Molecules

Editorial

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3 pages, 163 KiB

Open AccessEditorial

Renewable Green Platform Chemicals for Polymers

by Parijat Ray, Craig Smith, George P. Simon and Kei Saito

Molecules 2017, 22(3), 376; https://doi.org/10.3390/molecules22030376 - 28 Feb 2017

Cited by 17 | Viewed by 4739

Abstract

This Special Issue covered topics in the field of Green Chemistry.[...] Full article

(This article belongs to the Special Issue Frontier in Green Chemistry Approaches)

6 pages, 167 KiB

Open AccessEditorial

Flavonoids: From Structure to Health Issues

by Celestino Santos-Buelga and Arturo San Feliciano

Molecules 2017, 22(3), 477; https://doi.org/10.3390/molecules22030477 - 17 Mar 2017

Cited by 54 | Viewed by 8546

Abstract

Flavonoids are one of the largest groups of plant secondary metabolites.[...] Full article

(This article belongs to the Special Issue Flavonoids: From Structure to Health Issues)

Research

Jump to: Editorial, Review, Other

11 pages, 1993 KiB

Open AccessArticle

Flavonoids from Agrimonia pilosa Ledeb: Free Radical Scavenging and DNA Oxidative Damage Protection Activities and Analysis of Bioactivity-Structure Relationship Based on Molecular and Electronic Structures

by Liancai Zhu, Jinqiu Chen, Jun Tan, Xi Liu and Bochu Wang

Molecules 2017, 22(3), 195; https://doi.org/10.3390/molecules22030195 - 26 Feb 2017

Cited by 69 | Viewed by 7542

Abstract

To clarify the substantial basis of the excellent antioxidant capacity of Agrimonia pilosa Ledeb. Fourteen flavonoids were isolated and identified from Agrimonia pilosa Ledeb, seven of which have notable DPPH radical scavenging activities, i.e., catechin, luteolin, quercetin, quercitrin, hyperoside, rutin, luteolin-7-O-β-glucoside [...] Read more.

To clarify the substantial basis of the excellent antioxidant capacity of Agrimonia pilosa Ledeb. Fourteen flavonoids were isolated and identified from Agrimonia pilosa Ledeb, seven of which have notable DPPH radical scavenging activities, i.e., catechin, luteolin, quercetin, quercitrin, hyperoside, rutin, luteolin-7-O-β-glucoside with IC₅₀ values of 5.06, 7.29, 4.36, 7.12, 6.34, 6.36 and 8.12 µM, respectively. The DNA nicking assay showed that five flavonoids from Agrimonia pilosa Ledeb—taxifolin, catechin, hyperoside, quercitrin and rutin—have good protective activity against DNA oxidative damage. Further, we analyzed the bioactivity-structure relationship of these 14 flavonoids by applying quantum theory. According to their O-H bond dissociation enthalpy (BDE), C ring’s spin density and stable molecular structure, the relationship between their structures and radical scavenging capacities was evaluated and clarified. We found that among flavonoid aglycones from Agrimonia pilosa Ledeb, the O-H BDE of quercetin is lowest with the values of 69.02 and the O-H BDE of apigenin is highest with the values of 79.77. It is interesting that the O-H BDE value of isovitexin (78.55) with glycoside at C-6 position is lower than that of its aglycone (79.77) and vitexin (99.20) with glycoside at C-8 position. Further analysis indicated that the glycosidation of flavonoids at C-6 in the A-ring makes a more uniform distribution of spin density and improves the stability of free radicals leading to the increase in antioxidant capacity. Flavonoids with good antioxidant capacity might contribute to the pharmacological effects of Agrimonia pilosa Ledeb. Full article

(This article belongs to the Section Natural Products Chemistry)

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20 pages, 3147 KiB

Open AccessArticle

Luteolin Inhibits Fibrillary β-Amyloid_1–40-Induced Inflammation in a Human Blood-Brain Barrier Model by Suppressing the p38 MAPK-Mediated NF-κB Signaling Pathways

by Jun-Xia Zhang, Jian-Guo Xing, Lin-Lin Wang, Hai-Lun Jiang, Shui-Long Guo and Rui Liu

Molecules 2017, 22(3), 334; https://doi.org/10.3390/molecules22030334 - 24 Feb 2017

Cited by 99 | Viewed by 9795

Abstract

Amyloid-β peptides (Aβ) exist in several forms and are known as key modulators of Alzheimer’s disease (AD). Fibrillary Aβ (fAβ) has been found to disrupt the blood-brain barrier (BBB) by triggering and promoting inflammation. In this study, luteolin, a naturally occurring flavonoid that [...] Read more.

Amyloid-β peptides (Aβ) exist in several forms and are known as key modulators of Alzheimer’s disease (AD). Fibrillary Aβ (fAβ) has been found to disrupt the blood-brain barrier (BBB) by triggering and promoting inflammation. In this study, luteolin, a naturally occurring flavonoid that has shown beneficial properties in the central nervous system, was evaluated as a potential agent to preserve barrier function and inhibit inflammatory responses at the BBB that was injured by fAβ_1–40. We established an in vitro BBB model by co-culturing human brain microvascular endothelial cells (hBMECs) and human astrocytes (hAs) under fAβ_1–40-damaged conditions and investigated the effect of luteolin by analyzing cellular toxicity, barrier function, cytokine production and inflammation-related intracellular signaling pathways. Our results demonstrated that, in cells injured by fAβ_1–40, luteolin increased cell viability of hBMECs and hAs. The cytoprotection of the co-culture against the damage induced by fAβ_1–40 was also increased at both the apical and basolateral sides. Luteolin protected the barrier function by preserving transendothelial electrical resistance and relieving aggravated permeability in the human BBB model after being exposed to fAβ_1–40. Moreover, in both the apical and basolateral sides of the co-culture, luteolin reduced fAβ_1–40-induced inflammatory mediator and cytokine production, including cyclooxygenase-2 (COX-2), tumor necrosis factor α (TNF-α), interleukin 1 β (IL-1β), interleukin 6 (IL-6), and interleukin 8 (IL-8), however it did not show sufficient effects on scavenging intracellular reactive oxygen species (ROS) in hBMECs and hAs. The mechanism of BBB protection against fAβ_1–40-induced injury may be related to the regulation of inflammatory signal transduction, which involves inhibition of p38 mitogen-activated protein kinase (MAPK) activation, downregulation of phosphorylated inhibitory κB kinase (phosphor-IKK) levels, relief of inhibitory κB α (IκBα) degradation, blockage of nuclear factor κB (NF-κB) p65 nuclear translocation, and reduction of the release of inflammatory cytokines. Moreover, the employment of p38 MAPK and NF-κB inhibitors reversed luteolin-mediated barrier function and cytokine release. Taken together, luteolin may serve as a potential therapeutic agent for BBB protection by inhibiting inflammation following fAβ_1–40-induced injury. Full article

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17 pages, 2441 KiB

Open AccessArticle

Essential Oil of Aristolochia trilobata: Synthesis, Routes of Exposure, Acute Toxicity, Binary Mixtures and Behavioral Effects on Leaf-Cutting Ants

by Bruna Maria S. De Oliveira, Carlisson R. Melo, Péricles B. Alves, Abraão A. Santos, Ane Caroline C. Santos, Alisson Da S. Santana, Ana Paula A. Araújo, Pedro E. S. Nascimento, Arie F. Blank and Leandro Bacci

Molecules 2017, 22(3), 335; https://doi.org/10.3390/molecules22030335 - 25 Feb 2017

Cited by 31 | Viewed by 7065

Abstract

Plants of the genus Aristolochia have been frequently reported as important medicinal plants. Despite their high bioactive potential, to date, there are no reports of their effects on leaf-cutting ants. Therefore, the present study aimed to evaluate the insecticidal activity of the essential [...] Read more.

Plants of the genus Aristolochia have been frequently reported as important medicinal plants. Despite their high bioactive potential, to date, there are no reports of their effects on leaf-cutting ants. Therefore, the present study aimed to evaluate the insecticidal activity of the essential oil of Aristolochia trilobata and its major components on Atta sexdens and Acromyrmex balzani, two species of leaf-cutting ants. The bioassays were performed regarding routes of exposure, acute toxicity, binary mixtures of the major components and behavioral effects. Twenty-five components were identified in the essential oil of A. trilobata using a gas chromatographic system equipped with a mass spectrometer and a flame ionization detector. The components found in higher proportions were sulcatyl acetate, limonene, p-cymene and linalool. The essential oil of A. trilobata and its individual major components were efficient against A. balzani and A. sexdens workers when applied by fumigation. These components showed fast and efficient insecticidal activity on ants. The components acted synergistically and additively on A. balzani and A. sexdens, respectively, and caused a strong repellency/irritability in the ants. Thus, our results demonstrate the great potential of the essential oil of A. trilobata and its major components for the development of new insecticides. Full article

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

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17 pages, 6848 KiB

Open AccessArticle

Antimalarials with Benzothiophene Moieties as Aminoquinoline Partners

by Jelena Konstantinović, Milica Videnović, Jelena Srbljanović, Olgica Djurković-Djaković, Katarina Bogojević, Richard Sciotti and Bogdan Šolaja

Molecules 2017, 22(3), 343; https://doi.org/10.3390/molecules22030343 - 24 Feb 2017

Cited by 21 | Viewed by 7417

Abstract

Malaria is a severe and life-threatening disease caused by Plasmodium parasites that are spread to humans through bites of infected Anopheles mosquitoes. Here, we report on the efficacy of aminoquinolines coupled to benzothiophene and thiophene rings in inhibiting Plasmodium falciparum parasite growth. Synthesized [...] Read more.

Malaria is a severe and life-threatening disease caused by Plasmodium parasites that are spread to humans through bites of infected Anopheles mosquitoes. Here, we report on the efficacy of aminoquinolines coupled to benzothiophene and thiophene rings in inhibiting Plasmodium falciparum parasite growth. Synthesized compounds were evaluated for their antimalarial activity and toxicity, in vitro and in mice. Benzothiophenes presented in this paper showed improved activities against a chloroquine susceptible (CQS) strain, with potencies of IC₅₀ = 6 nM, and cured 5/5 Plasmodium berghei infected mice when dosed orally at 160 mg/kg/day × 3 days. In the benzothiophene series, the examined antiplasmodials were more active against the CQS strain D6, than against strains chloroquine resistant (CQR) W2 and multidrug-resistant (MDR) TM91C235. For the thiophene series, a very interesting feature was revealed: hypersensitivity to the CQR strains, resistance index (RI) of <1. This is in sharp contrast to chloroquine, indicating that further development of the series would provide us with more potent antimalarials against CQR strains. Full article

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

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13 pages, 2638 KiB

Open AccessArticle

Complexing Methylene Blue with Phosphorus Dendrimers to Increase Photodynamic Activity

by Monika Dabrzalska, Anna Janaszewska, Maria Zablocka, Serge Mignani, Jean Pierre Majoral and Barbara Klajnert-Maculewicz

Molecules 2017, 22(3), 345; https://doi.org/10.3390/molecules22030345 - 23 Feb 2017

Cited by 18 | Viewed by 6582

Abstract

The efficiency of photodynamic therapy is limited mainly due to low selectivity, unfavorable biodistribution of photosensitizers, and long-lasting skin sensitivity to light. However, drug delivery systems based on nanoparticles may overcome the limitations mentioned above. Among others, dendrimers are particularly attractive as carriers, [...] Read more.

The efficiency of photodynamic therapy is limited mainly due to low selectivity, unfavorable biodistribution of photosensitizers, and long-lasting skin sensitivity to light. However, drug delivery systems based on nanoparticles may overcome the limitations mentioned above. Among others, dendrimers are particularly attractive as carriers, because of their globular architecture and high loading capacity. The goal of the study was to check whether an anionic phosphorus dendrimer is suitable as a carrier of a photosensitizer—methylene blue (MB). As a biological model, basal cell carcinoma cell lines were used. We checked the influence of the MB complexation on its singlet oxygen production ability using a commercial fluorescence probe. Next, cellular uptake, phototoxicity, reactive oxygen species (ROS) generation, and cell death were investigated. The MB-anionic dendrimer complex (MB-1an) was found to generate less singlet oxygen; however, the complex showed higher cellular uptake and phototoxicity against basal cell carcinoma cell lines, which was accompanied with enhanced ROS production. Owing to the obtained results, we conclude that the photodynamic activity of MB complexed with an anionic dendrimer is higher than free MB against basal cell carcinoma cell lines. Full article

(This article belongs to the Special Issue Photodynamic Therapy)

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10 pages, 1157 KiB

Open AccessArticle

Microwave-Assisted Synthesis of some Novel Azoles and Azolopyrimidines as Antimicrobial Agents

by Sobhi M. Gomha, Thoraya A. Farghaly, Yahia Nasser Mabkhot, Mohie E. M. Zayed and Amany M. G. Mohamed

Molecules 2017, 22(3), 346; https://doi.org/10.3390/molecules22030346 - 23 Feb 2017

Cited by 28 | Viewed by 5734

Abstract

In this study, new derivatives of pyrazole, isoxazole, pyrazolylthiazole, and azolopyrimidine having a thiophene ring were synthesized under microwave irradiation. Their pharmacological activity toward bacteria and fungi inhibition was screened and compared to the references Chloramphenicol and Trimethoprim/sulphamethoxazole. The antimicrobial [...] Read more.

In this study, new derivatives of pyrazole, isoxazole, pyrazolylthiazole, and azolopyrimidine having a thiophene ring were synthesized under microwave irradiation. Their pharmacological activity toward bacteria and fungi inhibition was screened and compared to the references Chloramphenicol and Trimethoprim/sulphamethoxazole. The antimicrobial results of the investigated compounds revealed promising results and some derivatives have activities similar to the references used. Full article

(This article belongs to the Section Organic Chemistry)

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13 pages, 416 KiB

Open AccessArticle

Is Gamma Radiation Suitable to Preserve Phenolic Compounds and to Decontaminate Mycotoxins in Aromatic Plants? A Case-Study with Aloysia citrodora Paláu

by Eliana Pereira, Lillian Barros, Amilcar L. Antonio, Sandra Cabo Verde, Celestino Santos-Buelga, Isabel C. F. R. Ferreira and Paula Rodrigues

Molecules 2017, 22(3), 347; https://doi.org/10.3390/molecules22030347 - 23 Feb 2017

Cited by 31 | Viewed by 7230

Abstract

This study aimed to determine the effect of gamma radiation on the preservation of phenolic compounds and on decontamination of dry herbs in terms of ochratoxin A (OTA) and aflatoxin B1 (AFB1), using Aloysia citrodora Paláu as a case study. For this purpose, [...] Read more.

This study aimed to determine the effect of gamma radiation on the preservation of phenolic compounds and on decontamination of dry herbs in terms of ochratoxin A (OTA) and aflatoxin B1 (AFB1), using Aloysia citrodora Paláu as a case study. For this purpose, artificially contaminated dry leaves were submitted to gamma radiation at different doses (1, 5, and 10 kGy; at dose rate of 1.7 kGy/h). Phenolic compounds were analysed by HPLC-DAD-ESI/MS and mycotoxin levels were determined by HPLC-fluorescence. Eleven phenolic compounds were identified in the samples and despite the apparent degradation of some compounds (namely verbasoside), 1 and 10 kGy doses point to a preservation of the majority of the compounds. The mean mycotoxin reduction varied between 5.3% and 9.6% for OTA and from 4.9% to 5.2% for AFB1. It was not observed a significant effect of the irradiation treatments on mycotoxin levels, and a slight degradation of the phenolic compounds in the irradiated samples was observed. Full article

(This article belongs to the Collection Bioactive Compounds)

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10 pages, 502 KiB

Open AccessArticle

Screening of Six Medicinal Plant Extracts Obtained by Two Conventional Methods and Supercritical CO₂ Extraction Targeted on Coumarin Content, 2,2-Diphenyl-1-picrylhydrazyl Radical Scavenging Capacity and Total Phenols Content

by Maja Molnar, Igor Jerković, Dragica Suknović, Blanka Bilić Rajs, Krunoslav Aladić, Drago Šubarić and Stela Jokić

Molecules 2017, 22(3), 348; https://doi.org/10.3390/molecules22030348 - 24 Feb 2017

Cited by 42 | Viewed by 8576

Abstract

Six medicinal plants Helichrysum italicum (Roth) G. Don, Angelica archangelica L., Lavandula officinalis L., Salvia officinalis L., Melilotus officinalis L., and Ruta graveolens L. were used. The aim of the study was to compare their extracts obtained by Soxhlet (hexane) extraction, maceration with [...] Read more.

Six medicinal plants Helichrysum italicum (Roth) G. Don, Angelica archangelica L., Lavandula officinalis L., Salvia officinalis L., Melilotus officinalis L., and Ruta graveolens L. were used. The aim of the study was to compare their extracts obtained by Soxhlet (hexane) extraction, maceration with ethanol (EtOH), and supercritical CO₂ extraction (SC-CO₂) targeted on coumarin content (by high performance liquid chromatography with ultraviolet detection, HPLC-UV), 2,2-diphenyl-1-picrylhydrazyl radical (DPPH) scavenging capacity, and total phenols (TPs) content (by Folin–Ciocalteu assay). The highest extraction yields were obtained by EtOH, followed by hexane and SC-CO₂. The highest coumarin content (316.37 mg/100 g) was found in M. officinalis EtOH extracts, but its SC-CO₂ extraction yield was very low for further investigation. Coumarin was also found in SC-CO₂ extracts of S. officinalis, R. graveolens, A. archangelica, and L. officinalis. EtOH extracts of all plants exhibited the highest DPPH scavenging capacity. SC-CO₂ extracts exhibited antiradical capacity similar to hexane extracts, while S. officinalis SC-CO₂ extracts were the most potent (95.7%). EtOH extracts contained the most TPs (up to 132.1 mg gallic acid equivalents (GAE)/g from H. italicum) in comparison to hexane or SC-CO₂ extracts. TPs content was highly correlated to the DPPH scavenging capacity of the extracts. The results indicate that for comprehensive screening of different medicinal plants, various extraction techniques should be used in order to get a better insight into their components content or antiradical capacity. Full article

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

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10 pages, 1421 KiB

Open AccessCommunication

Comparison of Free Total Amino Acid Compositions and Their Functional Classifications in 13 Wild Edible Mushrooms

by Liping Sun, Qiuming Liu, Changjun Bao and Jian Fan

Molecules 2017, 22(3), 350; https://doi.org/10.3390/molecules22030350 - 24 Feb 2017

Cited by 80 | Viewed by 10145

Abstract

Thirteen popular wild edible mushroom species in Yunnan Province, Boletus bicolor, Boletus speciosus, Boletus sinicus, Boletus craspedius, Boletus griseus, Boletus ornatipes, Xerocomus, Suillus placidus, Boletinus pinetorus, Tricholoma terreum, Tricholomopsis lividipileata, Termitomyces microcarpus [...] Read more.

Thirteen popular wild edible mushroom species in Yunnan Province, Boletus bicolor, Boletus speciosus, Boletus sinicus, Boletus craspedius, Boletus griseus, Boletus ornatipes, Xerocomus, Suillus placidus, Boletinus pinetorus, Tricholoma terreum, Tricholomopsis lividipileata, Termitomyces microcarpus, and Amanita hemibapha, were analyzed for their free amino acid compositions by online pre-column derivazation reversed phase high-performance liquid chromatography (RP-HPLC) analysis. Twenty free amino acids, aspartic acid, glutamic acid, serine, glycine, alanine, praline, cysteine, valine, methionine, phenylalanine, isoleucine, leucine, lysine, histidine, threonine, asparagines, glutamine, arginine, tyrosine, and tryptophan, were determined. The total free amino acid (TAA) contents ranged from 1462.6 mg/100 g in B. craspedius to 13,106.2 mg/100 g in T. microcarpus. The different species showed distinct free amino acid profiles. The ratio of total essential amino acids (EAA) to TAA was 0.13–0.41. All of the analyzed species showed high contents of hydrophobic amino acids, at 33%–54% of TAA. Alanine, cysteine, glutamine, and glutamic acid were among the most abundant amino acids present in all species. The results showed that the analyzed mushrooms possessed significant free amino acid contents, which may be important compounds contributing to the typical mushroom taste, nutritional value, and potent antioxidant properties of these wild edible mushrooms. Furthermore, the principal component analysis (PCA) showed that the accumulative variance contribution rate of the first four principal components reached 94.39%. Cluster analysis revealed EAA composition and content might be an important parameter to separate the mushroom species, and T. microcarpus and A. hemibapha showed remarkable EAA content among the 13 species. Full article

(This article belongs to the Special Issue Selected papers from 2nd International Symposium on Phytochemicals in Medicine and Food (2-ISPMF, Fuzhou, 2017))

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15 pages, 5618 KiB

Open AccessArticle

Pt-Au/MO_x-CeO₂ (M = Mn, Fe, Ti) Catalysts for the Co-Oxidation of CO and H₂ at Room Temperature

by Xiaowei Hong, Ye Sun, Tianle Zhu and Zhiming Liu

Molecules 2017, 22(3), 351; https://doi.org/10.3390/molecules22030351 - 27 Feb 2017

Cited by 8 | Viewed by 7498

Abstract

A series of nanostructured Pt-Au/MO_x-CeO₂ (M = Mn, Fe, Ti) catalysts were prepared and their catalytic performance for the co-oxidation of carbon monoxide (CO) and hydrogen (H₂) were evaluated at room temperature. The results showed that MO_x [...] Read more.

A series of nanostructured Pt-Au/MO_x-CeO₂ (M = Mn, Fe, Ti) catalysts were prepared and their catalytic performance for the co-oxidation of carbon monoxide (CO) and hydrogen (H₂) were evaluated at room temperature. The results showed that MO_x promoted the CO oxidation of Pt-Au/CeO₂, but only the TiO₂ could enhance co-oxidation of CO and H₂ over Pt-Au/CeO₂. Related characterizations were conducted to clarify the promoting effect of MO_x. Temperature-programmed reduction of hydrogen (H₂-TPR) and X-ray photoelectron spectroscopy (XPS) results suggested that MO_x could improve the charge transfer from Au sites to CeO₂, resulting in a high concentration of Ce³⁺ and cationic Au species which benefits for the CO oxidation. In-situ diffuse reflectance infrared Fourier transform spectroscopy (In-situ DRIFTS) results indicated that TiO₂ could facilitate the oxidation of H₂ over the Pt-Au/TiO₂-CeO₂ catalyst. Full article

(This article belongs to the Special Issue Bimetallic Catalysis)

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11 pages, 823 KiB

Open AccessArticle

Binding and Conversion of Selenium in Candida utilis ATCC 9950 Yeasts in Bioreactor Culture

by Marek Kieliszek, Stanisław Błażejak and Eliza Kurek

Molecules 2017, 22(3), 352; https://doi.org/10.3390/molecules22030352 - 25 Feb 2017

Cited by 44 | Viewed by 6653

Abstract

Selenium is considered an essential component of all living organisms. The use of yeasts as a selenium supplement in human nutrition has gained much interest over the last decade. The accumulation and biochemical transformation of selenium in yeast cells is particularly interesting to [...] Read more.

Selenium is considered an essential component of all living organisms. The use of yeasts as a selenium supplement in human nutrition has gained much interest over the last decade. The accumulation and biochemical transformation of selenium in yeast cells is particularly interesting to many researchers. In this article, we present the results of the determination of selenium and selenomethionine content in the biomass of feed yeast Candida utilis ATCC 9950 obtained from the culture grown in a bioreactor. The results indicated that C. utilis cells performed the biotransformation of inorganic selenium(IV) to organic derivatives (e.g., selenomethionine). Selenium introduced (20–30 mg Se⁴⁺∙L⁻¹) to the experimental media in the form of sodium(IV) selenite (Na₂SeO₃) salt caused a significant increase in selenium content in the biomass of C. utilis,irrespective of the concentration. The highest amount of selenium (1841 μg∙g_d.w.⁻¹) was obtained after a 48-h culture in media containing 30 mg Se⁴⁺∙L⁻¹. The highest content of selenomethionine (238.8 μg∙g_d.w.⁻¹) was found after 48-h culture from the experimental medium that was supplemented with selenium at a concentration of 20 mg Se⁴⁺∙L⁻¹. Biomass cell in the cultures supplemented with selenium ranged from 1.5 to 14.1 g∙L⁻¹. The results of this study indicate that yeast cell biomass of C. utilis enriched mainly with the organic forms of selenium can be a valuable source of protein. It creates the possibility of obtaining selenium biocomplexes that can be used in the production of protein-selenium dietary supplements for animals and humans 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, 1879 KiB

Open AccessArticle

A UPLC-MS/MS Method for Simultaneous Determination of Free and Total Forms of a Phenolic Acid and Two Flavonoids in Rat Plasma and Its Application to Comparative Pharmacokinetic Studies of Polygonum capitatum Extract in Rats

by Yong Huang, Hui-Yuan Sun, Xiao-Li Qin, Yong-Jun Li, Shang-Gao Liao, Zi-Peng Gong, Yuan Lu, Yong-Lin Wang, Ai-Min Wang, Yan-Yu Lan and Lin Zheng

Molecules 2017, 22(3), 353; https://doi.org/10.3390/molecules22030353 - 25 Feb 2017

Cited by 31 | Viewed by 8029

Abstract

The principal active constituents of Polygonum capitatum are phenolic acids and flavonoids, such as gallic acid, quercitrin, and quercetin. The aim of this study was to develop and validate a method to determine the three constituents and the corresponding conjugated metabolites of Polygonum [...] Read more.

The principal active constituents of Polygonum capitatum are phenolic acids and flavonoids, such as gallic acid, quercitrin, and quercetin. The aim of this study was to develop and validate a method to determine the three constituents and the corresponding conjugated metabolites of Polygonum capitatum in vivo and to conduct pharmacokinetic studies on the herb, a well-known Miao medicinal plant in China. Gallic acid, quercitrin, and quercetin were analysed by ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-ESI-MS/MS). Protein precipitation in plasma samples was performed using methanol. For the determination of total forms of analytes, an additional process of hydrolysis was conducted using β-glucuronidase and sulphatase. The analytes were separated on a BEH C₁₈ column (50 mm × 2.1 mm; i.d., 1.7 μm) and quantified by multiple reaction monitoring (MRM) mode. The linear regression showed high linearity over a 729-fold dynamic range for the three analytes. The relative standard deviations of intra- and inter-day measurements were less than 9.5%, and the method was accurate to within −11.1% to 12.5%. The extraction recoveries for gallic acid, quercitrin, and quercetin were 94.3%–98.8%, 88.9%–98.8%, and 95.7%–98.5%, respectively. All samples were stable under short- and long-term storage conditions. The validated method was successfully applied to a comparative pharmacokinetic study of gallic acid, quercitrin, and quercetin in their free and total forms in rat plasma. The study revealed significantly higher exposure of the constituents in total forms for gallic acid and quercetin, while quercitrin was detected mainly in its corresponding free form in vivo. The established method was rapid and sensitive for the simultaneous quantification of free and total forms of multiple constituents of Polygonum capitatum extract in plasma. Full article

(This article belongs to the Collection Herbal Medicine Research)

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13 pages, 2959 KiB

Open AccessArticle

Glutathione Peroxidase-Like Activity of Amino-Substituted Water-Soluble Cyclic Selenides: A Shift of the Major Catalytic Cycle in Methanol

by Kenta Arai, Ayako Tashiro, Yuui Osaka and Michio Iwaoka

Molecules 2017, 22(3), 354; https://doi.org/10.3390/molecules22030354 - 25 Feb 2017

Cited by 22 | Viewed by 7218

Abstract

We previously reported that water-soluble cyclic selenides can mimic the antioxidative function of glutathione peroxidase (GPx) in water through a simple catalytic cycle, in which the selenide (>Se) is oxidized by H₂O₂ to the selenoxide (>Se=O) and the selenoxide is [...] Read more.

