chemical Engineering, The University of Texas at Austin, Austin, 78712-1589 TX, USA

Molecules 2017, 22(6), 956; https://doi.org/10.3390/molecules22060956 - 8 Jun 2017

Cited by 3 | Viewed by 3920

Abstract

Differences on herringbone molecular arrangement in two forms of long-chain 1,ω-alkanediols (C_nH_2n+2O₂ with n = 10, 11, 12, 13) are explained from the analysis of O-H···O hydrogen-bond sequences in infinite chains and the role of a [...] Read more.

Differences on herringbone molecular arrangement in two forms of long-chain 1,ω-alkanediols (C_nH_2n+2O₂ with n = 10, 11, 12, 13) are explained from the analysis of O-H···O hydrogen-bond sequences in infinite chains and the role of a C-H···O intramolecular hydrogen-bond in stabilization of a gauche defect, as well as the inter-grooving effectiveness on molecular packing. GIXD (Glancing Incidence X-ray Diffraction) experiments were conducted on polycrystalline monophasic samples. Diffracted intensities were treated with the multi-axial March-Dollase method to correlate energetic and geometrical features of molecular interactions with the crystalline morphology and textural pattern of samples. The monoclinic (P2₁/c, Z = 2) crystals of the even-numbered members (n = 10, 12; DEDOL and DODOL, respectively) are diametrical prisms with combined form {104}/{-104}/{001} and present a two-fold platelet-like preferred orientation, whereas orthorhombic (P2₁2₁2₁, Z = 4) odd-numbered members (n = 11, 13; UNDOL and TRDOL, respectively) present a dominant needle-like orientation on direction [101] (fiber texture). We show that crystalline structures of medium complexity and their microstructures can be determined from rapid GIXD experiments from standard radiation, combined with molecular replacement procedure using crystal structures of compounds with higher chain lengths as reference data. Full article

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11 pages, 775 KiB

Open AccessArticle

Synthesis and Evaluation of Antimicrobial Activity of [R₄W₄K]-Levofloxacin and [R₄W₄K]-Levofloxacin-Q Conjugates

by Neda Riahifard¹, Kathy Tavakoli¹, Jason Yamaki², Keykavous Parang^1,*

and Rakesh Tiwari^1,*

¹ Center for Targeted Drug Delivery, Department of Biomedical and Pharmaceutical Sciences, Chapman University School of Pharmacy, Harry and Diane Rinker Health Science Campus, Irvine, CA 92618, USA

² Department of Pharmacy Practice, Chapman University School of Pharmacy, Harry and Diane Rinker Health Science Campus, Irvine, CA 92618, USA

Molecules 2017, 22(6), 957; https://doi.org/10.3390/molecules22060957 - 8 Jun 2017

Cited by 34 | Viewed by 7859

Abstract

The development of a new class of antibiotics to fight bacterial resistance is a time-consuming effort associated with high-cost and commercial risks. Thus, modification, conjugation or combination of existing antibiotics to enhance their efficacy is a suitable strategy. We have previously reported that [...] Read more.

The development of a new class of antibiotics to fight bacterial resistance is a time-consuming effort associated with high-cost and commercial risks. Thus, modification, conjugation or combination of existing antibiotics to enhance their efficacy is a suitable strategy. We have previously reported that the amphiphilic cyclic peptide [R₄W₄] had antibacterial activity with a minimum inhibitory concentration (MIC) of 2.97 µg/mL against Methicillin-resistant Staphylococcus aureus (MRSA). Herein, we hypothesized that conjugation or combination of the amphiphilic cyclic peptide [R₄W₄] with levofloxacin or levofloxacin-Q could improve the antibacterial activity of levofloxacin and levofloxacin-Q. Fmoc/tBu solid-phase chemistry was employed to synthesize conjugates of [R₄W₄K]-levofloxacin-Q and [R₄W₄K]-levofloxacin. The carboxylic acid group of levofloxacin or levofloxacin-Q was conjugated with the amino group of β-alanine attached to lysine in the presence of 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexaﬂuorophosphate (HBTU) and N,N-diisopropylethylamine (DIPEA) for 3 h to afford the products. Antibacterial assays were conducted to determine the potency of conjugates [R₄W₄K]-levofloxacin-Q and [R₄W₄K]-levofloxacin against MRSA and Klebsiella pneumoniae. Although levofloxacin-Q was inactive even at a concentration of 128 µg/mL, [R₄W₄K]-levofloxacin-Q conjugate and the corresponding physical mixture showed MIC values of 8 µg/mL and 32 µg/mL against MRSA and Klebsiella pneumonia, respectively, possibly due to the activity of the peptide. On the other hand, [R₄W₄K]-levofloxacin conjugate (MIC = 32 µg/mL and MIC = 128 µg/mL) and the physical mixture (MIC = 8 µg/mL and 32 µg/mL) was less active than levofloxacin (MIC = 2 µg/mL and 4 = µg/mL) against MRSA and Klebsiella pneumoniae, respectively. The data showed that the conjugation of levofloxacin with [R₄W₄K] significantly reduced the antibacterial activity compared to the parent analogs, while [R₄W₄K]-levofloxacin-Q conjugate was more significantly potent than levofloxacin-Q alone. Full article

(This article belongs to the Special Issue Frontiers in Antimicrobial Drug Discovery and Design)

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11 pages, 696 KiB

Open AccessArticle

Ovicidal and Insecticidal Activities of Pyriproxyfen Derivatives with an Oxime Ester Group

by Guo-Shao Sun, Xin Xu, Shu-Hui Jin^*, Le Lin and Jian-Jun Zhang^*

Department of Applied Chemistry, College of Science, China Agricultural University, Beijing 100193, China

Molecules 2017, 22(6), 958; https://doi.org/10.3390/molecules22060958 - 8 Jun 2017

Cited by 18 | Viewed by 4542

Abstract

Based on the structural framework of a pyriproxyfen metabolite, nineteen oxime ester derivatives were synthesized via reaction of the carboxylic acids with 4-(2-(2-pyridinyloxy)ethoxy)benzaldehyde oxime. The corresponding structures were comprehensively characterized by ¹H-nuclear magnetic resonance (NMR), ¹³C-NMR, and electrospray ionization high-resolution mass [...] Read more.

Based on the structural framework of a pyriproxyfen metabolite, nineteen oxime ester derivatives were synthesized via reaction of the carboxylic acids with 4-(2-(2-pyridinyloxy)ethoxy)benzaldehyde oxime. The corresponding structures were comprehensively characterized by ¹H-nuclear magnetic resonance (NMR), ¹³C-NMR, and electrospray ionization high-resolution mass spectrometry (ESI-HRMS). All of the compounds were screened for their insecticidal activities against Plutella xylostella and Myzus persicae, and for their ovicidal activities against Helicoverpa armigera eggs. The results obtained show that most of the oxime ester derivatives displayed moderate to high insecticidal activities and ovicidal activities at a concentration of 600 ug/mL. In particular, the ovicidal activity of compounds 5j, 5o, 5p, 5q, and 5s was determined to be 100%. Importantly, some of the compounds presented even higher biological activities than the reference compound pyriproxyfen. For example, compound 5j displayed an insecticidal activity value of 87.5% against Myzus persicae, whereas the activity value of pyriproxyfen was 68.3% at a concentration of 600 ug/mL. Among the synthesized compounds 5j and 5s exhibited broad biological activity spectra. Full article

(This article belongs to the Section Medicinal Chemistry)

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13 pages, 12254 KiB

Open AccessArticle

3D Pharmacophore-Based Virtual Screening and Docking Approaches toward the Discovery of Novel HPPD Inhibitors

by Ying Fu¹

, Yi-Na Sun¹

, Ke-Han Yi¹, Ming-Qiang Li¹, Hai-Feng Cao¹, Jia-Zhong Li² and Fei Ye^1,*

¹ Department of Applied Chemistry, College of Science, Northeast Agricultural University, Harbin 150030, China

² School of Pharmacy, Lanzhou University, 199 West Donggang Rd., Lanzhou 730000, China

Molecules 2017, 22(6), 959; https://doi.org/10.3390/molecules22060959 - 9 Jun 2017

Cited by 49 | Viewed by 9154

Abstract

p-Hydroxyphenylpyruvate dioxygenase (HPPD) is not only the useful molecular target in treating life-threatening tyrosinemia type I, but also an important target for chemical herbicides. A combined in silico structure-based pharmacophore and molecular docking-based virtual screening were performed to identify novel potential HPPD [...] Read more.

p-Hydroxyphenylpyruvate dioxygenase (HPPD) is not only the useful molecular target in treating life-threatening tyrosinemia type I, but also an important target for chemical herbicides. A combined in silico structure-based pharmacophore and molecular docking-based virtual screening were performed to identify novel potential HPPD inhibitors. The complex-based pharmacophore model (CBP) with 0.721 of ROC used for screening compounds showed remarkable ability to retrieve known active ligands from among decoy molecules. The ChemDiv database was screened using CBP-Hypo2 as a 3D query, and the best-fit hits subjected to molecular docking with two methods of LibDock and CDOCKER in Accelrys Discovery Studio 2.5 (DS 2.5) to discern interactions with key residues at the active site of HPPD. Four compounds with top rankings in the HipHop model and well-known binding model were finally chosen as lead compounds with potential inhibitory effects on the active site of target. The results provided powerful insight into the development of novel HPPD inhibitors herbicides using computational techniques. Full article

(This article belongs to the Section Computational and Theoretical Chemistry)

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10 pages, 2364 KiB

Open AccessArticle

Isoprenoids Production from Lipid-Extracted Microalgal Biomass Residues Using Engineered E. coli

by Sumeng Wang and Jianming Yang^*

Key Lab of Applied Mycology, College of Life Sciences, Qingdao Agricultural University, Qingdao 266109, China

Molecules 2017, 22(6), 960; https://doi.org/10.3390/molecules22060960 - 9 Jun 2017

Cited by 6 | Viewed by 5022

Abstract

Microalgae are recognized as a third generation feedstock for biofuel production due to their rapid growth rates and lignin-free characteristics. In this study, a lipid extracted microalgal biomass residues was used as the raw material to produce isoprene, α-pinene and β-pinene with an [...] Read more.

Microalgae are recognized as a third generation feedstock for biofuel production due to their rapid growth rates and lignin-free characteristics. In this study, a lipid extracted microalgal biomass residues was used as the raw material to produce isoprene, α-pinene and β-pinene with an engineered E. coli strain. We adopted an optimal sulfuric acid hydrolysis method (1:7 ratio of solid to acid solution, 32% (w/v) concentration of sulfuric acid solution at 90 °C for 90 min) to efficiently convert holocellulose into glucose efficiently (6.37 g/L). Futhermore, we explored a novel detoxification strategy (phosphoric acid/calcium hydroxide) to remove inhibitors and notably acetic acid, furfural and 5-hydroxymethylfurfural (5-HMF) were reduced by 5.32%, different number given later 99.19% and 98.22%, respectively. Finally, the fermentation concentrations of isoprene (223.23 mg/L), α-pinene (382.21 μg/L) and β-pinene (17.4 mg/L) were achieved using the detoxified hydrolysate as the carbon source, equivalent to approximately 86.02%, 90.16% and 88.32% of those produced by the engineered E. coli strain fermented on pure glucose, respectively. Full article

(This article belongs to the Special Issue Isoprenoid Biosynthesis)

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15 pages, 5518 KiB

Open AccessArticle

New Strigolactone Mimics as Exogenous Signals for Rhizosphere Organisms

by Florin Oancea¹

, Emilian Georgescu², Radoslava Matusova³, Florentina Georgescu⁴, Alina Nicolescu^5,6

, Iuliana Raut¹, Maria-Luiza Jecu¹, Marius-Constantin Vladulescu⁴, Lucian Vladulescu⁴ and Calin Deleanu^5,6,*

¹ National Research & Development Institute for Chemistry & Petrochemistry–ICECHIM, Spl. Independentei 202, RO-060021 Bucharest, Romania

² Research Center Oltchim, St. Uzinei 1, RO-240050 Ramnicu Valcea, Romania

³ Plant Science and Biodiversity Center SAS, Institute of Plant Genetics and Biotechnology, PO Box 39A, 95007 Nitra, Slovakia

⁴ Research Department Teso Spec S. R. L., Str. Muncii 53, RO-915200 Fundulea, Romania

⁵ Centre of Organic Chemistry, Romanian Academy, Spl. Independentei 202B, RO-060023 Bucharest, Romania

⁶ Institute of Macromolecular Chemistry, Romanian Academy, Aleea Grigore Ghica Voda 41-A, 700487 Iasi, Romania

Molecules 2017, 22(6), 961; https://doi.org/10.3390/molecules22060961 - 9 Jun 2017

Cited by 24 | Viewed by 6279

Abstract

The importance of strigolactones in plant biology prompted us to synthesize simplified strigolactone mimics effective as exogenous signals for rhizosphere organisms. New strigolactone mimics easily derived from simple and available starting materials in significant amounts were prepared and fully characterized. These compounds contain [...] Read more.

The importance of strigolactones in plant biology prompted us to synthesize simplified strigolactone mimics effective as exogenous signals for rhizosphere organisms. New strigolactone mimics easily derived from simple and available starting materials in significant amounts were prepared and fully characterized. These compounds contain an aromatic or heterocyclic ring, usually present in various bioactive molecules, connected by an ether link to a furan-2-one moiety. The new synthesized strigolactone mimics were confirmed to be active on plant pathogenic fungi and parasitic weed seeds. Full article

(This article belongs to the Special Issue Natural Product Inspired Scaffolds Designs)

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13 pages, 2159 KiB

Open AccessArticle

Subcritical Water Chromatography with Electrochemical Detection

by Heather Anderson and Yu Yang^*

Department of Chemistry, East Carolina University, Science & Technology Building 584, Greenville, NC 27858, USA

Molecules 2017, 22(6), 962; https://doi.org/10.3390/molecules22060962 - 9 Jun 2017

Cited by 1 | Viewed by 5055

Abstract

Reverse phase liquid chromatography (RPLC) is a commonly used separation and analysis technique. RPLC typically employs mixtures of organic solvents and water or aqueous buffers as the mobile phase. With RPLC being used on a global scale, enormous quantities of organic solvents are [...] Read more.

Reverse phase liquid chromatography (RPLC) is a commonly used separation and analysis technique. RPLC typically employs mixtures of organic solvents and water or aqueous buffers as the mobile phase. With RPLC being used on a global scale, enormous quantities of organic solvents are consumed every day. In addition to the purchasing cost of the hazardous solvents, the issue of waste disposal is another concern. At ambient temperature, water is too polar to dissolve many organic substances. Therefore, although water is nontoxic it cannot be used to replace the mobile phase in RPLC since organic analytes will not be eluted. Subcritical water chromatography may be an alternative. The characteristics of water, such as polarity, surface tension, and viscosity, can be altered by manipulating water’s temperature, thus making it behave like an organic solvent. The aim of this study was to evaluate the feasibility of separation using water mobile phase and detection by an electrochemical (EC) detector. The classes of analytes studied were neurotransmitters/metabolites, nucleic acids/heterocyclic bases, and capsaicinoids. Both isothermal and temperature-programmed separations were carried out. The separation temperature ranged from 25 to 100 °C. For separations of all three classes of solutes, the retention time was decreased with increasing temperature, thus shortening the analysis time. The peaks also became narrower as temperature increased. The limit of detection of neurotransmitters/metabolites ranges from 0.112 to 0.224 ppm. Full article

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

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17 pages, 5165 KiB

Open AccessFeature PaperArticle

Self-Assembled Lipid Nanoparticles for Oral Delivery of Heparin-Coated Iron Oxide Nanoparticles for Theranostic Purposes

by Eleonora Truzzi¹, Chiara Bongio², Francesca Sacchetti¹, Eleonora Maretti¹

, Monica Montanari³, Valentina Iannuccelli¹

, Elena Vismara^2,* and Eliana Leo^1,*

¹ Department of Life Sciences, University of Modena and Reggio Emilia, via Campi 103, 41125 Modena, Italy

² Department of Chemistry, Materials and Chemical Engineering “G. Natta”, via Mancinelli 7, Politecnico di Milano, 20131 Milano, Italy

³ Department of Life Sciences, University of Modena and Reggio Emilia, via Campi 287, 41125 Modena, Italy

Molecules 2017, 22(6), 963; https://doi.org/10.3390/molecules22060963 - 9 Jun 2017

Cited by 30 | Viewed by 6022

Abstract

Recently, solid lipid nanoparticles (SLNs) have attracted increasing attention owing to their potential as an oral delivery system, promoting intestinal absorption in the lymphatic circulation which plays a role in disseminating metastatic cancer cells and infectious agents throughout the body. SLN features can [...] Read more.

Recently, solid lipid nanoparticles (SLNs) have attracted increasing attention owing to their potential as an oral delivery system, promoting intestinal absorption in the lymphatic circulation which plays a role in disseminating metastatic cancer cells and infectious agents throughout the body. SLN features can be exploited for the oral delivery of theranostics. Therefore, the aim of this work was to design and characterise self-assembled lipid nanoparticles (SALNs) to encapsulate and stabilise iron oxide nanoparticles non-covalently coated with heparin (Fe@hepa) as a model of a theranostic tool. SALNs were characterised for physico-chemical properties (particle size, surface charge, encapsulation efficiency, in vitro stability, and heparin leakage), as well as in vitro cytotoxicity by methyl thiazole tetrazolium (MTT) assay and cell internalisation in CaCo-2, a cell line model used as an indirect indication of intestinal lymphatic absorption. SALNs of about 180 nm, which are stable in suspension and have a high encapsulation efficiency (>90%) were obtained. SALNs were able to stabilise the heparin coating of Fe@hepa, which are typically unstable in physiological environments. Moreover, SALNs–Fe@hepa showed no cytotoxicity, although their ability to be internalised into CaCo-2 cells was highlighted by confocal microscopy analysis. Therefore, the results indicated that SALNs can be considered as a promising tool to orally deliver theranostic Fe@hepa into the lymphatic circulation, although further in vivo studies are needed to comprehend further potential applications. Full article

(This article belongs to the Special Issue Looking Forward to the Future of Heparin: New Sources, Developments and Applications)

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13 pages, 15475 KiB

Open AccessArticle

UV-Curable Aliphatic Silicone Acrylate Organic–Inorganic Hybrid Coatings with Antibacterial Activity

by Virginija Jankauskaitė^1,*, Algirdas Lazauskas², Egidijus Griškonis³

, Aistė Lisauskaitė¹ and Kristina Žukienė¹

¹ Faculty of Mechanical Engineering and Design, Kaunas University of Technology, Studentų St. 56, LT-51424 Kaunas, Lithuania

² Institute of Materials Science, Kaunas University of Technology, Baršausko St. 59, LT-51423 Kaunas, Lithuania

³ Faculty of Chemical Technology, Kaunas University of Technology, Radvilėnų St. 19, LT-50254 Kaunas, Lithuania

Molecules 2017, 22(6), 964; https://doi.org/10.3390/molecules22060964 - 9 Jun 2017

Cited by 10 | Viewed by 7816

Abstract

The most effective means to protect against bacterial invasion and to reduce the risk of healthcare-associated infections are antibacterial components synthesis. In this study, a novel process for the synthesis of organic–inorganic hybrid coatings containing silver nanoparticles is presented. Silver nanoparticles and polymer [...] Read more.

The most effective means to protect against bacterial invasion and to reduce the risk of healthcare-associated infections are antibacterial components synthesis. In this study, a novel process for the synthesis of organic–inorganic hybrid coatings containing silver nanoparticles is presented. Silver nanoparticles and polymer formation proceeds simultaneously through the in situ photoreduction of silver salt to silver nanoparticles and UV-crosslinking of bifunctional aliphatic silicone acrylate. The nanocomposite films with 0.5–1.43 wt % of silver nanoparticles concentration were obtained and investigated. The formation of silver nanoparticles in polymer matrix was confirmed via UV-visible spectroscopy, X-ray diffraction (XRD), Fourier transform infrared spectroscopy, scanning electron spectroscopy, and energy dispersive spectroscopy. Our investigations clearly show the formation of silver nanoparticles in silicone acrylate network. Direct photoreduction of silver salt by UV-radiation in the organic media produced silver nanoparticles exhibiting cubic crystal structure. The size of nanoparticles was determined to be near 20 ± 5 nm. The antibacterial activities of coatings were determined using the disc diffusion and direct contact methods. UV-curable silicone acrylate hybrid coatings exhibited antibacterial activity against harmful bacteria strains. Full article

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

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19 pages, 3943 KiB

Open AccessArticle

Extraction Optimization, Characterization, and Bioactivities of Polysaccharides from Pinelliae Rhizoma Praeparatum Cum Alumine Employing Ultrasound-Assisted Extraction

by Yu-Jie Liu^1,†, Xue-Lin Mo^1,†, Xiao-Zhang Tang¹, Jiang-Hua Li¹, Mei-Bian Hu¹, Dan Yan¹, Wei Peng¹ and Chun-Jie Wu^1,2,*

¹ College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China

² Key Research Laboratory of Traditional Chinese Medicine Processing Technology, State Administration of Traditional Chinese Medicine of People’s Republic of China, Chengdu 611137, China

^† These authors contributed equally to this manuscript.

Molecules 2017, 22(6), 965; https://doi.org/10.3390/molecules22060965 - 9 Jun 2017

Cited by 41 | Viewed by 6612

Abstract

In this study, the ultrasound-assisted extraction of polysaccharides (PSA) from Pinelliae Rhizoma Praeparatum Cum Alumine (PRPCA) was optimized by response surface methodology (RSM). The structural characteristics of PSA were analyzed by UV-vis spectroscopy, infrared spectroscopy, scanning electron microscopy, high performance gel permeation chromatography [...] Read more.

In this study, the ultrasound-assisted extraction of polysaccharides (PSA) from Pinelliae Rhizoma Praeparatum Cum Alumine (PRPCA) was optimized by response surface methodology (RSM). The structural characteristics of PSA were analyzed by UV-vis spectroscopy, infrared spectroscopy, scanning electron microscopy, high performance gel permeation chromatography and high performance liquid chromatography, respectively. In addition, antioxidant and antimicrobial activities of PSA were studied by different in vitro assays. Results indicated that the optimal extraction conditions were as follows: the ratio of water to raw of 30 mL/g, extraction time of 46.50 min, ultrasonic temperature of 72.00 °C, and ultrasonic power of 230 W. Under these conditions, the obtained PSA yield (13.21 ± 0.37%) was closely agreed with the predicted yield by the model. The average molecular weights of the PSA were estimated to be 5.34 × 10³ and 6.27 × 10⁵ Da. Monosaccharide composition analysis indicated that PSA consisted of mannose, galactose uronic acid, glucose, galactose, arabinose with a molar ratio of 1.83:0.55:75.75:1.94:0.45. Furthermore, PSA exhibited moderate antioxidant and antibacterial activities in vitro. Collectively, this study provides a promising strategy to obtain bioactive polysaccharides from processed products of herbal medicines. Full article

(This article belongs to the Special Issue Natural Polysaccharides)

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7 pages, 720 KiB

Open AccessFeature PaperArticle

Dichlorotrifluoromethoxyacetic Acid: Preparation and Reactivity

by Riadh Zriba¹, Alaric Desmarchelier¹, Frédéric Cadoret¹, Sébastien Bouvet¹, Anne-Laure Barthelemy¹, Bruce Pégot¹, Patrick Diter¹, Guillaume Dagousset¹, Jean-Claude Blazejewski¹, Elsa Anselmi^1,2, Yurii Yagupolskii³ and Emmanuel Magnier^1,*

¹ Institut Lavoisier de Versailles (ILV), UMR CNRS 8180, Université de Versailles, 45 avenue des Etats-Unis, 78035 Versailles CEDEX, France

² Infectiologie et Santé Publique (ISP), UMR 1282 INRA/Université de Tours (UFR Sciences & Techniques), Parc de Grandmont, 37200 Tours, France

³ Institute of Organic Chemistry, National Academy of Sciences of Ukraine, Murmans’ka Str. 5, 02094 Kyiv, Ukraine

Molecules 2017, 22(6), 966; https://doi.org/10.3390/molecules22060966 - 9 Jun 2017

Cited by 1 | Viewed by 4875

Abstract

We describe the first gram scale preparation of the reagent dichlorotrifluoromethoxyacetic acid. This stable compound is obtained in five steps starting from the cheap diethylene glycol. The reactivity of the sodium salt of this fluorinated acid was also tested and allowed the preparation [...] Read more.

We describe the first gram scale preparation of the reagent dichlorotrifluoromethoxyacetic acid. This stable compound is obtained in five steps starting from the cheap diethylene glycol. The reactivity of the sodium salt of this fluorinated acid was also tested and allowed the preparation of new amides. Full article

(This article belongs to the Special Issue Tri- and Di-Fluoromethylation and Tri- and Di-Fluoromethylchalcogenation Reactions)

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11 pages, 614 KiB

Open AccessArticle

Anti-Inflammatory and Neuroprotective Constituents from the Peels of Citrus grandis

by Ping-Chung Kuo^1,†

, Yu-Ren Liao^1,†, Hsin-Yi Hung^1,†, Chia-Wei Chuang², Tsong-Long Hwang^3,4,5

, Shiow-Chyn Huang⁶, Young-Ji Shiao⁷

, Daih-Huang Kuo⁸ and Tian-Shung Wu^1,8,*

¹ School of Pharmacy, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan

² Department of Chemistry, National Cheng Kung University, Tainan 701, Taiwan

³ Graduate Institute of Natural Products, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan

⁴ 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

⁵ Department of Anesthesiology, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan

⁶ Department of Pharmacy, Chia-Nan University of Pharmacy and Science, Tainan 717, Taiwan

⁷ Division of Basic Chinese Medicine, National Research Institute of Chinese Medicine, Ministry of Health and Welfare, Taipei 112, Taiwan

⁸ Department of Pharmacy, College of Pharmacy and Health Care, Tajen University, Pingtung 907, Taiwan

^† These authors contributed equally to this work.

Molecules 2017, 22(6), 967; https://doi.org/10.3390/molecules22060967 - 9 Jun 2017

Cited by 50 | Viewed by 6855

Abstract

A series of chromatographic separations performed on the ethanol extracts of the peels of Citrus grandis has led to the characterization of forty compounds, including seventeen coumarins, eight flavonoids, two triterpenoids, four benzenoids, two steroids, one lignan, one amide, and five other compounds, [...] Read more.