We previously reported that water-soluble cyclic selenides can mimic the antioxidative function of glutathione peroxidase (GPx) in water through a simple catalytic cycle, in which the selenide (>Se) is oxidized by H₂O₂ to the selenoxide (>Se=O) and the selenoxide is reduced by a thiol back to the selenide. In methanol, however, the GPx-like activity could not be explained by this simple scenario. To look into the reasons for the unusual behaviors in methanol, monoamino-substituted cyclic selenides with a variable ring size were synthesized, and the intermediates of the catalytic cycle were characterized by means of ⁷⁷Se-NMR and LC–MS spectroscopies. In water, it was confirmed that the selenide and the selenoxide mainly contribute to the antioxidative function, though a slight contribution from the dihydroxy selenane (>Se(OH)₂) was also suggested. In methanol, on the other hand, other active species, such as hydroxyselenonium (>Se⁺–OH) and hydroxy perhydroxy selenane (>Se(OH)(OOH)), could be generated to build another catalytic cycle. This over-oxidation would be more feasible for amino-substituted cyclic selenides, probably because the ammonium (NH₃⁺) group would transfer a proton to the selenoxide moiety to produce a hydroxyselenonium species in the absence of an additional proton source. Thus, a shift of the major catalytic cycle in methanol would make the GPx-like antioxidative function of selenides perplexing. 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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15 pages, 554 KiB

Open AccessArticle

Facial Regioselective Synthesis of Novel Bioactive Spiropyrrolidine/Pyrrolizine-Oxindole Derivatives via a Three Components Reaction as Potential Antimicrobial Agents

by Huwaida M. E. Hassaneen, Elshimaa M. Eid, Hamid A. Eid, Thoraya A. Farghaly and Yahia Nasser Mabkhot

Molecules 2017, 22(3), 357; https://doi.org/10.3390/molecules22030357 - 26 Feb 2017

Cited by 21 | Viewed by 5528

Abstract

This article presents the synthesis of new derivatives of spirooxindole-spiropiperidinone- pyrrolidines 6a–j and spirooxindole-spiropiperidinone-pyrrolizines 8a–j, through a 1,3-dipolar cycloaddition reaction of azomethineylides generated from isatin, sarcosine, and l-proline, through a decarboxylative route with dipolarophile 4a–j. All [...] Read more.

This article presents the synthesis of new derivatives of spirooxindole-spiropiperidinone- pyrrolidines 6a–j and spirooxindole-spiropiperidinone-pyrrolizines 8a–j, through a 1,3-dipolar cycloaddition reaction of azomethineylides generated from isatin, sarcosine, and l-proline, through a decarboxylative route with dipolarophile 4a–j. All of the newly synthesized compounds were evaluated for their antimicrobial activities and their minimum inhibitory concentration (MIC) against most of the test organisms. The tested compounds displayed excellent activity against all of the tested microorganisms. Full article

(This article belongs to the Collection Heterocyclic Compounds)

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11 pages, 2826 KiB

Open AccessArticle

Paeoniflorin Attenuates Cerebral Ischemia-Induced Injury by Regulating Ca²⁺/CaMKII/CREB Signaling Pathway

by Yuqin Zhang, Lifei Qiao, Wen Xu, Xiaoying Wang, Huang Li, Wei Xu, Kedan Chu and Yu Lin

Molecules 2017, 22(3), 359; https://doi.org/10.3390/molecules22030359 - 27 Feb 2017

Cited by 65 | Viewed by 6676

Abstract

Paeoniflorin (PF) is an active ingredient of Paeoniae Radix which possesses the neuroprotective effect. However, so far, the neuroprotective mechanism of PF has still not been fully uncovered. The Ca²⁺/Ca²⁺/calmodulin-dependent protein kinase II (CaMKII)/cAMP response element-binding (CREB) signaling pathway [...] Read more.

Paeoniflorin (PF) is an active ingredient of Paeoniae Radix which possesses the neuroprotective effect. However, so far, the neuroprotective mechanism of PF has still not been fully uncovered. The Ca²⁺/Ca²⁺/calmodulin-dependent protein kinase II (CaMKII)/cAMP response element-binding (CREB) signaling pathway plays an important role in the intracellular signal transduction pathway involved in cell proliferation, cell survival, inflammation and metabolism. Herein, the neuroprotective roles of PF in the models of middle cerebral artery occlusion (MCAO) followed by reperfusion in rats and N-methyl-d-aspartic acid (NMDA)-induced excitotoxicity in primary hippocampal neurons were investigated. Moreover, we attempted to confirm the hypothesis that its protection effect is via the modulation of the Ca²⁺/CaMKI)/CREB signaling pathway. In this study, PF not only significantly decreased neurological deficit scores and infarct volume in vivo, but also improved neurons’ cell viability, and inhibited neurons’ apoptosis and intracellular Ca²⁺ concentration in vitro. Furthermore, PF significantly up-regulated p-CREB and p-CaMKII, and down-regulated calmodulin (CaM) in vivo and in vitro. The results indicate that the protective effect of PF on cerebral ischemia reperfusion injury is possible through regulating the Ca²⁺/CaMKII/CREB signaling pathway. Full article

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11 pages, 23815 KiB

Open AccessArticle

The Structure-Activity Relationship of Pterostilbene Against Candida albicans Biofilms

by Dan-Dan Hu, Ri-Li Zhang, Yong Zou, Hua Zhong, En-Sheng Zhang, Xiang Luo, Yan Wang and Yuan-Ying Jiang

Molecules 2017, 22(3), 360; https://doi.org/10.3390/molecules22030360 - 27 Feb 2017

Cited by 16 | Viewed by 5799

Abstract

Candida albicans biofilms contribute to invasive infections and dramatic drug resistance, and anti-biofilm agents are urgently needed in the clinic. Pterostilbene (PTE) is a natural plant product with potentials to be developed as an anti-biofilm agent. In this study, we evaluated the structure-activity [...] Read more.

Candida albicans biofilms contribute to invasive infections and dramatic drug resistance, and anti-biofilm agents are urgently needed in the clinic. Pterostilbene (PTE) is a natural plant product with potentials to be developed as an anti-biofilm agent. In this study, we evaluated the structure-activity relationship (SAR) of PTE analogues against C. albicans biofilms. XTT (Sodium 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide inner salt) reduction assay was used to evaluate the activity of the analogues against C. albicans biofilms. Knowing that hyphal formation is essential for C. albicans biofilms, anti-hyphal assay was further carried out. By comparing a series of compounds tested in this study, we found that compounds with para-hydroxy (–OH) in partition A exhibited better activity than those with other substituents in the para position, and the double bond in partition B and meta-dimethoxy (–OCH₃) in partition C both contributed to the best activity. Consistent results were obtained by anti-hyphal assay. Collectively, para-hydroxy (–OH), double bond and meta-dimethoxy (–OCH₃) are all needed for the best activity of PTE against C. albicans biofilms. Full article

(This article belongs to the Special Issue Structure-Activity Relationship of Natural Products)

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9 pages, 1386 KiB

Open AccessArticle

Looking Inside the Intramolecular C−H∙∙∙O Hydrogen Bond in Lactams Derived from α-Methylbenzylamine

by Sandra Mejía, Julio M. Hernández-Pérez, Jacinto Sandoval-Lira and Fernando Sartillo-Piscil

Molecules 2017, 22(3), 361; https://doi.org/10.3390/molecules22030361 - 28 Feb 2017

Cited by 13 | Viewed by 6782

Abstract

Recently, strong evidence that supports the presence of an intramolecular C−H···O hydrogen bond in amides derived from the chiral auxiliary α-methylbenzylamine was disclosed. Due to the high importance of this chiral auxiliary in asymmetric synthesis, the inadvertent presence of this C−H···O interaction may [...] Read more.

Recently, strong evidence that supports the presence of an intramolecular C−H···O hydrogen bond in amides derived from the chiral auxiliary α-methylbenzylamine was disclosed. Due to the high importance of this chiral auxiliary in asymmetric synthesis, the inadvertent presence of this C−H···O interaction may lead to new interpretations upon stereochemical models in which this chiral auxiliary is present. Therefore, a series of lactams containing the chiral auxiliary α-methylbenzylamine (from three to eight-membered ring) were theoretically studied at the MP2/cc-pVDZ level of theory with the purpose of studying the origin and nature of the C−Hα···O interaction. NBO analysis revealed that rehybridization at C atom of the C−Hα bond (s-character at C is ~23%) and the subsequent bond polarization are the dominant effect over the orbital interaction energy n_(O)→σ*_C−Hα (E(2) < 2 kcal/mol), causing an important shortening of the C−Hα bond distance and an increment in the positive charge in the Hα atom. Full article

(This article belongs to the Special Issue Intramolecular Hydrogen Bonding 2017)

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14 pages, 8263 KiB

Open AccessArticle

An Investigation on the Quantitative Structure-Activity Relationships of the Anti-Inflammatory Activity of Diterpenoid Alkaloids

by Xiao Li, Ning Li, Zhenyu Sui, Kaishun Bi and Zuojing Li

Molecules 2017, 22(3), 363; https://doi.org/10.3390/molecules22030363 - 27 Feb 2017

Cited by 12 | Viewed by 6377

Abstract

Diterpenoid alkaloids are extracted from plants. These compounds have broad biological activities, including effects on the cardiovascular system, anti-inflammatory and analgesic actions, and anti-tumor activity. The anti-inflammatory activity was determined by carrageenan-induced rat paw edema and experimental trauma in rats. The number of [...] Read more.

Diterpenoid alkaloids are extracted from plants. These compounds have broad biological activities, including effects on the cardiovascular system, anti-inflammatory and analgesic actions, and anti-tumor activity. The anti-inflammatory activity was determined by carrageenan-induced rat paw edema and experimental trauma in rats. The number of studies focused on the determination, quantitation and pharmacological properties of these alkaloids has increased dramatically during the past few years. In this work we built a dataset composed of 15 diterpenoid alkaloid compounds with diverse structures, of which 11 compounds were included in the training set and the remaining compounds were included in the test set. The quantitative chemistry parameters of the 15 diterpenoid alkaloids compound were calculated using the HyperChem software, and the quantitative structure–activity relationship (QSAR) of these diterpenoid alkaloid compounds were assessed in an anti-inflammation model based on half maximal effective concentration (EC₅₀) measurements obtained from rat paw edema data. The QSAR prediction model is as follows:

\log (E C_{50}) = - 0.0260 \times SAA + 0.0086 \times SAG + 0.0011 \times VOL - 0.0641 \times HE - 0.2628 \times LogP - 0.5594 \times REF - 0.2211 \times POL - 0.1964 \times MASS + 0.088 \times BE + 0.1398 \times HF

(R² = 0.981, Q² = 0.92). The validated consensus EC₅₀ for the QSAR model, developed from the rat paw edema anti-inflammation model used in this study, indicate that this model was capable of effective prediction and can be used as a reliable computational predictor of diterpenoid alkaloid activity. Full article

(This article belongs to the Special Issue Structure-Activity Relationship of Natural Products)

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16 pages, 1558 KiB

Open AccessArticle

A General Asymmetric Synthesis of (R)-Matsutakeol and Flavored Analogs

by Jia Liu, Honglian Li, Chao Zheng, Shichao Lu, Xianru Guo, Xinming Yin, Risong Na, Bin Yu and Min Wang

Molecules 2017, 22(3), 364; https://doi.org/10.3390/molecules22030364 - 27 Feb 2017

Cited by 7 | Viewed by 6877

Abstract

An efficient and practical synthetic route toward chiral matsutakeol and analogs was developed by asymmetric addition of terminal alkyne to aldehydes. (R)-matsutakeol and other flavored substances were feasibly synthesized from various alkylaldehydes in high yield (up to 49.5%, in three steps) [...] Read more.

An efficient and practical synthetic route toward chiral matsutakeol and analogs was developed by asymmetric addition of terminal alkyne to aldehydes. (R)-matsutakeol and other flavored substances were feasibly synthesized from various alkylaldehydes in high yield (up to 49.5%, in three steps) and excellent enantiomeric excess (up to >99%). The protocols may serve as an alternative asymmetric synthetic method for active small-molecule library of natural fatty acid metabolites and analogs. These chiral allyl alcohols are prepared for food analysis and screening insect attractants. Full article

(This article belongs to the Special Issue Asymmetric Synthesis 2017)

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11 pages, 1077 KiB

Open AccessArticle

Synthesis and Characterization of a New Bivalent Ligand Combining Caffeine and Docosahexaenoic Acid

by Víctor Fernández-Dueñas, Jhonny Azuaje, Xavier Morató, Begoña Cordobilla, Joan Carles Domingo, Eddy Sotelo and Francisco Ciruela

Molecules 2017, 22(3), 366; https://doi.org/10.3390/molecules22030366 - 27 Feb 2017

Cited by 5 | Viewed by 6521

Abstract

Caffeine is a promising drug for the management of neurodegenerative diseases such as Parkinson’s disease (PD), demonstrating neuroprotective properties that have been attributed to its interaction with the basal ganglia adenosine A2A receptor (A2AR). However, the doses needed to exert these neuroprotective effects [...] Read more.

Caffeine is a promising drug for the management of neurodegenerative diseases such as Parkinson’s disease (PD), demonstrating neuroprotective properties that have been attributed to its interaction with the basal ganglia adenosine A2A receptor (A2AR). However, the doses needed to exert these neuroprotective effects may be too high. Thus, it is important to design novel approaches that selectively deliver this natural compound to the desired target. Docosahexaenoic acid (DHA) is the major omega-3 fatty acid in the brain and can act as a specific carrier of caffeine. Furthermore, DHA displays properties that may lead to its use as a neuroprotective agent. In the present study, we constructed a novel bivalent ligand covalently linking caffeine and DHA and assessed its pharmacological activity and safety profile in a simple cellular model. Interestingly, the new bivalent ligand presented higher potency as an A2AR inverse agonist than caffeine alone. We also determined the range of concentrations inducing toxicity both in a heterologous system and in primary striatal cultures. The novel strategy presented here of attaching DHA to caffeine may enable increased effects of the drug at desired sites, which could be of interest for the treatment of PD. Full article

(This article belongs to the Special Issue Adenosine Receptors)

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8 pages, 227 KiB

Open AccessArticle

Chemical Composition, In Vitro Antimicrobial, Free-Radical-Scavenging and Antioxidant Activities of the Essential Oil of Leucas inflata Benth

by Ramzi A. Mothana, Omar M. Noman, Ebtesam S. Al-Sheddi, Jamal M. Khaled, Mansour S. Al-Said and Adnan J. Al-Rehaily

Molecules 2017, 22(3), 367; https://doi.org/10.3390/molecules22030367 - 27 Feb 2017

Cited by 14 | Viewed by 5065

Abstract

The essential oil of Leucas inflata Balf.f. (Lamiaceae), collected in Yemen, was analyzed using gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS) techniques. Forty-three components were recognized, representing 89.2% of the total oil. The L. inflata volatile oil was found to contain a [...] Read more.

The essential oil of Leucas inflata Balf.f. (Lamiaceae), collected in Yemen, was analyzed using gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS) techniques. Forty-three components were recognized, representing 89.2% of the total oil. The L. inflata volatile oil was found to contain a high percentage of aliphatic acids (51.1%). Hexadecanoic acid (32.8%) and n-dodecanoic acid (7.8%) were identified as the major compounds. Oxygenated monoterpenes were distinguished as the second significant group of constituents (16.0%). Camphor (6.1%) and linalool (3.2%) were found to be the main components among the oxygenated monoterpenes. In addition, the volatile oil was assessed for its antimicrobial activity against four bacterial strains and one yeast species using broth micro-dilution assay for minimum inhibitory concentrations (MIC). In addition, antioxidant activity was measured utilizing the anti-radical activity of the sable free radical 2,2-diphenyl-1-picrylhydrazyl (DPPH) and β-Carotene-linoleic acid assays. The oil of L. inflata showed an excellent antibacterial activity against only the tested Gram-positive bacteria with a MIC-value of 0.81 mg/mL. Furthermore, the oil demonstrated, at a concentration of 1 mg/mL, a weak to moderate antiradical and antioxidant activity of 38% and 32%, respectively. Full article

10 pages, 412 KiB

Open AccessArticle

Antiprotozoal Activity of Triazole Derivatives of Dehydroabietic Acid and Oleanolic Acid

by Mariano Walter Pertino, Celeste Vega, Miriam Rolón, Cathia Coronel, Antonieta Rojas de Arias and Guillermo Schmeda-Hirschmann

Molecules 2017, 22(3), 369; https://doi.org/10.3390/molecules22030369 - 28 Feb 2017

Cited by 36 | Viewed by 6333

Abstract

Tropical parasitic diseases such as Chagas disease and leishmaniasis are considered a major public health problem affecting hundreds of millions of people worldwide. As the drugs currently used to treat these diseases have several disadvantages and side effects, there is an urgent need [...] Read more.

Tropical parasitic diseases such as Chagas disease and leishmaniasis are considered a major public health problem affecting hundreds of millions of people worldwide. As the drugs currently used to treat these diseases have several disadvantages and side effects, there is an urgent need for new drugs with better selectivity and less toxicity. Structural modifications of naturally occurring and synthetic compounds using click chemistry have enabled access to derivatives with promising antiparasitic activity. The antiprotozoal activity of the terpenes dehydroabietic acid, dehydroabietinol, oleanolic acid, and 34 synthetic derivatives were evaluated against epimastigote forms of Trypanosoma cruzi and promastigotes of Leishmaniabraziliensis and Leishmania infantum. The cytotoxicity of the compounds was assessed on NCTC-Clone 929 cells. The activity of the compounds was moderate and the antiparasitic effect was associated with the linker length between the diterpene and the triazole in dehydroabietinol derivatives. For the oleanolic acid derivatives, a free carboxylic acid function led to better antiparasitic activity. Full article

(This article belongs to the Special Issue Structure-Activity Relationship of Natural Products)

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18 pages, 3351 KiB

Open AccessArticle

A Computational Investigation of the Substituent Effects on Geometric, Electronic, and Optical Properties of Siloles and 1,4-Disilacyclohexa-2,5-dienes

by Aleksandra V. Denisova, Julius Tibbelin, Rikard Emanuelsson and Henrik Ottosson

Molecules 2017, 22(3), 370; https://doi.org/10.3390/molecules22030370 - 28 Feb 2017

Cited by 15 | Viewed by 5858

Abstract

Thirty two differently substituted siloles 1a–1p and 1,4-disilacyclohexa-2,5-dienes 2a–2p were investigated by quantum chemical calculations using the PBE0 hybrid density functional theory (DFT) method. The substituents included σ-electron donating and withdrawing, as well as π-electron donating and withdrawing groups, [...] Read more.

Thirty two differently substituted siloles 1a–1p and 1,4-disilacyclohexa-2,5-dienes 2a–2p were investigated by quantum chemical calculations using the PBE0 hybrid density functional theory (DFT) method. The substituents included σ-electron donating and withdrawing, as well as π-electron donating and withdrawing groups, and their effects when placed at the Si atom(s) or at the C atoms were examined. Focus was placed on geometries, frontier orbital energies and the energies of the first allowed electronic excitations. We analyzed the variation in energies between the orbitals which correspond to HOMO and LUMO for the two parent species, here represented as Δε_HL, motivated by the fact that the first allowed transitions involve excitation between these orbitals. Even though Δε_HL and the excitation energies are lower for siloles than for 1,4-disilacyclohexa-2,5-dienes the latter display significantly larger variations with substitution. The Δε_HL of the siloles vary within 4.57–5.35 eV (ΔΔε_HL = 0.78 eV) while for the 1,4-disilacyclohexa-2,5-dienes the range is 5.49–7.15 eV (ΔΔε_HL = 1.66 eV). The excitation energy of the first allowed transitions display a moderate variation for siloles (3.60–4.41 eV) whereas the variation for 1,4-disilacyclohexa-2,5-dienes is nearly doubled (4.69–6.21 eV). Cyclobutadisiloles combine the characteristics of siloles and 1,4-disilacyclohexa-2,5-diene by having even lower excitation energies than siloles yet also extensive variation in excitation energies to substitution of 1,4-disilacyclohexa-2,5-dienes (3.47–4.77 eV, variation of 1.30 eV). Full article

(This article belongs to the Special Issue Advances in Silicon Chemistry)

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11 pages, 1213 KiB

Open AccessArticle

Isolation and Structure Identification of Novel Brominated Diketopiperazines from Nocardia ignorata—A Lichen-Associated Actinobacterium

by Alba Noël, Solenn Ferron, Isabelle Rouaud, Nicolas Gouault, Jean-Pierre Hurvois and Sophie Tomasi

Molecules 2017, 22(3), 371; https://doi.org/10.3390/molecules22030371 - 28 Feb 2017

Cited by 18 | Viewed by 6700

Abstract

Actinobacteria are well known for their potential in biotechnology and their production of metabolites of interest. Lichens are a promising source of new bacterial strains, especially Actinobacteria, which afford a broad chemical diversity. In this context, the culture medium of the actinobacterium Nocardia [...] Read more.

Actinobacteria are well known for their potential in biotechnology and their production of metabolites of interest. Lichens are a promising source of new bacterial strains, especially Actinobacteria, which afford a broad chemical diversity. In this context, the culture medium of the actinobacterium Nocardia ignorata, isolated from the terrestrial lichen Collema auriforme, was studied. The strain was cultivated in a BioFlo 115 bioreactor, and the culture medium was extracted using an XAD7HP resin. Five known diketopiperazines: cyclo (l-Pro-l-OMet) (1), cyclo (l-Pro-l-Tyr) (2), cyclo (d-Pro-l-Tyr) (3), cyclo (l-Pro-l-Val) (4), cyclo (l-Pro-l-Leu) (5), and one auxin derivative: indole-carboxaldehyde (8) were isolated, along with two new brominated diketopiperazines: cyclo (d-Pro-l-Br-Tyr) (6) and cyclo (l-Pro-l-Br-Tyr) (7). Structure elucidation was performed using HRMS and 1D and 2D NMR analysis, and the synthesis of compounds 6 and 7 was carried out in order to confirm their structure. Full article

(This article belongs to the Special Issue Lichens: Chemistry, Ecological and Biological Activities)

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14 pages, 4372 KiB

Open AccessArticle

Antioxidant Activity of the Lignins Derived from Fluidized-Bed Fast Pyrolysis

by Sohail S. Qazi, Dongbing Li, Cedric Briens, Franco Berruti and Mamdouh M. Abou-Zaid

Molecules 2017, 22(3), 372; https://doi.org/10.3390/molecules22030372 - 1 Mar 2017

Cited by 32 | Viewed by 8000

Abstract

A challenge in recent years has been the rational use of forest and agriculture residues for the production of bio-fuel, biochemical, and other bioproducts. In this study, potentially useful compounds from pyrolytic lignins were identified by HPLC-MS/MS and untargeted metabolomics. The metabolites identified [...] Read more.

A challenge in recent years has been the rational use of forest and agriculture residues for the production of bio-fuel, biochemical, and other bioproducts. In this study, potentially useful compounds from pyrolytic lignins were identified by HPLC-MS/MS and untargeted metabolomics. The metabolites identified were 2-(4-allyl-2-methoxyphenoxy)-1-(4-hydroxy-3-methoxyphenyl)-1-propanol, benzyl benzoate, fisetinidol, phenyllactic acid, 2-phenylpropionic acid, 6,3′-dimethoxyflavone, and vanillin. The 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity (DPPH), trolox equivalent antioxidant capacity (TEAC), and total phenolics content (TPC) per gram of pyrolytic lignin ranged from 14 to 503 mg ascorbic acid equivalents, 35 to 277 mg trolox equivalents, and 0.42 to 50 mg gallic acid equivalents, respectively. A very significant correlation was observed between the DPPH and TPC (r = 0.8663, p ≤ 0.0001), TEAC and TPC (r = 0.8044, p ≤ 0.0001), and DPPH and TEAC (r = 0.8851, p ≤ 0.0001). The polyphenolic compounds in the pyrolytic lignins which are responsible for radical scavenging activity and antioxidant properties can be readily profiled with HPLC-MS/MS combined with untargeted metabolomics. The results also suggest that DPPH, TEAC, and TPC assays are suitable methods for the measurement of antioxidant activity in a variety of pyrolytic lignins. These data show that the pyrolytic lignins can be considered as promising sources of natural antioxidants and value-added chemicals. Full article

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17 pages, 3288 KiB

Open AccessArticle

Synthesis, X-ray Single Crystal Structure, Molecular Docking and DFT Computations on N-[(1E)-1-(2H-1,3-Benzodioxol-5-yl)-3-(1H-imidazol-1-yl)propylidene]-hydroxylamine: A New Potential Antifungal Agent Precursor

by Reem I. Al-Wabli, Alwah R. Al-Ghamdi, Hazem A. Ghabbour, Mohamed H. Al-Agamy, James Clemy Monicka, Issac Hubert Joe and Mohamed I. Attia

Molecules 2017, 22(3), 373; https://doi.org/10.3390/molecules22030373 - 28 Feb 2017

Cited by 13 | Viewed by 10686

Abstract

Mycoses are serious health problem, especially in immunocompromised individuals. A new imidazole-bearing compound containing an oxime functionality was synthesized and characterized with different spectroscopic techniques to be used for the preparation of new antifungal agents. The stereochemistry of the oxime double bond was [...] Read more.