A series of chromatographic separations performed on the ethanol extracts of the peels of Citrus grandis has led to the characterization of forty compounds, including seventeen coumarins, eight flavonoids, two triterpenoids, four benzenoids, two steroids, one lignan, one amide, and five other compounds, respectively. The chemical structures of the purified constituents were identified on the basis of spectroscopic elucidation, including 1D- and 2D-NMR, UV, IR, and mass spectrometric analysis. Most of the isolated compounds were examined for their inhibition of superoxide anion generation and elastase release by human neutrophils. Among the isolates, isomeranzin (3), 17,18-dihydroxybergamottin (12), epoxybergamottin (13), rhoifolin (19), vitexicarpin (22) and 4-hydroxybenzaldehyde (29) displayed the most significant inhibition of superoxide anion generation and elastase release with IC₅₀ values ranged from 0.54 to 7.57 μM, and 0.43 to 4.33 μM, respectively. In addition, 7-hydroxy-8-(2′-hydroxy-3′-methylbut-3′-enyl)coumarin (8) and 17,18-dihydroxybergamottin (12) also exhibited the protection of neurons against A-mediated neurotoxicity at 50 μM. Full article

(This article belongs to the Section Natural Products Chemistry)

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9 pages, 552 KiB

Open AccessArticle

Hemi-Synthesis and Anti-Oomycete Activity of Analogues of Isocordoin

by Beatriz Escobar¹, Iván Montenegro^2,3, Joan Villena³, Enrique Werner⁴, Patricio Godoy⁵, Yusser Olguín⁶ and Alejandro Madrid^1,*

¹ Departamento de Química, Facultad de Ciencias Naturales y Exactas, Universidad de Playa Ancha, Avda. Leopoldo Carvallo 270, Playa Ancha, Valparaíso 2340000, Chile

² Escuela de Obstetricia y Puericultura, Facultad de medicina, Campus de la Salud, Universidad de Valparaíso, Angamos 655, Reñaca, Viña del Mar 2520000, Chile

³ Centro de Investigaciones Biomédicas (CIB), Escuela de Medicina, Universidad de Valparaíso, Av. Hontaneda Nº 2664, Valparaíso 2340000, Chile

⁴ Departamento De Ciencias Básicas, Campus Fernando May Universidad del Biobío. Avda. Andrés Bello s/n casilla 447, Chillán 3780000, Chile

⁵ Instituto de Microbiología Clínica, Facultad de Medicina, Universidad Austral de Chile, Los Laureles s/n, Isla Teja, Valdivia 5090000, Chile

⁶ Center for Integrative Medicine and Innovative Science (CIMIS), Facultad de Medicina, Universidad Andrés Bello, Santiago 8320000, Chile

Molecules 2017, 22(6), 968; https://doi.org/10.3390/molecules22060968 - 10 Jun 2017

Cited by 11 | Viewed by 4666

Abstract

An efficient synthesis of a series of 4′-oxyalkyl-isocordoin analogues (2–8) is reported for the first time. Their structures were confirmed by ¹H-NMR, ¹³C-NMR, and HRMS. Their anti-oomycete activity was evaluated by mycelium and spores inhibition assay against [...] Read more.

An efficient synthesis of a series of 4′-oxyalkyl-isocordoin analogues (2–8) is reported for the first time. Their structures were confirmed by ¹H-NMR, ¹³C-NMR, and HRMS. Their anti-oomycete activity was evaluated by mycelium and spores inhibition assay against two selected pathogenic oomycetes strains: Saprolegnia parasitica and Saprolegnia australis. The entire series of isocordoin derivatives (except compound 7) showed high inhibitory activity against these oomycete strains. Among them, compound 2 exhibited strong activity, with minimum inhibitory concentration (MIC) and minimum oomyceticidal concentration (MOC) values of 50 µg/mL and 75 µg/mL, respectively. The results showed that 4′-oxyalkylated analogues of isocordoin could be potential anti-oomycete agents. Full article

(This article belongs to the Section Organic Chemistry)

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16 pages, 2211 KiB

Open AccessArticle

Docosahexaenoic Acid Induces Expression of Heme Oxygenase-1 and NAD(P)H:quinone Oxidoreductase through Activation of Nrf2 in Human Mammary Epithelial Cells

by Hye-Yoon Bang^1,2,†, Sin-Aye Park^1,†, Soma Saeidi^1,3

, Hye-Kyung Na⁴ and Young-Joon Surh^1,2,3,*

¹ Tumor Microenvironment Global Core Research Center and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 08826 Korea

² Cancer Research Institute, Seoul National University, Seoul 03080, Korea

³ Department of Molecular Medicine and Biopharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 08826, Korea

⁴ Department of Food and Nutrition, College of Human Ecology, Sungshin Women’s University, Seoul 01133, Korea

^† These authors contributed equally to this work.

Molecules 2017, 22(6), 969; https://doi.org/10.3390/molecules22060969 - 10 Jun 2017

Cited by 28 | Viewed by 7283

Abstract

Docosahexaenoic acid (DHA), an ω-3 fatty acid abundant in fish oils, has diverse health beneficial effects, such as anti-oxidative, anti-inflammatory, neuroprotective, and chemopreventive activities. In this study, we found that DHA induced expression of two representative antioxidant/cytoprotective enzymes, heme oxygenase-1 (HO-1) and NAD(P)H:quinone [...] Read more.

Docosahexaenoic acid (DHA), an ω-3 fatty acid abundant in fish oils, has diverse health beneficial effects, such as anti-oxidative, anti-inflammatory, neuroprotective, and chemopreventive activities. In this study, we found that DHA induced expression of two representative antioxidant/cytoprotective enzymes, heme oxygenase-1 (HO-1) and NAD(P)H:quinone oxidoreductase (NQO1), in human mammary epithealial (MCF-10A) cells. DHA-induced upregulation of these enzymes was accompanied by enhanced translocation of the redox-sensitive transcription factor Nrf2 into the nucleus and its binding to antioxidant response element. Nrf2 gene silencing by siRNA abolished the DHA-induced expression of HO-1 and NQO1 proteins. When MCF-10A cells were transfected with mutant constructs in which the cysteine 151 or 288 residue of Keap1 was replaced by serine, DHA-induced expression of HO-1 and NQO1 was markedly reduced. Moreover, DHA activated protein kinase C (PKC)δ and induced Nrf2 phosphorylation. DHA-induced phosphorylation of Nrf2 was abrogated by the pharmacological PKCδ inhibitor rottlerin or siRNA knockdown of its gene expression. The antioxidants N-acetyl-l-cysteine and Trolox attenuated DHA-induced activation of PKCδ, phosphorylation of Nrf2, and and its target protein expression. In conclusion, DHA activates Nrf2, possibly through modification of critical Keap1 cysteine 288 residue and PKCδ-mediated phosphorylation of Nrf2, leading to upregulation of HO-1 and NQO1 expression. Full article

(This article belongs to the Special Issue Cancer Chemoprevention)

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13 pages, 3603 KiB

Open AccessArticle

Synthesis and Bioactivity Evaluation of N-Arylsulfonylindole Analogs Bearing a Rhodanine Moiety as Antibacterial Agents

by Ming-Xia Song, Song-Hui Li, Jiao-Yang Peng, Ting-Ting Guo, Wen-Hui Xu, Shao-Feng Xiong and Xian-Qing Deng^*

Basic Medical and Pharmacy College, Jinggangshan University, Ji’an 343009, Jiangxi, China

Molecules 2017, 22(6), 970; https://doi.org/10.3390/molecules22060970 - 14 Jun 2017

Cited by 14 | Viewed by 4088

Abstract

Due to the rapidly growing bacterial resistance to antibiotics and the scarcity of novel agents under development, bacterial infections are still a pressing global problem, making new types of antibacterial agents, which are effective both alone and in combination with traditional antibiotics, urgently [...] Read more.

Due to the rapidly growing bacterial resistance to antibiotics and the scarcity of novel agents under development, bacterial infections are still a pressing global problem, making new types of antibacterial agents, which are effective both alone and in combination with traditional antibiotics, urgently needed. In this paper, seven series of N-arylsulfonylindole analogs 5–11 bearing rhodanine moieties were synthesized, characterized, and evaluated for antibacterial activity. According to the in vitro antimicrobial results, half of the synthesized compounds showed potent inhibition against four Gram-positive bacteria, with MIC values in the range of 0.5–8 µg/mL. For multidrug-resistant strains, compounds 6a and 6c were the most potent, with MIC values of 0.5 µg/mL, having comparable activity to gatifloxacin, moxiflocaxin and norfloxacin and being 128-fold more potent than oxacillin (MIC = 64 µg/mL) and 64-fold more active than penicillin (MIC = 32 µg/mL) against Staphylococcus aureus ATCC 43300. Full article

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10 pages, 1146 KiB

Open AccessArticle

Synthesis and Evaluation of Curcuminoid Analogues as Antioxidant and Antibacterial Agents

by Dalia R. Emam^1,*, Ahmad M. Alhajoj², Khaled M. Elattar³

, Nabila A. Kheder^4,5 and Ahmed A. Fadda^3,*

¹ Department of Chemistry, Faculty of Science, King Khalid University, Abha 9004, Saudi Arabia

² Department of Pharmacology, Faculty of Pharmacy, King Khalid University, Abha 61441, Saudi Arabia

³ Department of Chemistry, Faculty of Science, Mansoura University, Mansoura 35516, Egypt

⁴ Department of Pharmaceutical Chemistry, Faculty of Pharmacy, King Khalid University, Abha 61441, Saudi Arabia

⁵ Department of Chemistry, Faculty of Science, Cairo University, Giza 12613, Egypt

Molecules 2017, 22(6), 971; https://doi.org/10.3390/molecules22060971 - 11 Jun 2017

Cited by 13 | Viewed by 5021

Abstract

Diazocoupling reaction of curcumin with different diazonium salts of p-toluidine, 2-aminopyridine, and 4-aminoantipyrine in pyridine yielded the arylhydrazones 2a–c. Arylhydrazone of p-toluidine reacted with urea, thiourea, and guanidine nitrate to produce 5,6-dihydropyrimidines. Further reaction of 2a with 2,3-diaminopyrdine [...] Read more.

Diazocoupling reaction of curcumin with different diazonium salts of p-toluidine, 2-aminopyridine, and 4-aminoantipyrine in pyridine yielded the arylhydrazones 2a–c. Arylhydrazone of p-toluidine reacted with urea, thiourea, and guanidine nitrate to produce 5,6-dihydropyrimidines. Further reaction of 2a with 2,3-diaminopyrdine in sodium ethoxide solution yielded 1H-pyrido[2,3-b][1,4]diazepine derivative. Bis(2,5-dihydroisoxazole) is obtained from the reaction of 2a with hydroxylamine hydrochloride, while its reactions with hydrazines afforded the respective 4,5-dihydro-1H-pyrazoles. The target compounds were evaluated as antioxidant and antibacterial agents. The tested compounds showed good to moderate activities compared to ascorbic acid and chloramphenicol, respectively. Full article

(This article belongs to the Special Issue Curcumin an Example of Pleiotropic Agents—Design, Synthesis and Biological Evaluation of Curcumin Analogues or Curcumin Derivatives)

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16 pages, 3172 KiB

Open AccessArticle

Baccharis trimera (Less.) DC Exhibits an Anti-Adipogenic Effect by Inhibiting the Expression of Proteins Involved in Adipocyte Differentiation

by Daniele De Souza Marinho do Nascimento^1,2, Ruth Medeiros Oliveira^2,3, Rafael Barros Gomes Camara^2,4, Dayanne Lopes Gomes^1,2, Jessika Fernanda Santiago Monte², Mariana Santana Santos Pereira Costa^2,5, Júlia Moraes Fernandes⁶, Silvana Maria Zucolotto Langassner^1,6

and Hugo Alexandre Oliveira Rocha^1,2,*

¹ Programa de Pós-graduação em Ciencias da Saúde, Centro de Ciências da Saúde, Universidade Federal do Rio Grande do Norte-UFRN, R. Gen. Gustavo Cordeiro de Farias, s/n, Natal-RN 59012-570, Brazil

² Departamento de Bioquimica, Centro de Biociencias, Universidade Federal do Rio Grande do Norte-UFRN, Av. Salgado Filho 3000, Natal-RN 59078-970, Brazil

³ Instituto Federal de Educação, Ciência a Tecnologia do Rio Grande do Norte (IFRN), Rodovia RN-288, s/n-Nova Caicó, Caicó-RN 59300-000, Brazil

⁴ Escola Multicampi de Ciências Médicas do Rio Grande do Norte -EMCM/RN, Universidade Federal do Rio Grande do Norte-UFRN, Av. Cel. Martiniano, 354, Caicó-RN 59300-000, Brazil

⁵ Instituto Federal de Educação, Ciência a Tecnologia do Rio Grande do Norte (IFRN), Rua das margaridas, 300-Conjunto COHAB, Macau-RN 59500-000, Brazil

⁶ Departamento de Farmácia, Centro de Ciências da Saúde, Universidade Federal do Rio Grande do Norte-UFRN, Rua General Gustavo Cordeiro de Farias, s/n, Natal-RN 59012-570, Brazil

Molecules 2017, 22(6), 972; https://doi.org/10.3390/molecules22060972 - 12 Jun 2017

Cited by 15 | Viewed by 5489

Abstract

Baccharis trimera (Less.) DC (gorse) is a plant popularly used for the treatment of obesity. In this study, we prepared three B. trimera extracts aqueous extract (AE), decoction (AE-D), and methanol extract (ME) and investigated their antioxidant effects in six different tests and [...] Read more.

Baccharis trimera (Less.) DC (gorse) is a plant popularly used for the treatment of obesity. In this study, we prepared three B. trimera extracts aqueous extract (AE), decoction (AE-D), and methanol extract (ME) and investigated their antioxidant effects in six different tests and their anti-adipogenic effect in 3T3-L1 cells. The extracts showed a dose-dependent antioxidant activity in all tests. AE was the most potent antioxidant in copper and ferric ion chelation assays, whereas AE-D was the most potent in superoxide and hydroxyl radical scavenging assays, reducing power assay, and total antioxidant capacity analysis. Only ME showed a cytotoxic effect against 3T3-L1 cells. Lipid accumulation decreased in 3T3-L1 adipocytes in the presence of AE and AE-D extracts (0.5 to 1.0 mg/mL). In addition, the extracts dramatically attenuated the levels of adipogenic transcriptional factors, including CCAAT enhancer-binding protein α (C/EBPα), CCAAT enhancer-binding protein β (C/EBPβ), and gamma receptors by peroxisome proliferators (PPARγ), during adipogenesis. AE-D (1.0 mg/mL) caused an approximately 90% reduction in the levels of these molecules. We propose that B. trimera has an anti-adipogenic effect and could be used in the development of functional foods. Full article

(This article belongs to the Special Issue Plant Polyphenols as Potential Therapeutic Agents for Diabetes and Obesity)

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11 pages, 2813 KiB

Open AccessArticle

Oligonucleotides and ND-FISH Displaying Different Arrangements of Tandem Repeats and Identification of Dasypyrum villosum Chromosomes in Wheat Backgrounds

by Zhiqiang Xiao^1,†, Shuyao Tang^1,2,†, Ling Qiu¹, Zongxiang Tang^1,2,* and Shulan Fu^1,*

¹ Provincial Key Laboratory of Plant Breeding and Genetics, Sichuan Agriculture University, Chengdu 611130, China

² Institute of Ecological Agriculture, Sichuan Agricultural University, Chengdu 611130, China

^† These authors have contributed equally to this manuscript.

Molecules 2017, 22(6), 973; https://doi.org/10.3390/molecules22060973 - 14 Jun 2017

Cited by 42 | Viewed by 6112

Abstract

Oligonucleotide probes and the non-denaturing fluorescence in situ hybridization (ND-FISH) technique are widely used to analyze plant chromosomes because they are convenient tools. New oligonucleotide probes, Oligo-Ku, Oligo-3B117.1, Oligo-3B117.2, Oligo-3B117.2.1, Oligo-3B117.3, Oligo-3B117.4, Oligo-3B117.5, Oligo-3B117.6, Oligo-pTa71A-1, Oligo-pTa71A-2, Oligo-pTa71B-1, Oligo-pTa71B-2, Oligo-pTa71C-1, Oligo-pTa71C-2, Oligo-pTa71C-3 and Oligo-pTa71D [...] Read more.

Oligonucleotide probes and the non-denaturing fluorescence in situ hybridization (ND-FISH) technique are widely used to analyze plant chromosomes because they are convenient tools. New oligonucleotide probes, Oligo-Ku, Oligo-3B117.1, Oligo-3B117.2, Oligo-3B117.2.1, Oligo-3B117.3, Oligo-3B117.4, Oligo-3B117.5, Oligo-3B117.6, Oligo-pTa71A-1, Oligo-pTa71A-2, Oligo-pTa71B-1, Oligo-pTa71B-2, Oligo-pTa71C-1, Oligo-pTa71C-2, Oligo-pTa71C-3 and Oligo-pTa71D were designed based on the repetitive sequences KU.D15.15, pSc119.2-like sequence 3B117 and pTa71. Oligonucleotide probe (GT)₇ was also used. Oligo-Ku and (GT)₇ can be together used to identify Dasypyrum villosum from wheat chromosomes and to distinguish individual D. villosum chromosomes. The oligonucleotide probes that were derived from the same repeat sequence displayed different signal intensity and hybridization sites on the same chromosomes. Both the length and the nucleotide composition of oligonucleotide probes determined their signal intensity. For example, Oligo-3B117.2 (25 bp) and Oligo-pTa71A-2 (46 bp) produced the strongest signals on chromosomes of wheat (Triticum aestivum L.), rye (Secale cereale L.), barley (Hordeum vulgare ssp. vulgare) or D. villosum, the signal of Oligo-3B117.4 (18 bp) on the short arm of 7B chromosome was weaker than that of Oligo-3B117.2.1 (15 bp) and Oligo-3B117.3 (16 bp), and Oligo-pTa71A-1 (38 bp) produced the same strong signals as Oligo-pTa71A-2 did on 1B and 6B chromosomes, but its signals on 1R and 1V chromosomes were weaker than the ones of Oligo-pTa71A-2. Oligonucleotide probes and ND-FISH analysis can reflect the distribution and structural statues of different segments of tandem repeats on chromosomes. The possible reasons why different segments derived from the same repeat sequence produced different signal patterns are discussed. Full article

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

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22 pages, 487 KiB

Open AccessArticle

Reaction of bis[(2-chlorocarbonyl)phenyl] Diselenide with Phenols, Aminophenols, and Other Amines towards Diphenyl Diselenides with Antimicrobial and Antiviral Properties

by Mirosław Giurg^1,*, Anna Gołąb¹, Jakub Suchodolski², Rafał Kaleta¹, Anna Krasowska², Egbert Piasecki³ and Magdalena Piętka-Ottlik^4,*

¹ Department of Organic Chemistry, Faculty of Chemistry, Wrocław University of Science and Technology, Wybrzeże Wyspiańskiego 27, 50-370 Wrocław, Poland

² Department of Biotransformation, Faculty of Biotechnology, University of Wrocław, Joliot-Curie 14a, 50-383 Wrocław, Poland

³ Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Weigla 12, 53-114 Wrocław, Poland

⁴ Department of Organic and Pharmaceutical Technology, Faculty of Chemistry, Wrocław University of Science and Technology, Wybrzeże Wyspiańskiego 27, 50-370 Wrocław, Poland

Molecules 2017, 22(6), 974; https://doi.org/10.3390/molecules22060974 - 12 Jun 2017

Cited by 37 | Viewed by 6983

Abstract

A reaction of bis[(2-chlorocarbonyl)phenyl] diselenide with various mono and bisnucleophiles such as aminophenols, phenols, and amines have been studied as a convenient general route to a series of new antimicrobial and antiviral diphenyl diselenides. The compounds, particularly bis[2-(hydroxyphenylcarbamoyl)]phenyl diselenides and reference benzisoselenazol-3(2H [...] Read more.

A reaction of bis[(2-chlorocarbonyl)phenyl] diselenide with various mono and bisnucleophiles such as aminophenols, phenols, and amines have been studied as a convenient general route to a series of new antimicrobial and antiviral diphenyl diselenides. The compounds, particularly bis[2-(hydroxyphenylcarbamoyl)]phenyl diselenides and reference benzisoselenazol-3(2H)-ones, exhibited high antimicrobial activity against Gram-positive bacterial species (Enterococcus spp., Staphylococcus spp.), and some compounds were also active against Gram-negative E. coli and fungi (Candida spp., A. niger). The majority of compounds demonstrated high activity against human herpes virus type 1 (HHV-1) and moderate activity against encephalomyocarditis virus (EMCV), while they were generally inactive against vesicular stomatitis virus (VSV). Full article

(This article belongs to the Special Issue Celebrating Two Centuries of Research in Selenium Chemistry: State of the Art and New Prospectives)

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12 pages, 1067 KiB

Open AccessFeature PaperArticle

Inhibitory Effects of Diclofenac on Steroid Glucuronidation In Vivo Do Not Affect Hair-Based Doping Tests for Stanozolol

by Gergely Zachár¹

, Naved I.K. Deshmukh², Andrea Petróczi²

, Andrea D. Székely¹, Iltaf Shah³

, James Barker²

and Declan P. Naughton^2,*

¹ Department of Anatomy, Histology and Embryology, Semmelweis University, Tűzoltó u. 58, Budapest 1094, Hungary

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

³ Department of Chemistry, College of Science, United Arab Emirates University, Al Ain 009713, UAE

Molecules 2017, 22(6), 976; https://doi.org/10.3390/molecules22060976 - 12 Jun 2017

Viewed by 5159

Abstract

In vitro studies show that diclofenac inhibits enzymatic steroid glucuronidation. This study was designed to investigate the influence of diclofenac on the excretion of stanozolol and 3′-hydroxystanozolol via analyses in hair, blood and urine in vivo in a rat study. Brown Norway rats [...] Read more.

In vitro studies show that diclofenac inhibits enzymatic steroid glucuronidation. This study was designed to investigate the influence of diclofenac on the excretion of stanozolol and 3′-hydroxystanozolol via analyses in hair, blood and urine in vivo in a rat study. Brown Norway rats were administered with stanozolol (weeks 1–3) and diclofenac (weeks 1–6). Weekly assessment of steroid levels in hair was complemented with spot urine and serum tests. Levels of both stanozolol and 3′-hydroxystanozolol steadily increased in hair during stanozolol treatment and decreased post-treatment, but remained readily detectable for 6 weeks. In contrast, compared to control rats, diclofenac significantly reduced urinary excretion of 3′-hydroxystanozolol which was undetectable in most samples. This is the first report of diclofenac altering steroid metabolism in vivo, detrimentally affecting detection in urine, but not in hair, which holds considerable advantages over urinalysis for anti-doping tests. Full article

(This article belongs to the Section Metabolites)

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11 pages, 2452 KiB

Open AccessArticle

Hochu-ekki-to Treatment Improves Reproductive and Immune Modulation in the Stress-Induced Rat Model of Polycystic Ovarian Syndrome

by Eunkuk Park^1,2

, Chun Whan Choi³, Soo Jeong Kim^4,5, Yong-In Kim⁶, Samkee Sin⁷, Jong-Phil Chu¹ and Jun Young Heo^4,5,8,*

¹ Department of Medical Zoology, College of Medicine, Kyung Hee University, Seoul 130701, Korea

² Department of Medical Genetics, College of Medicine, Ajou University School of Medicine, Suwon 443721, Korea

³ Bio-Center, Gyeonggido Business and Science Accelerator, Suwon 16229, Korea

⁴ Department of Biochemistry, Chungnam National University School of Medicine, Daejeon 301747, Korea

⁵ Department of Medical Science, Chungnam National University School of Medicine, Daejeon 301747, Korea

⁶ International Biological Material Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, Korea

⁷ Institute of Korea Food and Drug Resource, Seoul 06622, Korea

⁸ Brain Research Institute, Chungnam National University School of Medicine, Daejeon 301747, Korea

Molecules 2017, 22(6), 978; https://doi.org/10.3390/molecules22060978 - 13 Jun 2017

Cited by 12 | Viewed by 5007

Abstract

The traditional herbal medicine, Hochu-ekki-to, has been shown to have preventive effects on viral infection and stress. This study aimed to evaluate the clinical effects of Hochu-ekki-to on two stress-related rat models of polycystic ovarian syndrome. Female Sprague-Dawley rats were divided into control [...] Read more.

The traditional herbal medicine, Hochu-ekki-to, has been shown to have preventive effects on viral infection and stress. This study aimed to evaluate the clinical effects of Hochu-ekki-to on two stress-related rat models of polycystic ovarian syndrome. Female Sprague-Dawley rats were divided into control and treatment groups, the latter of which were subjected to stress induced by exposure to adrenocorticotropic hormone (ACTH) or cold temperatures. After these stress inductions, rats were orally treated with dissolved Hochu-ekki-to once per day for 7 days. Rats subjected to the two different stressors exhibited upregulation of steroid hormone receptors (in ovaries) and reproductive hormones (in blood), and consequent stimulation of abnormal follicle development accompanied by elevation of Hsp 90 expression (in ovaries). Treatment with Hochu-ekki-to for 7 days after stress induction increased immune functions, reduced the stress-induced activation of Hsp 90, and normalized the levels of the tested steroid hormone receptors and reproductive hormones. Our findings suggest that stress stimulations may promote the activation of Hsp 90 via the dysregulation of steroid hormone receptors and reproductive hormones, but that post-stress treatment with Hochu-ekki-to improves reproductive and immune functions in the ovaries of stressed rats. Full article

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

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17 pages, 4254 KiB

Open AccessArticle

Multi-Dimensional Spectrum-Effect Relationship of the Impact of Chinese Herbal Formula Lichong Shengsui Yin on Ovarian Cancer

by Yanhong Wang^1,†, Yang Li^2,†, Yan Zhang¹, Guan Feng¹, Zhixin Yang¹, Qingxia Guan¹, Rui Wang¹ and Fengjuan Han^3,*

¹ College of Pharmacy, Heilongjiang University of Traditional Medicine, Harbin 150040, China

² Disha Pharmaceutical Group, Qingdao 266100, China

³ The First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin 150040, China

^† These authors contributed equally to this work.

Molecules 2017, 22(6), 979; https://doi.org/10.3390/molecules22060979 - 13 Jun 2017

Cited by 20 | Viewed by 5816

Abstract

Lichong Shengsui Yin (LCSSY) is an effective and classic compound prescription of Traditional Chinese Medicines (TCMs) used for the treatment of ovarian cancer. To investigate its pharmacodynamic basis for treating ovarian cancer, the multi-dimensional spectrum-effect relationship was determined. Four compositions (I to IV) [...] Read more.