Mycoses are serious health problem, especially in immunocompromised individuals. A new imidazole-bearing compound containing an oxime functionality was synthesized and characterized with different spectroscopic techniques to be used for the preparation of new antifungal agents. The stereochemistry of the oxime double bond was unequivocally determined via the single crystal X-ray technique. The title compound 4, C₁₃H₁₃N₃O₃·C₃H₈O, crystallizes in the monoclinic space group P2₁with a = 9.0963(3) Å, b = 14.7244(6) Å, c = 10.7035(4) Å, β = 94.298 (3)°, V = 1429.57(9) Å³, Z = 2. The molecules were packed in the crystal structure by eight intermolecular hydrogen bond interactions. A comprehensive spectral analysis of the title molecule 4 has been performed based on the scaled quantum mechanical (SQM) force field obtained by density-functional theory (DFT) calculations. A molecular docking study illustrated the binding mode of the title compound 4 into its target protein. The preliminary antifungal activity of the title compound 4 was determined using a broth microdilution assay. Full article

(This article belongs to the Section Medicinal Chemistry)

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10 pages, 462 KiB

Open AccessArticle

Influence of Indole-3-Acetic Acid and Gibberellic Acid on Phenylpropanoid Accumulation in Common Buckwheat (Fagopyrum esculentum Moench) Sprouts

by Chang Ha Park, Hyeon Ji Yeo, Yun Ji Park, Abubaker M. A. Morgan, Mariadhas Valan Arasu, Naif Abdullah Al-Dhabi and Sang Un Park

Molecules 2017, 22(3), 374; https://doi.org/10.3390/molecules22030374 - 28 Feb 2017

Cited by 54 | Viewed by 7827

Abstract

We investigated the effects of natural plant hormones, indole-3-acetic (IAA) acid and gibberellic acid (GA), on the growth parameters and production of flavonoids and other phenolic compounds in common buckwheat sprouts. A total of 17 phenolic compounds were identified using liquid chromatography-mass spectrometry [...] Read more.

We investigated the effects of natural plant hormones, indole-3-acetic (IAA) acid and gibberellic acid (GA), on the growth parameters and production of flavonoids and other phenolic compounds in common buckwheat sprouts. A total of 17 phenolic compounds were identified using liquid chromatography-mass spectrometry (LC-MS) analysis. Among these, seven compounds (4-hydroxybenzoic acid, catechin, chlorogenic acid, caffeic acid, epicatechin, rutin, and quercetin) were quantified by high-performance liquid chromatography (HPLC) after treating the common buckwheat sprouts with different concentrations of the hormones IAA and GA. At a concentration of 0.5 mg/L, both IAA and GA exhibited the highest levels of growth parameters (shoot length, root length, and fresh weight). The HPLC analysis showed that the treatment of sprouts with IAA at concentrations ranging from 0.1 to 1.0 mg/L produced higher or comparable levels of the total phenolic compounds than the control sprout and enhanced the production of rutin. Similarly, the supplementation with 0.1 and 0.5 mg/L GA increased the content of rutin in buckwheat sprouts. Our results suggested that the treatment with optimal concentrations of IAA and GA enhanced the growth parameters and accumulation of flavonoids and other phenolic compounds in buckwheat sprouts. Full article

(This article belongs to the Special Issue Green Production of Bioactive Natural Products)

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17 pages, 1707 KiB

Open AccessArticle

A Kinetic Approach in the Evaluation of Radical-Scavenging Efficiency of Sinapic Acid and Its Derivatives

by Neda Nićiforović, Tomaž Polak, Damjan Makuc, Nataša Poklar Ulrih and Helena Abramovič

Molecules 2017, 22(3), 375; https://doi.org/10.3390/molecules22030375 - 28 Feb 2017

Cited by 15 | Viewed by 5928

Abstract

A kinetic approach was used to determine the radical scavenging activities of sinapic acid and its derivatives: sinapine, 4-vinylsyringol, syringic acid, syringaldehyde, and ethyl, propyl and butyl sinapate. The responses were expressed as rates of 2,2-diphenyl-1-picrylhydrazyl radical (DPPH˙) scavenging (R_S), [...] Read more.

A kinetic approach was used to determine the radical scavenging activities of sinapic acid and its derivatives: sinapine, 4-vinylsyringol, syringic acid, syringaldehyde, and ethyl, propyl and butyl sinapate. The responses were expressed as rates of 2,2-diphenyl-1-picrylhydrazyl radical (DPPH˙) scavenging (R_S), superoxide radical (O₂˙⁻) scavenging (R_FF), and β-carotene bleaching in the emulsion system (R_B). For R_S and R_B, the esters of sinapic acid showed the highest responses while, for R_FF, this was seen for syringic acid. The effectiveness of the selected compounds for scavenging these free radicals was also determined at a fixed endpoint. The early response parameters were demonstrated to be good discriminators in assessing differences for antioxidants with comparable fixed endpoint activity. The primary feature that ranks the kinetic data and the endpoint determinations is interpreted in terms of the mechanisms of the reactions involved in each of the assays conducted. Full article

(This article belongs to the Section Molecular Diversity)

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13 pages, 9298 KiB

Open AccessArticle

Prevention of Bacterial Contamination of a Silica Matrix Containing Entrapped β-Galactosidase through the Action of Covalently Bound Lysozymes

by Heng Li, Shuai Li, Pu Tian, Zhuofu Wu and Zhengqiang Li

Molecules 2017, 22(3), 377; https://doi.org/10.3390/molecules22030377 - 28 Feb 2017

Cited by 17 | Viewed by 5613

Abstract

β-galactosidase was successfully encapsulated within an amino-functionalised silica matrix using a “fish-in-net” approach and molecular imprinting technique followed by covalent binding of lysozyme via a glutaraldehyde-based method. Transmission electron microscopy (TEM), X-ray diffraction (XRD), scanning electron microscopy (SEM), and Fourier transform infrared (FTIR) [...] Read more.

β-galactosidase was successfully encapsulated within an amino-functionalised silica matrix using a “fish-in-net” approach and molecular imprinting technique followed by covalent binding of lysozyme via a glutaraldehyde-based method. Transmission electron microscopy (TEM), X-ray diffraction (XRD), scanning electron microscopy (SEM), and Fourier transform infrared (FTIR) spectroscopy were used to characterise the silica matrix hosting the two enzymes. Both encapsulated β-galactosidase and bound lysozyme exhibited high enzymatic activities and outstanding operational stability in model reactions. Moreover, enzyme activities of the co-immobilised enzymes did not obviously change relative to enzymes immobilised separately. In antibacterial tests, bound lysozyme exhibited 95.5% and 89.6% growth inhibition of Staphylococcus aureus ATCC (American type culture collection) 653 and Escherichia coli ATCC 1122, respectively. In milk treated with co-immobilised enzymes, favourable results were obtained regarding reduction of cell viability and high lactose hydrolysis rate. In addition, when both co-immobilised enzymes were employed to treat milk, high operational and storage stabilities were observed. The results demonstrate that the use of co-immobilised enzymes holds promise as an industrial strategy for producing low lactose milk to benefit people with lactose intolerance. Full article

(This article belongs to the Special Issue Enzyme Immobilization 2016)

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15 pages, 1514 KiB

Open AccessCommunication

Excited-State Dynamics of the Thiopurine Prodrug 6-Thioguanine: Can N9-Glycosylation Affect Its Phototoxic Activity?

by Brennan Ashwood, Steffen Jockusch and Carlos E. Crespo-Hernández

Molecules 2017, 22(3), 379; https://doi.org/10.3390/molecules22030379 - 28 Feb 2017

Cited by 48 | Viewed by 7882

Abstract

6-Thioguanine, an immunosuppressant and anticancer prodrug, has been shown to induce DNA damage and cell death following exposure to UVA radiation. Its metabolite, 6-thioguanosine, plays a major role in the prodrug’s overall photoreactivity. However, 6-thioguanine itself has proven to be cytotoxic following UVA [...] Read more.

6-Thioguanine, an immunosuppressant and anticancer prodrug, has been shown to induce DNA damage and cell death following exposure to UVA radiation. Its metabolite, 6-thioguanosine, plays a major role in the prodrug’s overall photoreactivity. However, 6-thioguanine itself has proven to be cytotoxic following UVA irradiation, warranting further investigation into its excited-state dynamics. In this contribution, the excited-state dynamics and photochemical properties of 6-thioguanine are studied in aqueous solution following UVA excitation at 345 nm in order to provide mechanistic insight regarding its photochemical reactivity and to scrutinize whether N9-glycosylation modulates its phototoxicity in solution. The experimental results are complemented with time-dependent density functional calculations that include solvent dielectric effects by means of a reaction-field solvation model. UVA excitation results in the initial population of the S₂(ππ*) state, which is followed by ultrafast internal conversion to the S₁(nπ*) state and then intersystem crossing to the triplet manifold within 560 ± 60 fs. A small fraction (ca. 25%) of the population that reaches the S₁(nπ*) state repopulates the ground state. The T₁(ππ*) state decays to the ground state in 1.4 ± 0.2 μs under N₂-purged conditions, using a 0.2 mM concentration of 6-thioguanine, or it can sensitize singlet oxygen in 0.21 ± 0.02 and 0.23 ± 0.02 yields in air- and O₂-saturated solution, respectively. This demonstrates the efficacy of 6-thioguanine to act as a Type II photosensitizer. N9-glycosylation increases the rate of intersystem crossing from the singlet to triplet manifold, as well as from the T₁(ππ*) state to the ground state, which lead to a ca. 40% decrease in the singlet oxygen yield under air-saturated conditions. Enhanced vibronic coupling between the singlet and triplet manifolds due to a higher density of vibrational states is proposed to be responsible for the observed increase in the rates of intersystem crossing in 6-thioguanine upon N9-glycosylation. Full article

(This article belongs to the Special Issue Experimental and Computational Photochemistry of Bioorganic Molecules)

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18 pages, 2073 KiB

Open AccessArticle

Peripheral and Cerebral Resistance Arteries in the Spontaneously Hypertensive Heart Failure Rat: Effects of Stilbenoid Polyphenols

by Danielle I. Lee, Crystal Acosta, Christopher M. Anderson and Hope D. Anderson

Molecules 2017, 22(3), 380; https://doi.org/10.3390/molecules22030380 - 28 Feb 2017

Cited by 10 | Viewed by 5857

Abstract

Hypertension is associated with aberrant structure and mechanical properties of resistance arteries. We determined the effects of resveratrol, a non-flavonoid polyphenol found in foods such as red grapes, and structurally-similar analogues (pterostilbene and gnetol) on systolic blood pressure (SBP) and resistance arteries from [...] Read more.

Hypertension is associated with aberrant structure and mechanical properties of resistance arteries. We determined the effects of resveratrol, a non-flavonoid polyphenol found in foods such as red grapes, and structurally-similar analogues (pterostilbene and gnetol) on systolic blood pressure (SBP) and resistance arteries from the spontaneously hypertensive heart failure (SHHF) rat. SBP was elevated in 17-week-old SHHF vs. Sprague-Dawley rats (normotensive control; 194 ± 3 vs. 142 ± 6 mmHg, p < 0.01) and was unaffected by resveratrol, pterostilbene, or gnetol (2.5 mg/kg/d). Geometry and mechanical properties of pressurized mesenteric resistance arteries and middle cerebral arteries were calculated from media and lumen dimensions measured at incremental intraluminal pressures. SHHF arteries exhibited remodeling which consisted of augmented media-to-lumen ratios, and this was attenuated by stilbenoid treatment. Compliance was significantly reduced in SHHF middle cerebral arteries but not mesenteric arteries vis-à-vis increased wall component stiffness; stilbenoid treatment failed to normalize compliance and wall component stiffness. Our data suggest that neither AMPK nor ERK mediate stilbenoid effects. In conclusion, we observed arterial bed-specific abnormalities, where mesenteric resistance arteries exhibited remodeling and cerebral arteries exhibited remodeling and stiffening. Resveratrol, pterostilbene, and gnetol exhibited similar abilities to attenuate vascular alterations. Full article

(This article belongs to the Special Issue Polyphenols and Cardiovascular Disease)

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11 pages, 231 KiB

Open AccessArticle

Chemical Composition, Antioxidant, Antimicrobial and Cytotoxic Activities of Essential Oil from Premna microphylla Turczaninow

by Han-Yu Zhang, Yang Gao and Peng-Xiang Lai

Molecules 2017, 22(3), 381; https://doi.org/10.3390/molecules22030381 - 28 Feb 2017

Cited by 49 | Viewed by 7829

Abstract

Premna microphylla Turczaninow, an erect shrub, was widely used in Chinese traditional medicine to treat dysentery, appendicitis, and infections. In this study, the essential oil from P. microphylla Turcz. was obtained by hydrodistillation and analyzed by GC (Gas Chromatography) and GC-MS (Gas Chromatography-Mass [...] Read more.

Premna microphylla Turczaninow, an erect shrub, was widely used in Chinese traditional medicine to treat dysentery, appendicitis, and infections. In this study, the essential oil from P. microphylla Turcz. was obtained by hydrodistillation and analyzed by GC (Gas Chromatography) and GC-MS (Gas Chromatography-Mass Spectrometer). Fifty-six compounds were identified in the oil which comprised about 97.2% of the total composition of the oil. Major components of the oil were blumenol C (49.7%), β-cedrene (6.1%), limonene (3.8%), α-guaiene (3.3%), cryptone (3.1%), and α-cyperone (2.7%). Furthermore, we assessed the in vitro biological activities displayed by the oil obtained from the aerial parts of P. microphylla, namely the antioxidant, antimicrobial, and cytotoxic activities. The antioxidant activity of the essential oil was evaluated by 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity. For this, the IC50 value was estimated to be 0.451 mg/mL. The essential oil of P. microphylla exhibited considerable antibacterial capacity against Escherichia coli with an MIC (Minimum Inhibitory Concentration) value of 0.15 mg/mL, along with noticeable antibacterial ability against Bacillus subtilis and Staphylococcus aureus with an MIC value of 0.27 mg/mL. However, the essential oil did not show significant activity against fungus. The oil was tested for its cytotoxic activity towards HepG2 (liver hepatocellular cells) and MCF-7 Cells (human breast adenocarcinoma cell line) using the MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide) assay, and exerted cytotoxic activity with an IC50 of 0.072 and 0.188 mg/mL for 72 h. In conclusion, the essential oil from P. microphylla is an inexpensive but favorable resource with strong antibacterial capacity as well as cytotoxic activity. Thus, it has the potential for utilization in the cosmetics and pharmaceutical industries. Full article

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

12 pages, 5184 KiB

Open AccessCommunication

In Vitro Selection of DNA Aptamers that Binds Geniposide

by Aozhe Zhang, Dingran Chang, Zijian Zhang, Fan Li, Weihong Li, Xu Wang, Yingfu Li and Qian Hua

Molecules 2017, 22(3), 383; https://doi.org/10.3390/molecules22030383 - 28 Feb 2017

Cited by 12 | Viewed by 6874

Abstract

Geniposide is a key iridoid glycoside from Gardenia jasminoides fructus widely used in traditional Chinese herbal medicine. However, detection of this small molecule represents a significant challenge mostly due to the lack of specific molecular recognition elements. In this study, we have performed [...] Read more.

Geniposide is a key iridoid glycoside from Gardenia jasminoides fructus widely used in traditional Chinese herbal medicine. However, detection of this small molecule represents a significant challenge mostly due to the lack of specific molecular recognition elements. In this study, we have performed in vitro selection experiments to isolate DNA aptamers that can specifically bind geniposide. Using a stringent selection procedure, we have isolated DNA aptamers that can distinguish geniposide from genipin and glucose, two structural analogs of geniposide. Two top aptamers exhibit low micromolar binding affinity towards geniposide, but show significantly reduced affinity to genipin and glucose. These aptamers have the potential to be further developed into analytical tools for the detection of geniposide. Full article

(This article belongs to the Special Issue Nucleic Acid Aptamers)

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14 pages, 3951 KiB

Open AccessArticle

A Novel Polysaccharide Conjugate from Bullacta exarata Induces G1-Phase Arrest and Apoptosis in Human Hepatocellular Carcinoma HepG2 Cells

by Ningbo Liao, Liang Sun, Jiang Chen, Jianjun Zhong, Yanjun Zhang and Ronghua Zhang

Molecules 2017, 22(3), 384; https://doi.org/10.3390/molecules22030384 - 1 Mar 2017

Cited by 14 | Viewed by 5545

Abstract

Bullacta exarata has been consumed in Asia, not only as a part of the normal diet, but also as a traditional Chinese medicine with liver- and kidney-benefitting functions. Several scientific investigations involving extraction of biomolecules from this mollusk and pharmacological studies on their [...] Read more.

Bullacta exarata has been consumed in Asia, not only as a part of the normal diet, but also as a traditional Chinese medicine with liver- and kidney-benefitting functions. Several scientific investigations involving extraction of biomolecules from this mollusk and pharmacological studies on their biological activities have been carried out. However, little is known regarding the antitumor properties of polysaccharides from B. exarata, hence the polysaccharides from B. exarata have been investigated here. One polysaccharide conjugate BEPS-IA was isolated and purified from B. exarata. It mainly consisted of mannose and glucose in a molar ratio of 1:2, with an average molecular weight of 127 kDa. Thirteen general amino acids were identified to be components of the protein-bound polysaccharide. Methylation and NMR studies revealed that BEPS-IA is a heteropolysaccharide consisting of 1,4-linked-α-d-Glc, 1,6-linked-α-d-Man, 1,3,6-linked-α-d-Man, and 1-linked-α-d-Man residue, in a molar ratio of 6:1:1:1. In order to test the antitumor activity of BEPS-IA, we investigated its effect against the growth of human hepatocellular carcinoma cells HepG2 in vitro. The result showed that BEPS-IA dose-dependently exhibited an effective HepG2 cells growth inhibition with an IC₅₀ of 112.4 μg/mL. Flow cytometry analysis showed that BEPS-IA increased the populations of both apoptotic sub-G1 and G1 phase. The result obtained from TUNEL assay corroborated apoptosis which was shown in flow cytometry. Western blot analysis suggested that BEPS-IA induced apoptosis and growth inhibition were associated with up-regulation of p53, p21 and Bax, down-regulation of Bcl-2. These findings suggest that BEPS-IA may serve as a potential novel dietary agent for hepatocellular carcinoma. Full article

(This article belongs to the Special Issue Natural Polysaccharides)

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14 pages, 3520 KiB

Open AccessArticle

Effects and Mechanism of Blue Light on Monascus in Liquid Fermentation

by Xiaowei Zhang, Wenqing Liu, Xiying Chen, Junhui Cai, Changlu Wang and Weiwei He

Molecules 2017, 22(3), 385; https://doi.org/10.3390/molecules22030385 - 1 Mar 2017

Cited by 22 | Viewed by 6087

Abstract

The effect of light on Monascus and the underlying mechanism have received a great deal of interest for the industrial application of Monascus pigments. In this study, we have examined the effects of blue light on the culture morphology, mycelium growth, pigments, and [...] Read more.

The effect of light on Monascus and the underlying mechanism have received a great deal of interest for the industrial application of Monascus pigments. In this study, we have examined the effects of blue light on the culture morphology, mycelium growth, pigments, and citrinin yield of Monascus in liquid-state and oscillation fermentation, and explored the mechanism at a physiological level. It was found that blue light affected the colony morphology, the composition (chitin content), and permeability of the Monascus mycelium cell wall in static liquid culture, which indicates blue light benefits pigments secreting from aerial mycelium to culture medium. In liquid oscillation fermentation, the yields of Monascus pigments in fermentation broth (darkness 1741 U/g, blue light 2206 U/g) and mycelium (darkness 2442 U/g, blue light 1900 U/g) cultured under blue light and darkness are different. The total pigments produced per gram of Monascus mycelium under blue light was also higher (4663 U/g) than that in darkness (4352 U/g). However, the production of citrinin (88 μg/g) under blue light was evidently lower than that in darkness (150 μg/g). According to the degradation of citrinin caused by blue light and hydrogen peroxide, it can be concluded that blue light could degrade citrinin and inhibit the catalase activity of Monascus mycelium, subsequently suppressing the decomposition of hydrogen peroxide, which is the active species that degrades citrinin. Full article

(This article belongs to the Special Issue Nanozymes and Beyond)

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10 pages, 3537 KiB

Open AccessCommunication

Functional Analysis of a Wheat AGPase Plastidial Small Subunit with a Truncated Transit Peptide

by Yang Yang, Tian Gao, Mengjun Xu, Jie Dong, Hanxiao Li, Pengfei Wang, Gezi Li, Tiancai Guo, Guozhang Kang and Yonghua Wang

Molecules 2017, 22(3), 386; https://doi.org/10.3390/molecules22030386 - 1 Mar 2017

Cited by 17 | Viewed by 5597

Abstract

ADP-glucose pyrophosphorylase (AGPase), the key enzyme in starch synthesis, consists of two small subunits and two large subunits with cytosolic and plastidial isoforms. In our previous study, a cDNA sequence encoding the plastidial small subunit (TaAGPS1b) of AGPase in grains of bread wheat [...] Read more.

ADP-glucose pyrophosphorylase (AGPase), the key enzyme in starch synthesis, consists of two small subunits and two large subunits with cytosolic and plastidial isoforms. In our previous study, a cDNA sequence encoding the plastidial small subunit (TaAGPS1b) of AGPase in grains of bread wheat (Triticum aestivum L.) was isolated and the protein subunit encoded by this gene was characterized as a truncated transit peptide (about 50% shorter than those of other plant AGPS1bs). In the present study, TaAGPS1b was fused with green fluorescent protein (GFP) in rice protoplast cells, and confocal fluorescence microscopy observations revealed that like other AGPS1b containing the normal transit peptide, TaAGPS1b-GFP was localized in chloroplasts. TaAGPS1b was further overexpressed in a Chinese bread wheat cultivar, and the transgenic wheat lines exhibited a significant increase in endosperm AGPase activities, starch contents, and grain weights. These suggested that TaAGPS1b subunit was targeted into plastids by its truncated transit peptide and it could play an important role in starch synthesis in bread wheat grains. Full article

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11 pages, 1808 KiB

Open AccessArticle

Lipoic Acid as a Possible Pharmacological Source of Hydrogen Sulfide/Sulfane Sulfur

by Anna Bilska-Wilkosz, Małgorzata Iciek, Danuta Kowalczyk-Pachel, Magdalena Górny, Maria Sokołowska-Jeżewicz and Lidia Włodek

Molecules 2017, 22(3), 388; https://doi.org/10.3390/molecules22030388 - 2 Mar 2017

Cited by 34 | Viewed by 6502

Abstract

The aim of the present study was to verify whether lipoic acid (LA) itself is a source of H₂S and sulfane sulfur. It was investigated in vitro non-enzymatically and enzymatically (in the presence of rat tissue homogenate). The results indicate that [...] Read more.

The aim of the present study was to verify whether lipoic acid (LA) itself is a source of H₂S and sulfane sulfur. It was investigated in vitro non-enzymatically and enzymatically (in the presence of rat tissue homogenate). The results indicate that both H₂S and sulfane sulfur are formed from LA non-enzymatically in the presence of environmental light. These results suggest that H₂S is the first product of non-enzymatic light-dependent decomposition of LA that is, probably, next oxidized to sulfane sulfur-containing compound(s). The study performed in the presence of rat liver and kidney homogenate revealed an increase of H₂S level in samples containing LA and its reduced form dihydrolipoic acid (DHLA). It was accompanied by a decrease in sulfane sulfur level. It seems that, in these conditions, DHLA acts as a reducing agent that releases H₂S from an endogenous pool of sulfane sulfur compounds present in tissues. Simultaneously, it means that exogenous LA cannot be a direct donor of H₂S/sulfane sulfur in animal tissues. The present study is an initial approach to the question whether LA itself is a donor of H₂S/sulfane sulfur. Full article

(This article belongs to the Special Issue Sulfur Atom: Element for Adaptation to an Oxidative Environment 2016)

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11 pages, 762 KiB

Open AccessArticle

New Cytotoxic Seco-Type Triterpene and Labdane-Type Diterpenes from Nuxia oppositifolia

by Shaza M. Al-Massarani, Ali A. El-Gamal, Mohammad K. Parvez, Mohammed S. Al-Dosari, Mansour S. Al-Said, Maged S. Abdel-Kader and Omer A. Basudan

Molecules 2017, 22(3), 389; https://doi.org/10.3390/molecules22030389 - 2 Mar 2017

Cited by 8 | Viewed by 6107

Abstract

Chromatographic purification of the n-hexane and dichloromethane extracts of Nuxia oppositifolia aerial parts, growing in Saudi Arabia, resulted in the isolation and characterization of three new labdane-type diterpene acids, 2β-acetoxy-labda-7-en-15-oic acid (1), 2β-acetoxy-7-oxolabda-8-en-15-oic acid (2), 2β-acetoxy-6-oxolabda-7-en-15-oic acid ( [...] Read more.

Chromatographic purification of the n-hexane and dichloromethane extracts of Nuxia oppositifolia aerial parts, growing in Saudi Arabia, resulted in the isolation and characterization of three new labdane-type diterpene acids, 2β-acetoxy-labda-7-en-15-oic acid (1), 2β-acetoxy-7-oxolabda-8-en-15-oic acid (2), 2β-acetoxy-6-oxolabda-7-en-15-oic acid (3), and one new seco-triterpene, 3,4-seco olean-12-en-3,30 dioic acid (4), together with 10 known lupane, oleanane and ursane-type triterpenes, as well as the common phytosterols, β-sitosterol and stigmasterol (5–16). Their structures have been assigned on the basis of different spectroscopic techniques including 1D and 2D NMR. Moreover, 13 of the isolated compounds were tested on the human cancer cell lines HeLa (cervical), A549 (lung) and MDA (breast), and most of the compounds showed potent cytotoxic activities in vitro. Full article

(This article belongs to the Collection Bioactive Compounds)

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10 pages, 910 KiB

Open AccessArticle

Polysaccharide-Based Edible Coatings Containing Cellulase for Improved Preservation of Meat Quality during Storage

by Anna Zimoch-Korzycka and Andrzej Jarmoluk

Molecules 2017, 22(3), 390; https://doi.org/10.3390/molecules22030390 - 2 Mar 2017

Cited by 21 | Viewed by 5730

Abstract

The objectives of this study were to optimize the composition of edible food coatings and to extend the shelf-life of pork meat. Initially, nine meat samples were coated with solutions containing chitosan and hydroxypropyl methylcellulose at various cellulase concentrations: 0%, 0.05%, and 0.1%, [...] Read more.

The objectives of this study were to optimize the composition of edible food coatings and to extend the shelf-life of pork meat. Initially, nine meat samples were coated with solutions containing chitosan and hydroxypropyl methylcellulose at various cellulase concentrations: 0%, 0.05%, and 0.1%, stored for 0, 7, and 14 days. Uncoated meat served as the controls. The samples were tested for pH, water activity (a_w), total number of microorganisms (TNM), psychrotrophs (P), number of yeast and molds (NYM), colour, and thiobarbituric acid-reactive substances (TBARS). The pH and a_w values varied from 5.42 to 5.54 and 0.919 to 0.926, respectively. The reductions in the TNM, P, and NYM after 14 days of storage were approximately 2.71 log cycles, 1.46 log cycles, and 0.78 log cycles, respectively. The enzyme addition improved the stability of the red colour. Significant reduction in TBARS was noted with the inclusion of cellulase in the coating material. Overall, this study provides a promising alternative method for the preservation of pork meat in industry. Full article

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

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11 pages, 5237 KiB

Open AccessCommunication

Glycerol as Precursor of Organoselanyl and Organotellanyl Alkynes

by Eder J. Lenardão, Elton L. Borges, Guilherme Stach, Liane K. Soares, Diego Alves, Ricardo F. Schumacher, Luana Bagnoli, Francesca Marini and Gelson Perin

Molecules 2017, 22(3), 391; https://doi.org/10.3390/molecules22030391 - 2 Mar 2017

Cited by 7 | Viewed by 5821

Abstract

Herein we describe the synthesis of organoselanyl and organotellanyl alkynes by the addition of lithium alkynylchalcogenolate (Se and Te) to tosyl solketal, easily obtained from glycerol. The alkynylchalcogenolate anions were generated in situ and added to tosyl solketal in short reaction times, furnishing [...] Read more.