Lichong Shengsui Yin (LCSSY) is an effective and classic compound prescription of Traditional Chinese Medicines (TCMs) used for the treatment of ovarian cancer. To investigate its pharmacodynamic basis for treating ovarian cancer, the multi-dimensional spectrum-effect relationship was determined. Four compositions (I to IV) were obtained by extracting LCSSY successively with supercritical CO₂ fluid extraction, 75% ethanol reflux extraction, and the water extraction-ethanol precipitation method. Nine samples for pharmacological evaluation and fingerprint analysis were prepared by changing the content of the four compositions. The specific proportions of the four compositions were designed according to a four-factor, three-level L₉(3⁴) orthogonal test. The pharmacological evaluation included in vitro tumor inhibition experiments and the survival extension rate in tumor-bearing nude mice. The fingerprint analyzed by chromatographic condition I (high-performance liquid chromatography-photodiode array detec tor，HPLC-PDA) identified 19 common peaks. High-performance liquid chromatography-photodiode array detector-Evaporative Light-scattering Detector (HPLC-PDA-ELSD )hyphenated techniques were used to compensate for the use of a single detector, and the fingerprint analyzed by chromatographic condition II identified 28 common peaks in PDA and 23 common peaks in ELSD. Furthermore, multiple statistical analyses were utilized to calculate the relationships between the peaks and the pharmacological results. The union of the regression and the correlation analysis results were the peaks of X₅, X₉, X₁₁, X₁₂, X₁₆, X₁₈, Y₅, Y₈, Y₁₂, Y₁₄, Y₂₀, Z₄, Z₅, Z₆, and Z₈. The intersection of the regression and the correlation analysis results were the peaks of X₁₁, X₁₂, X₁₆, X₁₈, Y₅, Y₁₂, and Z₅. The correlated peaks were assigned by comparing the fingerprints with the negative control samples and reference standard samples, and identifying the structure using high-performance liquid chromatography-mass spectrometry detector(HPLC-MS). The results suggested that the pharmacodynamic basis of LCSSY on anti-ovarian cancer activities were germacrone, furandiene, β-elemene, calycosin-7-glucoside, ononin, epimedin B, icariin, ginsenoside Rc, astragaloside, ginsenoside Rd, astragaloside II, and some unknown components. Full article

(This article belongs to the Special Issue Natural Products and Chronic Diseases)

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13 pages, 1041 KiB

Open AccessArticle

Production of Putative Diterpene Carboxylic Acid Intermediates of Triptolide in Yeast

by Victor Forman^1,2

, Roberta Callari², Christophe Folly², Harald Heider² and Björn Hamberger^3,*

¹ Evolva A/S, Lersø Park Allé 42-44, Copenhagen Ø DK-2100, Denmark

² Evolva SA, Duggingerstrasse 23, Reinach CH-4153, Switzerland

³ Department of Biochemistry and Molecular Biology, Michigan State University, 603 Wilson Road, East Lansing, MI 48824, USA

Molecules 2017, 22(6), 981; https://doi.org/10.3390/molecules22060981 - 13 Jun 2017

Cited by 15 | Viewed by 6789

Abstract

The development of medical applications exploiting the broad bioactivities of the diterpene therapeutic triptolide from Tripterygium wilfordii is limited by low extraction yields from the native plant. Furthermore, the extraordinarily high structural complexity prevents an economically attractive enantioselective total synthesis. An alternative production [...] Read more.

The development of medical applications exploiting the broad bioactivities of the diterpene therapeutic triptolide from Tripterygium wilfordii is limited by low extraction yields from the native plant. Furthermore, the extraordinarily high structural complexity prevents an economically attractive enantioselective total synthesis. An alternative production route of triptolide through engineered Saccharomyces cerevisiae (yeast) could provide a sustainable source of triptolide. A potential intermediate in the unknown biosynthetic route to triptolide is the diterpene dehydroabietic acid. Here, we report a biosynthetic route to dehydroabietic acid by transient expression of enzymes from T. wilfordii and Sitka spruce (Picea sitchensis) in Nicotiana benthamiana. The combination of diterpene synthases TwTPS9, TwTPS27, and cytochromes P450 PsCYP720B4 yielded dehydroabietic acid and a novel analog, tentatively identified as ‘miltiradienic acid’. This biosynthetic pathway was reassembled in a yeast strain engineered for increased yields of the pathway intermediates, the diterpene olefins miltiradiene and dehydroabietadiene. Introduction in that strain of PsCYP720B4 in combination with two alternative NADPH-dependent cytochrome P450 reductases resulted in scalable in vivo production of dehydroabietic acid and its analog from glucose. Approaching future elucidation of the remaining biosynthetic steps to triptolide, our findings may provide an independent platform for testing of additional recombinant candidate genes, and ultimately pave the way to biotechnological production of the high value diterpenoid therapeutic. Full article

(This article belongs to the Special Issue Isoprenoid Biosynthesis)

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15 pages, 9115 KiB

Open AccessArticle

The Complete Chloroplast Genome Sequences of Fritillaria ussuriensis Maxim. and Fritillaria cirrhosa D. Don, and Comparative Analysis with Other Fritillaria Species

by Inkyu Park¹

, Wook Jin Kim¹, Sang-Min Yeo¹, Goya Choi¹, Young-Min Kang¹, Renzhe Piao² and Byeong Cheol Moon^1,*

¹ K-Herb Research Center, Korea Institute of Oriental Medicine, Daejeon 305-811, Korea

² Department of Agronomy, Yanbian University Agriculture College, Yanji 133002, China

Molecules 2017, 22(6), 982; https://doi.org/10.3390/molecules22060982 - 13 Jun 2017

Cited by 69 | Viewed by 7283

Abstract

The genus Fritillaria belongs to the widely distributed Liliaceae. The bulbs of Fritillaria, F. ussuriensis and F. cirrhosa are valuable herbaceous medicinal ingredients. However, they are still used indiscriminately in herbal medicine. Identification and molecular phylogenic analysis of Fritillaria species are therefore [...] Read more.

The genus Fritillaria belongs to the widely distributed Liliaceae. The bulbs of Fritillaria, F. ussuriensis and F. cirrhosa are valuable herbaceous medicinal ingredients. However, they are still used indiscriminately in herbal medicine. Identification and molecular phylogenic analysis of Fritillaria species are therefore required. Here, we report the complete chloroplast (CP) genome sequences of F. ussuriensis and F. cirrhosa. The two Fritillaria CP genomes were 151,524 and 151,083 bp in length, respectively, and each included a pair of inverted repeated regions (52,678 and 52,156 bp) that was separated by a large single copy region (81,732 and 81,390 bp), and a small single copy region (17,114 and 17,537 bp). A total of 111 genes in F. ussuriensis and 112 in F. cirrhosa comprised 77 protein-coding regions in F. ussuriensis and 78 in F. cirrhosa, 30 transfer RNA (tRNA) genes, and four ribosomal RNA (rRNA) genes. The gene order, content, and orientation of the two Fritillaria CP genomes exhibited the general structure of flowering plants, and were similar to those of other Fritillaria species. Comparison of the six Fritillaria species’ CP genomes indicated seven highly divergent regions in intergenic spacers and in the matK, rpoC1, rpoC2, ycf1, ycf2, ndhD, and ndhF coding regions. We established the position of the six species through phylogenic analysis. The complete chloroplast genome sequences of the two Fritillaria species and a comparison study are useful genomic information for identifying and for studying the phylogenetic relationship among Fritillaria species within the Liliaceae. Full article

(This article belongs to the Section Molecular Diversity)

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12 pages, 1231 KiB

Open AccessArticle

Evaluation of the Antidiabetic Activity and Chemical Composition of Geranium collinum Root Extracts—Computational and Experimental Investigations

by Sodik Numonov^1,2

, Salamet Edirs^1,3, Khayrulla Bobakulov⁴

, Muhammad Nasimullah Qureshi⁵

, Khurshed Bozorov^1,4

, Farukh Sharopov^1,6

, William N. Setzer⁷, Haiqing Zhao¹, Maidina Habasi¹, Mizhgona Sharofova⁸ and Haji Akber Aisa^1,*

¹ Key Laboratory of Plant Resources and Chemistry in Arid Regions, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Urumqi 830011, China

² State Scientifically-Experimental and Production Organization, Academy of Sciences of the Republic of Tajikistan, Dushanbe 734063, Tajikistan

³ University of Chinese Academy of Sciences, Beijing 100049, China

⁴ Institute of the Chemistry of Plant Substances, Academy of Sciences of the Republic of Uzbekistan, Tashkent 100170, Uzbekistan

⁵ Department of Chemistry, Abdul Wali Khan University, Mardan 23200, Pakistan

⁶ Department of Pharmaceutical Technology, Avicenna Tajik State Medical University, Rudaki Ave. 139, Dushanbe 734003, Tajikistan

⁷ Department of Chemistry, University of Alabama in Huntsville, Huntsville, AL 35899, USA

⁸ Institute of Avicenna’s Medicine and Pharmacology, Academy of the Tajik Traditional Medicine, Dushanbe 734062, Tajikistan

Molecules 2017, 22(6), 983; https://doi.org/10.3390/molecules22060983 - 13 Jun 2017

Cited by 33 | Viewed by 7207

Abstract

The root of Geranium collinum Steph is known in Tajik traditional medicine for its hepatoprotective, antioxidant, and anti-inflammatory therapeutic effects. The present study was conducted to evaluate of potential antidiabetic, antioxidant activities, total polyphenolic and flavonoid content from the different extracts (aqueous, aqueous-ethanolic) [...] Read more.

The root of Geranium collinum Steph is known in Tajik traditional medicine for its hepatoprotective, antioxidant, and anti-inflammatory therapeutic effects. The present study was conducted to evaluate of potential antidiabetic, antioxidant activities, total polyphenolic and flavonoid content from the different extracts (aqueous, aqueous-ethanolic) and individual compounds isolated of the root parts of G. collinum. The 50% aqueous-ethanolic extract possesses potent antidiabetic activity, with IC₅₀ values of 0.10 μg/mL and 0.09 μg/mL for the enzymes protein-tyrosine phosphatase (1B PTP-1B) and α-glucosidase, respectively. Phytochemical investigations of the 50% aqueous-ethanolic extract of G. collinum, led to the isolation of ten pure compounds identified as 3,3′,4,4′-tetra-O-methylellagic acid (1), 3,3′-di-O-methylellagic acid (2), quercetin (3), caffeic acid (4), (+)-catechin (5), (–)-epicatechin (6), (–)-epigallocatechin (7), gallic acid (8), β-sitosterol-3-O-β-d-glucopyranoside (9), and corilagin (10). Their structures were determined based on 1D and 2D NMR and mass spectrometric analyses. Three isolated compounds exhibited strong inhibitory activity against PTP-1B, with IC₅₀ values below 0.9 μg/mL, more effective than the positive control (1.46 μg/mL). Molecular docking analysis suggests polyphenolic compounds such as corilagin, catechin and caffeic acid inhibit PTP-1B and β-sitosterol-3-O-β-d-gluco-pyranoside inhibits α-glucosidase. The experimental results suggest that the biological activity of G. collinum is related to its polyphenol contents. The results are also in agreement with computational investigations. Furthermore, the potent antidiabetic activity of the 50% aqueous-ethanolic extract from G. collinum shows promise for its future application in medicine. To the best of our knowledge, we hereby report, for the first time, the antidiabetic activity of G. collinum. Full article

(This article belongs to the Special Issue Plant Polyphenols as Potential Therapeutic Agents for Diabetes and Obesity)

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15 pages, 1154 KiB

Open AccessArticle

A Simple Defined Medium for the Production of True Diketopiperazines in Xylella fastidiosa and Their Identification by Ultra-Fast Liquid Chromatography-Electrospray Ionization Ion Trap Mass Spectrometry

by Michelli Massaroli da Silva¹, Moacir dos Santos Andrade¹

, Anelize Bauermeister², Marcus Vinícius Merfa³, Moacir Rossi Forim¹, João Batista Fernandes¹

, Paulo Cezar Vieira¹

, Maria Fátima das Graças Fernandes da Silva^1,*

, Norberto Peporine Lopes², Marcos Antônio Machado³ and Alessandra Alves de Souza³

¹ Departamento de Química, Universidade Federal de São Carlos, CP 676, 13565-905 São Carlos-SP, Brazil

² Núcleo Pesquisas em Produtos Naturais e Sintéticos, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, 14040-903 Ribeirão Preto-SP, Brazil

³ Centro APTA Citros Sylvio Moreira, Instituto Agronômico, CP 04, 13490-970 Cordeirópolis-SP, Brazil

Molecules 2017, 22(6), 985; https://doi.org/10.3390/molecules22060985 - 13 Jun 2017

Cited by 11 | Viewed by 4922

Abstract

Diketopiperazines can be generated by non-enzymatic cyclization of linear dipeptides at extreme temperature or pH, and the complex medium used to culture bacteria and fungi including phytone peptone and trypticase peptone, can also produce cyclic peptides by heat sterilization. As a result, it [...] Read more.

Diketopiperazines can be generated by non-enzymatic cyclization of linear dipeptides at extreme temperature or pH, and the complex medium used to culture bacteria and fungi including phytone peptone and trypticase peptone, can also produce cyclic peptides by heat sterilization. As a result, it is not always clear if many diketopiperazines reported in the literature are artifacts formed by the different complex media used in microorganism growth. An ideal method for analysis of these compounds should identify whether they are either synthesized de novo from the products of primary metabolism and deliver true diketopiperazines. A simple defined medium (X. fastidiosa medium or XFM) containing a single carbon source and no preformed amino acids has emerged as a method with a particularly high potential for the grown of X. fastidiosa and to produce genuine natural products. In this work, we identified a range of diketopiperazines from X. fastidiosa 9a5c growth in XFM, using Ultra-Fast Liquid Chromatography coupled with mass spectrometry. Diketopiperazines are reported for the first time from X. fastidiosa, which is responsible for citrus variegated chlorosis. We also report here fatty acids from X. fastidiosa, which were not biologically active as diffusible signals, and the role of diketopiperazines in signal transduction still remains unknown. Full article

(This article belongs to the Section Natural Products Chemistry)

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14 pages, 1376 KiB

Open AccessArticle

Potential of Icariin Metabolites from Epimedium koreanum Nakai as Antidiabetic Therapeutic Agents

by Da Hye Kim¹, Hyun Ah Jung^2,*, Hee Sook Sohn², Jin Woong Kim³ and Jae Sue Choi^1,*

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

² Department of Food Science and Human Nutrition, Chonbuk National University, Jeonju 54896 Korea

³ College of Pharmacy, Seoul National University, Seoul 08826, Korea

Molecules 2017, 22(6), 986; https://doi.org/10.3390/molecules22060986 - 13 Jun 2017

Cited by 53 | Viewed by 6968

Abstract

The therapeutic properties of Epimedium koreanum are presumed to be due to the flavonoid component icariin, which has been reported to have broad pharmacological potential and has demonstrated anti-diabetic, anti-Alzheimer’s disease, anti-tumor, and hepatoprotective activities. Considering these therapeutic properties of icariin, its [...] Read more.

The therapeutic properties of Epimedium koreanum are presumed to be due to the flavonoid component icariin, which has been reported to have broad pharmacological potential and has demonstrated anti-diabetic, anti-Alzheimer’s disease, anti-tumor, and hepatoprotective activities. Considering these therapeutic properties of icariin, its deglycosylated icaritin and glycosylated flavonoids (icaeriside II, epimedin A, epimedin B, and epimedin C) were evaluated for their ability to inhibit protein tyrosine phosphatase 1B (PTP1B) and α-glucosidase. The results show that icaritin and icariside II exhibit potent inhibitory activities, with 50% inhibition concentration (IC₅₀) values of 11.59 ± 1.39 μM and 9.94 ± 0.15 μM against PTP1B and 74.42 ± 0.01 and 106.59 ± 0.44 μM against α-glucosidase, respectively. With the exceptions of icaritin and icariside II, glycosylated flavonoids did not exhibit any inhibitory effects in the two assays. Enzyme kinetics analyses revealed that icaritin and icariside II demonstrated noncompetitive-type inhibition against PTP1B, with inhibition constant (K_i) values of 11.41 and 11.66 μM, respectively. Moreover, molecular docking analysis confirmed that icaritin and icariside II both occupy the same site as allosteric ligand. Thus, the molecular docking simulation results were in close agreement with the experimental data with respect to inhibition activity. In conclusion, deglycosylated metabolites of icariin from E. koreanum might offer therapeutic potential for the treatment of type 2 diabetes mellitus. Full article

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11 pages, 999 KiB

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Antimicrobial Activity of Truncated and Polyvalent Peptides Derived from the FKCRRQWQWRMKKGLA Sequence against Escherichia coli ATCC 25922 and Staphylococcus aureus ATCC 25923

by Nataly De Jesús Huertas¹, Zuly Jenny Rivera Monroy¹, Ricardo Fierro Medina¹ and Javier Eduardo García Castañeda^2,*

¹ Chemistry Department, Universidad Nacional de Colombia, Bogotá Carrera 45 No. 26-85, Building 451, Office 409, Laboratory 334, Bogotá 11321, Colombia

² Pharmacy Department, Universidad Nacional de Colombia, Bogotá Carrera 45 No. 26-85, Building 450, office 203, Bogotá 11321, Colombia

Molecules 2017, 22(6), 987; https://doi.org/10.3390/molecules22060987 - 14 Jun 2017

Cited by 37 | Viewed by 8151

Abstract

Peptides derived from LfcinB were designed and synthesized, and their antibacterial activity was tested against Escherichia coli ATCC 25922 and Staphylococcus aureus ATCC 25923. Specifically, a peptide library was constructed by systemically removing the flanking residues (N or C-terminal) of Lfcin 17–31 ( [...] Read more.

Peptides derived from LfcinB were designed and synthesized, and their antibacterial activity was tested against Escherichia coli ATCC 25922 and Staphylococcus aureus ATCC 25923. Specifically, a peptide library was constructed by systemically removing the flanking residues (N or C-terminal) of Lfcin 17–31 (¹⁷FKCRRWQWRMKKLGA³¹), maintaining in all peptides the ²⁰RRWQWR²⁵ sequence that corresponds to the minimal antimicrobial motif. For this research, also included were (i) a peptide containing an Ala instead of Cys ([Ala¹⁹]-LfcinB 17–31) and (ii) polyvalent peptides containing the RRWQWR sequence and a non-natural amino acid (aminocaproic acid). We established that the lineal peptides LfcinB 17–25 and LfcinB 17–26 exhibited the greatest activity against E. coli ATCC 25922 and S. aureus ATCC 25923, respectively. On the other hand, polyvalent peptides, a dimer and a tetramer, exhibited the greatest antibacterial activity, indicating that multiple copies of the sequence increase the activity. Our results suggest that the dimeric and tetrameric sequence forms potentiate the antibacterial activity of lineal sequences that have exhibited moderate antibacterial activity. Full article

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

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10 pages, 851 KiB

Open AccessArticle

Serum Uromodulin Levels in Prediction of Acute Kidney Injury in the Early Phase of Acute Pancreatitis

by Beata Kuśnierz-Cabala¹, Agnieszka Gala-Błądzińska²

, Małgorzata Mazur-Laskowska³, Paulina Dumnicka⁴, Mateusz Sporek^5,6, Aleksandra Matuszyk⁵, Krzysztof Gil⁷

, Piotr Ceranowicz^8,*

, Jerzy Walocha⁵, Jakub Kucharz⁹, Michał Pędziwiatr¹⁰

, Krzysztof Bartuś¹¹, Rafał Trąbka¹¹ and Marek Kuźniewski¹²

¹ Department of Diagnostics, Chair of Clinical Biochemistry, Jagiellonian University Medical College, 31-501 Kraków, Poland

² St. Queen Jadwiga Clinical District Hospital No2 in Rzeszow, 35-301 Rzeszów, Poland

³ Department of Diagnostics, University Hospital, 31-501 Kraków, Poland

⁴ Department of Medical Diagnostics, Jagiellonian University Medical College, 30-688 Kraków, Poland

⁵ Department of Anatomy, Jagiellonian University Medical College, 31-034 Kraków, Poland

⁶ Surgery Department, The District Hospital, 34-200 Sucha Beskidzka, Poland

⁷ Department of Pathophysiology, Faculty of Medicine, Jagiellonian University Medical College, 31-121 Kraków, Poland

⁸ Department of Physiology, Jagiellonian University Medical College, 31-531 Kraków, Poland

⁹ Department of Experimental and Clinical Surgery, Jagiellonian University Medical College, 31-126 Kraków, Poland

¹⁰ 2nd Department of Surgery, Faculty of Medicine, Jagiellonian University Medical College, 31-501 Kraków, Poland

¹¹ Department of Cardiovascular Surgery and Transplantology, Faculty of Medicine, Jagiellonian University Medical College, 31-202 Kraków, Poland

¹² Chair and Department of Nephrology, Jagiellonian University Medical College, 31-501 Kraków, Poland

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Molecules 2017, 22(6), 988; https://doi.org/10.3390/molecules22060988 - 14 Jun 2017

Cited by 17 | Viewed by 4357

Abstract

In health, uromodulin is the main protein of urine. Serum uromodulin concentrations (sUMOD) have been shown to correlate with kidney function. Acute kidney injury (AKI) is among the main complications of severe acute pancreatitis (AP). No reports exist on sUMOD in patients with [...] Read more.

In health, uromodulin is the main protein of urine. Serum uromodulin concentrations (sUMOD) have been shown to correlate with kidney function. Acute kidney injury (AKI) is among the main complications of severe acute pancreatitis (AP). No reports exist on sUMOD in patients with AP, including the diagnostic usefulness for early prediction of AP severity. We measured sUMOD during first 72 h of AP. Sixty-six adult patients with AP were recruited at the surgical ward of the District Hospital in Sucha Beskidzka, Poland. AP was diagnosed according to the Revised Atlanta Classification. Blood samples were collected at 24, 48 and 72 h of AP, and sUMOD concentrations were measured with enzyme-linked immunosorbent test. sUMOD decreased non-significantly during the study. Patients with severe AP had non-significantly lower sUMOD concentrations than those with mild disease. Significant positive correlation was observed between sUMOD and estimated glomerular filtration rate on each day of the study and negative correlations were shown between sUMOD and age, serum creatinine, cystatin C and urea. Patients with AKI tended to have lower sUMOD. Although sUMOD correlated significantly with kidney function in the early phase of AP, measuring sUMOD did not allow to reliably predict AP severity or development of AKI. Full article

(This article belongs to the Section Bioorganic Chemistry)

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11 pages, 1105 KiB

Open AccessArticle

Five Unprecedented Secondary Metabolites from the Spider Parasitic Fungus Akanthomyces novoguineensis

by Soleiman E. Helaly^1,2,†

, Wilawan Kuephadungphan^1,3,†, Souwalak Phongpaichit^3,4, Janet Jennifer Luangsa-ard⁵, Vatcharin Rukachaisirikul^6,7 and Marc Stadler^1,*

¹ Department of Microbial Drugs, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany

² Department of Chemistry, Faculty of Science, Aswan University, Aswan 81528, Egypt

³ Department of Microbiology, Faculty of Science, Prince of Songkla University, Songkhla 90112, Thailand

⁴ Natural Products Research Center of Excellence and Department of Microbiology, Prince of Songkla University, Songkhla 90112, Thailand

⁵ National Centre for Genetic Engineering and Biotechnology (BIOTEC), Pathumthani 12120, Thailand

⁶ Department of Chemistry, Faculty of Science, Prince of Songkla University, Songkhla 90112, Thailand

⁷ Center of Excellence for Innovation in Chemistry, Prince of Songkla University, Songkhla 90112, Thailand

^† These authors contributed equally to this work.

Molecules 2017, 22(6), 991; https://doi.org/10.3390/molecules22060991 - 14 Jun 2017

Cited by 21 | Viewed by 5288

Abstract

Five new compounds including the glycosylated β-naphthol (1, akanthol), a glycosylated pyrazine (2, akanthozine), and three amide derivatives including a hydroxamic acid derivative (3–5) were isolated from the spider-associated fungus Akanthomyces novoguineensis (Cordycipitaceae, Ascomycota). Their [...] Read more.

Five new compounds including the glycosylated β-naphthol (1, akanthol), a glycosylated pyrazine (2, akanthozine), and three amide derivatives including a hydroxamic acid derivative (3–5) were isolated from the spider-associated fungus Akanthomyces novoguineensis (Cordycipitaceae, Ascomycota). Their structures were elucidated by using high resolution mass spectrometry (HRMS) and NMR spectroscopy. In this study, the antimicrobial, cytotoxic, anti-biofilm, and nematicidal activities of the new compounds were evaluated. The distribution pattern of secondary metabolites in the species was also revealed in which more isolates of A. novoguineensis were encountered and their secondary metabolite profiles were examined using analytical HPLC with diode array and mass spectrometric detection (HPLC-DAD/MS). Remarkably, all isolated compounds are specifically produced by A. novoguineensis. Full article

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21 pages, 3539 KiB

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Dynamic Allostery Modulates Catalytic Activity by Modifying the Hydrogen Bonding Network in the Catalytic Site of Human Pin1

by Jing Wang^1,†, Ryosuke Kawasaki^1,†, Jun-ichi Uewaki², Arif U. R. Rashid¹, Naoya Tochio² and Shin-ichi Tate^1,2,*

¹ Department of Mathematical and Life Sciences, School of Science, Hiroshima University, 1-3-1 Kagamiyama, Higashi-Hiroshima 739-8526, Japan

² Research Center for the Mathematics on Chromatin Live Dynamics (RcMcD), Hiroshima University, 1-3-1 Kagamiyama, Higashi-Hiroshima 739-8526, Japan

^† These authors contributed equally to this work.

Molecules 2017, 22(6), 992; https://doi.org/10.3390/molecules22060992 - 15 Jun 2017

Cited by 14 | Viewed by 5661

Abstract

Allosteric communication among domains in modular proteins consisting of flexibly linked domains with complimentary roles remains poorly understood. To understand how complementary domains communicate, we have studied human Pin1, a representative modular protein with two domains mutually tethered by a flexible linker: a [...] Read more.

Allosteric communication among domains in modular proteins consisting of flexibly linked domains with complimentary roles remains poorly understood. To understand how complementary domains communicate, we have studied human Pin1, a representative modular protein with two domains mutually tethered by a flexible linker: a WW domain for substrate recognition and a peptidyl-prolyl isomerase (PPIase) domain. Previous studies of Pin1 showed that physical contact between the domains causes dynamic allostery by reducing conformation dynamics in the catalytic domain, which compensates for the entropy costs of substrate binding to the catalytic site and thus increases catalytic activity. In this study, the S138A mutant PPIase domain, a mutation that mimics the structural impact of the interdomain contact, was demonstrated to display dynamic allostery by rigidification of the α2-α3 loop that harbors the key catalytic residue C113. The reduced dynamics of the α2-α3 loop stabilizes the C113–H59 hydrogen bond in the hydrogen-bonding network of the catalytic site. The stabilized hydrogen bond between C113 and H59 retards initiation of isomerization, which explains the reduced isomerization rate by ~20% caused by the S138A mutation. These results provide new insight into the interdomain allosteric communication of Pin1. Full article

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

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11 pages, 2236 KiB

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The Molecular Effect of Diagnostic Absorbed Doses from ¹³¹I on Papillary Thyroid Cancer Cells In Vitro

by Mariusz Stasiołek^1,†, Zbigniew Adamczewski^2,3,†

, Przemysław W. Śliwka³, Bartosz Puła⁴, Bolesław Karwowski⁵, Anna Merecz-Sadowska⁵, Marek Dedecjus⁶ and Andrzej Lewiński^2,3,*

¹ Department of Neurology, Polish Mother’s Memorial Hospital—Research Institute, 93-338 Lodz, Poland

² Department of Endocrinology and Metabolic Diseases, Medical University of Lodz, 93-338 Lodz; Poland

³ Department of Endocrinology and Metabolic Diseases, Polish Mother’s Memorial Hospital—Research Institute, 93-338 Lodz, Poland

⁴ Department of Hematology, Institute of Hematology and Transfusion Medicine, 02-776 Warsaw, Poland

⁵ Food Science Department, Medical University of Lodz, 90-151 Lodz, Poland

⁶ Department of Oncological Endocrinology and Nuclear Medicine, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, 02-781 Warsaw, Poland

^† These authors contributed equally to this work.

Molecules 2017, 22(6), 993; https://doi.org/10.3390/molecules22060993 - 15 Jun 2017

Cited by 6 | Viewed by 5182

Abstract

Diagnostic whole-body scan is a standard procedure in patients with thyroid cancer prior to the application of a therapeutic dose of ¹³¹I. Unfortunately, administration of the radioisotope in a diagnostic dose may decrease further radioiodine uptake—the phenomenon called “thyroid stunning”. We estimated [...] Read more.

Diagnostic whole-body scan is a standard procedure in patients with thyroid cancer prior to the application of a therapeutic dose of ¹³¹I. Unfortunately, administration of the radioisotope in a diagnostic dose may decrease further radioiodine uptake—the phenomenon called “thyroid stunning”. We estimated radiation absorbed dose-dependent changes in genetic material, in particular in the sodium iodide symporter (NIS) gene promoter, and the NIS protein level in a K1 cell line derived from the metastasis of a human papillary thyroid carcinoma exposed to ¹³¹I in culture. The different activities applied were calculated to result in absorbed doses of 5, 10 and 20 Gy. Radioiodine did not affect the expression of the NIS gene at the mRNA level, however, we observed significant changes in the NIS protein level in K1 cells. The decrease of the NIS protein level observed in the cells subjected to the lowest absorbed dose was paralleled by a significant increase in 8-oxo-dG concentrations (p < 0.01) and followed by late activation of the DNA repair pathways. Our findings suggest that the impact of ¹³¹I radiation on thyroid cells, in the range compared to doses absorbed during diagnostic procedures, is not linear and depends on various factors including the cellular components of thyroid pathology. Full article

(This article belongs to the Collection New Frontiers in Nucleic Acid Chemistry)

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14 pages, 1273 KiB

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Microwave-Assisted Facile Synthesis, Anticancer Evaluation and Docking Study of N-((5-(Substituted methylene amino)-1,3,4-thiadiazol-2-yl)methyl) Benzamide Derivatives

by Shailee V. Tiwari¹, Sumaiya Siddiqui¹, Julio A. Seijas²

, M. Pilar Vazquez-Tato², Aniket P. Sarkate³, Deepak K. Lokwani¹

and Anna Pratima G. Nikalje^1,*

¹ Y. B. Chavan College of Pharmacy, Dr. Rafiq Zakaria Campus, Rauza Bagh, Maharashtra, Aurangabad 431001, India

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

³ Department of Chemical Technology, Dr. Babasaheb Ambedkar Marathwada University, Maharashtra, Aurangabad 431004, India

Molecules 2017, 22(6), 995; https://doi.org/10.3390/molecules22060995 - 15 Jun 2017

Cited by 29 | Viewed by 6262

Abstract

In the present work, 12 novel Schiff’s bases containing a thiadiazole scaffold and benzamide groups coupled through appropriate pharmacophore were synthesized. These moieties are associated with important biological properties. A facile, solvent-free synthesis of a series of novel 7(a–l [...] Read more.

In the present work, 12 novel Schiff’s bases containing a thiadiazole scaffold and benzamide groups coupled through appropriate pharmacophore were synthesized. These moieties are associated with important biological properties. A facile, solvent-free synthesis of a series of novel 7(a–l) N-((5-(substituted methylene amino)-1,3,4-thiadiazol-2-yl)methyl) benzamide was carried out under microwave irradiation. Structures of the synthesized compounds were confirmed by IR, NMR, mass spectral study and elemental analysis. All the synthesized hybrids were evaluated for their in vitro anticancer activity against a panel of four human cancer cell lines, viz. SK-MEL-2 (melanoma), HL-60 (leukemia), HeLa (cervical cancer), MCF-7 (breast cancer) and normal breast epithelial cell (MCF-10A) using 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay method. Most of the synthesized compounds exhibited promising anticancer activity, showed comparable GI₅₀ values comparable to that of the standard drug Adriamycin. The compounds 7k, 7l, 7b, and 7a were found to be the most promising anticancer agents in this study. A molecular docking study was performed to predict the probable mechanism of action and computational study of the synthesized compounds 7(a–l) was performed to predict absorption, distribution, metabolism, excretion and toxicity (ADMET) properties, by using QikProp v3.5 (Schrödinger LLC). The results showed the good oral drug-like behavior of the synthesized compounds 7(a–l). Full article

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

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13 pages, 2209 KiB

Open AccessArticle

Synthesis and Biological Activity Evaluation of Novel Heterocyclic Pleuromutilin Derivatives

by Yunpeng Yi, Yunxing Fu, Pengcheng Dong, Wenwen Qin, Yu Liu, Jiangping Liang and Ruofeng Shang^*

Key Laboratory of New Animal Drug Project of Gansu Province, Key Laboratory of Veterinary Pharmaceutical Development, Ministry of Agriculture, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of CAAS, Lanzhou 730050, China

Molecules 2017, 22(6), 996; https://doi.org/10.3390/molecules22060996 - 15 Jun 2017

Cited by 19 | Viewed by 6336

Abstract

A series of pleuromutilin derivatives were synthesized by two synthetic procedures under mild reaction conditions and characterized by Nuclear Magnetic Resonance (NMR), Infrared Spectroscopy (IR), and High Resolution Mass Spectrometer (HRMS). Most of the derivatives with heterocyclic groups at the C-14 side of [...] Read more.

A series of pleuromutilin derivatives were synthesized by two synthetic procedures under mild reaction conditions and characterized by Nuclear Magnetic Resonance (NMR), Infrared Spectroscopy (IR), and High Resolution Mass Spectrometer (HRMS). Most of the derivatives with heterocyclic groups at the C-14 side of pleuromutilin exhibited excellent in vitro antibacterial activities against Staphylococcus aureus, methicillin-resistant Staphylococcus aureus (MRSA), methicillin-resistant Staphylococcus epidermidis (MRSE), and vancomycin-resistant Enterococcus (VRE) in vitro antibacterial activity. The synthesized derivatives which contained pyrimidine rings, 3a, 3b, and 3f, displayed modest antibacterial activities. Compound 3a, the most active antibacterial agent, displayed rapid bactericidal activity and affected bacterial growth in the same manner as that of tiamulin fumarate. Moreover, molecular docking studies of 3a and lefamulin provided similar information about the interactions between the compounds and 50S ribosomal subunit. The results of the study show that pyrimidine rings should be considered in the drug design of pleuromutilin derivatives. Full article

(This article belongs to the Section Medicinal Chemistry)

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16 pages, 2868 KiB

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Metabolomics Characterization of Two Apocynaceae Plants, Catharanthus roseus and Vinca minor, Using GC-MS and LC-MS Methods in Combination

by Qi Chen¹

, Xueyan Lu¹, Xiaorui Guo², Qingxi Guo^1,* and Dewen Li^2,*

¹ Center for Ecological Research, Northeast Forestry University, Harbin 150040, China

² Key Laboratory of Plant Ecology, Northeast Forestry University, Harbin 150040, China

Molecules 2017, 22(6), 997; https://doi.org/10.3390/molecules22060997 - 17 Jun 2017

Cited by 46 | Viewed by 9314

Abstract

Catharanthus roseus (C. roseus) and Vinca minor (V. minor) are two common important medical plants belonging to the family Apocynaceae. In this study, we used non-targeted GC-MS and targeted LC-MS metabolomics to dissect the metabolic profile of two plants [...] Read more.

Catharanthus roseus (C. roseus) and Vinca minor (V. minor) are two common important medical plants belonging to the family Apocynaceae. In this study, we used non-targeted GC-MS and targeted LC-MS metabolomics to dissect the metabolic profile of two plants with comparable phenotypic and metabolic differences. A total of 58 significantly different metabolites were present in different quantities according to PCA and PLS-DA score plots of the GC-MS analysis. The 58 identified compounds comprised 16 sugars, eight amino acids, nine alcohols and 18 organic acids. We subjected these metabolites into KEGG pathway enrichment analysis and highlighted 27 metabolic pathways, concentrated on the TCA cycle, glycometabolism, oligosaccharides, and polyol and lipid transporter (RFOS). Among the primary metabolites, trehalose, raffinose, digalacturonic acid and gallic acid were revealed to be the most significant marker compounds between the two plants, presumably contributing to species-specific phenotypic and metabolic discrepancy. The profiling of nine typical alkaloids in both plants using LC-MS method highlighted higher levels of crucial terpenoid indole alkaloid (TIA) intermediates of loganin, serpentine, and tabersonine in V. minor than in C. roseus. The possible underlying process of the metabolic flux from primary metabolism pathways to TIA synthesis was discussed and proposed. Generally speaking, this work provides a full-scale comparison of primary and secondary metabolites between two medical plants and a metabolic explanation of their TIA accumulation and phenotype differences. Full article

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11 pages, 1870 KiB

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Molecular Orientation of a Terbium(III)-Phthalocyaninato Double-Decker Complex for Effective Suppression of Quantum Tunneling of the Magnetization

by Tsutomu Yamabayashi¹, Keiichi Katoh^1,*

, Brian K. Breedlove¹ and Masahiro Yamashita^1,2,3,*

¹ Department of Chemistry, Graduate School of Science, Tohoku University, 6-3, Aramaki-Aza-Aoba, Aoba-ku, Sendai, Miyagi 980-8578, Japan

² WPI Research Center, Advanced Institute for Materials Research, Tohoku University, 2-1-1 Katahira, Aoba-ku, Sendai 980-8577, Japan

³ School of Materials Science and Engineering, Nankai University, Tianjin 300350, China

Molecules 2017, 22(6), 999; https://doi.org/10.3390/molecules22060999 - 15 Jun 2017

Cited by 32 | Viewed by 6151

Abstract

Single-molecule magnet (SMM) properties of crystals of a terbium(III)-phthalocyaninato double-decker complex with different molecular packings (1: TbPc₂, 2: TbPc₂·CH₂Cl₂) were studied to elucidate the relationship between the molecular packing and SMM properties. [...] Read more.

Single-molecule magnet (SMM) properties of crystals of a terbium(III)-phthalocyaninato double-decker complex with different molecular packings (1: TbPc₂, 2: TbPc₂·CH₂Cl₂) were studied to elucidate the relationship between the molecular packing and SMM properties. From single crystal X-ray analyses, the high symmetry of the coordination environment of 2 suggested that the SMM properties were improved. Furthermore, the shorter intermolecular Tb–Tb distance and relative collinear alignment of the magnetic dipole in 2 indicated that the magnetic dipole–dipole interactions were stronger than those in 1. This was confirmed by using direct current magnetic measurements. From alternating current magnetic measurements, the activation energy for spin reversal for 1 and 2 were similar. However, the relaxation time for 2 is three orders of magnitude slower than that for 1 in the low-T region due to effective suppression of the quantum tunneling of the magnetization. These results suggest that the SMM properties of TbPc₂ highly depend on the molecular packing. Full article

(This article belongs to the Special Issue Porphyrins and Phthalocyanines: Synthesis, Properties and Applications)

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12 pages, 3581 KiB

Open AccessArticle

Response Surface Optimized Infrared-Assisted Extraction and UHPLC Determination of Flavonoid Types from Flos Sophorae

by Qianqian Mou^1,2,†, Jingxia He^1,2,†, Rongli Yin², Bin Yang^1,3, Meihong Fu¹, Jing Fang¹ and Hua Li^1,3,*

¹ Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China

² College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China

³ State Key Laboratory of Dao-di Herbs, China Academy of Chinese Medical Sciences, Beijing 100700, China

^† These authors contributed equally to this work.

Molecules 2017, 22(6), 1000; https://doi.org/10.3390/molecules22061000 - 15 Jun 2017

Cited by 24 | Viewed by 5386

Abstract

Single-factor experiment and Box-Behnken design were applied to optimize the infrared-assisted extraction (IRAE) of rutin, quercetin, kaempferol, and isorhamnetin from Flos sophorae. Four factors (extract solvent, solid-liquid ration, extraction time, infrared power) affecting the extraction yield of flavonoids were studied. Under optimized conditions [...] Read more.

Single-factor experiment and Box-Behnken design were applied to optimize the infrared-assisted extraction (IRAE) of rutin, quercetin, kaempferol, and isorhamnetin from Flos sophorae. Four factors (extract solvent, solid-liquid ration, extraction time, infrared power) affecting the extraction yield of flavonoids were studied. Under optimized conditions the extraction yield was 33.199 ± 0.24 mg/g, which substantially improved, compared with heating reflux extraction (HRE) and ultrasonic-assisted extraction (UAE), while extraction time was only 9 min. The eluents were rich in 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azobis (2-methyl-propionamidine) dihydrochloride radical scavenging potential (IC₅₀ of DPPH: 53.44 ± 0.01 μg/mL, oxygen radical absorbance capacity (ORAC): 3785.83 ± 52 μmol/g) than the extracts obtained by HRE and UAE. In addition, an ultra-high performance liquid chromatography method was optimized for the identification and quantification of the tested flavonoids, and the method was validated based on its correlation coefficient (r), reproducibility (RSD, n = 5), and recovery values, which were 0.9994–0.9998, 0.74–1.83%, and 97.78–102.94%, respectively. These results confirmed that high extraction yield of flavonoids results in stronger antioxidant values and response surface methodology optimization of IRAE is a promising alternative to traditional extraction techniques for flavonoids from medicinal plants. 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, 2274 KiB

Open AccessArticle

Discovery of Indeno[1,2-c]quinoline Derivatives as Potent Dual Antituberculosis and Anti-Inflammatory Agents

by Chih-Hua Tseng^1,2,3,4,5

, Chun-Wei Tung^1,5,6

, Chen-Hsin Wu⁷, Cherng-Chyi Tzeng^3,5,7, Yen-Hsu Chen^8,9,10,11,*

, Tsong-Long Hwang^12,13,14,*

and Yeh-Long Chen^4,5,7,*

¹ School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan

² Department of Fragrance and Cosmetic Science, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan

³ Research Center for Natural Products and Drug Development, Kaohsiung Medical University, Kaohsiung 807, Taiwan

⁴ Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung 807, Taiwan

⁵ Department of Medical Research, Kaohsiung Medical University-Hospital, Kaohsiung 807, Taiwan

⁶ Ph.D. Program in Toxicology, Kaohsiung Medical University, Kaohsiung City 807, Taiwan

⁷ Department of Medicinal and Applied Chemistry, College of Life Science, Kaohsiung Medical University, Kaohsiung 807, Taiwan

⁸ Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Medical University-Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan

⁹ School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan

¹⁰ Department of Laboratory Medicine, Kaohsiung Medical University-Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan

¹¹ Center for Dengue Fever Control and Research, Kaohsiung Medical University, Kaohsiung 807, Taiwan

¹² Graduate Institute of Natural Products, College of Medicine, and Chinese Herbal Medicine Research Team, Healthy Aging Research Center, Chang Gung University, Taoyuan 333, Taiwan

¹³ 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

¹⁴ Department of Anesthesiology, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan

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Molecules 2017, 22(6), 1001; https://doi.org/10.3390/molecules22061001 - 16 Jun 2017

Cited by 34 | Viewed by 6361

Abstract

A series of indeno[1,2-c]quinoline derivatives were designed, synthesized and evaluated for their anti-tuberculosis (anti-TB) and anti-inflammatory activities. The minimum inhibitory concentration (MIC) of the newly synthesized compound was tested against Mycobacterium tuberculosis H₃₇R_V. Among the tested compounds, [...] Read more.

A series of indeno[1,2-c]quinoline derivatives were designed, synthesized and evaluated for their anti-tuberculosis (anti-TB) and anti-inflammatory activities. The minimum inhibitory concentration (MIC) of the newly synthesized compound was tested against Mycobacterium tuberculosis H₃₇R_V. Among the tested compounds, (E)-N′-[6-(4-hydroxypiperidin-1-yl)-11H-indeno[1,2-c]quinolin-11-ylidene]isonicotino-hydrazide (12), exhibited significant activities against the growth of M. tuberculosis (MIC values of 0.96 μg/mL) with a potency approximately equal to that of isoniazid (INH), an anti-TB drug. Important structure features were analyzed by quantitative structure–activity relationship (QSAR) analysis to give better insights into the structure determinants for predicting the anti-TB activity. The anti-inflammatory activity was induced by superoxide anion generation and neutrophil elastase (NE) release using the formyl-l-methionyl-l-leucyl-l-phenylalanine (fMLF)-activated human neutrophils method. Results indicated that compound 12 demonstrated a potent dual inhibitory effect on NE release and superoxide anion generation with IC₅₀ values of 1.76 and 1.72 μM, respectively. Our results indicated that compound 12 is a potential lead compound for the discovery of dual anti-TB and anti-inflammatory drug candidates. In addition, 6-[3-(hydroxymethyl)piperidin-1-yl]-9-methoxy-11H-indeno[1,2-c]quinolin-11-one (4g) showed a potent dual inhibitory effect on NE release and superoxide anion generation with IC₅₀ values of 0.46 and 0.68 μM, respectively, and is a potential lead compound for the discovery of anti-inflammatory drug candidates. Full article

(This article belongs to the Special Issue Frontiers in Antimicrobial Drug Discovery and Design)

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14 pages, 580 KiB

Open AccessArticle

Identification of Onosma visianii Roots Extract and Purified Shikonin Derivatives as Potential Acaricidal Agents against Tetranychus urticae

by Stefania Sut^1,†, Roman Pavela^2,†, Vladislav Kolarčik³, Loredana Cappellacci⁴

, Riccardo Petrelli⁴

, Filippo Maggi^4,*

, Stefano Dall’Acqua^1,*

and Giovanni Benelli⁵

¹ Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Via Marzolo, 35121 Padova, Italy

² Crop Research Institute, Drnovska 507, 161 06, Prague 6, Czech Republic

³ Department of Botany, Institute of Biology and Ecology, Faculty of Science, P.J. Šafárik University, Mánesova 23, 04154 Košice, Slovakia

⁴ School of Pharmacy, University of Camerino, Via Sant’Agostino 1, 62032 Camerino, Italy

⁵ Department of Agriculture, Food and Environment, University of Pisa, via del Borghetto 80, 56124 Pisa, Italy

^† These authors contributed equally to the work.

Molecules 2017, 22(6), 1002; https://doi.org/10.3390/molecules22061002 - 16 Jun 2017

Cited by 31 | Viewed by 6323

Abstract

There is an increasing need for the discovery of reliable and eco-friendly pesticides and natural plant-derived products may play a crucial role as source of new active compounds. In this research, a lipophilic extract of Onosma visianii roots extract containing 12% of shikonin [...] Read more.

There is an increasing need for the discovery of reliable and eco-friendly pesticides and natural plant-derived products may play a crucial role as source of new active compounds. In this research, a lipophilic extract of Onosma visianii roots extract containing 12% of shikonin derivatives demonstrated significant toxicity and inhibition of oviposition against Tetranychus urticae mites. Extensive chromatographic separation allowed the isolation of 11 naphthoquinone derivatives that were identified by spectral techniques and were tested against Tetranychus urticae. All the isolated compounds presented effects against the considered mite and isobutylshikonin (1) and isovalerylshikonin (2) were the most active, being valuable model compounds for the study of new anti-mite agents. Full article

(This article belongs to the Section Natural Products Chemistry)

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13 pages, 1847 KiB

Open AccessArticle

Anti-Inflammatory and Anti-Oxidant Potential of the Root Extract and Constituents of Doronicum austriacum

by Stefania Marzocco¹

, Simona Adesso^1,2, Mostafa Alilou³, Hermann Stuppner³ and Stefan Schwaiger^3,*

¹ Department of Pharmacy, University of Salerno, Via Giovanni Paolo II 132, I-84084 Fisciano SA, Italy

² PhD Program in Drug Discovery and Development, University of Salerno, Via Giovanni Paolo II 132, I-84084 Fisciano SA, Italy

³ Institute of Pharmacy, Pharmacognosy, Member of the CMBI, University of Innsbruck, CCB, Innrain 80-82, 6020 Innsbruck, Austria

Molecules 2017, 22(6), 1003; https://doi.org/10.3390/molecules22061003 - 16 Jun 2017

Cited by 25 | Viewed by 4815

Abstract

Background: Doronicum austriacum Jacq., Asteraceae, is a plant which is used in traditional alpine medicine. Historical sources describe the medical use of the root, but up until now only a few studies evaluated its pharmacological properties. The evaluation of the dichloromethane extract, and [...] Read more.

Background: Doronicum austriacum Jacq., Asteraceae, is a plant which is used in traditional alpine medicine. Historical sources describe the medical use of the root, but up until now only a few studies evaluated its pharmacological properties. The evaluation of the dichloromethane extract, and its major compounds for their anti-inflammatory and anti-oxidant potential was performed in macrophages J774A.1 and C6 astrocytes. Nitric oxide (NO) and reactive oxygen species (ROS) release, as well as nitrotyrosine formation, were evaluated. Moreover, in order to evaluate the potential anti-proliferative activity, under the same experimental conditions, 3-(4,5-dimethyltiazol-2yl)-2,5-phenyl-2H-tetrazolium bromide (MTT) assay was also performed. Our results indicate that Doronicum austriacum has a significant effect in inhibiting both pro-inflammatory and pro-oxidative mediators. All isolated compounds were able to significantly inhibit NO and ROS release both in macrophage and in astrocytes cells, even if the effect was more pronounced in macrophage. In particular, among the tested compounds, 6,12-dihydroxy-(−)-2S-tremetone exerted stronger activity. Both extract and single compounds did not affect cellular viability. This study provides evidence for the pharmacological anti-inflammatory and anti-oxidant potential of Doronicum austriacum extract. These effects could be due to the activity of its major constituents and subsequent identification of benzofurans as a promising compound class to combat inflammation and related diseases. Full article

(This article belongs to the Section Natural Products Chemistry)

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8 pages, 529 KiB

Open AccessArticle

Hydronopylformamides: Modification of the Naturally Occurring Compound (-)-β-Pinene to Produce Insect Repellent Candidates against Blattella germanica

by Shengliang Liao¹, Yan Liu², Hongyan Si¹, Zhuanquan Xiao³, Guorong Fan¹, Shangxing Chen¹, Peng Wang¹ and Zongde Wang^1,*

¹ College of Forestry, Jiangxi Agricultural University, Camphor Tree Engineering and Technology Research Center of State Forestry Administration and Jiangxi Province, Nanchang 330045, Jiangxi, China

² Yichun Hydrological Bureau of Jiangxi Province, Yichun 336000, Jiangxi, China

³ College of Chemistry and Chemical Engineering, Jiangxi Normal University, Nanchang 330027, China

Molecules 2017, 22(6), 1004; https://doi.org/10.3390/molecules22061004 - 16 Jun 2017

Cited by 10 | Viewed by 5295

Abstract

The development of a novel repellent plays an important role in the integrated control of Blattella germanica. A series of novel hydronopylformamides derivatives were synthesized from a naturally occurring compound (-)-β-pinene. The structures of these hydronopylformamides derivatives were characterized by Fourier transform [...] Read more.

The development of a novel repellent plays an important role in the integrated control of Blattella germanica. A series of novel hydronopylformamides derivatives were synthesized from a naturally occurring compound (-)-β-pinene. The structures of these hydronopylformamides derivatives were characterized by Fourier transform infrared spectroscopy (FTIR), nuclear magnetic resonance spectroscopy (¹H-NMR and ¹³C-NMR), and electron impact mass spectrometry (EI-MS). Repellency of these hydronopylformamides derivatives against Blattella germanica was evaluated by the using petri dish arena method. The results showed that four derivatives (compounds 8a, 8b, 8c and 8e) exhibited repellency against Blattella germanica at a concentration of 20 mg/mL. Compound 8a was the most active compound among these derivatives, where the repelling ratios of compound 8a against Blattella germanica were 66.10%, 50.46%, 48.26%, at concentrations of 20 mg/mL, 10 mg/mL, and 5 mg/mL, respectively. In addition, compound 8a showed better repellency than the traditional insect repellent N, N-diethyl-3-methylbenzamide (DEET), which indicated that compound 8a had a good application prospect in the prevention of Blattella germanica. This research hopes to promote the value-added utilization of (-)-β-pinene and the development of novel German cockroach repellents. Full article

(This article belongs to the Special Issue Natural Product Inspired Scaffolds Designs)

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13 pages, 2888 KiB

Open AccessArticle

Cholinesterase Inhibitory Activities of Adamantyl-Based Derivatives and Their Molecular Docking Studies

by Huey Chong Kwong¹, Siau Hui Mah^2,*

, Tze Shyang Chia³, Ching Kheng Quah³, Gin Keat Lim¹ and C. S. Chidan Kumar⁴

¹ School of Chemical Sciences, Universiti Sains Malaysia, Penang 11800 USM, Malaysia

² School of Biosciences, Taylor’s University, Lakeside Campus, 47500 Subang Jaya, Selangor, Malaysia

³ X-ray Crystallography Unit, School of Physics, Universiti Sains Malaysia, Penang 11800 USM, Malaysia

⁴ Department of Engineering Chemistry, Vidya Vikas Institute of Engineering & Technology, Visvesvaraya Technological University, Alanahalli, Mysuru 570028, Karnataka, India

Molecules 2017, 22(6), 1005; https://doi.org/10.3390/molecules22061005 - 17 Jun 2017

Cited by 9 | Viewed by 5556

Abstract

Adamantyl-based compounds are clinically important for the treatments of type 2 diabetes and for their antiviral abilities, while many more are under development for other pharmaceutical uses. This study focused on the acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities of adamantyl-based ester derivatives [...] Read more.