Herein we describe the synthesis of organoselanyl and organotellanyl alkynes by the addition of lithium alkynylchalcogenolate (Se and Te) to tosyl solketal, easily obtained from glycerol. The alkynylchalcogenolate anions were generated in situ and added to tosyl solketal in short reaction times, furnishing in all cases the respective products of substitution in good yields. Some of the prepared compounds were deprotected using an acidic resin to afford new water-soluble 3-organotellanylpropane-1,2-diols. The synthetic versatility of the new chalcogenyl alkynes was demonstrated in the iodocyclization of 2,2-dimethyl-1,3-dioxolanylmethyl(2-methoxyphenylethynyl)selane 3f, which afforded 3-iodo-2-(2,2-dimethyl-1,3-dioxolanylmethyl) selenanylbenzo[b]furan in 85% yield, opening a new way to access water-soluble Se-functionalized benzo[b]furanes. 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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9 pages, 2291 KiB

Open AccessArticle

Electrochemical Detecting Lung Cancer-Associated Antigen Based on Graphene-Gold Nanocomposite

by Zheng Wei, Junping Zhang, Aihua Zhang, Yanchun Wang and Xiaoping Cai

Molecules 2017, 22(3), 392; https://doi.org/10.3390/molecules22030392 - 2 Mar 2017

Cited by 34 | Viewed by 5673

Abstract

Using a Au nanoparticle/reduced graphene oxide composite (AuNP-RGO), a signal-enhanced electrochemical immunosensor without label was created to detect neuron-specific enolase (NSE). Furthermore, an environmentally-friendly method was developed to prepare AuNP-RGO by employing chitosan (CS), which served as reducing and stabilizing agent. We showed [...] Read more.

Using a Au nanoparticle/reduced graphene oxide composite (AuNP-RGO), a signal-enhanced electrochemical immunosensor without label was created to detect neuron-specific enolase (NSE). Furthermore, an environmentally-friendly method was developed to prepare AuNP-RGO by employing chitosan (CS), which served as reducing and stabilizing agent. We showed that the sensitivity of the immunosensor designed in this report was remarkably enhanced because of the numerous active sites in the sensor provided by the AuNP-RGO nanostructure. For the quantification of NSE, the immunosensor exhibited a positive linear relationship with the concentration in the range of 0.1 to 2000 ng/mL, where the limit of the detection was 0.05 ng/mL. Full article

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8 pages, 854 KiB

Open AccessArticle

New Marine Sterols from a Gorgonian Pinnigorgia sp.

by Yu-Chia Chang, Tsong-Long Hwang, Chih-Hua Chao and Ping-Jyun Sung

Molecules 2017, 22(3), 393; https://doi.org/10.3390/molecules22030393 - 3 Mar 2017

Cited by 10 | Viewed by 5269

Abstract

Continuous chemical investigation of the gorgonian coral Pinnigorgia sp. resulted in the isolation of two new sterols, 5α,6α-epoxy-(22E,24R)-3β,11-dihydroxy-9,11-secoergosta-7-en-9-one (1) and (22R)-acetoxy-(24ξ)-ergosta-5-en-3β,25-diol (2). The structures of sterols 1 and 2 were elucidated [...] Read more.

Continuous chemical investigation of the gorgonian coral Pinnigorgia sp. resulted in the isolation of two new sterols, 5α,6α-epoxy-(22E,24R)-3β,11-dihydroxy-9,11-secoergosta-7-en-9-one (1) and (22R)-acetoxy-(24ξ)-ergosta-5-en-3β,25-diol (2). The structures of sterols 1 and 2 were elucidated using spectroscopic methods. Sterol 1 displayed inhibitory effects on the generation of superoxide anions and the release of elastase by human neutrophils with IC₅₀ values of 8.65 and 5.86 μM, respectively. The structure of a known metabolite, pubinernoid A (3), is revised as (+)-loliolide (4). Full article

(This article belongs to the Section Natural Products Chemistry)

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11 pages, 1152 KiB

Open AccessArticle

In Vitro Activities of LCB 01-0648, a Novel Oxazolidinone, against Gram-Positive Bacteria

by Sang-Hun Oh, Josep Kim, Sung-Yoon Baek, Sang-Eun Chae, Hee-Soo Park, Young-Lag Cho and Jin-Hwan Kwak

Molecules 2017, 22(3), 394; https://doi.org/10.3390/molecules22030394 - 3 Mar 2017

Cited by 5 | Viewed by 5831

Abstract

Oxazolidinones are a novel class of synthetic antibacterial agents that inhibit bacterial protein synthesis. Here, we synthesized and tested a series of oxazolidinone compounds containing cyclic amidrazone. Among these compounds, we further investigated the antibacterial activities of LCB01-0648 against drug-susceptible or resistant Gram-positive [...] Read more.

Oxazolidinones are a novel class of synthetic antibacterial agents that inhibit bacterial protein synthesis. Here, we synthesized and tested a series of oxazolidinone compounds containing cyclic amidrazone. Among these compounds, we further investigated the antibacterial activities of LCB01-0648 against drug-susceptible or resistant Gram-positive cocci in comparison with those of six reference compounds. LCB01-0648 showed the most potent antimicrobial activities against clinically isolated Gram-positive bacteria. Against the methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant coagulase-negative staphylococci (MRCNS) isolates, LCB01-0648 showed the lowest MIC₉₀s (0.5 mg/L) among the tested compounds. In addition, LCB01-0648 had the lowest minimum inhibitory concentrations (MICs) against the four linezolid-resistant S. aureus (LRSA) strains (range 2–4 mg/L). The results of the time–kill studies demonstrated that LCB01-0648 at a concentration 8× the (MIC) showed bactericidal activity against methicillin-susceptible Staphylococcus aureus MSSA or MRSA, but showed a bacteriostatic effect against LRSA. These results indicate that LCB01-0648 could be a good antibacterial candidate against multidrug-resistant (MDR) Gram-positive cocci. Full article

(This article belongs to the Collection Antibiotics & Superbugs: New Strategies to Combat Antimicrobial Resistance)

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17 pages, 2085 KiB

Open AccessArticle

Optimization of Ultrasonic-Assisted Enzymatic Extraction Conditions for Improving Total Phenolic Content, Antioxidant and Antitumor Activities In Vitro from Trapa quadrispinosa Roxb. Residues

by Feng Li, Yi-Dan Mao, Yi-Fan Wang, Aun Raza, Li-Peng Qiu and Xiu-Quan Xu

Molecules 2017, 22(3), 396; https://doi.org/10.3390/molecules22030396 - 6 Mar 2017

Cited by 50 | Viewed by 7323

Abstract

Stems are the important residues of Trapa quadrispinosa Roxb., which are abundant in phenolic compounds. Ultrasonic-assisted enzymatic extraction (UAEE) is confirmed as a novel extraction technology with main advantages of enhancing extraction yield and physiological activities of the extracts from various plants. In [...] Read more.

Stems are the important residues of Trapa quadrispinosa Roxb., which are abundant in phenolic compounds. Ultrasonic-assisted enzymatic extraction (UAEE) is confirmed as a novel extraction technology with main advantages of enhancing extraction yield and physiological activities of the extracts from various plants. In this study, UAEE was applied to obtain the highest yield of phenolic content, strongest antioxidant, and antitumor activities and to optimize the extraction conditions using response surface methodology (RSM). The extracts from the stems of T. quadrispinosa were characterized by determination of their antioxidant activities through 2,2-azinobis(3-ethylbenzthiazoline)-6-sulfonic acid (ABTS), 1,1-Diphenyl-2-picrylhydrazxyl (DPPH) radical scavenging, total antioxidant capacity (TAC), ferric reducing antioxidant capacity (FRAC) methods and of their antitumor activity by MTT method. The selected key independent variables were cellulase concentration (X₁: 1.5%–2.5%), extraction time (X₂: 20–30 min) and extraction temperature (X₃: 40–60 °C). The optimal extraction conditions for total phenolic content (TPC) value of the extracts were determined as 1.74% cellulase concentration, 25.5 min ultrasonic extraction time and 49.0 °C ultrasonic temperature. Under these conditions, the highest TPC value of 53.6 ± 2.2 mg Gallic acid equivalent (GAE)/g dry weight (DW) was obtained, which agreed well with the predicted value (52.596 mg GAE/g·DW. Furthermore, the extracts obtained from UAEE presented highest antioxidant activities through ABTS, DPPH, TAC and FRAC methods were of 1.54 ± 0.09 mmol Trolox equivalent (TE)/g·DW; 1.45 ± 0.07 mmol·TE/g·DW; 45.2 ± 2.2 mg·GAE/g·DW; 50.4 ± 2.6 μmol FeSO₄ equivalent/g·DW and lowest IC₅₀ values of 160.4 ± 11.6 μg/mL, 126.1 ± 10.8 μg/mL, and 178.3 ± 13.1 μg/mL against Hela, HepG-2 and U251 tumor cells, respectively. The results indicated that the UAEE was an efficient alternative to improve extraction yield and enhance the antioxidant and antitumor activities of the extracts. The phenolic extracts from the stems of T. quadrispinosa had significant antioxidant and antitumor activities, which could be used as a source of potential antioxidant and antitumor agents. Full article

(This article belongs to the Special Issue Green Production of Bioactive Natural Products)

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10 pages, 1877 KiB

Open AccessCommunication

Identifying Natural syNergist from Pongamia pinnata Using High-Speed Counter-Current Chromatography Combined with Isobolographic Analysis

by Hao Yin, Yubai Wei, Rouwen Chen, Si Zhang, Lijuan Long, Hang Yin, Xinpeng Tian and Weihong He

Molecules 2017, 22(3), 397; https://doi.org/10.3390/molecules22030397 - 3 Mar 2017

Viewed by 3963

Abstract

For identifying the synergistic compounds from Pongamia pinnata, an approach based on high-speed counter-current chromatography (HSCCC) combined with isobolographic analysis was designed to detect the synergistic effects in the complex mixture [...] Full article

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14 pages, 2712 KiB

Open AccessArticle

Camellia sinensis L. Extract and Its Potential Beneficial Effects in Antioxidant, Anti-Inflammatory, Anti-Hepatotoxic, and Anti-Tyrosinase Activities

by Surached Thitimuta, Pimolpan Pithayanukul, Saruth Nithitanakool, Rapepol Bavovada, Jiraporn Leanpolchareanchai and Patchreenart Saparpakorn

Molecules 2017, 22(3), 401; https://doi.org/10.3390/molecules22030401 - 4 Mar 2017

Cited by 41 | Viewed by 10314

Abstract

The aims of this study were to investigate the potential benefits of antioxidant, anti-inflammatory, anti-hepatotoxic, and anti-tyrosinase activities of a methanolic extract of fresh tea leaves (FTE) (Camellia sinensis L.). The antioxidant capacity was investigated using three different methods at different temperatures. [...] Read more.

The aims of this study were to investigate the potential benefits of antioxidant, anti-inflammatory, anti-hepatotoxic, and anti-tyrosinase activities of a methanolic extract of fresh tea leaves (FTE) (Camellia sinensis L.). The antioxidant capacity was investigated using three different methods at different temperatures. The anti-inflammatory activity was studied in vitro by the inhibition of 5-lipoxygenase assay. The anti-hepatotoxic effect was investigated in CCl₄-induced liver injury in rats. The anti-tyrosinase activities of the FTE and its principal phenolic compounds were investigated in l-3,4-dihydroxyphenylalanine (l-DOPA) oxidation by a mushroom tyrosinase. A molecular docking study was conducted to determine how the FTE’s principal catechins interact with the tyrosinase. The FTE exhibited the best shelf life at low temperatures and demonstrated concentration-dependent antioxidant, anti-inflammatory, anti-hepatotoxic, and anti-tyrosinase effects compared to positive references. Treatment of rats with the FTE at 2000 mg/kg/day for 28 consecutive days reversed CCl₄-induced oxidative damage in hepatic tissues by lowering the levels of alanine aminotransferase by 69% and malondialdehyde by 90%. Our findings suggest that the FTE has the capacity to scavenge free radicals and can protect against oxidative stress induced by CCl₄ intoxication. The docking results were consistent with our in vitro data, indicating the anti-tyrosinase potency of the principal catechins. Full article

(This article belongs to the Special Issue Polyphenols and Antioxidants–The Chemistry of Tea)

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15 pages, 1393 KiB

Open AccessArticle

Screening of Peruvian Medicinal Plants for Tyrosinase Inhibitory Properties: Identification of Tyrosinase Inhibitors in Hypericum laricifolium Juss

by Yanymee Nimesia Guillen Quispe, Seung Hwan Hwang, Zhiqiang Wang and Soon Sung Lim

Molecules 2017, 22(3), 402; https://doi.org/10.3390/molecules22030402 - 4 Mar 2017

Cited by 41 | Viewed by 9736

Abstract

Tyrosinase inhibitors are of far-ranging importance in cosmetics, medicinal products, and food industries. Peru is a diverse country with a wide variety of plants that may contain excellent anti-tyrosinase inhibitors. In the present study, the tyrosinase inhibitory properties of 50 medicinal plant extracts [...] Read more.

Tyrosinase inhibitors are of far-ranging importance in cosmetics, medicinal products, and food industries. Peru is a diverse country with a wide variety of plants that may contain excellent anti-tyrosinase inhibitors. In the present study, the tyrosinase inhibitory properties of 50 medicinal plant extracts from Peru were investigated using tyrosinase assay. Among plant extracts, those that showed an inhibition rate >50% were Hypericum laricifolium Juss., Taraxacum officinaleF.H.Wigg., and Muehlenbeckia vulcanicaMeisn., with H. laricifolium Juss. showing the greatest anti-tyrosinase activity. Although H. laricifolium Juss. has been widely used as a medicinal plant by Peruvians, little is known regarding its bioactive components and effects on tyrosinase activity. For this reason, we attempted to discover tyrosinase inhibitors in H. laricifolium Juss. for the first time. The bioactive components were separated by Sephadex LH-20 chromatography and eluted with 100% methanol. Eight compounds were discovered and characterized by high-performance liquid chromatography coupled with diode array detection (HPLC-DAD): protocatechuic acid, p-hydroxybenzoic acid, chlorogenic acid, vanilic acid, caffeic acid, kaempferol 3-O-glucuronide, quercetin, and kaempferol. In addition, the concentration of these compounds required for 50% inhibition (IC₅₀) of tyrosinase activity were evaluated. Quercetin exhibited the strongest tyrosinase inhibition (IC₅₀ 14.29 ± 0.3 μM). Therefore, the Peruvian plant H. laricifolium Juss. could be a novel source for anti-tyrosinase activity. Full article

(This article belongs to the Special Issue Natural Product: A Continuing Source of Novel Drug Leads)

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15 pages, 12860 KiB

Open AccessArticle

2D-QSAR and 3D-QSAR/CoMSIA Studies on a Series of (R)-2-((2-(1H-Indol-2-yl)ethyl)amino)-1-Phenylethan-1-ol with Human β₃-Adrenergic Activity

by Gastón Apablaza, Luisa Montoya, Cesar Morales-Verdejo, Marco Mellado, Mauricio Cuellar, Carlos F. Lagos, Jorge Soto-Delgado, Hery Chung, Carlos David Pessoa-Mahana and Jaime Mella

Molecules 2017, 22(3), 404; https://doi.org/10.3390/molecules22030404 - 5 Mar 2017

Cited by 15 | Viewed by 7867

Abstract

The β₃ adrenergic receptor is raising as an important drug target for the treatment of pathologies such as diabetes, obesity, depression, and cardiac diseases among others. Several attempts to obtain selective and high affinity ligands have been made. Currently, Mirabegron is the [...] Read more.

The β₃ adrenergic receptor is raising as an important drug target for the treatment of pathologies such as diabetes, obesity, depression, and cardiac diseases among others. Several attempts to obtain selective and high affinity ligands have been made. Currently, Mirabegron is the only available drug on the market that targets this receptor approved for the treatment of overactive bladder. However, the FDA (Food and Drug Administration) in USA and the MHRA (Medicines and Healthcare products Regulatory Agency) in UK have made reports of potentially life-threatening side effects associated with the administration of Mirabegron, casting doubts on the continuity of this compound. Therefore, it is of utmost importance to gather information for the rational design and synthesis of new β₃ adrenergic ligands. Herein, we present the first combined 2D-QSAR (two-dimensional Quantitative Structure-Activity Relationship) and 3D-QSAR/CoMSIA (three-dimensional Quantitative Structure-Activity Relationship/Comparative Molecular Similarity Index Analysis) study on a series of potent β₃ adrenergic agonists of indole-alkylamine structure. We found a series of changes that can be made in the steric, hydrogen-bond donor and acceptor, lipophilicity and molar refractivity properties of the compounds to generate new promising molecules. Finally, based on our analysis, a summary and a regiospecific description of the requirements for improving β₃ adrenergic activity is given. Full article

(This article belongs to the Section Medicinal Chemistry)

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20 pages, 844 KiB

Open AccessArticle

Iridoids, Phenolic Compounds and Antioxidant Activity of Edible Honeysuckle Berries (Lonicera caerulea var. kamtschatica Sevast.)

by Alicja Z. Kucharska, Anna Sokół-Łętowska, Jan Oszmiański, Narcyz Piórecki and Izabela Fecka

Molecules 2017, 22(3), 405; https://doi.org/10.3390/molecules22030405 - 5 Mar 2017

Cited by 127 | Viewed by 13376

Abstract

Iridoid and polyphenol profiles of 30 different honeysuckle berry cultivars and genotypes were studied. Compounds were identified by ultra-performance liquid chromatography coupled with electrospray ionization mass spectrometry (UPLC-ESI-qTOF-MS/MS) in positive and negative ion modes and quantified by HPLC-PDA. The 50 identified compounds included [...] Read more.

Iridoid and polyphenol profiles of 30 different honeysuckle berry cultivars and genotypes were studied. Compounds were identified by ultra-performance liquid chromatography coupled with electrospray ionization mass spectrometry (UPLC-ESI-qTOF-MS/MS) in positive and negative ion modes and quantified by HPLC-PDA. The 50 identified compounds included 15 iridoids, 6 anthocyanins, 9 flavonols, 2 flavanonols (dihydroflavonols), 5 flavones, 6 flavan-3-ols, and 7 phenolic acids. 8-epi-Loganic acid, pentosyl-loganic acid, taxifolin 7-O-dihexoside, and taxifolin 7-O-hexoside were identified in honeysuckle berries for the first time. Iridoids and anthocyanins were the major groups of bioactive compounds of honeysuckle constituents. The total content of quantified iridoids and anthocyanins was between 128.42 mg/100 g fresh weight (fw) (‘Dlinnoplodnaya’) and 372 mg/100 g fw (‘Kuvshinovidnaya’) and between 150.04 mg/100 g fw (‘Karina’) and 653.95 mg/100 g fw (‘Amur’), respectively. Among iridoids, loganic acid was the dominant compound, and it represented between 22% and 73% of the total amount of quantified iridoids in honeysuckle berry. A very strong correlation was observed between the antioxidant potential and the quantity of anthocyanins. High content of iridoids in honeysuckle berries can complement antioxidant properties of phenolic compounds. Full article

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16 pages, 3843 KiB

Open AccessArticle

Evaluation of Maltose-Based Cationic Liposomes with Different Hydrophobic Tails for Plasmid DNA Delivery

by Bo Li, Liangliang Deng, Meiyan Liu and Youlin Zeng

Molecules 2017, 22(3), 406; https://doi.org/10.3390/molecules22030406 - 12 Mar 2017

Cited by 4 | Viewed by 6290

Abstract

In this paper, three cationic glycolipids with different hydrophobic chains Malt-DiC12MA (IX a), Malt-DiC14MA (IX b) and Malt-DiC16MA (IX c) were constructed by using maltose as starting material via peracetylation, selective 1-O-deacetylation, trichloroacetimidation, glycosylation, azidation, [...] Read more.

In this paper, three cationic glycolipids with different hydrophobic chains Malt-DiC12MA (IX a), Malt-DiC14MA (IX b) and Malt-DiC16MA (IX c) were constructed by using maltose as starting material via peracetylation, selective 1-O-deacetylation, trichloroacetimidation, glycosylation, azidation, deacetylation, Staudinger reaction, tertiary amination and quaternization. Target compounds and some intermediates were characterized by ¹H-NMR, ¹³C-NMR, ¹H-¹H COSY and ¹H-¹³C HSQC. The results of gel electrophoresis assay, atomic force microscopy images (AFM) and dynamic light scattering (DLS) demonstrate that all the liposomes could efficiently bind and compact DNA (N/P ratio less than 2) into nanoparticles with proper size (88 nm–146 nm, PDI < 0.4) and zeta potential (+15 mV–+26 mV). The transfection efficiency and cellular uptake of glycolipids in HEK293 cell were evaluated through the enhanced green fluorescent protein (EGFP) expression and Cy3-labeled pEGFP-C1 (Enhanced Green Fluorescent Protein plasmid) images, respectively. Importantly, it indicated that Malt-DiC14MA exhibited high gene transfer efficiency and better uptake capability at N/P ratios of 8:1. Additionally, the result of cell viability showed glycolipids exhibited low biotoxicity and good biocompatibility by thiazolyl blue tetrazolium bromide (MTT) assay. Full article

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

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11 pages, 1179 KiB

Open AccessArticle

Determination of the Clean Air Delivery Rate (CADR) of Photocatalytic Oxidation (PCO) Purifiers for Indoor Air Pollutants Using a Closed-Loop Reactor. Part I: Theoretical Considerations

by Éric Dumont and Valérie Héquet

Molecules 2017, 22(3), 407; https://doi.org/10.3390/molecules22030407 - 6 Mar 2017

Cited by 18 | Viewed by 6392

Abstract

This study demonstrated that a laboratory-scale recirculation closed-loop reactor can be an efficient technique for the determination of the Clean Air Delivery Rate (CADR) of PhotoCatalytic Oxidation (PCO) air purification devices. The recirculation closed-loop reactor was modeled by associating equations related to two [...] Read more.

This study demonstrated that a laboratory-scale recirculation closed-loop reactor can be an efficient technique for the determination of the Clean Air Delivery Rate (CADR) of PhotoCatalytic Oxidation (PCO) air purification devices. The recirculation closed-loop reactor was modeled by associating equations related to two ideal reactors: one is a perfectly mixed reservoir and the other is a plug flow system corresponding to the PCO device itself. Based on the assumption that the ratio between the residence time in the PCO device and the residence time in the reservoir τ_P/τ_R tends to 0, the model highlights that a lab closed-loop reactor can be a suitable technique for the determination of the efficiency of PCO devices. Moreover, if the single-pass removal efficiency is lower than 5% of the treated flow rate, the decrease in the pollutant concentration over time can be characterized by a first-order decay model in which the time constant is proportional to the CADR. The limits of the model are examined and reported in terms of operating conditions (experiment duration, ratio of residence times, and flow rate ranges). Full article

(This article belongs to the Special Issue Photon-involving Purification of Water and Air)

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14 pages, 3455 KiB

Open AccessArticle

Determination of the Clean Air Delivery Rate (CADR) of Photocatalytic Oxidation (PCO) Purifiers for Indoor Air Pollutants Using a Closed-Loop Reactor. Part II: Experimental Results

by Valérie Héquet, Frédéric Batault, Cécile Raillard, Frédéric Thévenet, Laurence Le Coq and Éric Dumont

Molecules 2017, 22(3), 408; https://doi.org/10.3390/molecules22030408 - 6 Mar 2017

Cited by 9 | Viewed by 5651

Abstract

The performances of a laboratory PhotoCatalytic Oxidation (PCO) device were determined using a recirculation closed-loop pilot reactor. The closed-loop system was modeled by associating equations related to two ideal reactors: a perfectly mixed reservoir with a volume of V_R = 0.42 m [...] Read more.

The performances of a laboratory PhotoCatalytic Oxidation (PCO) device were determined using a recirculation closed-loop pilot reactor. The closed-loop system was modeled by associating equations related to two ideal reactors: a perfectly mixed reservoir with a volume of V_R = 0.42 m³ and a plug flow system corresponding to the PCO device with a volume of V_P = 5.6 × 10⁻³ m³. The PCO device was composed of a pleated photocatalytic filter (1100 cm²) and two 18-W UVA fluorescent tubes. The Clean Air Delivery Rate (CADR) of the apparatus was measured under different operating conditions. The influence of three operating parameters was investigated: (i) light irradiance I from 0.10 to 2.0 mW·cm⁻²; (ii) air velocity v from 0.2 to 1.9 m·s⁻¹; and (iii) initial toluene concentration C₀ (200, 600, 1000 and 4700 ppbv). The results showed that the conditions needed to apply a first-order decay model to the experimental data (described in Part I) were fulfilled. The CADR values, ranging from 0.35 to 3.95 m³·h⁻¹, were mainly dependent on the light irradiance intensity. A square root influence of the light irradiance was observed. Although the CADR of the PCO device inserted in the closed-loop reactor did not theoretically depend on the flow rate (see Part I), the experimental results did not enable the confirmation of this prediction. The initial concentration was also a parameter influencing the CADR, as well as the toluene degradation rate. The maximum degradation rate r_max ranged from 342 to 4894 ppbv/h. Finally, this study evidenced that a recirculation closed-loop pilot could be used to develop a reliable standard test method to assess the effectiveness of PCO devices. Full article

(This article belongs to the Special Issue Photon-involving Purification of Water and Air)

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16 pages, 819 KiB

Open AccessArticle

Synthesis and Biological Activities of Ethyl 2-(2-pyridylacetate) Derivatives Containing Thiourea, 1,2,4-triazole, Thiadiazole and Oxadiazole Moieties

by Daniel Szulczyk, Piotr Tomaszewski, Michał Jóźwiak, Anna E. Kozioł, Tadeusz Lis, David Collu, Filippo Iuliano and Marta Struga

Molecules 2017, 22(3), 409; https://doi.org/10.3390/molecules22030409 - 6 Mar 2017

Cited by 20 | Viewed by 6581

Abstract

Thirty six novel heterocyclic derivatives of ethyl 2-(2-pyridylacetate) were efficiently synthesized. The new compounds involve the linkage of a 2-pyridyl ring with thiosemicarbazide (compounds 1–7), 1,2,4-triazole (compounds 1a–7a), 1,3,4-thiadiazole (compounds 1b–7b), and 1,3,4-oxadiazole (compounds [...] Read more.