Adamantyl-based compounds are clinically important for the treatments of type 2 diabetes and for their antiviral abilities, while many more are under development for other pharmaceutical uses. This study focused on the acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities of adamantyl-based ester derivatives with various substituents on the phenyl ring using Ellman’s colorimetric method. Compound 2e with a 2,4-dichloro electron-withdrawing substituent on the phenyl ring exhibited the strongest inhibition effect against AChE, with an IC₅₀ value of 77.15 µM. Overall, the adamantyl-based ester with the mono-substituent at position 3 of the phenyl ring exhibited good AChE inhibition effects with an ascending order for the substituents: Cl < NO₂ < CH₃ < OCH₃. Furthermore, compounds with electron-withdrawing groups (Cl and NO₂) substituted at position 3 on their phenyl rings demonstrated stronger AChE inhibition effects, in comparison to their respective positional isomers. On the other hand, compound 2j with a 3-methoxyphenyl ring showed the highest inhibition effect against BChE, with an IC₅₀ value of 223.30 µM. Molecular docking analyses were conducted for potential AChE and BChE inhibitors, and the results demonstrated that the peripheral anionic sites of target proteins were predominant binding sites for these compounds through hydrogen bonds and halogen interactions instead of hydrophobic interactions in the catalytic active site. 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, 1976 KiB

Open AccessArticle

Novel Tacrine-Scutellarin Hybrids as Multipotent Anti-Alzheimer’s Agents: Design, Synthesis and Biological Evaluation

by Katarina Spilovska^1,2, Jan Korabecny^1,3

, Vendula Sepsova^1,3

, Daniel Jun^1,3, Martina Hrabinova^1,3, Petr Jost¹, Lubica Muckova¹, Ondrej Soukup^2,3

, Jana Janockova³

, Tomas Kucera¹, Rafael Dolezal³, Eva Mezeiova^2,3, Daniel Kaping² and Kamil Kuca^3,*

¹ Department of Toxicology and Military Pharmacy, Faculty of Military Health Sciences, Trebesska 1575, 500 01 Hradec Kralove, Czech Republic

² National Institute of Mental Health, Topolova 748, 250 67 Klecany, Czech Republic

³ Biomedical Research Centre, University Hospital Hradec Kralove, Sokolska 581, 500 05 Hradec Kralove, Czech Republic

Molecules 2017, 22(6), 1006; https://doi.org/10.3390/molecules22061006 - 16 Jun 2017

Cited by 43 | Viewed by 8321

Abstract

A novel series of 6-chlorotacrine-scutellarin hybrids was designed, synthesized and the biological activity as potential anti-Alzheimer’s agents was assessed. Their inhibitory activity towards human acetylcholinesterase (hAChE) and human butyrylcholinesterase (hBChE), antioxidant activity, ability to cross the blood-brain barrier (BBB) [...] Read more.

A novel series of 6-chlorotacrine-scutellarin hybrids was designed, synthesized and the biological activity as potential anti-Alzheimer’s agents was assessed. Their inhibitory activity towards human acetylcholinesterase (hAChE) and human butyrylcholinesterase (hBChE), antioxidant activity, ability to cross the blood-brain barrier (BBB) and hepatotoxic profile were evaluated in vitro. Among these compounds, hybrid K1383, bearing two methylene tether between two basic scaffolds, was found to be very potent hAChE inhibitor (IC₅₀ = 1.63 nM). Unfortunately, none of the hybrids displayed any antioxidant activity (EC₅₀ ≥ 500 μM). Preliminary data also suggests a comparable hepatotoxic profile with 6-Cl-THA (established on a HepG2 cell line). Kinetic studies performed on hAChE with the most active compound in the study, K1383, pointed out to a mixed, non-competitive enzyme inhibition. These findings were further corroborated by docking studies. Full article

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

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28 pages, 4081 KiB

Open AccessArticle

Comprehensive Identification of Guan-Xin-Shu-Tong Capsule via a Mass Defect and Fragment Filtering Approach by High Resolution Mass Spectrometry: In Vitro and In Vivo Study

by Xun Gao¹, Jingqing Mu², Qing Li², Shaoyi Guan³, Ran Liu², Yiyang Du², Huifen Zhang^2,* and Kaishun Bi^2,*

¹ School of Traditional Chinese Medicine, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China

² School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China

³ The General Hospital of Shenyang Military, 83 Wenhua Road, Shenyang 110016, China

Molecules 2017, 22(6), 1007; https://doi.org/10.3390/molecules22061007 - 16 Jun 2017

Cited by 12 | Viewed by 6187

Abstract

The Guan-Xin-Shu-Tong capsule (GXSTC) is a well-known traditional Chinese medicine that is used for the treatment of coronary heart disease. Despite its common use in China, basic pharmacological research on its active components is limited. A comprehensive analytical method using quadrupole-time-of-flight mass spectrometry [...] Read more.

The Guan-Xin-Shu-Tong capsule (GXSTC) is a well-known traditional Chinese medicine that is used for the treatment of coronary heart disease. Despite its common use in China, basic pharmacological research on its active components is limited. A comprehensive analytical method using quadrupole-time-of-flight mass spectrometry (Q-TOF/MS), specifically with the Triple TOF 5600 platform, was developed to characterize the compounds in the GXSTC powder itself (in vitro) as well as the active components in healthy and heart disease model rats after its oral administration (in vivo). The 5600 platform was operated in both positive and negative ion modes, before the raw data were processed using the extracted ion chromatography (EIC), mass defect filtering (MDF) and fragment filtering (FF) techniques. With the aid of reference compounds for retention time and fragment ion comparisons, 18 compounds were unambiguously identified in vitro. An additional 56 other compounds were tentatively characterized using the accurate quasi-molecular ion mass and Tandem mass spectrometry (MS/MS) fragmentation pattern strategies. Among them, 30 compounds were characterized based on the MDF and FF approaches. Normal rats in addition to hyperlipidemic (HL) and acute blood stasis (ABS) model rats were given a single oral dose of GXSTC solution for subsequent blood analysis at 1 and 2 h after administration. A total of 24 prototypecomponents and 20 metabolites derived from GXSTC were differentially detected across the three animal groups, including the absence of four phase II phenolic acid metabolites in the ABS group and the presence of three diterpenoid-related metabolites exclusive to the HL group. The use of reference compounds as well as the mass defect and fragment-filtering strategies were critical to identify GXSTC compounds in vitro and in vivo. This can be used for further quality control and pharmacological studies aimed at characterizing the active and potential beneficial compounds of this ancient medicine. Full article

(This article belongs to the Section Natural Products Chemistry)

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12 pages, 4010 KiB

Open AccessArticle

In Vitro Comparative Study of the Inhibitory Effects of Mangiferin and Its Aglycone Norathyriol towards UDP-Glucuronosyl Transferase (UGT) Isoforms

by Dan Sun^1,†, Chun-Ze Zhang^2,†, Rui-Xue Ran³, Yun-Feng Cao⁴, Zuo Du^4,5, Zhi-Wei Fu^4,5, Chun-Ting Huang^4,5, Zhen-Ying Zhao⁶, Wei-Hua Zhang^2,* and Zhong-Ze Fang^4,5,*

¹ College of Life Sciences, Nankai University, Tianjin 300071, China

² Department of Colorectal Surgery, Tianjin Union Medical Center, Tianjin 300121, China

³ Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnosis, School of Pharmacy, Tianjin Medical University, Tianjin 300070, China

⁴ Key Laborotary of Liaoning Tumor Clinical Metabolomics (KLLTCM), Jinzhou 121001, Liaoning, China

⁵ Department of Toxicology, School of Public Health, Tianjin Medical University, 22 Qixiangtai Road, Heping District, Tianjin 300070, China

⁶ Tianjin Union Medical Center, 190 Jieyuan Road, Hongqiao District, Tianjin 300121, China

^† These two authors equally contributed to this work.

Molecules 2017, 22(6), 1008; https://doi.org/10.3390/molecules22061008 - 16 Jun 2017

Cited by 27 | Viewed by 5401

Abstract

Mangiferin (MGF), the predominant constituent of extracts of the mango plant Mangifera Indica L., has been investigated extensively because of its remarkable pharmacological effects. In vitro recombinant UGTs-catalyzed glucuronidation of 4-methylumbelliferone (4-MU) was used to investigate the inhibition of mangiferin and aglycone norathyriol [...] Read more.

Mangiferin (MGF), the predominant constituent of extracts of the mango plant Mangifera Indica L., has been investigated extensively because of its remarkable pharmacological effects. In vitro recombinant UGTs-catalyzed glucuronidation of 4-methylumbelliferone (4-MU) was used to investigate the inhibition of mangiferin and aglycone norathyriol towards various isoforms of UGTs in our study, which evaluated the inhibitory capacity of MGF and its aglycone norathyriol (NTR) towards UDP-glucuronosyltransferase (UGT) isoforms. Initial screening experiment showed that deglycosylation of MGF into NTR strongly increased the inhibitory effects towards almost all the tested UGT isoforms at a concentration of 100 μM. Kinetic experiments were performed to further characterize the inhibition of UGT1A3, UGT1A7 and UGT1A9 by NTR. NTR competitively inhibited UGT1A3, UGT1A7 and UGT1A9, with an IC₅₀ value of 8.2, 4.4, and 12.3 μM, and a Ki value of 1.6, 2.0, and 2.8 μM, respectively. In silico docking showed that only NTR could dock into the activity cavity of UGT1A3, UGT1A7 and UGT1A9. The binding free energy of NTR to UGT1A3, 1A7, 1A9 were −7.4, −7.9 and −4.0 kcal/mol, respectively. Based on the inhibition evaluation standard ([I]/Ki < 0.1, low possibility; 0.1 < [I]/Ki < 1, medium possibility; [I]/Ki > 1, high possibility), an in vivo herb–drug interaction between MGF/NTR and drugs mainly undergoing UGT1A3-, UGT1A7- or UGT1A9-catalyzed metabolism might occur when the plasma concentration of NTR is above 1.6, 2.0 and 2.8 μM, respectively. Full article

(This article belongs to the Section Metabolites)

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12 pages, 4018 KiB

Open AccessArticle

Mechanistic Explanation of the Weak Carbonic Anhydrase’s Esterase Activity

by Paolo Piazzetta^*, Tiziana Marino

and Nino Russo^*

Dipartimento di Chimica e Tecnologie Chimiche (CTC), Università della Calabria, 87036 Arcavacata di Rende (CS), Italy

Molecules 2017, 22(6), 1009; https://doi.org/10.3390/molecules22061009 - 18 Jun 2017

Cited by 8 | Viewed by 6421

Abstract

In order to elucidate the elementary mechanism of the promiscuous esterase activity of human carbonic anhydrase (h-CA), we present an accurate theoretical investigation on the hydrolysis of fully-acetylated d-glucose functionalized as sulfamate. This h-CA’s inhibitor is of potential relevance in cancer therapy. [...] Read more.

In order to elucidate the elementary mechanism of the promiscuous esterase activity of human carbonic anhydrase (h-CA), we present an accurate theoretical investigation on the hydrolysis of fully-acetylated d-glucose functionalized as sulfamate. This h-CA’s inhibitor is of potential relevance in cancer therapy. The study has been performed within the framework of three-layer ONIOM (QM-high:QM’-medium:MM-low) hybrid approach. The computations revealed that the hydrolysis process is not energetically favored, in agreement with the observed weak carbonic anhydrase’s esterase activity. Full article

(This article belongs to the Special Issue Metallopeptides)

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13 pages, 1828 KiB

Open AccessArticle

Synthesis and Evaluation of Phenylxanthine Derivatives as Potential Dual A2AR Antagonists/MAO-B Inhibitors for Parkinson’s Disease

by Xuebao Wang

, Chao Han, Yong Xu, Kaiqi Wu, Shuangya Chen, Mangsha Hu, Luyao Wang, Yun Ye and Faqing Ye^*

School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, China

Molecules 2017, 22(6), 1010; https://doi.org/10.3390/molecules22061010 - 17 Jun 2017

Cited by 17 | Viewed by 6438

Abstract

The aim of this research was to prove the speculation that phenylxanthine (PX) derivatives possess adenosine A2A receptor (A2AR)-blocking properties and to screening and evaluate these PX derivatives as dual A2AR antagonists/MAO-B inhibitors for Parkinson′s disease. To explore this hypothesis, two series of [...] Read more.

The aim of this research was to prove the speculation that phenylxanthine (PX) derivatives possess adenosine A2A receptor (A2AR)-blocking properties and to screening and evaluate these PX derivatives as dual A2AR antagonists/MAO-B inhibitors for Parkinson′s disease. To explore this hypothesis, two series of PX derivatives were prepared and their antagonism against A2AR and inhibition against MAO-B were determined in vitro. In order to evaluate further the antiparkinsonian properties, pharmacokinetic and haloperidol-induced catalepsy experiments were carried out in vivo. The PX-D and PX-E analogues acted as potent A2AR antagonists with Ki values ranging from 0.27 to 10 μM, and these analogues displayed relatively mild MAO-B inhibition potencies, with inhibitor dissociation constants (Ki values) ranging from 0.25 to 10 μM. Further, the compounds PX-D-P6 and PX-E-P8 displayed efficacious antiparkinsonian properties in haloperidol-induced catalepsy experiments, verifying that these two compounds were potent A2AR antagonists and MAO-B inhibitors. We conclude that PX-D and PX-E analogues are a promising candidate class of dual-acting compounds for treating Parkinson′s disease. Full article

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

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14 pages, 884 KiB

Open AccessArticle

Sensory Characteristics and Volatile Components of Dry Dog Foods Manufactured with Sorghum Fractions

by Brizio Di Donfrancesco and Kadri Koppel^*

Center for Sensory Analysis and Consumer Behavior, Kansas State University, 1310 Research Park Dr, Manhattan, KS 66502, USA

Molecules 2017, 22(6), 1012; https://doi.org/10.3390/molecules22061012 - 17 Jun 2017

Cited by 14 | Viewed by 6813

Abstract

Descriptive sensory analysis and gas chromatography-mass spectrometry (GC-MS) with a modified headspace solid-phase microextraction (SPME) method was performed on three extruded dry dog food diets manufactured with different fractions of red sorghum and a control diet containing corn, brewer’s rice, and wheat as [...] Read more.

Descriptive sensory analysis and gas chromatography-mass spectrometry (GC-MS) with a modified headspace solid-phase microextraction (SPME) method was performed on three extruded dry dog food diets manufactured with different fractions of red sorghum and a control diet containing corn, brewer’s rice, and wheat as a grain source in order to determine the effect of sorghum fractions on dry dog food sensory properties. The aroma compounds and flavor profiles of samples were similar with small differences, such as higher toasted aroma notes, and musty and dusty flavor in the mill-feed sample. A total of 37 compounds were tentatively identified and semi-quantified. Aldehydes were the major group present in the samples. The total volatile concentration was low, reflecting the mild aroma of the samples. Partial least squares regression was performed to identify correlations between sensory characteristics and detected aroma compounds. Possible relationships, such as hexanal and oxidized oil, and broth aromatics were identified. Volatile compounds were also associated with earthy, musty, and meaty aromas and flavor notes. This study showed that extruded dry dog foods manufactured with different red sorghum fractions had similar aroma, flavor, and volatile profiles. Full article

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

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14 pages, 13733 KiB

Open AccessArticle

Repositioning FDA Drugs as Potential Cruzain Inhibitors from Trypanosoma cruzi: Virtual Screening, In Vitro and In Vivo Studies

by Isidro Palos¹

, Edgar E. Lara-Ramirez², Julio Cesar Lopez-Cedillo³, Carlos Garcia-Perez⁴, Muhammad Kashif⁴

, Virgilio Bocanegra-Garcia⁴, Benjamin Nogueda-Torres³ and Gildardo Rivera^4,*

¹ Unidad Académica Multidisciplinaria Reynosa-Rodhe, Universidad Autónoma de Tamaulipas, Carr. Reynosa-San Fernando, s/n, Reynosa 88779, México

² Unidad de Investigación Biomédica de Zacatecas, Instituto Mexicano del Seguro Social (IMSS), Alameda Trinidad García de la Cadena, s/n, Zacatecas 98000, México

³ Departamento de Parasitología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Prolongación de Carpio y Plan de Ayala, s/n, Ciudad de México 11340, México

⁴ Laboratory of Pharmaceutical Biothecnology, Centro de Biotecnología Genómica, Instituto Politécnico Nacional, Boulevard del Maestro, s/n, Esq. Elías Piña, Reynosa 88710, México

Molecules 2017, 22(6), 1015; https://doi.org/10.3390/molecules22061015 - 18 Jun 2017

Cited by 40 | Viewed by 7580

Abstract

Chagas disease (CD) is a neglected disease caused by the parasite Trypanosoma cruzi, which affects underdeveloped countries. The current drugs of choice are nifurtimox and benznidazole, but both have severe adverse effects and less effectivity in chronic infections; therefore, the need to [...] Read more.

Chagas disease (CD) is a neglected disease caused by the parasite Trypanosoma cruzi, which affects underdeveloped countries. The current drugs of choice are nifurtimox and benznidazole, but both have severe adverse effects and less effectivity in chronic infections; therefore, the need to discover new drugs is essential. A computer-guided drug repositioning method was applied to identify potential FDA drugs (approved and withdrawn) as cruzain (Cz) inhibitors and trypanocidal effects were confirmed by in vitro and in vivo studies. 3180 FDA drugs were virtually screened using a structure-based approach. From a first molecular docking analysis, a set of 33 compounds with the best binding energies were selected. Subsequent consensus affinity binding, ligand amino acid contact clustering analysis, and ranked position were used to choose four known pharmacological compounds to be tested in vitro. Mouse blood samples infected with trypomastigotes from INC-5 and NINOA strains were used to test the trypanocidal effect of four selected compounds. Among these drugs, one fibrate antilipemic (etofyllin clofibrate) and three β-lactam antibiotics (piperacillin, cefoperazone, and flucloxacillin) showed better trypanocidal effects (LC₅₀ range 15.8–26.1 μg/mL) in comparison with benznidazole and nifurtimox (LC₅₀ range 33.1–46.7 μg/mL). A short-term in vivo evaluation of these compounds showed a reduction of parasitemia in infected mice (range 90–60%) at 6 h, but this was low compared to benznidazole (50%). This work suggests that four known FDA drugs could be used to design and obtain new trypanocidal agents. Full article

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

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10 pages, 1406 KiB

Open AccessArticle

Structural Characterization of a Rhamnogalacturonan I Domain from Ginseng and Its Inhibitory Effect on Galectin-3

by Huimin Shi, Li Yu, Yun Shi, Jiaojiao Lu, He Teng, Yifa Zhou and Lin Sun^*

Jilin Province Key Laboratory on Chemistry and Biology of Natural Drugs in Changbai Mountain, School of Life Sciences, Northeast Normal University, Changchun 130024, China

Molecules 2017, 22(6), 1016; https://doi.org/10.3390/molecules22061016 - 18 Jun 2017

Cited by 32 | Viewed by 7147

Abstract

A rhamnogalacturonan I domain, named RG-I-3A, was prepared from ginseng pectin by pectinase digestion and chromatography separation. Monosaccharide composition analysis revealed that it was mainly composed of galacturonic acid, rhamnose, galactose, and arabinose in a molar ratio of 32.5:11.2:31.9:16.5, with a molecular weight [...] Read more.

A rhamnogalacturonan I domain, named RG-I-3A, was prepared from ginseng pectin by pectinase digestion and chromatography separation. Monosaccharide composition analysis revealed that it was mainly composed of galacturonic acid, rhamnose, galactose, and arabinose in a molar ratio of 32.5:11.2:31.9:16.5, with a molecular weight of 50 kDa. Partial acid hydrolysis, monoclonal antibody detection, and NMR spectra analysis suggested RG-I-3A was composed of →4)-α-GalpA-(1→2)-α-Rhap-(1→disaccharide repeating units as backbone, with β-1,4-galactan, α-1,5-arabinan, AG-I, and AG-II side chains substituted via the O-4 of Rhap. Galectin-3-mediated hemagglutination and biolayer interferometry assay indicated that RG-I-3A had inhibitory activity on galectin-3. These findings suggest the potential use of this ginseng RG-I domain as a galectin-3 inhibitor in drug development applications. Full article

(This article belongs to the Special Issue Natural Polysaccharides)

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17 pages, 2393 KiB

Open AccessArticle

Systemic Induction of the Defensin and Phytoalexin Pisatin Pathways in Pea (Pisum sativum) against Aphanomyces euteiches by Acetylated and Nonacetylated Oligogalacturonides

by Sameh Selim^1,*

, Jean Sanssené², Stéphanie Rossard³ and Josiane Courtois⁴

¹ HydrISE, UniLaSalle, Beauvais, SFR Condorcet 3417, 19 Rue Pierre Waguet, BP 30313, F-60026 Beauvais CEDEX, France

² Current address: JS Consulting, 17c Avenue Jean Jaurès, 31290 Villefranche de Lauragais, France

³ Current address: University of Technology of Compiègne (UTC), Centre Pierre Guillaumat, Rue du Docteur Schweitzer, F-60203 Compiègne CEDEX, France

⁴ Laboratoire des Polysaccharides Microbiens et Végétaux, Université de Picardie Jules Verne, Avenue des Facultés, Le Bailly, F-80025 Amiens CEDEX, France

Molecules 2017, 22(6), 1017; https://doi.org/10.3390/molecules22061017 - 19 Jun 2017

Cited by 28 | Viewed by 8145

Abstract

Oligogalacturonides (OGs) are known for their powerful ability to stimulate the plant immune system but little is known about their mode of action in pea (Pisum sativum). In the present study, we investigated the elicitor activity of two fractions of OGs, [...] Read more.

Oligogalacturonides (OGs) are known for their powerful ability to stimulate the plant immune system but little is known about their mode of action in pea (Pisum sativum). In the present study, we investigated the elicitor activity of two fractions of OGs, with polymerization degrees (DPs) of 2–25, in pea against Aphanomyces euteiches. One fraction was nonacetylated (OGs − Ac) whereas the second one was 30% acetylated (OGs + Ac). OGs were applied by injecting the upper two rachises of the plants at three- and/or four-weeks-old. Five-week-old roots were inoculated with 10⁵ zoospores of A. euteiches. The root infection level was determined at 7, 10 and 14 days after inoculation using the quantitative real-time polymerase chain reaction (qPCR). Results showed significant root infection reductions namely 58, 45 and 48% in the plants treated with 80 µg OGs + Ac and 59, 56 and 65% with 200 µg of OGs − Ac. Gene expression results showed the upregulation of genes involved in the antifungal defensins, lignans and the phytoalexin pisatin pathways and a priming effect in the basal defense, SA and ROS gene markers as a response to OGs. The reduction of the efficient dose in OGs + Ac is suggesting that acetylation is necessary for some specific responses. Our work provides the first evidence for the potential of OGs in the defense induction in pea against Aphanomyces root rot. 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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14 pages, 3608 KiB

Open AccessArticle

Determination of Structural Requirements of N-Substituted Tetrahydro-β-Carboline Imidazolium Salt Derivatives Using in Silico Approaches for Designing MEK-1 Inhibitors

by Jingwei Liang^†, Mingyang Wang^†, Xinyang Li, Xin He, Chong Cao and Fanhao Meng^*

¹ School of Pharmacy, China Medical University, Liaoning 110122, China

^† These authors contributed equally to this work

Molecules 2017, 22(6), 1020; https://doi.org/10.3390/molecules22061020 - 19 Jun 2017

Cited by 7 | Viewed by 5997

Abstract

Novel N-substituted tetrahydro-β-carboline imidazolium salt derivatives proved to have potent antitumor activity in past research. The Topomer CoMFA and CoMSIA function in Sybyl-X 2.0 software was applied for the identification of important features of N-substituted tetrahydro-β-carboline-imidazolium salt derivative moieties. In the [...] Read more.

Novel N-substituted tetrahydro-β-carboline imidazolium salt derivatives proved to have potent antitumor activity in past research. The Topomer CoMFA and CoMSIA function in Sybyl-X 2.0 software was applied for the identification of important features of N-substituted tetrahydro-β-carboline-imidazolium salt derivative moieties. In the case of Topomer CoMFA, all the compounds were split into two fragments which were used to generate a 3D invariant representation, the statistical results of the Topomer CoMFA model: q² value of 0.700; r² value of 0.954; with 5 optimum components. The database alignment was utilized for building the CoMSIA model, and the CoMSIA model had q² and r² values of 0.615 and 0.897, with 4 optimum components. Target fishing of the PharmMapper platform was utilised for finding potential targets, the human mitogen-activated protein kinase 1 (MEK-1) was found to be the primary potential target for the three compounds with the fit scores of 6.288, 5.741, and 6.721. The molecular docking technique of MOE 2015 was carried out to identify the interactions of amino acids surrounding the ligand, and correlating QASR contour maps were used to identify structural requirements of N-substituted tetrahydro-β-carboline imidazolium salt moieties. Molecular dynamics and simulation studies proved that the target protein was stable for 0.8–5 ns. The pivotal moieties of N-substituted tetrahydro-β-carboline imidazolium salt derivatives and its potential targets were verified by the QASR study, PharmMapper, and the molecular docking study which would be helpful to design novel MEK-1 inhibitors for anticancer drugs. 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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10 pages, 4489 KiB

Open AccessArticle

The Effects of Selected Sesquiterpenes from Myrica rubra Essential Oil on the Efficacy of Doxorubicin in Sensitive and Resistant Cancer Cell Lines

by Martin Ambrož¹, Petra Matoušková¹

, Adam Skarka², Martina Zajdlová¹, Kateřina Žáková¹ and Lenka Skálová^1,*

¹ Department of Biochemical Sciences, Faculty of Pharmacy, Charles University, Heyrovského 1203, 50005 Hradec Králové, Czech Republic

² Department of Chemistry, Faculty of Science, University of Hradec Králové, Hradecká 1285, 50003 Hradec Králové, Czech Republic

Molecules 2017, 22(6), 1021; https://doi.org/10.3390/molecules22061021 - 20 Jun 2017

Cited by 33 | Viewed by 6279

Abstract

β-caryophyllene oxide (CAO), α-humulene (HUM), trans-nerolidol (NER) and valencene (VAL) are constituents of the essential oil of Myrica rubra (MEO), which has significant antiproliferative effect in various cancer cell lines. In the present study, we compared the antiproliferative effect of these sesquiterpenes alone [...] Read more.