Thirty six novel heterocyclic derivatives of ethyl 2-(2-pyridylacetate) were efficiently synthesized. The new compounds involve the linkage of a 2-pyridyl ring with thiosemicarbazide (compounds 1–7), 1,2,4-triazole (compounds 1a–7a), 1,3,4-thiadiazole (compounds 1b–7b), and 1,3,4-oxadiazole (compounds 1f–7f) moieties. The last group of compounds 1e–7e involves the connection of a 2-pyridyl ring with 1,2,4-triazole and thiourea. ¹H-NMR, ¹³C-NMR and MS methods were used to confirm the structures of the obtained derivatives. The molecular structures of 3, 3b, 7a and 7f were further confirmed by X-ray crystallography. All obtained compounds were tested in vitro against a number of microorganisms, including Gram-positive cocci, Gram-negative rods and Candida albicans. In addition, the obtained compounds were tested for cytotoxicity and antiviral activity against HIV-1. Full article

(This article belongs to the Section Medicinal Chemistry)

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14 pages, 3300 KiB

Open AccessArticle

DL0410 Ameliorates Memory and Cognitive Impairments Induced by Scopolamine via Increasing Cholinergic Neurotransmission in Mice

by Wenwen Lian, Jiansong Fang, Lvjie Xu, Wei Zhou, De Kang, Wandi Xiong, Hao Jia, Ai-Lin Liu and Guan-Hua Du

Molecules 2017, 22(3), 410; https://doi.org/10.3390/molecules22030410 - 6 Mar 2017

Cited by 50 | Viewed by 7534

Abstract

Deficiency of the cholinergic system is thought to play a vital role in cognitive impairment of dementia. DL0410 was discovered as a dual inhibitor of acetylcholinesterase (AChE) and butyrylcholinestease (BuChE), with potent efficiency in in-vitro experiments, but its in vivo effect on the [...] Read more.

Deficiency of the cholinergic system is thought to play a vital role in cognitive impairment of dementia. DL0410 was discovered as a dual inhibitor of acetylcholinesterase (AChE) and butyrylcholinestease (BuChE), with potent efficiency in in-vitro experiments, but its in vivo effect on the cholinergic model has not been evaluated, and its action mechanism has also not been illustrated. In the present study, the capability of DL0410 in ameliorating the amnesia induced by scopolamine was investigated, and its effect on the cholinergic system in the hippocampus and its binding mode in the active site of AChE was also explored. Mice were administrated DL0410 (3 mg/kg, 10 mg/kg, and 30 mg/kg), and mice treated with donepezil were used as a positive control. The Morris water maze, escape learning task, and passive avoidance task were used as behavioral tests. The test results indicated that DL0410 could significantly improve the learning and memory impairments induced by scopolamine, with 10 mg/kg performing best. Further, DL0410 inhibited the AChE activity and increased acetylcholine (ACh) levels in a dose-dependent manner, and interacted with the active site of AChE in a similar manner as donepezil. However, no difference in the activity of BuChE was found in this study. All of the evidence indicated that its AChE inhibition is an important mechanism in the anti-amnesia effect. In conclusion, DL0410 could be an effective therapeutic drug for the treatment of dementia, especially Alzheimer’s disease. 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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12 pages, 3163 KiB

Open AccessArticle

Facilitated Visual Interpretation of Scores in Principal Component Analysis by Bioactivity-Labeling of 1H-NMR Spectra—Metabolomics Investigation and Identification of a New α-Glucosidase Inhibitor in Radix Astragali

by Yueqiu Liu, Nils T. Nyberg, Anna K. Jäger and Dan Staerk

Molecules 2017, 22(3), 411; https://doi.org/10.3390/molecules22030411 - 6 Mar 2017

Cited by 14 | Viewed by 5692

Abstract

Radix Astragali is a component of several traditional medicines used for the treatment of type 2 diabetes in China. Radix Astragali is known to contain isoflavones, which inhibit α-glucosidase in the small intestines, and thus lowers the blood glucose levels. In this study, [...] Read more.

Radix Astragali is a component of several traditional medicines used for the treatment of type 2 diabetes in China. Radix Astragali is known to contain isoflavones, which inhibit α-glucosidase in the small intestines, and thus lowers the blood glucose levels. In this study, 21 samples obtained from different regions of China were extracted with ethyl acetate, then the IC50-values were determined, and the crude extracts were analyzed by 1H-NMR spectroscopy. A principal component analysis of the 1H-NMR spectra labeled with their IC50-values, that is, bioactivity-labeled 1H-NMR spectra, showed a clear correlation between spectral profiles and the α-glucosidase inhibitory activity. The loading plot and LC-HRMS/NMR of microfractions indicated that previously unknown long chain ferulates could be partly responsible for the observed antidiabetic activity of Radix Astragali. Subsequent preparative scale isolation revealed a compound not previously reported, linoleyl ferulate (1), showing α-glucosidase inhibitory activity (IC50 0.5 mM) at a level comparable to the previously studied isoflavones. A closely related analogue, hexadecyl ferulate (2), did not show significant inhibitory activity, and the double bonds in the alcohol part of 1 seem to be important structural features for the α-glucosidase inhibitory activity. This proof of concept study demonstrates that bioactivity-labeling of the 1H-NMR spectral data of crude extracts allows global and nonselective identification of individual constituents contributing to the crude extract’s bioactivity. Full article

(This article belongs to the Special Issue Natural Product: A Continuing Source of Novel Drug Leads)

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16 pages, 1209 KiB

Open AccessArticle

Metabolite Profiling of Eastern Teaberry (Gaultheria procumbens L.) Lipophilic Leaf Extracts with Hyaluronidase and Lipoxygenase Inhibitory Activity

by Piotr Michel, Aleksandra Owczarek, Magdalena Matczak, Martyna Kosno, Paweł Szymański, Elżbieta Mikiciuk-Olasik, Anna Kilanowicz, Wiktor Wesołowski and Monika A. Olszewska

Molecules 2017, 22(3), 412; https://doi.org/10.3390/molecules22030412 - 6 Mar 2017

Cited by 32 | Viewed by 8180

Abstract

The phytochemical profile and anti-inflammatory activity of Gaultheria procumbens dry lipophilic leaf extracts were evaluated. Forty compounds were identified by GC-MS, representing 86.36% and 81.97% of the petroleum ether (PE) and chloroform (CHE) extracts, respectively, with ursolic acid (28.82%), oleanolic acid (10.11%), methyl [...] Read more.

The phytochemical profile and anti-inflammatory activity of Gaultheria procumbens dry lipophilic leaf extracts were evaluated. Forty compounds were identified by GC-MS, representing 86.36% and 81.97% of the petroleum ether (PE) and chloroform (CHE) extracts, respectively, with ursolic acid (28.82%), oleanolic acid (10.11%), methyl benzoate (10.03%), and methyl salicylate (6.88%) dominating in CHE, and methyl benzoate (21.59%), docosane (18.86%), and octacosane (11.72%) prevailing in PE. Three components of CHE were fully identified after flash chromatography isolation and spectroscopic studies as (6S,9R)-vomifoliol (4.35%), 8-demethyl-latifolin (1.13%), and 8-demethylsideroxylin (2.25%). Hyaluronidase and lipoxygenase inhibitory activity was tested for CHE (IC50 = 282.15 ± 10.38 μg/mL and 899.97 ± 31.17 μg/mL, respectively), PE (IC50 = 401.82 ± 16.12 μg/mL and 738.49 ± 15.92 μg/mL), and nine of the main constituents versus heparin (IC50 = 366.24 ± 14.72 μg/mL) and indomethacin (IC50 = 92.60 ± 3.71 μg/mL) as positive controls. With the best activity/concentration relationships, ursolic and oleanolic acids were recommended as analytical markers for the extracts and plant material. Seasonal variation of both markers following foliar development was investigated by UHPLC-PDA. The highest levels of ursolic (5.36–5.87 mg/g DW of the leaves) and oleanolic (1.14–1.26 mg/g DW) acids were observed between August and October, indicating the optimal season for harvesting. Full article

(This article belongs to the Section Natural Products Chemistry)

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10 pages, 4463 KiB

Open AccessArticle

Cathodic Aromatic C,C Cross-Coupling Reaction via Single Electron Transfer Pathway

by Yang Qu, Hiroyuki Tateno, Yoshimasa Matsumura, Tsuneo Kashiwagi and Mahito Atobe

Molecules 2017, 22(3), 413; https://doi.org/10.3390/molecules22030413 - 7 Mar 2017

Cited by 8 | Viewed by 7067

Abstract

We have successfully developed a novel cathodic cross-coupling reaction of aryl halides with arenes. Utilization of the cathodic single electron transfer (SET) mechanism for activation of aryl halides enables the cross-coupling reaction to proceed without the need for any transition metal catalysts or [...] Read more.

We have successfully developed a novel cathodic cross-coupling reaction of aryl halides with arenes. Utilization of the cathodic single electron transfer (SET) mechanism for activation of aryl halides enables the cross-coupling reaction to proceed without the need for any transition metal catalysts or single electron donors in a mild condition. The SET from a cathode to an aryl halide initiates a radical chain by giving an anion radical of the aryl halide. The following propagation cycle also consists entirely of anion radical intermediates. Full article

(This article belongs to the Special Issue Organic Electrochemistry)

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17 pages, 3066 KiB

Open AccessArticle

Influence of Se/N Codoping on the Structural, Optical, Electronic and Photocatalytic Properties of TiO₂

by Yelda Y. Gurkan, Esra Kasapbasi, Nazli Turkten and Zekiye Cinar

Molecules 2017, 22(3), 414; https://doi.org/10.3390/molecules22030414 - 7 Mar 2017

Cited by 19 | Viewed by 6059

Abstract

Se⁴⁺ and N³⁻ ions were used as codopants to enhance the photocatalytic activity of TiO₂ under sunlight irradiation. The Se/N codoped photocatalysts were prepared through a simple wet-impregnation method followed by heat treatment using SeCl₄ and urea as the [...] Read more.

Se⁴⁺ and N³⁻ ions were used as codopants to enhance the photocatalytic activity of TiO₂ under sunlight irradiation. The Se/N codoped photocatalysts were prepared through a simple wet-impregnation method followed by heat treatment using SeCl₄ and urea as the dopant sources. The prepared photocatalysts were well characterized by X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), UV-diffuse reflectance spectroscopy (UV-DRS), scanning electron microscopy (SEM) and Raman spectroscopy. The codoped samples showed photoabsorption in the visible light range from 430 nm extending up to 580 nm. The photocatalytic activity of the Se/N codoped photocatalysts was evaluated by degradation of 4-nitrophenol (4-NP). The degradation of 4-NP was highly increased for the Se/N codoped samples compared to the undoped and single doped samples under both UV-A and sunlight irradiation. Aiming to determine the electronic structure and dopant locations, quantum chemical modeling of the undoped and Se/N codoped anatase clusters was performed using Density Functional Theory (DFT) calculations with the hybrid functional (B3LYP) and double-zeta (LanL2DZ) basis set. The results revealed that Se/N codoping of TiO₂ reduces the band gap due to mixing of N2p with O2p orbitals in the valence band and also introduces additional electronic states originating from Se3p orbitals in the band gap. Full article

(This article belongs to the Special Issue Photon-involving Purification of Water and Air)

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12 pages, 1905 KiB

Open AccessArticle

Simultaneous Determination of Three Furanocoumarins by UPLC/MS/MS: Application to Pharmacokinetic Study of Angelica dahurica Radix after Oral Administration to Normal and Experimental Colitis-Induced Rats

by Youn-Hwan Hwang, Hye Jin Yang and Jin Yeul Ma

Molecules 2017, 22(3), 416; https://doi.org/10.3390/molecules22030416 - 7 Mar 2017

Cited by 23 | Viewed by 5515

Abstract

In traditional oriental medicine, Angelica dahurica Radix (ADR) is used in the treatment of gastrointestinal, respiratory, neuromuscular, and dermal disorders. We evaluated the pharmacokinetic profiles of oxypeucedanin, imperatorin, and isoimperatorin, major active ingredients of ADR, in normal and 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis [...] Read more.

In traditional oriental medicine, Angelica dahurica Radix (ADR) is used in the treatment of gastrointestinal, respiratory, neuromuscular, and dermal disorders. We evaluated the pharmacokinetic profiles of oxypeucedanin, imperatorin, and isoimperatorin, major active ingredients of ADR, in normal and 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis rats. A rapid, sensitive, and validated UPLC/MS/MS method was established for evaluating the pharmacokinetics of three furanocoumarins. After oral administration of ADR (0.5 and 1.0 g/kg), blood samples were collected periodically from the tail vein. In colitis rats, the time to reach the peak concentration (T_max) of imperatorin and isoimperatorin was significantly delayed (p < 0.05). Lower peak plasma concentrations (C_max) and longer mean residence times for all furanocoumarins were also observed (p < 0.05) compared with normal rats. There was no significant difference in the area under the plasma concentration–time curve or elimination half-lives. Thus, the delayed T_max and decreased C_max, with no influence on the elimination half-life, could be colitis-related changes in the drug-absorption phase. Therefore, the prescription and use of ADR in colitis patients should receive more attention. Full article

(This article belongs to the Section Natural Products Chemistry)

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15 pages, 3908 KiB

Open AccessArticle

A Focused Multiple Reaction Monitoring (MRM) Quantitative Method for Bioactive Grapevine Stilbenes by Ultra-High-Performance Liquid Chromatography Coupled to Triple-Quadrupole Mass Spectrometry (UHPLC-QqQ)

by Elías Hurtado-Gaitán, Susana Sellés-Marchart, Ascensión Martínez-Márquez, Antonio Samper-Herrero and Roque Bru-Martínez

Molecules 2017, 22(3), 418; https://doi.org/10.3390/molecules22030418 - 7 Mar 2017

Cited by 20 | Viewed by 9466

Abstract

Grapevine stilbenes are a family of polyphenols which derive from trans-resveratrol having antifungal and antimicrobial properties, thus being considered as phytoalexins. In addition to their diverse bioactive properties in animal models, they highlight a strong potential in human health maintenance and promotion. [...] Read more.

Grapevine stilbenes are a family of polyphenols which derive from trans-resveratrol having antifungal and antimicrobial properties, thus being considered as phytoalexins. In addition to their diverse bioactive properties in animal models, they highlight a strong potential in human health maintenance and promotion. Due to this relevance, highly-specific qualitative and quantitative methods of analysis are necessary to accurately analyze stilbenes in different matrices derived from grapevine. Here, we developed a rapid, sensitive, and specific analysis method using ultra-high-performance liquid chromatography coupled to triple-quadrupole mass spectrometry (UHPLC-QqQ) in MRM mode to detect and quantify five grapevine stilbenes, trans-resveratrol, trans-piceid, trans-piceatannol, trans-pterostilbene, and trans-ε-viniferin, whose interest in relation to human health is continuously growing. The method was optimized to minimize in-source fragmentation of piceid and to avoid co-elution of cis-piceid and trans-resveratrol, as both are detected with resveratrol transitions. The applicability of the developed method of stilbene analysis was tested successfully in different complex matrices including cellular extracts of Vitis vinifera cell cultures, reaction media of biotransformation assays, and red wine. 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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17 pages, 4150 KiB

Open AccessArticle

A Palladium Catalyst System for the Efficient Cross-Coupling Reaction of Aryl Bromides and Chlorides with Phenylboronic Acid: Synthesis and Biological Activity Evaluation

by Boubakri Lamia, Ahlem Chakchouk-Mtibaa, Bilel Hallouma, Lamjed Mansour, Lotfi Mellouli, Ismail Özdemir, Sedat Yaşar and Naceur Hamdi

Molecules 2017, 22(3), 420; https://doi.org/10.3390/molecules22030420 - 7 Mar 2017

Cited by 10 | Viewed by 6137

Abstract

New benzimidazolium salts 1a–c and their palladium bis-N-heterocyclic carbene complexes 2a–c and palladium PEPPSI-type complexes 3a–c were designed, synthesized and structurally characterized by NMR (1H and 13C), IR, DART-TOF mass spectrometry and elemental analysis. Then these complexes 2–3 were employed in the Suzuki-Miyaura [...] Read more.

New benzimidazolium salts 1a–c and their palladium bis-N-heterocyclic carbene complexes 2a–c and palladium PEPPSI-type complexes 3a–c were designed, synthesized and structurally characterized by NMR (1H and 13C), IR, DART-TOF mass spectrometry and elemental analysis. Then these complexes 2–3 were employed in the Suzuki-Miyaura cross-coupling reaction of substituted arenes with phenylboronic acid under mild conditions in toluene and DMF/H2O (1/1) to afford functionalized biaryl derivatives in good to excellent yields. The antibacterial activity of palladium bis-N-heterocyclic carbene complexes 2a–c and palladium PEPPSI-type complexes 3a–c was measured by disc diffusion method against Gram positive and Gram negative bacteria. Compounds 2a, 2c and 3a–c exhibited potential antibacterial activity against four bacterial species among the five used indicator cells. The product 2b inhibits the growth of the all five tested microorganisms. Moreover, the antioxidant activity determination of these complexes 2–3, using 2.2-diphenyl-1-picrylhydrazyl (DPPH) as a reagent, showed that compounds 2a–c and 3b possess DPPH antiradical activity. The higher antioxidant activity was obtained from the product 2b which has radical scavenging activity comparable to that of the two used positive controls (gallic acid “GA“ and tutylatedhydroxytoluene “BHT“). Investigation of the anti-acetylcholinesterase activity of the studied complexes showed that compounds 2b, 3a, and 3b exhibited moderate activity at 100 μg/mL and product 2b is the most active. Full article

(This article belongs to the Section Organometallic Chemistry)

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15 pages, 882 KiB

Open AccessArticle

Comparison of the Sulfonamide Inhibition Profiles of the β- and γ-Carbonic Anhydrases from the Pathogenic Bacterium Burkholderia pseudomallei

by Daniela Vullo, Sonia Del Prete, Pietro Di Fonzo, Vincenzo Carginale, W. Alexander Donald, Claudiu T. Supuran and Clemente Capasso

Molecules 2017, 22(3), 421; https://doi.org/10.3390/molecules22030421 - 7 Mar 2017

Cited by 35 | Viewed by 5744

Abstract

We have cloned, purified, and characterized a β-carbonic anhydrase (CA, EC 4.2.1.1), BpsCAβ, from the pathogenic bacterium Burkholderia pseudomallei, responsible for the tropical disease melioidosis. The enzyme showed high catalytic activity for the physiologic CO₂ hydration reaction to bicarbonate and protons, [...] Read more.

We have cloned, purified, and characterized a β-carbonic anhydrase (CA, EC 4.2.1.1), BpsCAβ, from the pathogenic bacterium Burkholderia pseudomallei, responsible for the tropical disease melioidosis. The enzyme showed high catalytic activity for the physiologic CO₂ hydration reaction to bicarbonate and protons, with the following kinetic parameters: k_cat of 1.6 × 10⁵ s⁻¹ and k_cat/K_M of 3.4 × 10⁷ M⁻¹ s⁻¹. An inhibition study with a panel of 38 sulfonamides and one sulfamate—including 15 compounds that are used clinically—revealed an interesting structure–activity relationship for the interaction of this enzyme with these inhibitors. Many simple sulfonamides and clinically used agents such as topiramate, sulpiride, celecoxib, valdecoxib, and sulthiame were ineffective BpsCAβ inhibitors (K_I > 50 µM). Other drugs, such as ethoxzolamide, dorzolamide, brinzolamide, zonisamide, indisulam, and hydrochlorothiazide were moderately potent micromolar inhibitors. The best inhibition was observed with benzene-1,3-disulfonamides—benzolamide and its analogs acetazolamide and methazolamide—which showed K_I in the range of 185–745 nM. The inhibition profile of BpsCAβ is very different from that of the γ-class enzyme from the same pathogen, BpsCAγ. Thus, identifying compounds that would effectively interact with both enzymes is relatively challenging. However, benzolamide was one of the best inhibitors of both of these CAs with K_I of 653 and 185 nM, respectively, making it an interesting lead compound for the design of more effective agents, which may be useful tools for understanding the pathogenicity of this bacterium. Full article

(This article belongs to the Special Issue Sulfonamides)

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16 pages, 2549 KiB

Open AccessArticle

Which Specialized Metabolites Does the Native Subantarctic Gastropod Notodiscus hookeri Extract from the Consumption of the Lichens Usnea taylorii and Pseudocyphellaria crocata?

by Alice Gadea, Pierre Le Pogam, Grichka Biver, Joël Boustie, Anne-Cécile Le Lamer, Françoise Le Dévéhat and Maryvonne Charrier

Molecules 2017, 22(3), 425; https://doi.org/10.3390/molecules22030425 - 8 Mar 2017

Cited by 8 | Viewed by 6431

Abstract

Notodiscus hookeri is the only representative of terrestrial gastropods on Possession Island and exclusively feeds on lichens. The known toxicity of various lichen metabolites to plant-eating invertebrates led us to propose that N. hookeri evolved means to protect itself from their adverse effects. [...] Read more.

Notodiscus hookeri is the only representative of terrestrial gastropods on Possession Island and exclusively feeds on lichens. The known toxicity of various lichen metabolites to plant-eating invertebrates led us to propose that N. hookeri evolved means to protect itself from their adverse effects. To validate this assumption, the current study focused on the consumption of two lichen species: Usnea taylorii and Pseudocyphellaria crocata. A controlled feeding experiment was designed to understand how the snail copes with the unpalatable and/or toxic compounds produced by these lichen species. The occurrence of two snail ecophenotypes, represented by a mineral shell and an organic shell, led to address the question of a metabolic response specific to the phenotype. Snails were fed for two months with one of these lichens and the chemical profiles of biological samples of N. hookeri (i.e., crop, digestive gland, intestine, and feces) were established by HPLC-DAD-MS and compared to that of the lichens. N. hookeri appears as a generalist lichen feeder able to consume toxic metabolite-containing lichens, independently of the ecophenotype. The digestive gland did not sequester lichen metabolites. The snail metabolism might be based on four non-exclusive processes according to the concerned metabolites (avoidance, passive transport, hydrolysis, and excretion). Full article

(This article belongs to the Special Issue Lichens: Chemistry, Ecological and Biological Activities)

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16 pages, 2968 KiB

Open AccessArticle

Chroman-4-One Derivatives Targeting Pteridine Reductase 1 and Showing Anti-Parasitic Activity

by Flavio Di Pisa, Giacomo Landi, Lucia Dello Iacono, Cecilia Pozzi, Chiara Borsari, Stefania Ferrari, Matteo Santucci, Nuno Santarem, Anabela Cordeiro-da-Silva, Carolina B. Moraes, Laura M. Alcantara, Vanessa Fontana, Lucio H. Freitas-Junior, Sheraz Gul, Maria Kuzikov, Birte Behrens, Ina Pöhner, Rebecca C. Wade, Maria Paola Costi and Stefano Mangani

Molecules 2017, 22(3), 426; https://doi.org/10.3390/molecules22030426 - 8 Mar 2017

Cited by 49 | Viewed by 11286

Abstract

Flavonoids have previously been identified as antiparasitic agents and pteridine reductase 1 (PTR1) inhibitors. Herein, we focus our attention on the chroman-4-one scaffold. Three chroman-4-one analogues (1–3) of previously published chromen-4-one derivatives were synthesized and biologically evaluated against parasitic [...] Read more.

Flavonoids have previously been identified as antiparasitic agents and pteridine reductase 1 (PTR1) inhibitors. Herein, we focus our attention on the chroman-4-one scaffold. Three chroman-4-one analogues (1–3) of previously published chromen-4-one derivatives were synthesized and biologically evaluated against parasitic enzymes (Trypanosoma brucei PTR1–TbPTR1 and Leishmania major–LmPTR1) and parasites (Trypanosoma brucei and Leishmania infantum). A crystal structure of TbPTR1 in complex with compound 1 and the first crystal structures of LmPTR1-flavanone complexes (compounds 1 and 3) were solved. The inhibitory activity of the chroman-4-one and chromen-4-one derivatives was explained by comparison of observed and predicted binding modes of the compounds. Compound 1 showed activity both against the targeted enzymes and the parasites with a selectivity index greater than 7 and a low toxicity. Our results provide a basis for further scaffold optimization and structure-based drug design aimed at the identification of potent anti-trypanosomatidic compounds targeting multiple PTR1 variants. Full article

(This article belongs to the Special Issue COST CM1307: Targeted Chemotherapy towards Diseases Caused by Endoparasites—Proceedings in Medicinal and Natural Product Chemistry)

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16 pages, 3211 KiB

Open AccessArticle

Theoretical Reactivity Study of Indol-4-Ones and Their Correlation with Antifungal Activity

by María De los Ángeles Zermeño-Macías, Marco Martín González-Chávez, Francisco Méndez, Rodolfo González-Chávez and Arlette Richaud

Molecules 2017, 22(3), 427; https://doi.org/10.3390/molecules22030427 - 8 Mar 2017

Cited by 16 | Viewed by 5070

Abstract

Chemical reactivity descriptors of indol-4-ones obtained via density functional theory (DFT) and hard–soft acid–base (HSAB) principle were calculated to prove their contribution in antifungal activity [...] Full article

(This article belongs to the Special Issue Density Functional Theory and Reactivity Indices: Applications in Organic Chemical Reactivity)

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16 pages, 2951 KiB

Open AccessArticle

New Insights in Thrombin Inhibition Structure–Activity Relationships by Characterization of Octadecasaccharides from Low Molecular Weight Heparin

by Pierre A. J. Mourier, Olivier Y. Guichard, Fréderic Herman, Philippe Sizun and Christian Viskov

Molecules 2017, 22(3), 428; https://doi.org/10.3390/molecules22030428 - 8 Mar 2017

Cited by 7 | Viewed by 6159

Abstract

Low Molecular Weight Heparins (LMWH) are complex anticoagulant drugs that mainly inhibit the blood coagulation cascade through indirect interaction with antithrombin. While inhibition of the factor Xa is well described, little is known about the polysaccharide structure inhibiting thrombin. In fact, a minimal [...] Read more.

Low Molecular Weight Heparins (LMWH) are complex anticoagulant drugs that mainly inhibit the blood coagulation cascade through indirect interaction with antithrombin. While inhibition of the factor Xa is well described, little is known about the polysaccharide structure inhibiting thrombin. In fact, a minimal chain length of 18 saccharides units, including an antithrombin (AT) binding pentasaccharide, is mandatory to form the active ternary complex for LMWH obtained by alkaline β-elimination (e.g., enoxaparin). However, the relationship between structure of octadecasaccharides and their thrombin inhibition has not been yet assessed on natural compounds due to technical hurdles to isolate sufficiently pure material. We report the preparation of five octadecasaccharides by using orthogonal separation methods including size exclusion, AT affinity, ion pairing and strong anion exchange chromatography. Each of these octadecasaccharides possesses two AT binding pentasaccharide sequences located at various positions. After structural elucidation using enzymatic sequencing and NMR, in vitro aFXa and aFIIa were determined. The biological activities reveal the critical role of each pentasaccharide sequence position within the octadecasaccharides and structural requirements to inhibit thrombin. Significant differences in potency, such as the twenty-fold magnitude difference observed between two regioisomers, further highlights the importance of depolymerisation process conditions on LMWH biological activity. 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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9 pages, 1174 KiB

Open AccessCommunication

A Direct Method for β-Selective Glycosylation with an N-Acetylglucosamine Donor Armed by a 4-O-TBDMS Protecting Group

by Hidenori Tanaka, Yu Hamaya and Hiyoshizo Kotsuki

Molecules 2017, 22(3), 429; https://doi.org/10.3390/molecules22030429 - 8 Mar 2017

Cited by 4 | Viewed by 5991

Abstract

A new direct method for β-selective glycosylation with an N-acetylglucosamine (GlcNAc) donor was developed. This substrate, which can be readily prepared from commercially available GlcNAc in two steps, contains a 4-O-tert-butyldimethylsilyl (TBDMS) protecting group as a key component. [...] Read more.

A new direct method for β-selective glycosylation with an N-acetylglucosamine (GlcNAc) donor was developed. This substrate, which can be readily prepared from commercially available GlcNAc in two steps, contains a 4-O-tert-butyldimethylsilyl (TBDMS) protecting group as a key component. We found that this functionality could have a favorable effect on the reactivity of the GlcNAc donor. Glycosylation with the armed donor using primary alcohols in the presence of a catalytic amount of trimethylsilyl trifluoromethanesulfonate (TMSOTf) in 1,2-dichloroethane smoothly gave the desired coupling products in good yields with complete β-selectivity, while sterically hindered acceptors were less efficient. Full article

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

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13 pages, 1366 KiB

Open AccessArticle

The Emission of the Floral Scent of Four Osmanthus fragrans Cultivars in Response to Different Temperatures

by Jianxin Fu, Dan Hou, Chao Zhang, Zhiyi Bao, Hongbo Zhao and Shaoqing Hu

Molecules 2017, 22(3), 430; https://doi.org/10.3390/molecules22030430 - 8 Mar 2017

Cited by 43 | Viewed by 7738

Abstract

Floral scent is an important part of volatile organic compounds (VOCs) emitted from plants, and is influenced by many environmental and endogenous factors. To investigate the influence of temperature on the emission of the floral scent of Osmanthus fragrans, the number of [...] Read more.

Floral scent is an important part of volatile organic compounds (VOCs) emitted from plants, and is influenced by many environmental and endogenous factors. To investigate the influence of temperature on the emission of the floral scent of Osmanthus fragrans, the number of chemical compounds and their relative release amounts from four cultivars of O. fragrans under different temperature treatments, were identified using the solid-phase microextraction (SPME) technique and gas chromatography-mass spectrometry (GC-MS) in this study. Results revealed that the numbers and release amounts of floral scent components were significantly influenced by different temperatures, and depend on different cultivars and different types of compounds. Overall, most cultivars had the largest number of chemical compounds in 19 °C and the numbers of chemical compounds decreased with the increase or decrease in the temperature. Alcohols and ketones were the two main kinds of compounds responding to temperature change. The response of a specific chemical compound to temperature change was different in four cultivars. Generally, linalool, α-ionone, β-ionone, and γ-decalactone accounted for the highest proportion in the nine main compounds, and changes of these four chemical compounds to different temperatures had obvious contributions to the floral scent of O. fragrans. The results obtained provide evidence that temperatures can greatly influence the emission of floral scent. Full article

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

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16 pages, 4866 KiB

Open AccessArticle

Anti-Influenza Virus (H5N1) Activity Screening on the Phloroglucinols from Rhizomes of Dryopteris crassirhizoma

by Juan Wang, Yan-Tao Yan, Shen-Zhen Fu, Bing Peng, Lin-Lin Bao, Yan-Ling Zhang, Jing-Hong Hu, Zu-Ping Zeng, Dong-Hao Geng and Zeng-Ping Gao

Molecules 2017, 22(3), 431; https://doi.org/10.3390/molecules22030431 - 8 Mar 2017

Cited by 34 | Viewed by 6411

Abstract

For screening the active phloroglucinols on influenza virus (H5N1) from Dryopteris crassirhizoma NaKai, a database was established including twenty-three phloroglucinols that had been isolated from Dryopteris crassirhizoma. Their inhibitory effect on the neuraminidase (NA) of influenza virus H5N1 was screened by molecular [...] Read more.

For screening the active phloroglucinols on influenza virus (H5N1) from Dryopteris crassirhizoma NaKai, a database was established including twenty-three phloroglucinols that had been isolated from Dryopteris crassirhizoma. Their inhibitory effect on the neuraminidase (NA) of influenza virus H5N1 was screened by molecular docking. As a result, three candidates were selected. The rhizomes of D. crassirhizoma were subjected to isolation and purification processes to obtain the inhibitor candidates. Thirteen phloroglucinols were obtained, including three selected candidates and two new phloroglucinols. The five phloroglucinols were investigated for their inhibitory activity on NA in vitro. The results showed that dryocrassin ABBA and filixic acid ABA exhibited inhibitory effects on NA with IC₅₀ as 18.59 ± 4.53 and 29.57 ± 2.48 μM, respectively, and the other three phloroglucinols showed moderate inhibitory activity. Moreover, the anti-influenza virus (H5N1) activity and cytotoxicity of dryocrassin ABBA and filixic acid ABA were tested on Madin-Darby canine kidney (MDCK) cells with the cell counting kit-8 (CCK8) method. The results confirmed that dryocrassin ABBA exhibited an inhibitory activity with low cytotoxicity (TC₅₀ > 400 μM) against influenza virus (H5N1) which will have to be investigated in further detail. In conclusion, phloroglucinols from D. crassirhizoma were shown to have anti-influenza virus activity, and especially dryocrassin ABBA, one of the phloroglucinols, may have the potential to control influenza virus (H5N1) infection. Full article

(This article belongs to the Section Natural Products Chemistry)

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13 pages, 12366 KiB

Open AccessArticle

The Novel Property of Heptapeptide of Microcin C7 in Affecting the Cell Growth of Escherichia coli

by Rensen Ran, Huan Zeng, Dong Zhao, Ruiyuan Liu and Xia Xu

Molecules 2017, 22(3), 432; https://doi.org/10.3390/molecules22030432 - 8 Mar 2017

Cited by 13 | Viewed by 5881

Abstract

Microcin C7 (McC), widely distributed in enterobacteria, is a promising antibiotic against antibiotic resistance [...] Full article

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

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12 pages, 1765 KiB

Open AccessArticle

Low-Dose Endotoxin Induces Late Preconditioning, Increases Peroxynitrite Formation, and Activates STAT3 in the Rat Heart

by Márton Pipicz, Gabriella F. Kocsis, László Sárváry-Arantes, Péter Bencsik, Zoltán V. Varga, Péter Ferdinandy and Tamás Csont

Molecules 2017, 22(3), 433; https://doi.org/10.3390/molecules22030433 - 8 Mar 2017

Cited by 11 | Viewed by 6204

Abstract

Administration of low-dose endotoxin (lipopolysaccharide, LPS) 24 h before a lethal ischemia induces pharmacological late preconditioning. The exact mechanism of this phenomenon is not clear. Here we aimed to investigate whether low-dose LPS exerts late effects on peroxynitrite formation and activation of Akt, [...] Read more.

Administration of low-dose endotoxin (lipopolysaccharide, LPS) 24 h before a lethal ischemia induces pharmacological late preconditioning. The exact mechanism of this phenomenon is not clear. Here we aimed to investigate whether low-dose LPS exerts late effects on peroxynitrite formation and activation of Akt, Erk, and STAT3 in the heart. Male Wistar rats were injected with LPS (S. typhimurium; 0.5 mg/kg i.p.) or saline. Twenty-four hours later, hearts were isolated, perfused for 10 min, and then used for biochemical analyses. LPS pretreatment enhanced cardiac formation of the peroxynitrite marker 3-nitrotyrosine. LPS pretreatment also increased cardiac levels of the peroxynitrite precursor nitric oxide (NO) and superoxide. The activities of Ca2+-independent NO synthase and xanthine oxidoreductase increased in LPS-pretreated hearts. LPS pretreatment resulted in significantly enhanced phosphorylation of STAT3 and non-significantly increased phosphorylation of Akt without affecting the activation of Erk. In separate experiments, isolated working hearts were subjected to 30 min global ischemia and 20 min reperfusion. LPS pretreatment significantly improved ischemia-reperfusion-induced deterioration of cardiac function. We conclude that LPS pretreatment enhances cardiac peroxynitrite formation and activates STAT3 24 h later, which may contribute to LPS-induced late preconditioning. Full article

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

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14 pages, 3859 KiB

Open AccessArticle

The Influence of pH on the Scleroglucan and Scleroglucan/Borax Systems

by Claudia Mazzuca, Gianfranco Bocchinfuso, Antonio Palleschi, Paolo Conflitti, Mario Grassi, Chiara Di Meo, Franco Alhaique and Tommasina Coviello

Molecules 2017, 22(3), 435; https://doi.org/10.3390/molecules22030435 - 9 Mar 2017

Cited by 12 | Viewed by 5492

Abstract

The effects that an increase of environmental pH has on the triple helix of scleroglucan (Sclg) and on the Sclg/borax hydrogel are reported. Rheological experiments show that the hydrogel is less sensitive to pH increase than Sclg alone, while at pH = 14 [...] Read more.

The effects that an increase of environmental pH has on the triple helix of scleroglucan (Sclg) and on the Sclg/borax hydrogel are reported. Rheological experiments show that the hydrogel is less sensitive to pH increase than Sclg alone, while at pH = 14 a dramatic viscosity decrease takes place for both systems. This effect is evidenced also by the reduced water uptake and anisotropic elongation detected, at pH = 14, by the swelling behaviour of tablets prepared with the Sclg/borax system. On the opposite, a different behaviour was observed with guar gum and locust bean gum tablets, tested as reference polysaccharides. The effect of pH on the structure of Sclg and Sclg/borax was investigated also by means of spectroscopic approaches based on the interaction between Congo red (CR) and the Sclg triple helix. Obtained results indicated that the CR absorbance maximum is shifted as a function of pH and by the presence of borax. Principal component analysis allowed very precise identification of the pH value at which the Sclg helix collapses. Molecular dynamics simulations of the Sclg/borax–CR complex indicated that, at physiological pH, only a few ordered configurations are populated, according to the induced circular dichroism (CD) spectrum evidence. Full article

(This article belongs to the Section Medicinal Chemistry)

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16 pages, 5868 KiB

Open AccessArticle

Bufalin Induces Apoptosis of Human Osteosarcoma U-2 OS Cells through Endoplasmic Reticulum Stress, Caspase- and Mitochondria-Dependent Signaling Pathways

by Ching-Hsiao Lee, Yung-Luen Shih, Mei-Hui Lee, Man-Kuan Au, Yung-Liang Chen, Hsu-Feng Lu and Jing-Gung Chung

Molecules 2017, 22(3), 437; https://doi.org/10.3390/molecules22030437 - 10 Mar 2017

Cited by 57 | Viewed by 7162

Abstract

Bone cancer is one of the cancer-related diseases, and there are increased numbers of patients with bone cancer worldwide. Therefore the efficacy of treatment of bone cancer is considered extremely vital. Bufalin has been showed to have biological activities including anticancer activities in [...] Read more.

Bone cancer is one of the cancer-related diseases, and there are increased numbers of patients with bone cancer worldwide. Therefore the efficacy of treatment of bone cancer is considered extremely vital. Bufalin has been showed to have biological activities including anticancer activities in vitro and in vivo. However, the exact associated mechanisms for bufalin induced apoptosis in human bone cancer cells are still unclear. In the present study, we investigated the effect of bufalin on the cytotoxic effects in U-2 OS human osteosarcoma cells. For examining apoptotic cell deaths, we used flow cytometry assay, Annexin V/PI double staining, and TUNNEL assay. Reactive oxygen species (ROS), Ca²⁺, mitochondrial membrane potential (ΔΨ_m), and caspase-8, -9 and -3 activities were measured by flow cytometry assay. Furthermore, western blotting and a confocal laser microscopy examination were used for measuring the alterations of apoptotic associated protein expression and translocation, respectively. The results indicated that bufalin induced cell morphological changes, decreased the viable cell number, induced apoptotic cell death, and increased the apoptotic cell number, and affected apoptotic associated protein expression in U-2 OS cells. Bufalin increased apoptotic proteins such as Bak, and decreased anti-apoptotic proteins such as Bcl-2 and Bcl-x in U-2 OS cells. Furthermore, bufalin increased the protein levels of cytochrome c (Cyto c), AIF (Apoptosis inducing factor) and Endo G (Endonuclease G) in cytoplasm that were also confirmed by confocal microscopy examination. Based on those findings, bufalin induced apoptotic cell death in U-2 OS cells may be via endoplasmic reticulum (ER) stress, caspase-, and mitochondria-dependent pathways; thus, we may suggest that bufalin could be used as an anti-cancer agent for the treatment of osteosarcoma in the future, and further in vivo studies are needed. Full article

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20 pages, 3252 KiB

Open AccessArticle

High Hydrostatic Pressure (HHP)-Induced Structural Modification of Patatin and Its Antioxidant Activities

by Rizwan Elahi and Tai-Hua Mu

Molecules 2017, 22(3), 438; https://doi.org/10.3390/molecules22030438 - 10 Mar 2017

Cited by 37 | Viewed by 7445

Abstract

Patatin represents a group of homologous primary storage proteins (with molecular weights ranging from 40 kDa to 45 kDa) found in Solanum tuberosum L. This group comprises 40% of the total soluble proteins in potato tubers. Here, patatin (40 kDa) was extracted from [...] Read more.

Patatin represents a group of homologous primary storage proteins (with molecular weights ranging from 40 kDa to 45 kDa) found in Solanum tuberosum L. This group comprises 40% of the total soluble proteins in potato tubers. Here, patatin (40 kDa) was extracted from potato fruit juice using ammonium sulfate precipitation (ASP) and exposed to high hydrostatic pressure (HHP) treatment (250, 350, 450, and 550 MPa). We investigated the effect of HHP treatment on the structure, composition, heat profile, and antioxidant potential, observing prominent changes in HHP-induced patatin secondary structure as compared with native patatin (NP). Additionally, significant (p < 0.05) increases in β-sheet content along with decreases in α-helix content were observed following HHP treatment. Thermal changes observed by differential scanning calorimetry (DSC) also showed a similar trend following HHP treatment; however, the enthalpy of patatin was also negatively affected by pressurization, and free sulfhydryl content and surface hydrophobicity significantly increased with pressurization up to 450 MPa, although both interactions progressively decreased at 550 MPa. The observed physicochemical changes suggested conformational modifications in patatin induced by HHP treatment. Moreover, our results indicated marked enhancement of antioxidant potential, as well as iron chelation activities, in HHP-treated patatin as compared with NP. These results suggested that HHP treatment offers an effective and green process for inducing structural modifications and improving patatin functionality. Full article

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

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8 pages, 387 KiB

Open AccessArticle

Four Pentasaccharide Resin Glycosides from Argyreia acuta

by Bang-Wei Yu, Jing-Jing Sun, Jie-Tao Pan, Xiu-Hong Wu, Yong-Qin Yin, You-Shao Yan and Jia-Yan Hu

Molecules 2017, 22(3), 440; https://doi.org/10.3390/molecules22030440 - 11 Mar 2017

Cited by 6 | Viewed by 4064

Abstract

Four pentasaccharide resin glycosides, acutacoside F–I (1–4), were isolated from the aerial parts of Argyreia acuta. These compounds were characterized as a group of macrolactones of operculinic acid A, and their lactonization site of 11S-hydroxyhexadecanoic acid [...] Read more.

Four pentasaccharide resin glycosides, acutacoside F–I (1–4), were isolated from the aerial parts of Argyreia acuta. These compounds were characterized as a group of macrolactones of operculinic acid A, and their lactonization site of 11S-hydroxyhexadecanoic acid was esterified at the second saccharide moiety (Rhamnose) at C-2. The absolute configuration of the aglycone was S. Their structures were elucidated by established spectroscopic and chemical methods. Full article

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18 pages, 2810 KiB

Open AccessArticle

Solventless Synthesis of Poly(pyrazolyl)phenyl-methane Ligands and Thermal Transformation of Tris(3,5-dimethylpyrazol-1-yl)phenylmethane

by Edith Rodríguez-Venegas, Efrén V. García-Báez, Francisco J. Martínez-Martínez, Alejandro Cruz and Itzia I. Padilla-Martínez

Molecules 2017, 22(3), 441; https://doi.org/10.3390/molecules22030441 - 11 Mar 2017

Cited by 1 | Viewed by 6511

Abstract

The solventless synthesis of tris(pyrazolyl)phenylmethane ligands of formula C₆H₅C(Pz^R2)₃ (R = H, Me), starting from PhCCl₃ and 3,5-dimethylpyrazole (Pz^Me2) or pyrazole (Pz) was performed. The sterically crowded C₆H₅C(Pz^Me2 [...] Read more.

The solventless synthesis of tris(pyrazolyl)phenylmethane ligands of formula C₆H₅C(Pz^R2)₃ (R = H, Me), starting from PhCCl₃ and 3,5-dimethylpyrazole (Pz^Me2) or pyrazole (Pz) was performed. The sterically crowded C₆H₅C(Pz^Me2)₃ is thermally transformed into the bis(pyrazolyl)(p-pyrazolyl)phenylmethane ligand Pz^Me2-C₆H₄CH(Pz^Me2)₂. In this compound both Pz^Me2 rings are linked through the N-atom to the methine C-atom. At higher temperatures, the binding mode of Pz^Me2 changes from N1 to C4. All transformations occurred via quinonoid carbocation intermediates that undergo an aromatic electrophilic substitution on the 4-position of Pz^Me2. Reaction conditions were established to obtain five tris(pyrazolyl)phenylmethane ligands in moderate to good yields. ¹H- and ¹³C-NMR spectroscopy and X-ray diffraction of single crystals support the proposed structures. Full article

(This article belongs to the Section Organic Chemistry)

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14 pages, 1609 KiB

Open AccessArticle

A Strategy for Simultaneous Isolation of Less Polar Ginsenosides, Including a Pair of New 20-Methoxyl Isomers, from Flower Buds of Panax ginseng

by Sha-Sha Li, Ke-Ke Li, Fei Xu, Li Tao, Li Yang, Shu-Xiao Chen and Xiao-Jie Gong

Molecules 2017, 22(3), 442; https://doi.org/10.3390/molecules22030442 - 10 Mar 2017

Cited by 14 | Viewed by 7162

Abstract

The present study was designed to simultaneously isolate the less polar ginsenosides from the flower buds of Panax ginseng (FBPG). Five ginsenosides, including a pair of new 20-methoxyl isomers, were extracted from FBPG and purified through a five-step integrated strategy, by combining ultrasonic [...] Read more.

The present study was designed to simultaneously isolate the less polar ginsenosides from the flower buds of Panax ginseng (FBPG). Five ginsenosides, including a pair of new 20-methoxyl isomers, were extracted from FBPG and purified through a five-step integrated strategy, by combining ultrasonic extraction, Diaion Hp-20 macroporous resin column enrichment, solid phase extraction (SPE), reversed-phase high-performance liquid chromatography (RP-HPLC) analysis and preparation, and nuclear magnetic resonance (NMR) analysis. The quantification of the five ginsenosides was also discussed by a developed method with validations within acceptable limits. Ginsenoside Rg5 showed content of about 1% in FBPG. The results indicated that FBPG might have many different ginsenosides with diverse chemical structures, and the less polar ginsenosides were also important to the quality control and standardization of FBPG. Full article

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

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11 pages, 2132 KiB

Open AccessArticle

AM-2201 Inhibits Multiple Cytochrome P450 and Uridine 5′-Diphospho-Glucuronosyltransferase Enzyme Activities in Human Liver Microsomes

by Ju-Hyun Kim, Soon-Sang Kwon, Tae Yeon Kong, Jae Chul Cheong, Hee Seung Kim, Moon Kyo In and Hye Suk Lee

Molecules 2017, 22(3), 443; https://doi.org/10.3390/molecules22030443 - 10 Mar 2017

Cited by 16 | Viewed by 7473

Abstract

AM-2201 is a synthetic cannabinoid that acts as a potent agonist at cannabinoid receptors and its abuse has increased. However, there are no reports of the inhibitory effect of AM-2201 on human cytochrome P450 (CYP) or uridine 5′-diphospho-glucuronosyltransferase (UGT) enzymes. We evaluated the [...] Read more.

AM-2201 is a synthetic cannabinoid that acts as a potent agonist at cannabinoid receptors and its abuse has increased. However, there are no reports of the inhibitory effect of AM-2201 on human cytochrome P450 (CYP) or uridine 5′-diphospho-glucuronosyltransferase (UGT) enzymes. We evaluated the inhibitory effect of AM-2201 on the activities of eight major human CYPs (1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, and 3A4) and six major human UGTs (1A1, 1A3, 1A4, 1A6, 1A9, and 2B7) enzymes in pooled human liver microsomes using liquid chromatography–tandem mass spectrometry to investigate drug interaction potentials of AM-2201. AM-2201 potently inhibited CYP2C9-catalyzed diclofenac 4′-hydroxylation, CYP3A4-catalyzed midazolam 1′-hydroxylation, UGT1A3-catalyzed chenodeoxycholic acid 24-acyl-glucuronidation, and UGT2B7-catalyzed naloxone 3-glucuronidation with IC50 values of 3.9, 4.0, 4.3, and 10.0 μM, respectively, and showed mechanism-based inhibition of CYP2C8-catalyzed amodiaquine N-deethylation with a Ki value of 2.1 μM. It negligibly inhibited CYP1A2, CYP2A6, CYP2B6, CYP2C19, CYP2D6, UGT1A1, UGT1A4, UGT1A6, and UGT1A9 activities at 50 μM in human liver microsomes. These in vitro results indicate that AM-2201 needs to be examined for potential pharmacokinetic drug interactions in vivo due to its potent inhibition of CYP2C8, CYP2C9, CYP3A4, UGT1A3, and UGT2B7 enzyme activities. Full article

(This article belongs to the Section Medicinal Chemistry)

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7 pages, 525 KiB

Open AccessArticle

Secondary Metabolites from the Marine-Derived Fungus Dichotomomyces sp. L-8 and Their Cytotoxic Activity

by Li-Hong Huang, Yan-Xiu Chen, Jian-Chen Yu, Jie Yuan, Hou-Jin Li, Wen-Zhe Ma, Ramida Watanapokasin, Kun-Chao Hu, Shah Iram Niaz, De-Po Yang and Wen-Jian Lan

Molecules 2017, 22(3), 444; https://doi.org/10.3390/molecules22030444 - 11 Mar 2017

Cited by 11 | Viewed by 5904

Abstract

Bioassay-guided isolation of the secondary metabolites from the fungus Dichotomomyces sp. L-8 associated with the soft coral Lobophytum crassum led to the discovery of two new compounds, dichotones A and B (1 and 2), together with four known compounds including [...] Read more.

Bioassay-guided isolation of the secondary metabolites from the fungus Dichotomomyces sp. L-8 associated with the soft coral Lobophytum crassum led to the discovery of two new compounds, dichotones A and B (1 and 2), together with four known compounds including dichotocejpin C (3), bis-N-norgliovictin (4), bassiatin (5) and (3R,6R)-bassiatin (6). The structures of these compounds were determined by 1D, 2D NMR and mass spectrometry. (3R,6R)-bassiatin (6) displayed significant cytotoxic activities against the human breast cancer cell line MDA-MB-435 and the human lung cancer cell line Calu3 with IC₅₀ values of 7.34 ± 0.20 and 14.54 ± 0.01 μM, respectively, while bassiatin (5), the diastereomer of compound 6, was not cytotoxic. Full article

(This article belongs to the Special Issue Metabolites of Terrestrial and Marine Origin on the Age-Related Disorders)

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12 pages, 4780 KiB

Open AccessFeature PaperArticle

A Model Study of the Photochemical Fate of As(III) in Paddy-Water

by Luca Carena and Davide Vione

Molecules 2017, 22(3), 445; https://doi.org/10.3390/molecules22030445 - 11 Mar 2017

Cited by 7 | Viewed by 4823

Abstract

The APEX (Aqueous Photochemistry of Environmentally-occurring Xenobiotics) software previously developed by one of us was used to model the photochemistry of As(III) in paddy-field water, allowing a comparison with biotic processes. The model included key paddy-water variables, such as the shielding effect of [...] Read more.

The APEX (Aqueous Photochemistry of Environmentally-occurring Xenobiotics) software previously developed by one of us was used to model the photochemistry of As(III) in paddy-field water, allowing a comparison with biotic processes. The model included key paddy-water variables, such as the shielding effect of the rice canopy on incident sunlight and its monthly variations, water pH, and the photochemical parameters of the chromophoric dissolved organic matter (CDOM) occurring in paddy fields. The half-life times (t_1/2) of As(III) photooxidation to As(V) would be ~20–30 days in May. In contrast, the photochemical oxidation of As(III) would be much slower in June and July due to rice-canopy shading of radiation because of plant growth, despite higher sunlight irradiance. At pH < 8 the photooxidation of As(III) would mainly be accounted for by reaction with transient species produced by irradiated CDOM (here represented by the excited triplet states ³CDOM^*, neglecting the possibly more important reactions with poorly known species such as the phenoxy radicals) and, to a lesser extent, with the hydroxyl radicals (HO^•). However, the carbonate radicals (CO₃^•−) could be key photooxidants at pH > 8.5 provided that the paddy-water ³CDOM^* is sufficiently reactive toward the oxidation of CO₃²⁻. In particular, if paddy-water ³CDOM^* oxidizes the carbonate anion with a second-order reaction rate constant near (or higher than) 10⁶ M⁻¹·s⁻¹, the photooxidation of As(III) could be quite fast at pH > 8.5. Such pH conditions can be produced by elevated photosynthetic activity that consumes dissolved CO₂. Full article

(This article belongs to the Special Issue Photon-involving Purification of Water and Air)

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18 pages, 11700 KiB

Open AccessArticle

CDC25 Inhibition in Acute Myeloid Leukemia–A Study of Patient Heterogeneity and the Effects of Different Inhibitors

by Annette K. Brenner, Håkon Reikvam, Kristin Paulsen Rye, Karen Marie Hagen, Antonio Lavecchia and Øystein Bruserud

Molecules 2017, 22(3), 446; https://doi.org/10.3390/molecules22030446 - 11 Mar 2017

Cited by 13 | Viewed by 5514

Abstract

Cell division cycle 25 (CDC25) protein phosphatases regulate cell cycle progression through the activation of cyclin-dependent kinases (CDKs), but they are also involved in chromatin modulation and transcriptional regulation. CDC25 inhibition is regarded as a possible therapeutic strategy for the treatment of human [...] Read more.