β-caryophyllene oxide (CAO), α-humulene (HUM), trans-nerolidol (NER) and valencene (VAL) are constituents of the essential oil of Myrica rubra (MEO), which has significant antiproliferative effect in various cancer cell lines. In the present study, we compared the antiproliferative effect of these sesquiterpenes alone and in combination with the cytostatic drug doxorubicin (DOX) in cancer cell lines with different sensitivity to DOX. Two ovarian cancer cell lines (sensitive A2780 and partly resistant SKOV3) and two lymphoblast cancer cell lines (sensitive CCRF/CEM and completely resistant CEM/ADR) were used. The observed effects varied among sesquiterpenes and also differed in individual cell lines, with only VAL being effective in all the cell lines. A strong synergism of DOX with NER was found in the A2780 cells, while DOX acted synergistically with HUM and CAO in the SKOV3 cells. In the CCRF/CEM cells, a synergism of DOX with CAO and NER was observed. In resistant CEM/ADR cells, sesquiterpenes did not increase DOX efficacy, although they significantly increased accumulation of DOX (up to 10-times) and rhodamine-123 (substrate of efflux transporter ABCB1) within cancer cells. In conclusion, the tested sesquiterpenes were able to improve DOX efficacy in the sensitive and partly resistant cancer cells, but not in cells completely resistant to DOX. Full article

(This article belongs to the Special Issue Essential Oils: Chemistry and Bioactivity)

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10 pages, 6331 KiB

Open AccessArticle

Complex Coacervation of Soy Proteins, Isoflavones and Chitosan

by Yu-Hsuan Hsiao¹, Sheng-Yang Hsia², Yin-Ching Chan^3,† and Jung-Feng Hsieh^1,2,*,†

¹ Ph.D. Program in Nutrition & Food Science, Fu Jen Catholic University, Taipei 24205, Taiwan

² Department of Food Science, Fu Jen Catholic University, Taipei 24205, Taiwan

³ Department of Food and Nutrition, Providence University, Shalu District, Taichung 43301, Taiwan

^† These authors contributed equally to this work.

Molecules 2017, 22(6), 1022; https://doi.org/10.3390/molecules22061022 - 20 Jun 2017

Cited by 10 | Viewed by 8110

Abstract

In this study, the chitosan-induced coacervation of soy protein-isoflavone complexes in soymilk was investigated. Most of the soymilk proteins, including β-conglycinin (7S), glycinin (11S), and isoflavones, were found to coacervate into the soymilk pellet fraction (SPF) following the addition of 0.5% chitosan. The [...] Read more.

In this study, the chitosan-induced coacervation of soy protein-isoflavone complexes in soymilk was investigated. Most of the soymilk proteins, including β-conglycinin (7S), glycinin (11S), and isoflavones, were found to coacervate into the soymilk pellet fraction (SPF) following the addition of 0.5% chitosan. The total protein in the soymilk supernatant fraction (SSF) decreased from 18.1 ± 0.3 mg/mL to 1.6 ± 0.1 mg/mL, and the pH values decreased slightly, from 6.6 ± 0.0 to 6.0 ± 0.0. The results of SDS-PAGE revealed that the 7S α’, 7S α, 7S β, 11S A3, and 11S acidic subunits, as well as the 11S basic proteins in the SSF, decreased to 0.7 ± 0.5%, 0.2 ± 0.1%, 0.1 ± 0.0%, 0.2 ± 0.2%, 0.2 ± 0.2% and 0.3 ± 0.2%, respectively. We also found that isoflavones in the SSF, including daidzein, glycitein, and genistein, decreased to 9.6 ± 2.3%, 5.7 ± 0.9% and 5.9 ± 1.5%, respectively. HPLC analysis indicated that isoflavones mixed with soy proteins formed soy protein-isoflavone complexes and were precipitated into the SPF by 0.5% chitosan. Full article

(This article belongs to the Special Issue Protein-Carbohydrate Interactions)

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8 pages, 596 KiB

Open AccessArticle

Phenolic Glycosides from Capsella bursa-pastoris (L.) Medik and Their Anti-Inflammatory Activity

by Joon Min Cha¹, Won Se Suh¹, Tae Hyun Lee¹, Lalita Subedi^2,3, Sun Yeou Kim^2,3

and Kang Ro Lee^1,*

¹ Natural Products Laboratory, School of Pharmacy, Sungkyunkwan University, Suwon 16419, Korea

² Gachon Institute of Pharmaceutical Science, Gachon University, 191 Hambakmoero, Yeonsu-gu, Incheon 21936, Korea

³ College of Pharmacy, Gachon University, 191 Hambakmoero, Yeonsu-gu, Incheon 21936, Korea

Molecules 2017, 22(6), 1023; https://doi.org/10.3390/molecules22061023 - 20 Jun 2017

Cited by 31 | Viewed by 9709

Abstract

A new sesquilignan glycoside 1, together with seven known phenolic glycosides 2–8 were isolated from the aerial parts of Capsella bursa-pastoris. The chemical structure of the new compound 1 was elucidated by extensive nuclear magnetic resonance (NMR) data (¹ [...] Read more.

A new sesquilignan glycoside 1, together with seven known phenolic glycosides 2–8 were isolated from the aerial parts of Capsella bursa-pastoris. The chemical structure of the new compound 1 was elucidated by extensive nuclear magnetic resonance (NMR) data (¹H- and ¹³C-NMR, ¹H-¹H correlation spectroscopy (¹H-¹H COSY), heteronuclear single-quantum correlation (HSQC), heteronuclear multiple bond correlation (HMBC), and nuclear overhauser effect spectroscopy (NOESY)) and HR-FABMS analysis. The anti-inflammatory effects of 1–8 were evaluated in lipopolysaccharide (LPS)-stimulated murine microglia BV-2 cells. Compounds 4 and 7 exhibited moderate inhibitory effects on nitric oxide production in LPS-activated BV-2 cells, with IC₅₀ values of 17.80 and 27.91 µM, respectively. Full article

(This article belongs to the Collection Bioactive Compounds)

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18 pages, 3692 KiB

Open AccessArticle

The Antiproliferative Effect of Cyclodipeptides from Pseudomonas aeruginosa PAO1 on HeLa Cells Involves Inhibition of Phosphorylation of Akt and S6k Kinases

by Laura Hernández-Padilla¹, Dolores Vázquez-Rivera¹, Luis A. Sánchez-Briones¹, Alma L. Díaz-Pérez¹, José Moreno-Rodríguez², Mario A. Moreno-Eutimio², Victor Meza-Carmen¹, Homero Reyes-De la Cruz³

and Jesús Campos-García^1,*

¹ Laboratorio de Biotecnología Microbiana, Instituto de Investigaciones Químico-Biológicas, Universidad Michoacana de San Nicolás de Hidalgo, 58030 Morelia, Michoacán, Mexico

² División de Investigación, Hospital Juárez de México, 07760 Ciudad de México, Mexico

³ Laboratorio de Control Traduccional, Instituto de Investigaciones Químico-Biológicas, Universidad Michoacana de San Nicolás de Hidalgo, 58030 Morelia, Michoacán, Mexico. delacruz@umich.mx

Molecules 2017, 22(6), 1024; https://doi.org/10.3390/molecules22061024 - 20 Jun 2017

Cited by 22 | Viewed by 6692

Abstract

Pseudomonas aeruginosa PAO1, a potential pathogen of plants and animals, produces the cyclodipeptides cyclo(l-Pro-l-Tyr), cyclo(l-Pro-l-Phe), and cyclo(l-Pro-l-Val) (PAO1-CDPs), whose effects have been implicated in inhibition of human tumor cell line proliferation. Our purpose was to investigate in depth in the mechanisms of HeLa [...] Read more.

Pseudomonas aeruginosa PAO1, a potential pathogen of plants and animals, produces the cyclodipeptides cyclo(l-Pro-l-Tyr), cyclo(l-Pro-l-Phe), and cyclo(l-Pro-l-Val) (PAO1-CDPs), whose effects have been implicated in inhibition of human tumor cell line proliferation. Our purpose was to investigate in depth in the mechanisms of HeLa cell proliferation inhibition by the PAO1-CDPs. The results indicate that PAO1-CDPs, both purified individually and in mixtures, inhibited HeLa cell proliferation by arresting the cell cycle at the G0–G1 transition. The crude PAO1-CDPs mixture promoted cell death in HeLa cells in a dose-dependent manner, showing efficacy similar to that of isolated PAO1-CDPs (LD₅₀ of 60–250 µM) and inducing apoptosis with EC₅₀ between 0.6 and 3.0 µM. Moreover, PAO1-CDPs showed a higher proapoptotic activity (~10³–10⁵ fold) than their synthetic analogs did. Subsequently, the PAO1-CDPs affected mitochondrial membrane potential and induced apoptosis by caspase-9-dependent pathway. The mechanism of inhibition of cells proliferation in HeLa cells involves inhibition of phosphorylation of both Akt-S473 and S6k-T389 protein kinases, showing a cyclic behavior of their expression and phosphorylation in a time and concentration-dependent fashion. Taken together our findings indicate that PI3K–Akt–mTOR–S6k signaling pathway blockage is involved in the antiproliferative effect of the PAO1-CDPs. Full article

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

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16 pages, 2448 KiB

Open AccessArticle

Screening and Identification of the Metabolites in Rat Plasma and Urine after Oral Administration of Areca catechu L. Nut Extract by Ultra-High-Pressure Liquid Chromatography Coupled with Linear Ion Trap–Orbitrap Tandem Mass Spectrometry

by Lulu Li^1,†, Zhiqiang Luo^1,†, Yang Liu^1,*, Hao Wang¹, Aoxue Liu¹, Guohua Yu¹, Mengwei Li¹, Ruirui Yang¹, Xinjing Chen¹, Jialian Zhu¹ and Baosheng Zhao^2,*

¹ School of Chinese Materia Medica, Beijing University of Chinese Medicine, No. 6, Zhonghuan South Road, Wangjing, Chaoyang District, Beijing 100102, China

² Research Institute of Chinese Medicine, Beijing University of Chinese Medicine, No. 11, North Third Ring Road, Chaoyang District, Beijing 100029, China

^† These authors contributed equally to this work.

Molecules 2017, 22(6), 1026; https://doi.org/10.3390/molecules22061026 - 21 Jun 2017

Cited by 14 | Viewed by 5977

Abstract

Areca catechu L. nut, a well-known toxic traditional herbal medicine, has been widely used to treat various diseases in China and many other Asian countries for centuries. However, to date the in vivo absorption and metabolism of its multiple bioactive or toxic components [...] Read more.

Areca catechu L. nut, a well-known toxic traditional herbal medicine, has been widely used to treat various diseases in China and many other Asian countries for centuries. However, to date the in vivo absorption and metabolism of its multiple bioactive or toxic components still remain unclear. In this study, liquid chromatography coupled with tandem mass spectrometry was used to analyze the major components and their metabolites in rat plasma and urine after oral administration of Areca catechu L. nut extract (ACNE). A total of 12 compounds, including 6 alkaloids, 3 tannins and 3 amino acids, were confirmed or tentatively identified from ACNE. In vivo, 40 constituents, including 8 prototypes and 32 metabolites were identified in rat plasma and urine samples. In summary, this study showed an insight into the metabolism of ACNE in vivo, which may provide helpful chemical information for better understanding of the toxicological and pharmacological profiles of ACNE. Full article

(This article belongs to the Section Metabolites)

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23 pages, 9431 KiB

Open AccessArticle

Molecular Quantum Similarity, Chemical Reactivity and Database Screening of 3D Pharmacophores of the Protein Kinases A, B and G from Mycobacterium tuberculosis

by Alejandro Morales-Bayuelo

Fondo Nacional de Desarrollo Científico y Tecnológico (FONDECYT), Proyecto Postdoctoral No. 3150035, Talca, 3660300, Chile

Molecules 2017, 22(6), 1027; https://doi.org/10.3390/molecules22061027 - 21 Jun 2017

Cited by 13 | Viewed by 4985

Abstract

Mycobacterium tuberculosis remains one of the world’s most devastating pathogens. For this reason, we developed a study involving 3D pharmacophore searching, selectivity analysis and database screening for a series of anti-tuberculosis compounds, associated with the protein kinases A, B, and G. This theoretical [...] Read more.

Mycobacterium tuberculosis remains one of the world’s most devastating pathogens. For this reason, we developed a study involving 3D pharmacophore searching, selectivity analysis and database screening for a series of anti-tuberculosis compounds, associated with the protein kinases A, B, and G. This theoretical study is expected to shed some light onto some molecular aspects that could contribute to the knowledge of the molecular mechanics behind interactions of these compounds, with anti-tuberculosis activity. Using the Molecular Quantum Similarity field and reactivity descriptors supported in the Density Functional Theory, it was possible to measure the quantification of the steric and electrostatic effects through the Overlap and Coulomb quantitative convergence (alpha and beta) scales. In addition, an analysis of reactivity indices using global and local descriptors was developed, identifying the binding sites and selectivity on these anti-tuberculosis compounds in the active sites. Finally, the reported pharmacophores to PKn A, B and G, were used to carry out database screening, using a database with anti-tuberculosis drugs from the Kelly Chibale research group (http://www.kellychibaleresearch.uct.ac.za/), to find the compounds with affinity for the specific protein targets associated with PKn A, B and G. In this regard, this hybrid methodology (Molecular Mechanic/Quantum Chemistry) shows new insights into drug design that may be useful in the tuberculosis treatment today. Full article

(This article belongs to the Section Molecular Diversity)

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8 pages, 498 KiB

Open AccessArticle

Synthesis and Bioactivity Characterization of Scutellarein Sulfonated Derivative

by Ting Gu^1,2, Yue Zhong^1,2, Yu-Ting Lu^1,2, Ying Sun^1,2, Ze-Xi Dong^1,2, Wen-Yu Wu^1,2, Zhi-Hao Shi³, Nian-Guang Li^1,2,*, Xin Xue^1,2, Fang Fang^1,2, He-Min Li^1,2 and Yu-Ping Tang^1,*

¹ National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, China

² Department of Medicinal Chemistry, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, China

³ Department of Organic Chemistry, China Pharmaceutical University, Nanjing, Jiangsu 211198, China

Molecules 2017, 22(6), 1028; https://doi.org/10.3390/molecules22061028 - 21 Jun 2017

Cited by 8 | Viewed by 4989

Abstract

Scutellarin (1) has been widely used to treat acute cerebral infarction in clinic, but poor aqueous solubility decreases its bioavailability. Interestingly, scutellarin (1) could be metabolized into scutellarein (2) in vivo. In this study, a sulfonic group [...] Read more.

Scutellarin (1) has been widely used to treat acute cerebral infarction in clinic, but poor aqueous solubility decreases its bioavailability. Interestingly, scutellarin (1) could be metabolized into scutellarein (2) in vivo. In this study, a sulfonic group was introduced at position C-8 of scutellarein (2) to enhance the aqueous solubility of the obtained derivative (3). DPPH (1,1-diphenyl-2-picrylhydrazyl)-radical scavenging ability and antithrombic activity were also conducted to determine its bioactivity. The result showed that scutellarein derivate (3) could be a better agent for ischemic cerebrovascular disease treatment. Full article

(This article belongs to the Special Issue Synthesis and Modification of Natural Product)

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13 pages, 11875 KiB

Open AccessArticle

Virtual Screening against Phosphoglycerate Kinase 1 in Quest of Novel Apoptosis Inhibitors

by Jie Xia¹

, Bo Feng¹, Qianhang Shao², Yuhe Yuan², Xiang Simon Wang³, Naihong Chen² and Song Wu^1,*

¹ State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Department of New Drug Research and Development, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China

² Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China

³ Molecular Modeling and Drug Discovery Core Laboratory for District of Columbia Center for AIDS Research (DC CFAR), Department of Pharmaceutical Sciences, College of Pharmacy, Howard University, Washington, DC 20059, USA

Molecules 2017, 22(6), 1029; https://doi.org/10.3390/molecules22061029 - 21 Jun 2017

Cited by 10 | Viewed by 5925

Abstract

Inhibition of apoptosis is a potential therapy to treat human diseases such as neurodegenerative disorders (e.g., Parkinson’s disease), stroke, and sepsis. Due to the lack of druggable targets, it remains a major challenge to discover apoptosis inhibitors. The recent repositioning of a marketed [...] Read more.

Inhibition of apoptosis is a potential therapy to treat human diseases such as neurodegenerative disorders (e.g., Parkinson’s disease), stroke, and sepsis. Due to the lack of druggable targets, it remains a major challenge to discover apoptosis inhibitors. The recent repositioning of a marketed drug (i.e., terazosin) as an anti-apoptotic agent uncovered a novel target (i.e., human phosphoglycerate kinase 1 (hPgk1)). In this study, we developed a virtual screening (VS) pipeline based on the X-ray structure of Pgk1/terazosin complex and applied it to a screening campaign for potential anti-apoptotic agents. The hierarchical filters in the pipeline (i.e., similarity search, a pharmacophore model, a shape-based model, and molecular docking) rendered 13 potential hits from Specs chemical library. By using PC12 cells (exposed to rotenone) as a cell model for bioassay, we first identified that AK-918/42829299, AN-465/41520984, and AT-051/43421517 were able to protect PC12 cells from rotenone-induced cell death. Molecular docking suggested these hit compounds were likely to bind to hPgk1 in a similar mode to terazosin. In summary, we not only present a versatile VS pipeline for potential apoptosis inhibitors discovery, but also provide three novel-scaffold hit compounds that are worthy of further development and biological study. Full article

(This article belongs to the Section Medicinal Chemistry)

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Review

Jump to: Research, Other

23 pages, 6048 KiB

Open AccessReview

Insights into Penicillium brasilianum Secondary Metabolism and Its Biotechnological Potential

by Jaqueline Moraes Bazioli¹, Luciana Da Silva Amaral²

, Taícia Pacheco Fill^1,* and Edson Rodrigues-Filho^2,*

¹ Instituto de Química, Universidade Estadual de Campinas, CP 6154, 13083-970 Campinas, Brazil

² Departamento de Química, Universidade Federal de São Carlos, CP 676, 13.565-905 São Carlos, SP, Brazil

Molecules 2017, 22(6), 858; https://doi.org/10.3390/molecules22060858 - 20 Jun 2017

Cited by 31 | Viewed by 9749

Abstract

Over the past few years Penicillium brasilianum has been isolated from many different environmental sources as soil isolates, plant endophytes and onion pathogen. All investigated strains share a great ability to produce bioactive secondary metabolites. Different authors have investigated this great capability and [...] Read more.

Over the past few years Penicillium brasilianum has been isolated from many different environmental sources as soil isolates, plant endophytes and onion pathogen. All investigated strains share a great ability to produce bioactive secondary metabolites. Different authors have investigated this great capability and here we summarize the metabolic potential and the biological activities related to P. brasilianum’s metabolites with diverse structures. They include secondary metabolites of an alkaloid nature, i.e., 2,5-diketopiperazines, cyclodepsipeptides, meroterpenoids and polyketides. Penicillium brasilianum is also described as a great source of enzymes with biotechnological application potential, which is also highlighted in this review. Additionally, this review will focus on several aspects of Penicillium brasilianum and interesting genomic insights. Full article

(This article belongs to the Special Issue Expanding the Potential of Metabolomics for Under Investigated Organisms and in Drug Discovery)

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46 pages, 10198 KiB

Open AccessReview

Exploring Anti-Prion Glyco-Based and Aromatic Scaffolds: A Chemical Strategy for the Quality of Life

by María Teresa Blázquez-Sánchez^†, Ana M. De Matos^† and Amélia P. Rauter^*

¹ Centro de Química e Bioquímica, Faculdade de Ciências, Universidade de Lisboa, Ed C8, Piso 5, Campo Grande, 1749-016 Lisboa, Portugal

^† Both authors contributed equally to this review.

Molecules 2017, 22(6), 864; https://doi.org/10.3390/molecules22060864 - 24 May 2017

Cited by 10 | Viewed by 7976

Abstract

Prion diseases are fatal neurodegenerative disorders caused by protein misfolding and aggregation, affecting the brain progressively and consequently the quality of life. Alzheimer’s is also a protein misfolding disease, causing dementia in over 40 million people worldwide. There are no therapeutics able to [...] Read more.

Prion diseases are fatal neurodegenerative disorders caused by protein misfolding and aggregation, affecting the brain progressively and consequently the quality of life. Alzheimer’s is also a protein misfolding disease, causing dementia in over 40 million people worldwide. There are no therapeutics able to cure these diseases. Cellular prion protein is a high-affinity binding partner of amyloid β (Aβ) oligomers, the most toxic species in Alzheimer’s pathology. These findings motivate the development of new chemicals for a better understanding of the events involved. Disease control is far from being reached by the presently known therapeutics. In this review we describe the synthesis and mode of action of molecular entities with intervention in prion diseases’ biological processes and, if known, their role in Alzheimer’s. A diversity of structures is covered, based on glycans, steroids and terpenes, heterocycles, polyphenols, most of them embodying aromatics and a structural complexity. These molecules may be regarded as chemical tools to foster the understanding of the complex mechanisms involved, and to encourage the scientific community towards further developments for the cure of these devastating diseases. Full article

(This article belongs to the Special Issue Women in Organic Chemistry)

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18 pages, 4136 KiB

Open AccessReview

Recent Advances in C–C and C–N Bond Forming Reactions Catalysed by Polystyrene-Supported Copper Complexes

by Pavel Drabina, Jan Svoboda

and Miloš Sedlák^*

Institute of Organic Chemistry and Technology, Faculty of Chemical Technology, University of Pardubice, Studentská 573, 532 10 Pardubice, Czech Republic

Molecules 2017, 22(6), 865; https://doi.org/10.3390/molecules22060865 - 24 May 2017

Cited by 27 | Viewed by 7137

Abstract

This present mini-review covers recently published results on Cu(I) and Cu(II) complexes immobilized on polystyrene carriers, which are used as heterogeneous, eco-friendly reusable catalysts applied for carbon–carbon and carbon–nitrogen forming reactions. Recent advances and trends in this area are demonstrated in the examples [...] Read more.

This present mini-review covers recently published results on Cu(I) and Cu(II) complexes immobilized on polystyrene carriers, which are used as heterogeneous, eco-friendly reusable catalysts applied for carbon–carbon and carbon–nitrogen forming reactions. Recent advances and trends in this area are demonstrated in the examples of oxidative homocoupling of terminal alkynes, the synthesis of propargylamines, nitroaldolization reactions, azide alkyne cycloaddition, N-arylation of nitrogen containing compounds, aza-Michael additions, asymmetric Friedel–Crafts reactions, asymmetric Mukaiyama aldol reactions, and asymmetric 1,3-dipolar cycloaddition of azomethine ylides. The type of polystyrene matrix used for the immobilization of complexes is discussed in this paper, and particularly, the efficiency of the catalysts from the point of view of the overall reaction yield, and possible enantioselectivity and potential reusing, is reviewed. Full article

(This article belongs to the Section Organic Chemistry)

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93 pages, 9539 KiB

Open AccessReview

Natural Products as Alternative Choices for P-Glycoprotein (P-gp) Inhibition

by Saikat Dewanjee^1,*

, Tarun K. Dua¹, Niloy Bhattacharjee¹, Anup Das², Moumita Gangopadhyay³, Ritu Khanra¹, Swarnalata Joardar¹, Muhammad Riaz⁴

, Vincenzo De Feo^5,*

and Muhammad Zia-Ul-Haq^6,*

¹ Advanced Pharmacognosy Research Laboratory, Department of Pharmaceutical Technology, Jadavpur University, Raja S C Mullick Road, Kolkata 700032, India

² Department of Pharmaceutical Technology, ADAMAS University, Barasat, Kolkata 700126, India

³ Department of Bioechnology, ADAMAS University, Barasat, Kolkata 700126, India

⁴ Department of Pharmacy, Shaheed Benazir Bhutto University, Sheringal 18050, Pakistan

⁵ Department of Pharmacy, Salerno University, Fisciano 84084, Salerno, Italy

⁶ Environment Science Department, Lahore College for Women University, Jail Road, Lahore 54600, Pakistan

Molecules 2017, 22(6), 871; https://doi.org/10.3390/molecules22060871 - 25 May 2017

Cited by 172 | Viewed by 20535

Abstract

Multidrug resistance (MDR) is regarded as one of the bottlenecks of successful clinical treatment for numerous chemotherapeutic agents. Multiple key regulators are alleged to be responsible for MDR and making the treatment regimens ineffective. In this review, we discuss MDR in relation to [...] Read more.

Multidrug resistance (MDR) is regarded as one of the bottlenecks of successful clinical treatment for numerous chemotherapeutic agents. Multiple key regulators are alleged to be responsible for MDR and making the treatment regimens ineffective. In this review, we discuss MDR in relation to P-glycoprotein (P-gp) and its down-regulation by natural bioactive molecules. P-gp, a unique ATP-dependent membrane transport protein, is one of those key regulators which are present in the lining of the colon, endothelial cells of the blood brain barrier (BBB), bile duct, adrenal gland, kidney tubules, small intestine, pancreatic ducts and in many other tissues like heart, lungs, spleen, skeletal muscles, etc. Due to its diverse tissue distribution, P-gp is a novel protective barrier to stop the intake of xenobiotics into the human body. Over-expression of P-gp leads to decreased intracellular accretion of many chemotherapeutic agents thus assisting in the development of MDR. Eventually, the effectiveness of these drugs is decreased. P-gp inhibitors act by altering intracellular ATP levels which are the source of energy and/or by affecting membrane contours to increase permeability. However, the use of synthetic inhibitors is known to cause serious toxicities. For this reason, the search for more potent and less toxic P-gp inhibitors of natural origin is underway. The present review aims to recapitulate the research findings on bioactive constituents of natural origin with P-gp inhibition characteristics. Natural bioactive constituents with P-gp modulating effects offer great potential for semi-synthetic modification to produce new scaffolds which could serve as valuable investigative tools to recognize the function of complex ABC transporters apart from evading the systemic toxicities shown by synthetic counterparts. Despite the many published scientific findings encompassing P-gp inhibitors, however, this article stand alones because it provides a vivid picture to the readers pertaining to Pgp inhibitors obtained from natural sources coupled with their mode of action and structures. It provides first-hand information to the scientists working in the field of drug discovery to further synthesise and discover new P-gp inhibitors with less toxicity and more efficacies. Full article

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13 pages, 1674 KiB

Open AccessReview

Current Perspective on In Vivo Molecular Imaging of Immune Cells

by Anushree Seth^1,2,†, Hye Sun Park^1,2,† and Kwan Soo Hong^1,2,3,*

¹ Bioimaging Research Team, Korea Basic Science Institute, Cheongju 28119, Korea

² Immunotherapy Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, Korea

³ Graduate School of Analytical Science and Technology, Chungnam National University, Daejeon 34134, Korea

^† These authors contributed equally to this work.