Cell division cycle 25 (CDC25) protein phosphatases regulate cell cycle progression through the activation of cyclin-dependent kinases (CDKs), but they are also involved in chromatin modulation and transcriptional regulation. CDC25 inhibition is regarded as a possible therapeutic strategy for the treatment of human malignancies, including acute myeloid leukemia (AML). We investigated the in vitro effects of CDC25 inhibitors on primary human AML cells derived from 79 unselected patients in suspension cultures. Both the previously well-characterized CDC25 inhibitor NSC95397, as well as five other inhibitors (BN82002 and the novel small molecular compounds ALX1, ALX2, ALX3, and ALX4), only exhibited antiproliferative effects for a subset of patients when tested alone. These antiproliferative effects showed associations with differences in genetic abnormalities and/or AML cell differentiation. However, the responders to CDC25 inhibition could be identified by analysis of global gene expression profiles. The differentially expressed genes were associated with the cytoskeleton, microtubules, and cell signaling. The constitutive release of 28 soluble mediators showed a wide variation among patients and this variation was maintained in the presence of CDC25 inhibition. Finally, NSC95397 had no or only minimal effects on AML cell viability. In conclusion, CDC25 inhibition has antiproliferative effects on primary human AML cells for a subset of patients, and these patients can be identified by gene expression profiling. Full article

(This article belongs to the Special Issue Kinase Inhibitors)

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12 pages, 725 KiB

Open AccessArticle

Alkoxy and Enediyne Derivatives Containing 1,4-Benzoquinone Subunits—Synthesis and Antitumor Activity

by Monika Kadela-Tomanek, Ewa Bębenek, Elwira Chrobak, Małgorzata Latocha and Stanisław Boryczka

Molecules 2017, 22(3), 447; https://doi.org/10.3390/molecules22030447 - 11 Mar 2017

Cited by 22 | Viewed by 5120

Abstract

The compounds produced by a living organism are most commonly as medicinal agents and starting materials for the preparation of new semi-synthetic derivatives. One of the largest groups of natural compounds consists of products containing a 1,4-benzoquinone subunit. This fragment occurs in three [...] Read more.

The compounds produced by a living organism are most commonly as medicinal agents and starting materials for the preparation of new semi-synthetic derivatives. One of the largest groups of natural compounds consists of products containing a 1,4-benzoquinone subunit. This fragment occurs in three enediyne antibiotics, dynemicin A, deoxydynemicin A, and uncilamicin, which exhibit high biological activity. A series of alkoxy derivatives containing 1,4-naphthoquinone, 5,8-quinolinedione, and 2-methyl-5,8-quinolinedione moieties was synthesized. Moreover, the 1,4-benzoquinone subunit was contacted with an enediyne fragment. All obtained compounds were characterized by spectroscopy and spectrometry methods. The resulting alkane, alkene, alkyne and enediyne derivatives were tested as antitumor agents. They showed high cytotoxic activity depending on the type of 1,4-benzoquinone subunit and the employed tumor cell lines. The synthesized derivatives fulfill the Lipinski Rule of Five and have low permeability through the blood–brain barrier. Full article

(This article belongs to the Section Medicinal Chemistry)

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13 pages, 1970 KiB

Open AccessArticle

Chemical Composition and Biological Activity of Allium cepa L. and Allium × cornutum (Clementi ex Visiani 1842) Methanolic Extracts

by Željana Fredotović, Matilda Šprung, Barbara Soldo, Ivica Ljubenkov, Irena Budić-Leto, Tea Bilušić, Vedrana Čikeš-Čulić and Jasna Puizina

Molecules 2017, 22(3), 448; https://doi.org/10.3390/molecules22030448 - 11 Mar 2017

Cited by 93 | Viewed by 11129

Abstract

Here, we report a comparative study of the phytochemical profile and the biological activity of two onion extracts, namely Allium cepa L. and Allium × cornutum (Clementi ex Visiani 1842), members of the family Amaryllidaceae. The identification of flavonoids and anthocyanins, and their [...] Read more.

Here, we report a comparative study of the phytochemical profile and the biological activity of two onion extracts, namely Allium cepa L. and Allium × cornutum (Clementi ex Visiani 1842), members of the family Amaryllidaceae. The identification of flavonoids and anthocyanins, and their individual quantities, was determined by high-performance liquid chromatography (HPLC). The potency of both extracts to scavenge free radicals was determined by the DPPH (2,2′-diphenyl-1-picrylhydrazyl) radical-scavenging activity and oxygen radical absorbance capacity (ORAC) methods. The DNA protective role was further tested by the single-cell gel electrophoresis (COMET) assay and by Fenton’s reagent causing double-strand breaks on the closed circular high copy pUC19 plasmid isolated from Escherichia coli. In the presence of both extracts, a significant decrease in DNA damage was observed, which indicates a protective role of Allium cepa and Allium × cornutum on DNA strand breaks. Additionally, cytotoxicity was tested on glioblastoma and breast cancer cell lines. The results showed that both extracts had antiproliferative effects, but the most prominent decrease in cellular growth was observed in glioblastoma cells. Full article

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12 pages, 2247 KiB

Open AccessArticle

Three-Component Reaction of Benzylamines, Diethyl Phosphite and Triethyl Orthoformate: Dependence of the Reaction Course on the Structural Features of the Substrates and Reaction Conditions

by Patrycja Miszczyk, Ilona Turowska-Tyrk, Paweł Kafarski and Ewa Chmielewska

Molecules 2017, 22(3), 450; https://doi.org/10.3390/molecules22030450 - 11 Mar 2017

Cited by 4 | Viewed by 7778

Abstract

The reaction between benzyl amines, triethyl orthoformate, and diethyl phosphite affords either bisphosphonic (compound 1) or N-benzylaminobenzylphosphonic (compound 2) acid depending on the reaction conditions. The final output of the reaction can be manipulated by the choice of reaction conditions, [...] Read more.

The reaction between benzyl amines, triethyl orthoformate, and diethyl phosphite affords either bisphosphonic (compound 1) or N-benzylaminobenzylphosphonic (compound 2) acid depending on the reaction conditions. The final output of the reaction can be manipulated by the choice of reaction conditions, particularly the molar ratio of substrates. Full article

(This article belongs to the Special Issue Women in Organic Chemistry)

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18 pages, 1146 KiB

Open AccessArticle

Chemical Constituents of Smilax china L. Stems and Their Inhibitory Activities against Glycation, Aldose Reductase, α-Glucosidase, and Lipase

by Hee Eun Lee, Jin Ah Kim and Wan Kyunn Whang

Molecules 2017, 22(3), 451; https://doi.org/10.3390/molecules22030451 - 11 Mar 2017

Cited by 35 | Viewed by 8119

Abstract

The search for natural inhibitors with anti-diabetes properties has gained increasing attention. Among four selected Smilacaceae family plants, Smilax china L. stems (SCS) showed significant in vitro anti-glycation and rat lens aldose reductase inhibitory activities. Bioactivity-guided isolation was performed with SCS and four [...] Read more.

The search for natural inhibitors with anti-diabetes properties has gained increasing attention. Among four selected Smilacaceae family plants, Smilax china L. stems (SCS) showed significant in vitro anti-glycation and rat lens aldose reductase inhibitory activities. Bioactivity-guided isolation was performed with SCS and four solvent fractions were obtained, which in turn yielded 10 compounds, including one phenolic acid, three chlorogenic acids, four flavonoids, one stilbene, and one phenylpropanoid glycoside; their structures were elucidated using nuclear magnetic resonance and mass spectrometry. All solvent fractions, isolated compounds, and stem extracts from plants sourced from six different provinces of South Korea were next tested for their inhibitory effects against advanced glycation end products, as well as aldose reductase. α-Glucosidase, and lipase assays were also performed on the fractions and compounds. Since compounds 3, 4, 6, and 8 appeared to be the superior inhibitors among the tested compounds, a comparative study was performed via high-performance liquid chromatography with photodiode array detection using a self-developed analysis method to confirm the relationship between the quantity and bioactivity of the compounds in each extract. The findings of this study demonstrate the potent therapeutic efficacy of SCS and its potential use as a cost-effective natural alternative medicine against type 2 diabetes and its complications. Full article

(This article belongs to the Section Natural Products Chemistry)

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10 pages, 1181 KiB

Open AccessArticle

Synthetic Peptides Derived from Bovine Lactoferricin Exhibit Antimicrobial Activity against E. coli ATCC 11775, S. maltophilia ATCC 13636 and S. enteritidis ATCC 13076

by Nataly De Jesús Huertas Méndez, Yerly Vargas Casanova, Anyelith Katherine Gómez Chimbi, Edith Hernández, Aura Lucia Leal Castro, Javier Mauricio Melo Diaz, Zuly Jenny Rivera Monroy and Javier Eduardo García Castañeda

Molecules 2017, 22(3), 452; https://doi.org/10.3390/molecules22030452 - 12 Mar 2017

Cited by 40 | Viewed by 8860

Abstract

Linear, dimeric, tetrameric, and cyclic peptides derived from lactoferricin B–containing non-natural amino acids and the RWQWR motif were synthesized, purified, and characterized using RP-HPLC, MALDI-TOF mass spectrometry, and circular dichroism. The antibacterial activity of peptides against Escherichia coli ATCC 11775, Stenotrophomonas maltophilia ATCC [...] Read more.

Linear, dimeric, tetrameric, and cyclic peptides derived from lactoferricin B–containing non-natural amino acids and the RWQWR motif were synthesized, purified, and characterized using RP-HPLC, MALDI-TOF mass spectrometry, and circular dichroism. The antibacterial activity of peptides against Escherichia coli ATCC 11775, Stenotrophomonas maltophilia ATCC 13636, and Salmonella enteritidis ATCC 13076 was evaluated. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were determined. The synthetic bovine lactoferricin exhibited antibacterial activity against E. coli ATCC 11775 and S. enteritidis ATCC 13076. The dimeric peptide (RRWQWR)₂K-Ahx exhibited the highest antibacterial activity against the tested bacterial strain. The monomeric, cyclic, tetrameric, and palindromic peptides containing the RWQWR motif exhibited high and specific activity against E. coli ATCC 11775. The results suggest that short peptides derived from lactoferricin B could be considered as potential candidates for the development of antibacterial agents against infections caused by E. coli. Full article

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

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9 pages, 2134 KiB

Open AccessArticle

2-Hydroxymelatonin, a Predominant Hydroxylated Melatonin Metabolite in Plants, Shows Antitumor Activity against Human Colorectal Cancer Cells

by Yi Yang, Rui Zhou, So-Yeon Park, Kyoungwhan Back, Woo Kyun Bae, Kyung Keun Kim and Hangun Kim

Molecules 2017, 22(3), 453; https://doi.org/10.3390/molecules22030453 - 14 Mar 2017

Cited by 17 | Viewed by 5886

Abstract

2-Hydroxymelatonin is a predominant hydroxylated melatonin metabolite in plants. To investigate whether it has potent cytotoxic effects on colorectal cancer cells, four colorectal cancer cell lines, Caco2, HCT116, DLD1, and CT26, were treated with 2-hydroxymelatonin and melatonin. 2-Hydroxymelatonin had a much lower IC [...] Read more.

2-Hydroxymelatonin is a predominant hydroxylated melatonin metabolite in plants. To investigate whether it has potent cytotoxic effects on colorectal cancer cells, four colorectal cancer cell lines, Caco2, HCT116, DLD1, and CT26, were treated with 2-hydroxymelatonin and melatonin. 2-Hydroxymelatonin had a much lower IC₅₀ value than melatonin in the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The cytotoxic effect of 2-hydroxymelatonin was much stronger than that of melatonin at high concentrations (1000 or 2000 μM) in HCT116, DLD1, and CT26 cells, but only at intermediate concentrations (250 or 500 μM) in Caco2 cells. The cytotoxicity of 2-hydroxymelatonin was induced through activation of the apoptotic signaling pathway, as confirmed by Hoechst staining and Annexin V-FITC/propidium iodide double labeling of cells treated with a lethal dose (1 mM). However, sub-lethal doses of 2-hydroxymelatonin inhibited the invasive ability of Caco2 cells. Epithelial-mesenchymal transition (EMT) markers were significantly regulated by 2-hydroxymelatonin. Overall, the anti-cancer activity of 2-hydroxymelatonin is more potent than that of melatonin. Taken together, 2-hydroxymelatonin exhibits potent anti-cancer activity against human colorectal cancer cells via induction of apoptosis and inhibition of EMT. Full article

(This article belongs to the Special Issue Metabolites of Terrestrial and Marine Origin on the Age-Related Disorders)

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10 pages, 5649 KiB

Open AccessArticle

The Vital Dye CDr10b Labels the Zebrafish Mid-Intestine and Lumen

by Veronika Sander, Shantanu Patke, Jung Y. Lee, Young-Tae Chang and Alan J. Davidson

Molecules 2017, 22(3), 454; https://doi.org/10.3390/molecules22030454 - 13 Mar 2017

Cited by 2 | Viewed by 6976

Abstract

We describe the use of the fluorescent reporter compound CDr10b to label mid-intestinal structures in zebrafish larvae after simple immersion. CDr10b is deposited into the gut where it initially fills the lumen and is excreted. Using laser-mediated injury of the intestine, we show [...] Read more.

We describe the use of the fluorescent reporter compound CDr10b to label mid-intestinal structures in zebrafish larvae after simple immersion. CDr10b is deposited into the gut where it initially fills the lumen and is excreted. Using laser-mediated injury of the intestine, we show that CDr10b provides a useful readout of the integrity and repair of the epithelial cell barrier. In addition, CDr10b specifically labels the absorptive mid-intestine segment that is analogous to the mammalian small intestine. By perturbing retinoic acid signaling, which regulates the size of the mid-intestine segment, we show that CDr10b is a valuable tool to rapidly assess developmental malformations of the intestine in live animals. Full article

(This article belongs to the Section Molecular Diversity)

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15 pages, 1318 KiB

Open AccessArticle

Bovine Colostrum Whey Protein Hydrolysate Inhibits Cell DNA Damage and LDL Oxidation In Vitro

by Shu-Hua Chiang, Shiu-Yu Wang, Chi-Yue Chang and Chih-Wei Chen

Molecules 2017, 22(3), 456; https://doi.org/10.3390/molecules22030456 - 13 Mar 2017

Cited by 15 | Viewed by 4983

Abstract

Whey protein isolated from bovine colostrums collected on the second day postpartum was two-stage hydrolyzed by alcalase and flavourzyme [...] Full article

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17 pages, 4398 KiB

Open AccessArticle

Optimization of Conditions for Cyanidin-3-OGlucoside (C3G) Nanoliposome Production by Response Surface Methodology and Cellular Uptake Studies in Caco-2 Cells

by Tisong Liang, Rongfa Guan, Haitao Shen, Qile Xia and Mingqi Liu

Molecules 2017, 22(3), 457; https://doi.org/10.3390/molecules22030457 - 13 Mar 2017

Cited by 38 | Viewed by 6597

Abstract

We aimed to optimize the formulation of C3G nanoliposomes using response surface methodology. Additionally, we evaluated the stability, particle change, and encapsulation efficiency (EE) of C3G nanoliposomes under different temperatures and storage durations, as well as in simulated gastrointestinal juice (SGF) and simulated [...] Read more.

We aimed to optimize the formulation of C3G nanoliposomes using response surface methodology. Additionally, we evaluated the stability, particle change, and encapsulation efficiency (EE) of C3G nanoliposomes under different temperatures and storage durations, as well as in simulated gastrointestinal juice (SGF) and simulated intestinal fluid. The morphology of C3G nanoliposomes was observed by transmission electron microscope. The ability of C3G nanoliposomes to affect cancer cell morphology and inhibit cancer cell proliferation was studied with Caco-2 cells. Reverse-phase evaporation method is a simple and efficient method for liposome preparation. The optimal preparation conditions for this method were as follows: C3G concentration of 0.17 mg/mL, phosphatidylcholine/cholesterol ratio of 2.87, and rotary evaporation temperature of 41.41 °C. At optimal conditions, the particle size and EE of the C3G nanoliposomes were 165.78 ± 4.3 nm and 70.43% ± 1.95%, respectively. The C3G nanoliposomes showed an acceptable stability in SGF at 37 °C for 4 h, but were unstable under extended storage durations and high temperatures. Moreover, our results showed that different concentrations of C3G nanoliposomes affected the morphology and inhibited the proliferation of Caco-2 cells. Full article

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10 pages, 303 KiB

Open AccessArticle

Computational Prediction of the Protonation Sites of Ac-Lys-(Ala)n-Lys-NH2 Peptides through Conceptual DFT Descriptors

by Sebastián Sastre, Juan Frau and Daniel Glossman-Mitnik

Molecules 2017, 22(3), 458; https://doi.org/10.3390/molecules22030458 - 13 Mar 2017

Cited by 9 | Viewed by 4453

Abstract

Six density functionals (M11, M11L, MN12L, MN12SX, N12, and N12SX) in connection with the Def2TZVP basis set and the SMD solvation model (water as a solvent) have been assessed for the calculation of the molecular structure and properties of several peptides with the [...] Read more.

Six density functionals (M11, M11L, MN12L, MN12SX, N12, and N12SX) in connection with the Def2TZVP basis set and the SMD solvation model (water as a solvent) have been assessed for the calculation of the molecular structure and properties of several peptides with the general formulaAc-Lys-(Ala)n-Lys-NH2,withn=0to5 [...] Full article

(This article belongs to the Special Issue The Molecular Electron Density Theory: A Modern View of Molecular Reactivity in Organic Chemistry)

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7 pages, 475 KiB

Open AccessArticle

Essential Oil Composition and Bioactivities of Waldheimia glabra (Asteraceae) from Qinghai-Tibet Plateau

by Ji De, Yan Lu, Lijun Ling, Nan Peng and Yang Zhong

Molecules 2017, 22(3), 460; https://doi.org/10.3390/molecules22030460 - 13 Mar 2017

Cited by 19 | Viewed by 5466

Abstract

Waldheimia glabra is traditionally used as incense and as an anti-influenza drug by Tibetans in China. Here, we collected W. glabra from the Gangs Rinpoche mountain at an altitude of 5200 m, and analyzed its essential oil by gas chromatography-mass spectrometry (GC-MS) combined [...] Read more.

Waldheimia glabra is traditionally used as incense and as an anti-influenza drug by Tibetans in China. Here, we collected W. glabra from the Gangs Rinpoche mountain at an altitude of 5200 m, and analyzed its essential oil by gas chromatography-mass spectrometry (GC-MS) combined with the retention indices (RI). Twenty-seven compounds, representing 72.4% of the total essential oil, were identified, including α-bisabolol (20.2%), valeranone (11.8%), chamazulene (9.9%), spathulenol (8.2%), β-caryophyllene (6.1%), and caryophyllene oxide (5.2%). Bioactivity evaluation of the essential oil revealed that it exhibited potent anti-influenza effect on viruses H3N2 and anti-inflammatory effect by inhibiting the lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW 264.7 macrophages, but no anti-complementary activity. Full article

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

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18 pages, 1717 KiB

Open AccessArticle

Pyrrole and Fused Pyrrole Compounds with Bioactivity against Inflammatory Mediators

by Samar Said Fatahala, Sherifa Hasabelnaby, Ayman Goudah, Ghada I. Mahmoud and Rania Helmy Abd-El Hameed

Molecules 2017, 22(3), 461; https://doi.org/10.3390/molecules22030461 - 17 Mar 2017

Cited by 52 | Viewed by 10260

Abstract

A new series of pyrrolopyridines and pyrrolopyridopyrimidines have been synthesized from aminocyanopyrroles. The synthesized compounds have been characterized by FTIR, ¹H-NMR and mass spectroscopy. The final compounds have been screened for in vitro pro-inflammatory cytokine inhibitory and in vivo anti-inflammatory activity. The [...] Read more.

A new series of pyrrolopyridines and pyrrolopyridopyrimidines have been synthesized from aminocyanopyrroles. The synthesized compounds have been characterized by FTIR, ¹H-NMR and mass spectroscopy. The final compounds have been screened for in vitro pro-inflammatory cytokine inhibitory and in vivo anti-inflammatory activity. The biological results revealed that among all tested compounds some fused pyrroles, namely the pyrrolopyridines 3i and 3l, show promising activity. A docking study of the active synthesized molecules confirmed the biological results and revealed a new binding pose in the COX-2 binding site. Full article

(This article belongs to the Section Medicinal Chemistry)

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13 pages, 1851 KiB

Open AccessArticle

Induction of G2M Arrest by Flavokawain A, a Kava Chalcone, Increases the Responsiveness of HER2-Overexpressing Breast Cancer Cells to Herceptin

by Danielle D. Jandial, Lauren S. Krill, Lixia Chen, Chunli Wu, Yu Ke, Jun Xie, Bang H. Hoang and Xiaolin Zi

Molecules 2017, 22(3), 462; https://doi.org/10.3390/molecules22030462 - 14 Mar 2017

Cited by 49 | Viewed by 7828

Abstract

HER2/neu positive breast tumors predict a high mortality and comprise 25%–30% of breast cancer. We have shown that Flavokawain A (FKA) preferentially reduces the viabilities of HER2-overexpressing breast cancer cell lines (i.e., SKBR3 and MCF7/HER2) versus those with less HER2 expression (i.e., MCF7 [...] Read more.

HER2/neu positive breast tumors predict a high mortality and comprise 25%–30% of breast cancer. We have shown that Flavokawain A (FKA) preferentially reduces the viabilities of HER2-overexpressing breast cancer cell lines (i.e., SKBR3 and MCF7/HER2) versus those with less HER2 expression (i.e., MCF7 and MDA-MB-468). FKA at cytotoxic concentrations to breast cancer cell lines also has a minimal effect on the growth of non-malignant breast epithelial MCF10A cells. FKA induces G2M arrest in cell cycle progression of HER2-overexpressing breast cancer cell lines through inhibition of Cdc2 and Cdc25C phosphorylation and downregulation of expression of Myt1 and Wee1 leading to increased Cdc2 kinase activities. In addition, FKA induces apoptosis in SKBR3 cells by increasing the protein expression of Bim and BAX and decreasing expression of Bcl₂, Bcl_X/L, XIAP, and survivin. FKA also downregulates the protein expression of HER-2 and inhibits AKT phosphorylation. Herceptin plus FKA treatment leads to an enhanced growth inhibitory effect on HER-2 overexpressing breast cancer cell lines through downregulation of Myt1, Wee1, Skp2, survivin, and XIAP. Our results suggest FKA as a promising and novel apoptosis inducer and G2 blocking agent that, in combination with Herceptin, enhances for the treatment of HER2-overexpressing breast cancer. Full article

(This article belongs to the Special Issue Cancer Chemoprevention)

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12 pages, 4621 KiB

Open AccessArticle

Bactericidal Effect of Pterostilbene Alone and in Combination with Gentamicin against Human Pathogenic Bacteria

by Wee Xian Lee, Dayang Fredalina Basri and Ahmad Rohi Ghazali

Molecules 2017, 22(3), 463; https://doi.org/10.3390/molecules22030463 - 17 Mar 2017

Cited by 38 | Viewed by 8690

Abstract

The antibacterial activity of pterostilbene in combination with gentamicin against six strains of Gram-positive and Gram-negative bacteria were investigated. The minimum inhibitory concentration and minimum bactericidal concentration of pterostilbene were determined using microdilution technique whereas the synergistic antibacterial activities of pterostilbene in combination [...] Read more.

The antibacterial activity of pterostilbene in combination with gentamicin against six strains of Gram-positive and Gram-negative bacteria were investigated. The minimum inhibitory concentration and minimum bactericidal concentration of pterostilbene were determined using microdilution technique whereas the synergistic antibacterial activities of pterostilbene in combination with gentamicin were assessed using checkerboard assay and time-kill kinetic study. Results of the present study showed that the combination effects of pterostilbene with gentamicin were synergistic (FIC index < 0.5) against three susceptible bacteria strains: Staphylococcus aureus ATCC 25923, Escherichia coli O157 and Pseudomonas aeruginosa 15442. However, the time-kill study showed that the interaction was indifference which did not significantly differ from the gentamicin treatment. Furthermore, time-kill study showed that the growth of the tested bacteria was completely attenuated with 2 to 8 h treatment with 0.5 × MIC of pterostilbene and gentamicin. The identified combinations could be of effective therapeutic value against bacterial infections. These findings have potential implications in delaying the development of bacterial resistance as the antibacterial effect was achieved with the lower concentrations of antibacterial agents. Full article

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

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10 pages, 2865 KiB

Open AccessArticle

Spirobifluorene Core-Based Novel Hole Transporting Materials for Red Phosphorescence OLEDs

by Ramanaskanda Braveenth, Hyeong Woo Bae, Quynh Pham Bao Nguyen, Haye Min Ko, Choong Hun Lee, Hyeong Jun Kim, Jang Hyuk Kwon and Kyu Yun Chai

Molecules 2017, 22(3), 464; https://doi.org/10.3390/molecules22030464 - 14 Mar 2017

Cited by 13 | Viewed by 8458

Abstract

Two new hole transporting materials, named HTM 1A and HTM 1B, were designed and synthesized in significant yields using the well-known Buchwald Hartwig and Suzuki cross- coupling reactions. Both materials showed higher decomposition temperatures (over 450 °C) at 5% weight reduction and [...] Read more.

Two new hole transporting materials, named HTM 1A and HTM 1B, were designed and synthesized in significant yields using the well-known Buchwald Hartwig and Suzuki cross- coupling reactions. Both materials showed higher decomposition temperatures (over 450 °C) at 5% weight reduction and HTM 1B exhibited a higher glass transition temperature of 180 °C. Red phosphorescence-based OLED devices were fabricated to analyze the device performances compared to Spiro-NPB and NPB as reference hole transporting materials. Devices consist of hole transporting material as HTM 1B showed better maximum current and power efficiencies of 16.16 cd/A and 11.17 lm/W, at the same time it revealed an improved external quantum efficiency of 13.64%. This efficiency is considerably higher than that of Spiro-NPB and NPB-based reference devices. Full article

(This article belongs to the Special Issue Organic Light Emitting Diodes)

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10 pages, 2852 KiB

Open AccessArticle

Laxative Effects of Total Diterpenoids Extracted from the Roots of Euphorbia pekinensis Are Attributable to Alterations of Aquaporins in the Colon

by Kuilong Wang, Lian Liu, Jianyu Huang, Hongli Yu, Hao Wu, Yu Duan, Xiaobing Cui, Xingde Zhang, Liping Liu and Wei Wang

Molecules 2017, 22(3), 465; https://doi.org/10.3390/molecules22030465 - 14 Mar 2017

Cited by 17 | Viewed by 4779

Abstract

This study was designed to evaluate the toxic effects of total diterpenoids extracted from the roots of Euphorbia pekinensis (TDEP) on the mouse colon and to clarify the mechanism. Dried powdered roots of E. pekinensis were extracted with chloroform, and then the extract [...] Read more.