Molecules 2017, 22(6), 881; https://doi.org/10.3390/molecules22060881 - 26 May 2017

Cited by 21 | Viewed by 6971

Abstract

Contemporaneous development of improved immune cell-based therapies, and powerful imaging tools, has prompted growth in technologies for immune cell tracking in vivo. Over the past couple of decades, imaging tools such as magnetic resonance imaging (MRI) and optical imaging have successfully monitored the [...] Read more.

Contemporaneous development of improved immune cell-based therapies, and powerful imaging tools, has prompted growth in technologies for immune cell tracking in vivo. Over the past couple of decades, imaging tools such as magnetic resonance imaging (MRI) and optical imaging have successfully monitored the trafficking patterns of therapeutic immune cells and assisted the evaluation of the success or failure of immunotherapy. Recent advancements in imaging technology have made imaging an indispensable module of immune cell-based therapies. In this review, emerging applications of non-radiation imaging modalities for the tracking of a range of immune cells are discussed. Applications of MRI, NIR, and other imaging tools have demonstrated the potential of non-invasively surveying the fate of both phagocytic and non-phagocytic immune cells in vivo. Full article

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

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12 pages, 3633 KiB

Open AccessReview

Synthesis and Structural Modification of Marine Natural Products

by Juan Zhang^1,2, Hua Zhang¹, Luis Alexandre Muehlmann², Cheng-Shi Jiang^1,* and Yue-Wei Guo^3,*

¹ School of Biological Science and Technology, University of Jinan, Jinan 250022, China

² Faculdade de Ceilândia, University of Brasília, Brasilia 70910900, Brazil

³ Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China

Molecules 2017, 22(6), 882; https://doi.org/10.3390/molecules22060882 - 26 May 2017

Cited by 6 | Viewed by 6485

Abstract

In the last decades, marine natural products (MNPs), have attracted extensive interest from both chemists and pharmacologists due to their chemical and bioactive diversities. This special issue, collecting total synthesis and structural modification of six different type of bioactive MNPs, is expected to [...] Read more.

In the last decades, marine natural products (MNPs), have attracted extensive interest from both chemists and pharmacologists due to their chemical and bioactive diversities. This special issue, collecting total synthesis and structural modification of six different type of bioactive MNPs, is expected to inspire and attract more research effects invested into MNP research. Full article

(This article belongs to the Special Issue Synthesis and Modification of Natural Product)

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15 pages, 620 KiB

Open AccessFeature PaperReview

Cellular and Molecular Targets of Resveratrol on Lymphoma and Leukemia Cells

by Raffaele Frazzi^* and Manuela Guardi

Laboratory of Translational Research, Arcispedale S. Maria Nuova IRCCS, Viale Risorgimento 80, 42124 Reggio Emilia, Italy

Molecules 2017, 22(6), 885; https://doi.org/10.3390/molecules22060885 - 27 May 2017

Cited by 25 | Viewed by 7999

Abstract

Resveratrol (RSV) is a well known chemopreventive molecule featuring anti-cancer properties. Our paper describes the main molecular targets of RSV linked to its antiproliferative activity on lymphoma and leukemia experimental models. It discusses further the most recent and most promising among these molecular [...] Read more.

Resveratrol (RSV) is a well known chemopreventive molecule featuring anti-cancer properties. Our paper describes the main molecular targets of RSV linked to its antiproliferative activity on lymphoma and leukemia experimental models. It discusses further the most recent and most promising among these molecular targets for a translational application. Full article

(This article belongs to the Special Issue Improvements for Resveratrol Efficacy)

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12 pages, 1171 KiB

Open AccessReview

Recent Advances in the Development of Mammalian Geranylgeranyl Diphosphate Synthase Inhibitors

by Staci L. Haney¹, Veronica S. Wills², David F. Wiemer² and Sarah A. Holstein^1,*

¹ Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA

² Department of Chemistry, University of Iowa, Iowa City, IA 52242, USA

Molecules 2017, 22(6), 886; https://doi.org/10.3390/molecules22060886 - 27 May 2017

Cited by 26 | Viewed by 7297

Abstract

The enzyme geranylgeranyl diphosphate synthase (GGDPS) catalyzes the synthesis of the 20-carbon isoprenoid geranylgeranyl diphosphate (GGPP). GGPP is the isoprenoid donor for protein geranylgeranylation reactions catalyzed by the enzymes geranylgeranyl transferase (GGTase) I and II. Inhibitors of GGDPS result in diminution of protein [...] Read more.

The enzyme geranylgeranyl diphosphate synthase (GGDPS) catalyzes the synthesis of the 20-carbon isoprenoid geranylgeranyl diphosphate (GGPP). GGPP is the isoprenoid donor for protein geranylgeranylation reactions catalyzed by the enzymes geranylgeranyl transferase (GGTase) I and II. Inhibitors of GGDPS result in diminution of protein geranylgeranylation through depletion of cellular GGPP levels, and there has been interest in GGDPS inhibitors as potential anti-cancer agents. Here we discuss recent advances in the development of GGDPS inhibitors, including insights gained by structure-function relationships, and review the preclinical data that support the continued development of this novel class of drugs. Full article

(This article belongs to the Special Issue Isoprenoid Biosynthesis)

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51 pages, 14036 KiB

Open AccessFeature PaperReview

Recent Advances in Asymmetric Organocatalyzed Conjugate Additions to Nitroalkenes

by Diego A. Alonso^*, Alejandro Baeza^*

, Rafael Chinchilla^*

, Cecilia Gómez^*, Gabriela Guillena^*

, Isidro M. Pastor^*

and Diego J. Ramón^*

Department of Organic Chemistry and Institute of Organic Synthesis (ISO), Faculty of Sciences, University of Alicante, PO Box 99, 03080 Alicante, Spain

Molecules 2017, 22(6), 895; https://doi.org/10.3390/molecules22060895 - 29 May 2017

Cited by 131 | Viewed by 10952

Abstract

The asymmetric conjugate addition of carbon and heteroatom nucleophiles to nitroalkenes is a very interesting tool for the construction of highly functionalized synthetic building blocks. Thanks to the rapid development of asymmetric organocatalysis, significant progress has been made during the last years in [...] Read more.

The asymmetric conjugate addition of carbon and heteroatom nucleophiles to nitroalkenes is a very interesting tool for the construction of highly functionalized synthetic building blocks. Thanks to the rapid development of asymmetric organocatalysis, significant progress has been made during the last years in achieving efficiently this process, concerning chiral organocatalysts, substrates and reaction conditions. This review surveys the advances in asymmetric organocatalytic conjugate addition reactions to α,β-unsaturated nitroalkenes developed between 2013 and early 2017. Full article

(This article belongs to the Special Issue Asymmetric Synthesis 2017)

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19 pages, 3652 KiB

Open AccessFeature PaperReview

Applications of Fluorogens with Rotor Structures in Solar Cells

by Kok-Haw Ong

and Bin Liu^*

Institute of Materials Research & Engineering, Agency for Science, Technology and Research (A*STAR), 2 Fusionopolis Way, Innovis, #08-03, Singapore 138634, Singapore

Molecules 2017, 22(6), 897; https://doi.org/10.3390/molecules22060897 - 29 May 2017

Cited by 19 | Viewed by 5515

Abstract

Solar cells are devices that convert light energy into electricity. To drive greater adoption of solar cell technologies, higher cell efficiencies and reductions in manufacturing cost are necessary. Fluorogens containing rotor structures may be helpful in addressing some of these challenges due to [...] Read more.

Solar cells are devices that convert light energy into electricity. To drive greater adoption of solar cell technologies, higher cell efficiencies and reductions in manufacturing cost are necessary. Fluorogens containing rotor structures may be helpful in addressing some of these challenges due to their unique twisted structures and photophysics. In this review, we discuss the applications of rotor-containing molecules as dyes for luminescent down-shifting layers and luminescent solar concentrators, where their aggregation-induced emission properties and large Stokes shifts are highly desirable. We also discuss the applications of molecules containing rotors in third-generation solar cell technologies, namely dye-sensitized solar cells and organic photovoltaics, where the twisted 3-dimensional rotor structures are used primarily for aggregation control. Finally, we discuss perspectives on the future role of molecules containing rotor structures in solar cell technologies. Full article

(This article belongs to the Special Issue Aggregation-Induced Emission: Commemorative Issue in Honor of Professor Ben Zhong Tang’s Research Achievements on the Occasion of His 60th Birthday)

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16 pages, 1227 KiB

Open AccessReview

The Antidiabetic Mechanisms of Polyphenols Related to Increased Glucagon-Like Peptide-1 (GLP1) and Insulin Signaling

by J. Abraham Domínguez Avila¹

, Joaquín Rodrigo García², Gustavo A. González Aguilar¹

and Laura A. De la Rosa^3,*

¹ Coordinación de Tecnología de Alimentos de Origen Vegetal, Centro de Investigación en Alimentación y Desarrollo A. C., Carretera a La Victoria km 0.6, AP 1735, Hermosillo 83304, Sonora, Mexico

² Departamento de Ciencias de la Salud, Instituto de Ciencias Biomédicas, Universidad Autónoma de Ciudad Juárez, Anillo Envolvente del PRONAF y Estocolmo s/n, Ciudad Juárez 32310, Chihuahua, Mexico

³ Departamento de Ciencias Químico-Biológicas, Instituto de Ciencias Biomédicas, Universidad Autónoma de Ciudad Juárez, Anillo Envolvente del PRONAF y Estocolmo s/n, Ciudad Juárez 32310, Chihuahua, Mexico

Molecules 2017, 22(6), 903; https://doi.org/10.3390/molecules22060903 - 30 May 2017

Cited by 117 | Viewed by 17689

Abstract

Type-2 diabetes mellitus (T2DM) is an endocrine disease related to impaired/absent insulin signaling. Dietary habits can either promote or mitigate the onset and severity of T2DM. Diets rich in fruits and vegetables have been correlated with a decreased incidence of T2DM, apparently due [...] Read more.

Type-2 diabetes mellitus (T2DM) is an endocrine disease related to impaired/absent insulin signaling. Dietary habits can either promote or mitigate the onset and severity of T2DM. Diets rich in fruits and vegetables have been correlated with a decreased incidence of T2DM, apparently due to their high polyphenol content. Polyphenols are compounds of plant origin with several documented bioactivities related to health promotion. The present review describes the antidiabetic effects of polyphenols, specifically related to the secretion and effects of insulin and glucagon-like peptide 1 (GLP1), an enteric hormone that stimulates postprandial insulin secretion. The evidence suggests that polyphenols from various sources stimulate L-cells to secrete GLP1, increase its half-life by inhibiting dipeptidyl peptidase-4 (DPP4), stimulate β-cells to secrete insulin and stimulate the peripheral response to insulin, increasing the overall effects of the GLP1-insulin axis. The glucose-lowering potential of polyphenols has been evidenced in various acute and chronic models of healthy and diabetic organisms. Some polyphenols appear to exert their effects similarly to pharmaceutical antidiabetics; thus, rigorous clinical trials are needed to fully validate this claim. The broad diversity of polyphenols has not allowed for entirely describing their mechanisms of action, but the evidence advocates for their regular consumption. Full article

(This article belongs to the Special Issue Plant Polyphenols as Potential Therapeutic Agents for Diabetes and Obesity)

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33 pages, 9965 KiB

Open AccessReview

Systematic Review of Chemical Constituents in the Genus Lycium (Solanaceae)

by Dan Qian^1,2

, Yaxing Zhao³, Guang Yang² and Luqi Huang^2,*

¹ Experimental Research Center, China Academy of Chinese Medical Sciences, Beijing 100700, China

² The State Key Laboratory Breeding Base of Dao-di Herbs, National Resource Center for Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China

³ School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, China

Molecules 2017, 22(6), 911; https://doi.org/10.3390/molecules22060911 - 8 Jun 2017

Cited by 164 | Viewed by 12861

Abstract

The Lycium genus is widely used as a traditional Chinese medicine and functional food. Many of the chemical constituents of the genus Lycium were reported previously. In this review, in addition to the polysaccharides, we have enumerated 355 chemical constituents and nutrients, including [...] Read more.

The Lycium genus is widely used as a traditional Chinese medicine and functional food. Many of the chemical constituents of the genus Lycium were reported previously. In this review, in addition to the polysaccharides, we have enumerated 355 chemical constituents and nutrients, including 22 glycerogalactolipids, 29 phenylpropanoids, 10 coumarins, 13 lignans, 32 flavonoids, 37 amides, 72 alkaloids, four anthraquinones, 32 organic acids, 39 terpenoids, 57 sterols, steroids, and their derivatives, five peptides and three other constituents. This comprehensive study could lay the foundation for further research on the Lycium genus. Full article

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11 pages, 1557 KiB

Open AccessReview

Bioactive Natural Product and Superacid Chemistry for Lead Compound Identification: A Case Study of Selective hCA III and L-Type Ca²⁺ Current Inhibitors for Hypotensive Agent Discovery

by Hélène Carreyre¹, Grégoire Carré², Maurice Ouedraogo³, Clarisse Vandebrouck², Jocelyn Bescond², Claudiu T. Supuran^4,*

and Sébastien Thibaudeau^1,*

¹ Superacid Group/Organic Synthesis Team, Université de Poitiers, IC2MP—UMR CNRS 7285, 86073 Poitiers CEDEX 09, France

² STIM—ERL CNRS 7368 Université de Poitiers, 86073 Poitiers Cedex 9, France

³ Laboratoire de Physiologie Animale, Université de Ouagadougou, 03 BP 7021 Ouagadougou 01, Burkina Faso

⁴ Department of Neurofarba, Sez, Chimica Farmaceutica e Nutraceutica, University of Florence, 50019 Sesto Fiorentino, Italy

Molecules 2017, 22(6), 915; https://doi.org/10.3390/molecules22060915 - 31 May 2017

Cited by 6 | Viewed by 5490

Abstract

Dodoneine (Ddn) is one of the active compounds identified from Agelanthus dodoneifolius, which is a medicinal plant used in African pharmacopeia and traditional medicine for the treatment of hypertension. In the context of a scientific program aiming at discovering new hypotensive agents [...] Read more.

Dodoneine (Ddn) is one of the active compounds identified from Agelanthus dodoneifolius, which is a medicinal plant used in African pharmacopeia and traditional medicine for the treatment of hypertension. In the context of a scientific program aiming at discovering new hypotensive agents through the original combination of natural product discovery and superacid chemistry diversification, and after evidencing dodoneine’s vasorelaxant effect on rat aorta, superacid modifications allowed us to generate original analogues which showed selective human carbonic anhydrase III (hCA III) and L-type Ca²⁺ current inhibition. These derivatives can now be considered as new lead compounds for vasorelaxant therapeutics targeting these two proteins. Full article

(This article belongs to the Special Issue Carbonic Anhydrase Inhibitors from Natural Products)

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9 pages, 1450 KiB

Open AccessReview

Chemical Methods to Knock Down the Amyloid Proteins

by Na Gao¹, Yong-Xiang Chen¹, Yu-Fen Zhao¹ and Yan-Mei Li^1,2,*

¹ Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing 100084, China

² Beijing Institute for Brain Disorders, Beijing 100069, China

Molecules 2017, 22(6), 916; https://doi.org/10.3390/molecules22060916 - 1 Jun 2017

Cited by 15 | Viewed by 7733

Abstract

Amyloid proteins are closely related with amyloid diseases and do tremendous harm to human health. However, there is still a lack of effective strategies to treat these amyloid diseases, so it is important to develop novel methods. Accelerating the clearance of amyloid proteins [...] Read more.

Amyloid proteins are closely related with amyloid diseases and do tremendous harm to human health. However, there is still a lack of effective strategies to treat these amyloid diseases, so it is important to develop novel methods. Accelerating the clearance of amyloid proteins is a favorable method for amyloid disease treatment. Recently, chemical methods for protein reduction have been developed and have attracted much attention. In this review, we focus on the latest progress of chemical methods that knock down amyloid proteins, including the proteolysis-targeting chimera (PROTAC) strategy, the “recognition-cleavage” strategy, the chaperone-mediated autophagy (CMA) strategy, the selectively light-activatable organic and inorganic molecules strategy and other chemical strategies. Full article

(This article belongs to the Special Issue Women in Organic Chemistry)

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11 pages, 3740 KiB

Open AccessReview

Exploring Adenosine Receptor Ligands: Potential Role in the Treatment of Cardiovascular Diseases

by Werner J. Geldenhuys¹

, Ahmad Hanif¹, June Yun² and Mohammed A. Nayeem^1,*

¹ Department of Pharmaceutical Sciences, West Virginia University, School of Pharmacy, Morgantown, WV 26506, USA

² Department of Integrative Medical Sciences, Northeast Ohio Medical University College of Medicine, Rootstown, OH 44272, USA

Molecules 2017, 22(6), 917; https://doi.org/10.3390/molecules22060917 - 1 Jun 2017

Cited by 21 | Viewed by 6566

Abstract

Cardiovascular diseases remain the number one diseases affecting patients’ morbidity and mortality. The adenosine receptors are G-protein coupled receptors which have been of interest for drugs target for the treatment of multiple diseases ranging from cardiovascular to neurological. Adenosine receptors have been connected [...] Read more.

Cardiovascular diseases remain the number one diseases affecting patients’ morbidity and mortality. The adenosine receptors are G-protein coupled receptors which have been of interest for drugs target for the treatment of multiple diseases ranging from cardiovascular to neurological. Adenosine receptors have been connected to several biological pathways affecting the physiology and pathology of the cardiovascular system. In this review, we will cover the different adenosine receptor ligands that have been identified to interact with adenosine receptors and affect the vascular system. These ligands will be evaluated from clinical as well as medicinal chemistry perspectives with more emphasis on how structural changes in structure translate into ligand potency and efficacy. Adenosine receptors represent a novel therapeutic target for development of treatment options treating a wide variety of diseases, including vascular disease and obesity. Full article

(This article belongs to the Special Issue Adenosine Receptors)

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14 pages, 684 KiB

Open AccessReview

Physicochemical Properties, Biological Activity, Health Benefits, and General Limitations of Aged Black Garlic: A Review

by Ji Hyeon Ryu^1,2 and Dawon Kang^1,2,*

¹ Department of Convergence Medical Science, Gyeongsang National University, Jinju 52727, Korea

² Department of Physiology and Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju 52727, Korea

Molecules 2017, 22(6), 919; https://doi.org/10.3390/molecules22060919 - 1 Jun 2017

Cited by 130 | Viewed by 22788

Abstract

Garlic (Allium sativum) has been used as a medicinal food since ancient times. However, some people are reluctant to ingest raw garlic due to its unpleasant odor and taste. Therefore, many types of garlic preparations have been developed to reduce these attributes without [...] Read more.

Garlic (Allium sativum) has been used as a medicinal food since ancient times. However, some people are reluctant to ingest raw garlic due to its unpleasant odor and taste. Therefore, many types of garlic preparations have been developed to reduce these attributes without losing biological functions. Aged black garlic (ABG) is a garlic preparation with a sweet and sour taste and no strong odor. It has recently been introduced to Asian markets as a functional food. Extensive in vitro and in vivo studies have demonstrated that ABG has a variety of biological functions such as antioxidant, anti-inflammatory, anti-cancer, anti-obesity, anti-diabetic, anti-allergic, cardioprotective, and hepatoprotective effects. Recent studies have compared the biological activity and function of ABG to those of raw garlic. ABG shows lower anti-inflammatory, anti-coagulation, immunomodulatory, and anti-allergic effects compared to raw garlic. This paper reviews the physicochemical properties, biological activity, health benefits, adverse effects, and general limitations of ABG. Full article

(This article belongs to the Special Issue The Chemistry of Alliums)

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24 pages, 4357 KiB

Open AccessReview

An Overview of Structurally Modified Glycyrrhetinic Acid Derivatives as Antitumor Agents

by Bing Xu^†, Gao-Rong Wu^†, Xin-Yu Zhang, Meng-Meng Yan, Rui Zhao, Nan-Nan Xue, Kang Fang, Hui Wang, Meng Chen, Wen-Bo Guo, Peng-Long Wang^*

and Hai-Min Lei^*

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

^† These authors contributed equally to this work.

Molecules 2017, 22(6), 924; https://doi.org/10.3390/molecules22060924 - 2 Jun 2017

Cited by 55 | Viewed by 7979

Abstract

Glycyrrhetinic Acid (GA), a triterpenoid aglycone component of the natural product glycyrrhizinic acid, was found to possess remarkable anti-proliferative and apoptosis-inducing activity in various cancer cell lines. Though GA was not as active as other triterpenes, such as betulinic acid and [...] Read more.

Glycyrrhetinic Acid (GA), a triterpenoid aglycone component of the natural product glycyrrhizinic acid, was found to possess remarkable anti-proliferative and apoptosis-inducing activity in various cancer cell lines. Though GA was not as active as other triterpenes, such as betulinic acid and oleanolic acid, it could trigger apoptosis in tumor cells and it can be obtained easily and cheaply, which has stimulated scientific interest in using GA as a scaffold to synthesize new antitumor agents. The structural modifications of GA reported in recent decades can be divided into four groups, which include structural modifications on ring-A, ring-C, ring-E and multiple ring modifications. The lack of a comprehensive and recent review on this topic prompted us to gather more new information. This overview is dedicated to summarizing and updating the structural modification of GA to improve its antitumor activity published between 2005 and 2016. We reviewed a total of 210 GA derivatives that we encountered and compiled the most active GA derivatives along with their activity profile in different series. Furthermore, the structure activity relationships of these derivatives are briefly discussed. The included information is expected to be of benefit to further studies of structural modifications of GA to enhance its antitumor activity. Full article

(This article belongs to the Special Issue Synthesis and Modification of Natural Product)

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18 pages, 256 KiB

Open AccessReview

Selenium Enrichment of Horticultural Crops

by Martina Puccinelli¹

, Fernando Malorgio¹ and Beatrice Pezzarossa^2,*

¹ Department of Agriculture, Food and Environment, University of Pisa, via del Borghetto 80, 56124 Pisa, Italy

² Institute of Ecosystem Study, CNR, via Moruzzi 1, 56124 Pisa, Italy

Molecules 2017, 22(6), 933; https://doi.org/10.3390/molecules22060933 - 4 Jun 2017

Cited by 125 | Viewed by 9491

Abstract

The ability of some crops to accumulate selenium (Se) is crucial for human nutrition and health. Selenium has been identified as a cofactor of the enzyme glutathione peroxidase, which is a catalyzer in the reduction of peroxides that can damage cells and tissues, [...] Read more.

The ability of some crops to accumulate selenium (Se) is crucial for human nutrition and health. Selenium has been identified as a cofactor of the enzyme glutathione peroxidase, which is a catalyzer in the reduction of peroxides that can damage cells and tissues, and can act as an antioxidant. Plants are the first link in the food chain, which ends with humans. Increasing the Se quantity in plant products, including leafy and fruity vegetables, and fruit crops, without exceeding the toxic threshold, is thus a good way to increase animal and human Se intake, with positive effects on long-term health. In many Se-enriched plants, most Se is in its major organic form. Given that this form is more available to humans and more efficient in increasing the selenium content than inorganic forms, the consumption of Se-enriched plants appears to be beneficial. An antioxidant effect of Se has been detected in Se-enriched vegetables and fruit crops due to an improved antioxidative status and to a reduced biosynthesis of ethylene, which is the hormone with a primary role in plant senescence and fruit ripening. This thus highlights the possible positive effect of Se in preserving a longer shelf-life and longer-lasting quality. Full article

(This article belongs to the Special Issue Celebrating Two Centuries of Research in Selenium Chemistry: State of the Art and New Prospectives)

23 pages, 325 KiB

Open AccessReview

Fruits of Black Chokeberry Aronia melanocarpa in the Prevention of Chronic Diseases

by Tunde Jurikova¹

, Jiri Mlcek^2,*, Sona Skrovankova², Daniela Sumczynski², Jiri Sochor³, Irena Hlavacova², Lukas Snopek²

and Jana Orsavova⁴

¹ Institute for teacher training, Faculty of Central European Studies, Constantine the Philosopher University in Nitra, Drazovska 4, Nitra SK-949 74, Slovakia

² Department of Food Analysis and Chemistry, Faculty of Technology, Tomas Bata University in Zlín, nám. T. G. Masaryka 5555, CZ-760 01 Zlín, Czech Republic

³ Department of Viticulture and Enology, Faculty of Horticulture, Mendel University in Brno, Valticka 337, CZ-691 44 Lednice, Czech Republic

⁴ Language Centre, Faculty of Humanities, Tomas Bata University in Zlín, nám. T. G. Masaryka 5555, CZ-760 01 Zlín, Czech Republic

Molecules 2017, 22(6), 944; https://doi.org/10.3390/molecules22060944 - 7 Jun 2017

Cited by 187 | Viewed by 24595

Abstract

In recent years, growing attention has been focused on the utilization of natural sources of antioxidants in the prevention of chronic diseases. Black chokeberry (Aronia melanocarpa) represents a lesser known fruit species utilized mainly as juices, purees, jams, jellies and wine, [...] Read more.

In recent years, growing attention has been focused on the utilization of natural sources of antioxidants in the prevention of chronic diseases. Black chokeberry (Aronia melanocarpa) represents a lesser known fruit species utilized mainly as juices, purees, jams, jellies and wine, as important food colorants or nutritional supplements. The fruit is valued as a great source of antioxidants, especially polyphenols, such as phenolic acids (neochlorogenic and chlorogenic acids) and flavonoids (anthocyanins, proanthocyanidins, flavanols and flavonols), particularly cyanidin-3-galactoside and cyanidin-3-arabinoside, as well as (−)-epicatechin units. The berries of A. melanocarpa, due to the presence and the high content of these bioactive components, exhibit a wide range of positive effects, such as strong antioxidant activity and potential medicinal and therapeutic benefits (gastroprotective, hepatoprotective, antiproliferative or anti-inflammatory activities). They could be also contributory toward the prevention of chronic diseases including metabolic disorders, diabetes and cardiovascular diseases, because of supportive impacts on lipid profiles, fasting plasma glucose and blood pressure levels. Full article

(This article belongs to the Special Issue Natural Products and Chronic Diseases)

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17 pages, 2062 KiB

Open AccessFeature PaperReview

Integral Design Methodology of Photocatalytic Reactors for Air Pollution Remediation

by Claudio Passalía¹, Orlando M. Alfano^2,* and Rodolfo J. Brandi²

¹ Facultad de Ingeniería y Ciencias Hídricas, Universidad Nacional del Litoral and CONICET, Santa Fe 3000, Argentina

² Instituto de Desarrollo Tecnológico para la Industria Química (CONICET-UNL), Santa Fe 3000, Argentina

Molecules 2017, 22(6), 945; https://doi.org/10.3390/molecules22060945 - 7 Jun 2017

Cited by 22 | Viewed by 5424

Abstract

An integral reactor design methodology was developed to address the optimal design of photocatalytic wall reactors to be used in air pollution control. For a target pollutant to be eliminated from an air stream, the proposed methodology is initiated with a mechanistic derived [...] Read more.

An integral reactor design methodology was developed to address the optimal design of photocatalytic wall reactors to be used in air pollution control. For a target pollutant to be eliminated from an air stream, the proposed methodology is initiated with a mechanistic derived reaction rate. The determination of intrinsic kinetic parameters is associated with the use of a simple geometry laboratory scale reactor, operation under kinetic control and a uniform incident radiation flux, which allows computing the local superficial rate of photon absorption. Thus, a simple model can describe the mass balance and a solution may be obtained. The kinetic parameters may be estimated by the combination of the mathematical model and the experimental results. The validated intrinsic kinetics obtained may be directly used in the scaling-up of any reactor configuration and size. The bench scale reactor may require the use of complex computational software to obtain the fields of velocity, radiation absorption and species concentration. The complete methodology was successfully applied to the elimination of airborne formaldehyde. The kinetic parameters were determined in a flat plate reactor, whilst a bench scale corrugated wall reactor was used to illustrate the scaling-up methodology. In addition, an optimal folding angle of the corrugated reactor was found using computational fluid dynamics tools. Full article

(This article belongs to the Special Issue Photon-involving Purification of Water and Air)

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27 pages, 2879 KiB

Open AccessReview

Origins, Phytochemistry, Pharmacology, Analytical Methods and Safety of Cortex Moutan (Paeonia suffruticosa Andrew): A Systematic Review

by Zhiqiang Wang^1,2,3, Chunnian He^2,3,*

, Yong Peng^2,3, Feihu Chen^1,* and Peigen Xiao^2,3

¹ School of Pharmacy, Anhui Medical University, Hefei 230032, China

² Institute of Medicinal Plant Development, Chinese Academy of Medical Science, Peking Union Medical College, Beijing 100193, China

³ Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing 100193, China

Molecules 2017, 22(6), 946; https://doi.org/10.3390/molecules22060946 - 7 Jun 2017

Cited by 73 | Viewed by 11427

Abstract

Cortex Moutan (CM), a well-known traditional Chinese medicine, is commonly used for treating various diseases in China and other eastern Asian countries. Recorded in Pharmacopeias of several countries, CM is now drawing increasing attention and under extensive studies in various fields. Phytochemical studies [...] Read more.

Cortex Moutan (CM), a well-known traditional Chinese medicine, is commonly used for treating various diseases in China and other eastern Asian countries. Recorded in Pharmacopeias of several countries, CM is now drawing increasing attention and under extensive studies in various fields. Phytochemical studies indicate that CM contains many valuable secondary metabolites, such as monoterpene glycosides and phenols. Ample evidence from pharmacological researches suggest that CM has a wide spectrum of activities, such as anti-inflammatory, anti-oxidant, anti-tumor, anti-diabetic, cardiovascular protective, neuroprotective, hepatoprotective effects. Moreover, various analytical methods were established for the quality evaluation and safety control of CM. This review synopsizes updated information concerning the origins, phytochemistry, pharmacology, analytical method and safety of CM, aiming to provide favorable references for modern CM research and application. In conclusion, continuing pharmacological investigations concerning CM should be conducted to unravel its pharmacological mechanisms. Further researches are necessary to obtain comprehensive and applicable analytical approach for quality evaluation and establish harmonized criteria of CM. Full article

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13 pages, 778 KiB

Open AccessReview

Bioactive Mushroom Polysaccharides: A Review on Monosaccharide Composition, Biosynthesis and Regulation

by Qiong Wang^1,3, Feng Wang²

, Zhenghong Xu^1,3 and Zhongyang Ding^1,3,*

¹ Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi 214122, China

² School of Food and Biological Engineering, Jiangsu University, Zhenjiang 212013, China

³ National Engineering Laboratory for Cereal Fermentation Technology, Jiangnan University, Wuxi 214122, China

Molecules 2017, 22(6), 955; https://doi.org/10.3390/molecules22060955 - 13 Jun 2017

Cited by 177 | Viewed by 14138

Abstract

Mushrooms are widely distributed around the world and are heavily consumed because of their nutritional value and medicinal properties. Polysaccharides (PSs) are an important component of mushrooms, a major factor in their bioactive properties, and have been intensively studied during the past two [...] Read more.

Mushrooms are widely distributed around the world and are heavily consumed because of their nutritional value and medicinal properties. Polysaccharides (PSs) are an important component of mushrooms, a major factor in their bioactive properties, and have been intensively studied during the past two decades. Monosaccharide composition/combinations are important determinants of PS bioactivities. This review summarizes: (i) monosaccharide composition/combinations in various mushroom PSs, and their relationships with PS bioactivities; (ii) possible biosynthetic pathways of mushroom PSs and effects of key enzymes on monosaccharide composition; (iii) regulation strategies in PS biosynthesis, and prospects for controllable biosynthesis of PSs with enhanced bioactivities. Full article

(This article belongs to the Special Issue Natural Polysaccharides)

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19 pages, 2713 KiB

Open AccessReview

Targeted Magnetic Nanotheranostics of Cancer

by Irina Belyanina¹, Olga Kolovskaya^1,2, Sergey Zamay², Ana Gargaun³, Tatiana Zamay^1,2 and Anna Kichkailo^1,2,*

¹ Krasnoyarsk State Medical University named after prof. V.F. Voino-Yaseneckii, 660022 Krasnoyarsk, Russia

² Federal Research Center, KSC Siberian Branch of Russian Academy of Science, 660022 Krasnoyarsk, Russia

³ Independent Researcher Vancouver, Vancouver, BC V6K 1C4, Canada

Molecules 2017, 22(6), 975; https://doi.org/10.3390/molecules22060975 - 12 Jun 2017

Cited by 50 | Viewed by 9865

Abstract

Current advances in targeted magnetic nanotheranostics are summarized in this review. Unique structural, optical, electronic and thermal properties of magnetic materials in nanometer scale are attractive in the field of biomedicine. Magnetic nanoparticles functionalized with therapeutic molecules, ligands for targeted delivery, fluorescent and [...] Read more.

Current advances in targeted magnetic nanotheranostics are summarized in this review. Unique structural, optical, electronic and thermal properties of magnetic materials in nanometer scale are attractive in the field of biomedicine. Magnetic nanoparticles functionalized with therapeutic molecules, ligands for targeted delivery, fluorescent and other chemical agents can be used for cancer diagnostic and therapeutic purposes. High selectivity, small size, and low immunogenicity of synthetic nucleic acid aptamers make them attractive delivery agents for therapeutic purposes. Properties, production and functionalization of magnetic nanoparticles and aptamers as ligands for targeted delivery are discussed herein. In recent years, magnetic nanoparticles have been widely used in diagnostic methods, such as scintigraphy, single photon emission computed tomography (SPECT), positron emission tomography (PET), magnetic resonance imaging (MRI), and Raman spectroscopy. Therapeutic purposes of magnetic nanoconstructions are also promising. They are used for effective drug delivery, magnetic mediated hypertermia, and megnetodynamic triggering of apoptosis. Thus, magnetic nanotheranostics opens a new venue for complex differential diagnostics, and therapy of metastatic cancer. Full article

(This article belongs to the Special Issue Nucleic Acid Chemistry and Nucleic Acid Drugs: A Themed Issue in Honor of Professor Lihe Zhang on the Occasion of His 80th Birthday)

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26 pages, 6044 KiB

Open AccessReview

Fluoroalkyl Amino Reagents (FARs): A General Approach towards the Synthesis of Heterocyclic Compounds Bearing Emergent Fluorinated Substituents

by Bruno Commare¹, Etienne Schmitt¹, Fallia Aribi¹, Armen Panossian¹, Jean-Pierre Vors², Sergiy Pazenok³ and Frédéric R. Leroux^1,*

¹ University of Strasbourg, CNRS, LCM UMR 7509, 67000 Strasbourg, France

² Bayer S.A.S., 14 Impasse Pierre Baizet, BP 99163, 69263 Lyon CEDEX 09, France

³ Bayer AG, Alfred-Nobel-Strasse 50, 40789 Monheim, Germany

Molecules 2017, 22(6), 977; https://doi.org/10.3390/molecules22060977 - 12 Jun 2017

Cited by 18 | Viewed by 10631

Abstract

Fluorinated heterocycles are important building blocks in pharmaceutical, agrochemical and material sciences. Therefore, organofluorine chemistry has witnessed high interest in the development of efficient methods for the introduction of emergent fluorinated substituents (EFS) onto heterocycles. In this context, fluoroalkyl amino reagents (FARs)—a class [...] Read more.

Fluorinated heterocycles are important building blocks in pharmaceutical, agrochemical and material sciences. Therefore, organofluorine chemistry has witnessed high interest in the development of efficient methods for the introduction of emergent fluorinated substituents (EFS) onto heterocycles. In this context, fluoroalkyl amino reagents (FARs)—a class of chemicals that was slightly forgotten over the last decades—has emerged again recently and proved to be a powerful tool for the introduction of various fluorinated groups onto (hetero)aromatic derivatives. Full article

(This article belongs to the Special Issue Tri- and Di-Fluoromethylation and Tri- and Di-Fluoromethylchalcogenation Reactions)

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47 pages, 13415 KiB

Open AccessReview

Modifications of Porphyrins and Hydroporphyrins for Their Solubilization in Aqueous Media

by Michael Luciano

and Christian Brückner^*

Department of Chemistry, University of Connecticut, Storrs, CT 06269-3060, USA

Molecules 2017, 22(6), 980; https://doi.org/10.3390/molecules22060980 - 13 Jun 2017

Cited by 81 | Viewed by 16202

Abstract

The increasing popularity of porphyrins and hydroporphyrins for use in a variety of biomedical (photodynamic therapy, fluorescence tagging and imaging, photoacoustic imaging) and technical (chemosensing, catalysis, light harvesting) applications is also associated with the growing number of methodologies that enable their solubilization in [...] Read more.

The increasing popularity of porphyrins and hydroporphyrins for use in a variety of biomedical (photodynamic therapy, fluorescence tagging and imaging, photoacoustic imaging) and technical (chemosensing, catalysis, light harvesting) applications is also associated with the growing number of methodologies that enable their solubilization in aqueous media. Natively, the vast majority of synthetic porphyrinic compounds are not water-soluble. Moreover, any water-solubility imposes several restrictions on the synthetic chemist on when to install solubilizing groups in the synthetic sequence, and how to isolate and purify these compounds. This review summarizes the chemical modifications to render synthetic porphyrins water-soluble, with a focus on the work disclosed since 2000. Where available, practical data such as solubility, indicators for the degree of aggregation, and special notes for the practitioner are listed. We hope that this review will guide synthetic chemists through the many strategies known to make porphyrins and hydroporphyrins water soluble. Full article

(This article belongs to the Special Issue Porphyrins and Phthalocyanines: Synthesis, Properties and Applications)

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24 pages, 807 KiB

Open AccessReview

Essential Oils of Oregano: Biological Activity beyond Their Antimicrobial Properties

by Nayely Leyva-López

, Erick P. Gutiérrez-Grijalva

, Gabriela Vazquez-Olivo

and J. Basilio Heredia^*

Centro de Investigación en Alimentación y Desarrollo A.C., Carretera a El Dorado km 5.5 Col. El Diez C.P., Culiacán, Sinaloa 80129, Mexico

Molecules 2017, 22(6), 989; https://doi.org/10.3390/molecules22060989 - 14 Jun 2017

Cited by 325 | Viewed by 53783

Abstract

Essential oils of oregano are widely recognized for their antimicrobial activity, as well as their antiviral and antifungal properties. Nevertheless, recent investigations have demonstrated that these compounds are also potent antioxidant, anti-inflammatory, antidiabetic and cancer suppressor agents. These properties of oregano essential oils [...] Read more.

Essential oils of oregano are widely recognized for their antimicrobial activity, as well as their antiviral and antifungal properties. Nevertheless, recent investigations have demonstrated that these compounds are also potent antioxidant, anti-inflammatory, antidiabetic and cancer suppressor agents. These properties of oregano essential oils are of potential interest to the food, cosmetic and pharmaceutical industries. The aim of this manuscript is to review the latest evidence regarding essential oils of oregano and their beneficial effects on health. Full article

(This article belongs to the Special Issue Essential Oils: Chemistry and Bioactivity)

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20 pages, 1373 KiB

Open AccessFeature PaperReview

Protein Interaction and Na/K-ATPase-Mediated Signal Transduction

by Xiaoyu Cui and Zijian Xie^*

Marshall Institute for Interdisciplinary Research, Marshall University, Huntington, WV 25703, USA

Molecules 2017, 22(6), 990; https://doi.org/10.3390/molecules22060990 - 14 Jun 2017

Cited by 128 | Viewed by 13159

Abstract

The Na/K-ATPase (NKA), or Na pump, is a member of the P-type ATPase superfamily. In addition to pumping ions across cell membrane, it is engaged in assembly of multiple protein complexes in the plasma membrane. This assembly allows NKA to perform many non-pumping [...] Read more.

The Na/K-ATPase (NKA), or Na pump, is a member of the P-type ATPase superfamily. In addition to pumping ions across cell membrane, it is engaged in assembly of multiple protein complexes in the plasma membrane. This assembly allows NKA to perform many non-pumping functions including signal transduction that are important for animal physiology and disease progression. This article will focus on the role of protein interaction in NKA-mediated signal transduction, and its potential utility as target for developing new therapeutics. Full article

(This article belongs to the Special Issue Cardiotonic Steroids)

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26 pages, 5794 KiB

Open AccessReview

Coumarin–Tetrapyrrolic Macrocycle Conjugates: Synthesis and Applications

by Ana F. R. Cerqueira

, Vítor A. S. Almodôvar, Maria G. P. M. S. Neves

and Augusto C. Tomé^*

Department of Chemistry and QOPNA, University of Aveiro, 3810-193 Aveiro, Portugal

Molecules 2017, 22(6), 994; https://doi.org/10.3390/molecules22060994 - 15 Jun 2017

Cited by 22 | Viewed by 8802

Abstract

This review covers the synthesis of coumarin–porphyrin, coumarin–phthalocyanine and coumarin–corrole conjugates and their potential applications. While coumarin–phthalocyanine conjugates were obtained almost exclusively by tetramerization of coumarin-functionalized phthalonitriles, coumarin–porphyrin and coumarin–corrole conjugates were prepared by complementary approaches: (a) direct synthesis of the tetrapyrrolic macrocycle [...] Read more.

This review covers the synthesis of coumarin–porphyrin, coumarin–phthalocyanine and coumarin–corrole conjugates and their potential applications. While coumarin–phthalocyanine conjugates were obtained almost exclusively by tetramerization of coumarin-functionalized phthalonitriles, coumarin–porphyrin and coumarin–corrole conjugates were prepared by complementary approaches: (a) direct synthesis of the tetrapyrrolic macrocycle using formylcoumarins and pyrrole or (b) by functionalization of the tetrapyrrolic macrocycle. In the last approach a range of reaction types were used, namely 1,3-dipolar cycloadditions, hetero-Diels–Alder, Sonogashira, alkylation or acylation reactions. This is clearly a more versatile approach, leading to a larger diversity of conjugates and allowing the access to conjugates bearing one to up to 16 coumarin units. Full article

(This article belongs to the Special Issue Porphyrins and Phthalocyanines: Synthesis, Properties and Applications)

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14 pages, 1832 KiB

Open AccessReview

Deoxyelephantopin and Isodeoxyelephantopin as Potential Anticancer Agents with Effects on Multiple Signaling Pathways

by Tahir Mehmood¹, Amara Maryam¹, Hamed A. Ghramh^2,3, Muhammad Khan^1,*

and Tonghui Ma^1,*

¹ College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, China

² Research Center for Advanced Materials Science, King Khalid University, Abha 61413, P.O. Box 9004, Saudi Arabia

³ Department of Biology, Faculty of Science, King Khalid University, Abha 61413, P.O. Box 9004, Saudi Arabia

Molecules 2017, 22(6), 1013; https://doi.org/10.3390/molecules22061013 - 21 Jun 2017

Cited by 34 | Viewed by 7638

Abstract

Cancer is the 2nd leading cause of death worldwide. The development of drugs to target only one specific signaling pathway has limited therapeutic success. Developing chemotherapeutics to target multiple signaling pathways has emerged as a new prototype for cancer treatment. Deoxyelephantopin (DET) and [...] Read more.

Cancer is the 2nd leading cause of death worldwide. The development of drugs to target only one specific signaling pathway has limited therapeutic success. Developing chemotherapeutics to target multiple signaling pathways has emerged as a new prototype for cancer treatment. Deoxyelephantopin (DET) and isodeoxyelephantopin (IDET) are sesquiterpene lactone components of “Elephantopus scaber and Elephantopus carolinianus”, traditional Chinese medicinal herbs that have long been used as folk medicines to treat liver diseases, diabetes, diuresis, bronchitis, fever, diarrhea, dysentery, cancer, and inflammation. Recently, the anticancer activity of DET and IDET has been widely investigated. Here, our aim is to review the current status of DET and IDET, and discuss their anticancer activity with specific emphasis on molecular targets and mechanisms used by these compounds to trigger apoptosis pathways which may help to further design and conduct research to develop them as lead therapeutic drugs for cancer treatments. The literature has shown that DET and IDET induce apoptosis through multiple signaling pathways which are deregulated in cancer cells and suggested that by targeting multiple pathways simultaneously, these compounds could selectively kill cancer cells. This review suggests that DET and IDET hold promising anticancer activity but additional studies and clinical trials are needed to validate and understand their therapeutic effect to develop them into potent therapeutics for the treatment of cancer. Full article

(This article belongs to the Collection Bioactive Compounds)

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24 pages, 3073 KiB

Open AccessReview

Cancer Chemoprevention by Resveratrol: The p53 Tumor Suppressor Protein as a Promising Molecular Target

by Danielly C. Ferraz da Costa¹, Eliane Fialho^2,* and Jerson L. Silva^3,*

¹ Instituto de Nutrição, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, 20550-013, Brazil

² Instituto de Nutrição Josué de Castro, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil

³ Instituto de Bioquímica Médica Leopoldo de Meis & Instituto Nacional de Ciência e Tecnologia de Biologia Estrutural e Bioimagem, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, 21941-902, Brazil

Molecules 2017, 22(6), 1014; https://doi.org/10.3390/molecules22061014 - 18 Jun 2017

Cited by 57 | Viewed by 19352

Abstract

Increasing epidemiological and experimental evidence has demonstrated an inverse relationship between the consumption of plant foods and the incidence of chronic diseases, including cancer. Microcomponents that are naturally present in such foods, especially polyphenols, are responsible for the benefits to human health. Resveratrol [...] Read more.

Increasing epidemiological and experimental evidence has demonstrated an inverse relationship between the consumption of plant foods and the incidence of chronic diseases, including cancer. Microcomponents that are naturally present in such foods, especially polyphenols, are responsible for the benefits to human health. Resveratrol is a diet-derived cancer chemopreventive agent with high therapeutic potential, as demonstrated by different authors. The aim of this review is to collect and present recent evidence from the literature regarding resveratrol and its effects on cancer prevention, molecular signaling (especially regarding the involvement of p53 protein), and therapeutic perspectives with an emphasis on clinical trial results to date. Full article

(This article belongs to the Special Issue Improvements for Resveratrol Efficacy)

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27 pages, 1849 KiB

Open AccessReview

Leptadenia reticulata (Retz.) Wight & Arn. (Jivanti): Botanical, Agronomical, Phytochemical, Pharmacological, and Biotechnological Aspects

by Sudipta Kumar Mohanty^1,2, Mallappa Kumara Swamy^2,3,*

, Uma Rani Sinniah^3,* and Maniyam Anuradha²

¹ Instituto de Biología, Universidad Nacional Autónoma de México, Ciudad Universitaria, Coyoacan, Ciudad de México C.P. 04510, Mexico

² School of Life Sciences, Padmashree Institute of Management and Sciences, Kommagatta, Kengeri, Bengaluru 560060, India

³ Department of Crop Science, Faculty of Agriculture, Universiti Putra Malaysia, Serdang, Selangor, Darul Ehsan 43400, Malaysia

Molecules 2017, 22(6), 1019; https://doi.org/10.3390/molecules22061019 - 19 Jun 2017

Cited by 94 | Viewed by 12744

Abstract

Leptadenia reticulata (Retz.) Wight & Arn. (Apocynaceae), is a traditional medicinal plant species widely used to treat various ailments such as tuberculosis, hematopoiesis, emaciation, cough, dyspnea, fever, burning sensation, night blindness, cancer, and dysentery. In Ayurveda, it is known for its revitalizing, rejuvenating, [...] Read more.

Leptadenia reticulata (Retz.) Wight & Arn. (Apocynaceae), is a traditional medicinal plant species widely used to treat various ailments such as tuberculosis, hematopoiesis, emaciation, cough, dyspnea, fever, burning sensation, night blindness, cancer, and dysentery. In Ayurveda, it is known for its revitalizing, rejuvenating, and lactogenic properties. This plant is one of the major ingredients in many commercial herbal formulations, including Speman, Envirocare, Calshakti, Antisept, and Chyawanprash. The therapeutic potential of this herb is because of the presence of diverse bioactive compounds such as α-amyrin, β-amyrin, ferulic acid, luteolin, diosmetin, rutin, β-sitosterol, stigmasterol, hentricontanol, a triterpene alcohol simiarenol, apigenin, reticulin, deniculatin, and leptaculatin. However, most biological studies on L. reticulata are restricted to crude extracts, and many biologically active compounds are yet to be identified in order to base the traditional uses of L. reticulata on evidence-based data. At present, L. reticulata is a threatened endangered plant because of overexploitation, unscientific harvesting, and habitat loss. The increased demand from pharmaceutical, nutraceutical, and veterinary industries has prompted its large-scale propagation. However, its commercial cultivation is hampered because of the non-availability of genuine planting material and the lack of knowledge about its agronomical practices. In this regard, micropropagation techniques will be useful to obtain true-to-type L. reticulata planting materials from an elite germplasm to meet the current demand. Adopting other biotechnological approaches such as synthetic seed technology, cryopreservation, cell culture, and genetic transformation can help conservation as well as increased metabolite production from L. reticulata. The present review summarizes scientific information on the botanical, agronomical, phytochemical, pharmacological, and biotechnological aspects of L. reticulata. This comprehensive information will certainly allow better utilization of this industrially important herb towards the discovery of lead drug molecules. Full article

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13 pages, 2383 KiB

Open AccessReview

From Farm to Pharma: An Overview of Industrial Heparin Manufacturing Methods

by Jan-Ytzen Van der Meer^*, Edwin Kellenbach

and Leendert J. Van den Bos

Development and Technical Support Aspen Oss, Kloosterstraat 6, P.O. Box 98, 5340 AB Oss, The Netherlands

Molecules 2017, 22(6), 1025; https://doi.org/10.3390/molecules22061025 - 21 Jun 2017

Cited by 94 | Viewed by 14091

Abstract

The purification of heparin from offal is an old industrial process for which commercial recipes date back to 1922. Although chemical, chemoenzymatic, and biotechnological alternatives for this production method have been published in the academic literature, animal-tissue is still the sole source for [...] Read more.

The purification of heparin from offal is an old industrial process for which commercial recipes date back to 1922. Although chemical, chemoenzymatic, and biotechnological alternatives for this production method have been published in the academic literature, animal-tissue is still the sole source for commercial heparin production in industry. Heparin purification methods are closely guarded industrial secrets which are not available to the general (scientific) public. However by reviewing the academic and patent literature, we aim to provide a comprehensive overview of the general methods used in industry for the extraction of heparin from animal tissue. Full article

(This article belongs to the Special Issue Looking Forward to the Future of Heparin: New Sources, Developments and Applications)

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1 pages, 139 KiB

Open AccessErratum

Erratum: Jiang, J.; et al. Expeditious Synthesis of Dianionic-Headed 4-Sulfoalkanoic Acid Surfactants. Molecules 2017, 22, 640

by Jianhui Jiang^1,2 and Jiaxi Xu^1,*

¹ State Key Laboratory of Chemical Resource Engineering, Department of Organic Chemistry, Faculty of Science, Beijing University of Chemical Technology, Beijing 100029, China

² Engineering Laboratory of Chemical Resources Utilization in South Xinjiang of Xinjiang Production and Construction Corps, College of Life Sciences, Tarim University, Alar, Xinjiang 843300, China

Molecules 2017, 22(6), 877; https://doi.org/10.3390/molecules22060877 - 26 May 2017

Cited by 1 | Viewed by 2598

Abstract

The authors wish to make the following change to their paper [1]. [...] Full article

(This article belongs to the Section Organic Chemistry)

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Photophysics and Photochemistry of Canonical Nucleobases’ Thioanalogs: From Quantum Mechanical Studies to Time Resolved Experiments

by Serra Arslancan¹, Lara Martínez-Fernández^2,*

and Inés Corral^1,3,*

¹ Departamento de Química, Módulo 13, Universidad Autónoma de Madrid, Madrid 28049, Spain

² Istituto Biostrutture e Bioimmagini-Consiglio Nazionale delle Ricerche, Via Mezzocannone 16, Napoli I-80134, Italy

³ Institute for Advanced Research in Chemical Sciences (IADCHEM), Universidad Autónoma de Madrid, Madrid 28049, Spain

Molecules 2017, 22(6), 998; https://doi.org/10.3390/molecules22060998 - 18 Jun 2017

Cited by 62 | Viewed by 7865

Abstract

Interest in understanding the photophysics and photochemistry of thiated nucleobases has been awakened because of their possible involvement in primordial RNA or their potential use as photosensitizers in medicinal chemistry. The interpretation of the photodynamics of these systems, conditioned by their intricate potential [...] Read more.

Interest in understanding the photophysics and photochemistry of thiated nucleobases has been awakened because of their possible involvement in primordial RNA or their potential use as photosensitizers in medicinal chemistry. The interpretation of the photodynamics of these systems, conditioned by their intricate potential energy surfaces, requires the powerful interplay between experimental measurements and state of the art molecular simulations. In this review, we provide an overview on the photophysics of natural nucleobases’ thioanalogs, which covers the last 30 years and both experimental and computational contributions. For all the canonical nucleobase’s thioanalogs, we have compiled the main steady state absorption and emission features and their interpretation in terms of theoretical calculations. Then, we revise the main topographical features, including stationary points and interstate crossings, of their potential energy surfaces based on quantum mechanical calculations and we conclude, by combining the outcome of different spectroscopic techniques and molecular dynamics simulations, with the mechanism by which these nucleobase analogs populate their triplet excited states, which are at the origin of their photosensitizing properties. Full article

(This article belongs to the Special Issue Experimental and Computational Photochemistry of Bioorganic Molecules)

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