This study was designed to evaluate the toxic effects of total diterpenoids extracted from the roots of Euphorbia pekinensis (TDEP) on the mouse colon and to clarify the mechanism. Dried powdered roots of E. pekinensis were extracted with chloroform, and then the extract (6.7 g) was subjected to column chromatography and preparative TLC, giving TDEP. Using the HPLC-DAD method, the purity of TDEP was determined as 85.26%. Mice were orally administered with TDEP (3.942, 19.71 and 39.42 mg/kg), after which fecal water content and colon water content were examined. Both of them increased over time after TDEP administration, accompanied by severe diarrhea. Three hours after TDEP administration, the animals were sacrificed to obtain their colons. The mRNA and protein expression levels of aquaporin 1 (AQP1), AQP3 and AQP4 in the colon were measured using real-time RT-PCR and Western blotting, respectively. TDEP significantly increased the levels of AQP3 and AQP4, but decreased that of AQP1 in dose-dependent manners. Similarly, Pekinenin C, a casbane diterpenoid, significantly increased AQP3 protein and mRNA expressions in human intestinal epithelial cells (HT-29). Histopathological examination revealed that the colon was not significantly damaged. The laxative effects of E. pekinensis were associated with the alterations of AQPs in the colon by TDEP. Full article

(This article belongs to the Section Natural Products Chemistry)

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10 pages, 6786 KiB

Open AccessCommunication

Separation of Alkyne Enantiomers by Chiral Column HPLC Analysis of Their Cobalt-Complexes

by Qiaoyun Liu, Jing Wang, Junfei Li, Xiaolei Wang, Shichao Lu, Xuan Li, Yaling Gong and Shu Xu

Molecules 2017, 22(3), 466; https://doi.org/10.3390/molecules22030466 - 20 Mar 2017

Viewed by 5620

Abstract

Separation of the enantiomers of new chiral alkynes in strategic syntheses and bioorthogonal studies is always problematic. The chiral column high-performance liquid chromatography (HPLC) method in general could not be directly used to resolve such substrates, since the differentiation of the alkyne segment [...] Read more.

Separation of the enantiomers of new chiral alkynes in strategic syntheses and bioorthogonal studies is always problematic. The chiral column high-performance liquid chromatography (HPLC) method in general could not be directly used to resolve such substrates, since the differentiation of the alkyne segment with the other alkane/alkene segment is not significant in the stationary phase, and the alkyne group is not a good UV chromophore. Usually, a pre-column derivatization reaction with a tedious workup procedure is needed. Making use of easily-prepared stable alkyne-cobalt-complexes, we developed a simple and general method by analyzing the in situ generated cobalt-complex of chiral alkynes using chiral column HPLC. This new method is especially suitable for the alkynes without chromophores and other derivable groups. Full article

(This article belongs to the Section Organometallic Chemistry)

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14 pages, 3969 KiB

Open AccessArticle

Synthesis and Evaluation of New Pyrazoline Derivatives as Potential Anticancer Agents in HepG-2 Cell Line

by Weijie Xu, Ying Pan, Hong Wang, Haiyan Li, Qing Peng, Duncan Wei, Cheng Chen and Jinhong Zheng

Molecules 2017, 22(3), 467; https://doi.org/10.3390/molecules22030467 - 16 Mar 2017

Cited by 31 | Viewed by 6780

Abstract

Cancer is a major public health concern worldwide. Adverse effects of cancer treatments still compromise patients’ quality of life. To identify new potential anticancer agents, a series of novel pyrazoline derivatives were synthesized and evaluated for cytotoxic effects on HepG-2 (human liver hepatocellular [...] Read more.

Cancer is a major public health concern worldwide. Adverse effects of cancer treatments still compromise patients’ quality of life. To identify new potential anticancer agents, a series of novel pyrazoline derivatives were synthesized and evaluated for cytotoxic effects on HepG-2 (human liver hepatocellular carcinoma cell line) and primary hepatocytes. Compound structures were confirmed by ¹H-NMR, mass spectrometry, and infrared imaging. An in vitro assay demonstrated that several compounds exerted cytotoxicity in the micromolar range. Benzo[b]thiophen-2-yl-[5-(4-hydroxy-3,5-dimethoxy-phenyl)-3-(2-hydroxy-phenyl)-4,5-dihydo-pyrazol-1-yl]-methanone (b17) was the most effective anticancer agent against HepG-2 cells owing to its notable inhibitory effect on HepG-2 with an IC₅₀ value of 3.57 µM when compared with cisplatin (IC₅₀ = 8.45 µM) and low cytotoxicity against primary hepatocytes. Cell cycle analysis and apoptosis/necrosis evaluation using this compound revealed that b17 notably arrested HepG-2 cells in the G₂/M phase and induced HepG-2 cells apoptosis. Our findings indicate that compound b17 may be a promising anticancer drug candidate. Full article

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9 pages, 905 KiB

Open AccessArticle

Ellagitannins of Davidia involucrata. I. Structure of Davicratinic Acid A and Effects of Davidia Tannins on Drug-Resistant Bacteria and Human Oral Squamous Cell Carcinomas

by Yuuki Shimozu, Yuriko Kimura, Akari Esumi, Hiroe Aoyama, Teruo Kuroda, Hiroshi Sakagami and Tsutomu Hatano

Molecules 2017, 22(3), 470; https://doi.org/10.3390/molecules22030470 - 15 Mar 2017

Cited by 23 | Viewed by 6042

Abstract

We isolated a new ellagitannin, davicratinic acid A (5), together with four known ellagitannins, davidiin (1), granatin A (2), pedunculagin (3), and 3-O-galloylgranatin A (4), from an aqueous acetone extract of [...] Read more.

We isolated a new ellagitannin, davicratinic acid A (5), together with four known ellagitannins, davidiin (1), granatin A (2), pedunculagin (3), and 3-O-galloylgranatin A (4), from an aqueous acetone extract of dried Davidia involucrata leaves. The known ellagitannins were identified based on spectroscopic data. The structure of davicratinic acid A (5), a monomeric ellagitannin possessing a unique, skew-boat glucopyranose core, was established based on spectroscopic data. Additionally, we examined the effects of several tannins with good yields from this plant on drug-resistant bacteria and human oral squamous cell carcinomas, and found that davidiin (1) exhibited the most potent antibacterial and antitumor properties among the tannins examined. Full article

(This article belongs to the Section Bioorganic Chemistry)

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10 pages, 1617 KiB

Open AccessArticle

A Metabolomic Approach for the Discrimination of Red Ginseng Root Parts and Targeted Validation

by Gyo In, Hyun Kyu Seo, Hee-Won Park and Kyoung Hwa Jang

Molecules 2017, 22(3), 471; https://doi.org/10.3390/molecules22030471 - 15 Mar 2017

Cited by 17 | Viewed by 4980

Abstract

Ginsenosides are used as existing markers of red ginseng (RG) quality, and ginsenoside ratios are also indicative of the different components of red ginseng. For the analysis and classification of ginsenoside content, red ginseng was separated into three parts, namely, main roots, lateral [...] Read more.

Ginsenosides are used as existing markers of red ginseng (RG) quality, and ginsenoside ratios are also indicative of the different components of red ginseng. For the analysis and classification of ginsenoside content, red ginseng was separated into three parts, namely, main roots, lateral roots, and fine roots, and each extract was subjected to ultra-performance liquid chromatography quadruple time-of-flight mass spectrometry (UPLC-QToF-MS) with multivariate statistical analysis. Principal component analysis (PCA) showed a clear discrimination between the extracts of main roots and fine roots and suggested discrimination markers (four for the main roots and five for the fine roots). The fine root markers were identified as ginsenoside. We identified two markers for the main roots of red ginseng in this study. Moreover, the contents of 22 ginsenosides were analyzed in all three components of red ginseng. Fine roots have the highest protopanaxadiol (PPD)/protopanaxatriol (PPT) ratio. The PPD group of ginsenosides, which is quantitatively dominant in fine roots, clearly distinguishes the main roots from the other parts. Full article

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

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13 pages, 3114 KiB

Open AccessArticle

A Flavone Constituent from Myoporum bontioides Induces M-Phase Cell Cycle Arrest of MCF-7 Breast Cancer Cells

by Jing-Ru Weng, Li-Yuan Bai, Wei-Yu Lin, Chang-Fang Chiu, Yu-Chang Chen, Shi-Wei Chao and Chia-Hsien Feng

Molecules 2017, 22(3), 472; https://doi.org/10.3390/molecules22030472 - 15 Mar 2017

Cited by 16 | Viewed by 5800

Abstract

Abstract: Myoporum bontioides is a traditional medicinal plant in Asia with various biological activities, including anti-inflammatory and anti-bacterial characteristics. To identify the bioactive constituents from M. bontioides, a newly-identified flavone, 3,4′-dimethoxy-3′,5,7-trihydroxyflavone (compound 1), along with eight known compounds, were investigated [...] Read more.

Abstract: Myoporum bontioides is a traditional medicinal plant in Asia with various biological activities, including anti-inflammatory and anti-bacterial characteristics. To identify the bioactive constituents from M. bontioides, a newly-identified flavone, 3,4′-dimethoxy-3′,5,7-trihydroxyflavone (compound 1), along with eight known compounds, were investigated in human MCF-7 breast cancer, SCC4 oral cancer, and THP-1 monocytic leukemia cells. Among these compounds, compound 1 exhibited the strongest antiproliferative activity with half-maximal inhibitory concentration (IC₅₀) values ranging from 3.3 μM (MCF-7) to 8.6 μM (SCC4). Flow cytometric analysis indicated that compound 1 induced G2/M cell cycle arrest in MCF-7 cells. Mechanistic evidence suggests that the G2/M arrest could be attributable to compound 1’s modulatory effects on the phosphorylation and expression of numerous key signaling effectors, including cell division cycle 2 (CDC2), CDC25C, and p53. Notably, compound 1 downregulated the expression of histone deacetylase 2 (HDAC2) and HDAC4, leading to increased histone H3 acetylation and p21 upregulation. Together, these findings suggest the translational potential of compound 1 as a breast cancer treatment. Full article

(This article belongs to the Section Natural Products Chemistry)

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13 pages, 885 KiB

Open AccessArticle

Valorization of Phosphorus Secondary Raw Materials by Acidithiobacillus ferrooxidans

by Małgorzata Wyciszkiewicz, Agnieszka Saeid, Przemysław Malinowski and Katarzyna Chojnacka

Molecules 2017, 22(3), 473; https://doi.org/10.3390/molecules22030473 - 16 Mar 2017

Cited by 24 | Viewed by 6104

Abstract

This paper presents the possibility of producing phosphorus fertilizers through Acidithiobacillus ferrooxidans utilization in secondary raw materials solubilization. Phosphorus was obtained from the bones of poultry and fish as well as from Morocco phosphorite. Four doses of poultry bones and fish bones were [...] Read more.

This paper presents the possibility of producing phosphorus fertilizers through Acidithiobacillus ferrooxidans utilization in secondary raw materials solubilization. Phosphorus was obtained from the bones of poultry and fish as well as from Morocco phosphorite. Four doses of poultry bones and fish bones were used in the experiment (2, 4, 10 and 20 g/L) and two doses (2 and 4 g/L) of phosphorite were also used. The experimenters measured the final pH, which increased in proportion to the increase in the number of poultry bone doses, whereas in the case of fish bones it decreased in proportion to the increase in the number of fish bone doses. Only in the case of phosphorite, where 10 g/L were used, there was a slight increase in pH during solubilization observed. The highest phosphorus concentration of 1.9% (expressed as P₂O₅) was found for the solubilization performed on fish bones with the highest dose (20 g/L). The formulation obtained in this study meets the necessary requirements for use as a bio-fertilizer because of the relatively low content of P₂O₅ and the low content of toxic elements. The results confirm the utilization of Acidithiobacillus ferrooxidans in the biosolubilization of phosphorus renewable raw materials that can alleviate the problem of the world’s depleting phosphorite deposits. Full article

(This article belongs to the Special Issue Green Production of Bioactive Natural Products)

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14 pages, 1872 KiB

Open AccessFeature PaperArticle

Anti-Cancer Activity of Resveratrol and Derivatives Produced by Grapevine Cell Suspensions in a 14 L Stirred Bioreactor

by Laetitia Nivelle, Jane Hubert, Eric Courot, Philippe Jeandet, Aziz Aziz, Jean-Marc Nuzillard, Jean-Hugues Renault, Christophe Clément, Laurent Martiny, Dominique Delmas and Michel Tarpin

Molecules 2017, 22(3), 474; https://doi.org/10.3390/molecules22030474 - 16 Mar 2017

Cited by 61 | Viewed by 7775

Abstract

In the present study, resveratrol and various oligomeric derivatives were obtained from a 14 L bioreactor culture of elicited grapevine cell suspensions (Vitis labrusca L.). The crude ethyl acetate stilbene extract obtained from the culture medium was fractionated by centrifugal partition chromatography [...] Read more.

In the present study, resveratrol and various oligomeric derivatives were obtained from a 14 L bioreactor culture of elicited grapevine cell suspensions (Vitis labrusca L.). The crude ethyl acetate stilbene extract obtained from the culture medium was fractionated by centrifugal partition chromatography (CPC) using a gradient elution method and the major stilbenes contained in the fractions were subsequently identified by using a ¹³C-NMR-based dereplication procedure and further 2D NMR analyses including HSQC, HMBC, and COSY. Beside δ-viniferin (2), leachianol F (4) and G (4′), four stilbenes (resveratrol (1), ε-viniferin (5), pallidol (3) and a newly characterized dimer (6)) were recovered as pure compounds in sufficient amounts to allow assessment of their biological activity on the cell growth of three different cell lines, including two human skin malignant melanoma cancer cell lines (HT-144 and SKMEL-28) and a healthy human dermal fibroblast HDF line. Among the dimers obtained in this study, the newly characterized resveratrol dimer (6) has never been described in nature and its biological potential was evaluated here for the first time. ε-viniferin as well as dimer (6) showed IC₅₀ values on the three tested cell lines lower than the ones exerted by resveratrol and pallidol. However, activities of the first two compounds were significantly decreased in the presence of fetal bovine serum although that of resveratrol and pallidol was not. The differential tumor activity exerted by resveratrol on healthy and cancer lines was also discussed. Full article

(This article belongs to the Special Issue Improvements for Resveratrol Efficacy)

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9 pages, 1095 KiB

Open AccessArticle

Briarenols C–E, New Polyoxygenated Briaranes from the Octocoral Briareum excavatum

by Nan-Fu Chen, Yin-Di Su, Tsong-Long Hwang, Zuo-Jian Liao, Kuan-Hao Tsui, Zhi-Hong Wen, Yang-Chang Wu and Ping-Jyun Sung

Molecules 2017, 22(3), 475; https://doi.org/10.3390/molecules22030475 - 17 Mar 2017

Cited by 14 | Viewed by 4479

Abstract

Three new polyoxygenated briarane diterpenoids, briarenols C–E (1–3), were isolated from the octocoral Briareum excavatum. The structures of briaranes 1–3 were elucidated by interpretation of spectroscopic data, and the methylenecyclohexane ring in 1 was found to [...] Read more.

Three new polyoxygenated briarane diterpenoids, briarenols C–E (1–3), were isolated from the octocoral Briareum excavatum. The structures of briaranes 1–3 were elucidated by interpretation of spectroscopic data, and the methylenecyclohexane ring in 1 was found to exist in a twisted boat conformation. Briarenol D (2) displayed an inhibitory effect on the release of elastase by human neutrophils with an IC₅₀ value of 4.65 μM. Briarenol E (3) was found to inhibit the protein expression of pro-inflammatory inducible nitric oxide synthase (iNOS) in a murine macrophage-like cell line, RAW 264.7, stimulated with lipopolysaccharides (LPS). Full article

(This article belongs to the Section Natural Products Chemistry)

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20 pages, 2954 KiB

Open AccessArticle

Analysis of Chemical Constituents of Melastoma dodecandrum Lour. by UPLC-ESI-Q-Exactive Focus-MS/MS

by Jinfeng Wang, Ziyao Jia, Zhihao Zhang, Yutong Wang, Xi Liu, Linghua Wang and Ruichao Lin

Molecules 2017, 22(3), 476; https://doi.org/10.3390/molecules22030476 - 17 Mar 2017

Cited by 79 | Viewed by 8637

Abstract

The ethnic drug Melastoma dodecandrum Lour. (MDL) is widely distributed throughout South China, and is the major component of Gong Yan Ping Tablets/Capsules and Zi Di Ning Xue San. Although the pharmacological effects of MDL have been well documented, its chemical profile has [...] Read more.

The ethnic drug Melastoma dodecandrum Lour. (MDL) is widely distributed throughout South China, and is the major component of Gong Yan Ping Tablets/Capsules and Zi Di Ning Xue San. Although the pharmacological effects of MDL have been well documented, its chemical profile has not been fully determined. In this study, we have developed a rapid and sensitive UPLC-ESI-Q-Exactive Focus-MS/MS method to characterize the chemical constituents of MDL in the positive and negative ionization modes. A comparison of the chromatographic and spectrometric data obtained using this method with data from databases, the literature and reference standards allowed us to identify or tentatively characterize 109 compounds, including 26 fatty acids, 26 organic acids, 33 flavonoids, six tannins, 10 triterpenoids, two steroids and six other compounds. Notably, 55 of the compounds characterized in this study have never been detected before in this plant. The information obtained in this study therefore enriches our understanding of the chemical composition of MDL and could be used in quality control, pharmacological research and the development of drugs based on MDL. In addition, this study represents the first reported comprehensive analysis of the chemical constituents of MDL. Full article

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16 pages, 2420 KiB

Open AccessArticle

Quality Evaluation and Chemical Markers Screening of Salvia miltiorrhiza Bge. (Danshen) Based on HPLC Fingerprints and HPLC-MSⁿ Coupled with Chemometrics

by Wenyi Liang, Wenjing Chen, Lingfang Wu, Shi Li, Qi Qi, Yaping Cui, Linjin Liang, Ting Ye and Lanzhen Zhang

Molecules 2017, 22(3), 478; https://doi.org/10.3390/molecules22030478 - 17 Mar 2017

Cited by 69 | Viewed by 7958

Abstract

Danshen, the dried root of Salvia miltiorrhiza Bge., is a widely used commercially available herbal drug, and unstable quality of different samples is a current issue. This study focused on a comprehensive and systematic method combining fingerprints and chemical identification with chemometrics for [...] Read more.

Danshen, the dried root of Salvia miltiorrhiza Bge., is a widely used commercially available herbal drug, and unstable quality of different samples is a current issue. This study focused on a comprehensive and systematic method combining fingerprints and chemical identification with chemometrics for discrimination and quality assessment of Danshen samples. Twenty-five samples were analyzed by HPLC-PAD and HPLC-MSⁿ. Forty-nine components were identified and characteristic fragmentation regularities were summarized for further interpretation of bioactive components. Chemometric analysis was employed to differentiate samples and clarify the quality differences of Danshen including hierarchical cluster analysis, principal component analysis, and partial least squares discriminant analysis. Consistent results were that the samples were divided into three categories which reflected the difference in quality of Danshen samples. By analyzing the reasons for sample classification, it was revealed that the processing method had a more obvious impact on sample classification than the geographical origin, it induced the different content of bioactive compounds and finally lead to different qualities. Cryptotanshinone, trijuganone B, and 15,16-dihydrotanshinone I were screened out as markers to distinguish samples by different processing methods. The developed strategy could provide a reference for evaluation and discrimination of other traditional herbal medicines. Full article

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18 pages, 2384 KiB

Open AccessArticle

Design of New Benzo[h]chromene Derivatives: Antitumor Activities and Structure-Activity Relationships of the 2,3-Positions and Fused Rings at the 2,3-Positions

by Rawda M. Okasha, Fawzia F. Alblewi, Tarek H. Afifi, Arshi Naqvi, Ahmed M. Fouda, Al-Anood M. Al-Dies and Ahmed M. El-Agrody

Molecules 2017, 22(3), 479; https://doi.org/10.3390/molecules22030479 - 18 Mar 2017

Cited by 51 | Viewed by 8328

Abstract

A series of novel 4H-benzo[h]chromenes 4, 6–11, 13, 14; 7H-benzo[h]chromeno[2,3-d]pyrimidines 15–18, 20, and 14H-benzo[h]chromeno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidine derivatives [...] Read more.

A series of novel 4H-benzo[h]chromenes 4, 6–11, 13, 14; 7H-benzo[h]chromeno[2,3-d]pyrimidines 15–18, 20, and 14H-benzo[h]chromeno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidine derivatives 19a–e, 24 was prepared. The structures of the synthesized compounds were characterized on the basis of their spectral data. Some of the target compounds were examined for their antiproliferative activity against three cell lines; breast carcinoma (MCF-7), human colon carcinoma (HCT-116) and hepatocellular carcinoma (HepG-2). The cytotoxic behavior has been tested using MTT assay and the inhibitory activity was referenced to three standard anticancer drugs: vinblastine, colchicine and doxorubicin. The bioassays demonstrated that some of the new compounds exerted remarkable inhibitory effects as compared to the standard drugs on the growth of the three tested human tumor cell lines. The structure–activity relationships (SAR) study highlights that the antitumor activity of the target compounds was significantly affected by the lipophilicity of the substituent at 2- or 3- and fused rings at the 2,3-positions. Full article

(This article belongs to the Collection Heterocyclic Compounds)

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20 pages, 5367 KiB

Open AccessArticle

Energy of Intramolecular Hydrogen Bonding in ortho-Hydroxybenzaldehydes, Phenones and Quinones. Transfer of Aromaticity from ipso-Benzene Ring to the Enol System(s)

by Danuta Rusinska-Roszak

Molecules 2017, 22(3), 481; https://doi.org/10.3390/molecules22030481 - 18 Mar 2017

Cited by 40 | Viewed by 14072

Abstract

Intramolecular hydrogen bonding (HB) is one of the most studied noncovalent interactions of molecules. Many physical, spectral, and topological properties of compounds are under the influence of HB, and there are many parameters used to notice and to describe these changes. Hitherto, no [...] Read more.

Intramolecular hydrogen bonding (HB) is one of the most studied noncovalent interactions of molecules. Many physical, spectral, and topological properties of compounds are under the influence of HB, and there are many parameters used to notice and to describe these changes. Hitherto, no general method of measurement of the energy of intramolecular hydrogen bond (E_HB) has been put into effect. We propose the molecular tailoring approach (MTA) for E_HB calculation, modified to apply it to Ar-O-H∙∙∙O=C systems. The method, based on quantum calculations, was checked earlier for hydroxycarbonyl-saturated compounds, and for structures with resonance-assisted hydrogen bonding (RAHB). For phenolic compounds, the accuracy, repeatability, and applicability of the method is now confirmed for nearly 140 structures. For each structure its aromaticity HOMA indices were calculated for the central (ipso) ring and for the quasiaromatic rings given by intramolecular HB. The comparison of calculated HB energies and values of estimated aromaticity indices allowed us to observe, in some substituted phenols and quinones, the phenomenon of transfer of aromaticity from the ipso-ring to the H-bonded ring via the effect of electron delocalization. Full article

(This article belongs to the Special Issue Intramolecular Hydrogen Bonding 2017)

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11 pages, 765 KiB

Open AccessArticle

In Vitro Antioxidant Activity and In Vivo Anti-Fatigue Effect of Sea Horse (Hippocampus) Peptides

by Zebin Guo, Duanquan Lin, Juanjuan Guo, Yi Zhang and Baodong Zheng

Molecules 2017, 22(3), 482; https://doi.org/10.3390/molecules22030482 - 18 Mar 2017

Cited by 65 | Viewed by 7477

Abstract

This study investigated changes the in vitro antioxidant activity of Hippocampus polypeptides during enzymatic hydrolysis, including the effects of enzyme species, enzyme concentration, material–liquid ratio, hydrolysis time, pH, and temperature of the reaction system. Its in vivo anti-fatigue activity was also studied. Hippocampus [...] Read more.

This study investigated changes the in vitro antioxidant activity of Hippocampus polypeptides during enzymatic hydrolysis, including the effects of enzyme species, enzyme concentration, material–liquid ratio, hydrolysis time, pH, and temperature of the reaction system. Its in vivo anti-fatigue activity was also studied. Hippocampus peptide prepared by papain digestion exhibited the highest 1,1-diphenyl-2-picryl-hydrazyl free radical scavenging rate (71.89% ± 1.50%) and strong hydroxyl radical scavenging rate (75.53% ± 0.98%), compared to those prepared by five other commonly used enzymes (i.e., trypsin, neutral protease, compound protease, flavorzyme, and alkaline protease). Additionally, maximum antioxidant activity of Hippocampus polypeptide prepared by papain digestion was reached after hydrolysis for 40 min at pH 6.0 and 60 °C of the reaction system by using 2000 U/g enzyme and a material–liquid ratio of 1:15. Moreover, compared with the control group, Hippocampus peptide prolonged the swimming time by 33%–40%, stabilized the blood glucose concentration, increased liver glycogen levels, and decreased blood lactate levels and blood urea nitrogen levels in mice (p < 0.01). In conclusion, these results indicated that Hippocampus polypeptide prepared by papain digestion under optimal conditions exhibited high degrees of antioxidant and anti-fatigue activity. Full article

(This article belongs to the Special Issue Selected papers from 2nd International Symposium on Phytochemicals in Medicine and Food (2-ISPMF, Fuzhou, 2017))

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16 pages, 632 KiB

Open AccessArticle

Synthesis of Randomly Substituted Anionic Cyclodextrins in Ball Milling

by László Jicsinszky, Marina Caporaso, Emanuela Calcio Gaudino, Cristina Giovannoli and Giancarlo Cravotto

Molecules 2017, 22(3), 485; https://doi.org/10.3390/molecules22030485 - 19 Mar 2017

Cited by 13 | Viewed by 5601

Abstract

A number of influencing factors mean that the random substitution of cyclodextrins (CD) in solution is difficult to reproduce. Reaction assembly in mechanochemistry reduces the number of these factors. However, lack of water can improve the reaction outcomes by minimizing the reagent’s hydrolysis. [...] Read more.

A number of influencing factors mean that the random substitution of cyclodextrins (CD) in solution is difficult to reproduce. Reaction assembly in mechanochemistry reduces the number of these factors. However, lack of water can improve the reaction outcomes by minimizing the reagent’s hydrolysis. High-energy ball milling is an efficient, green and simple method for one-step reactions and usually reduces degradation and byproduct formation. Anionic CD derivatives have successfully been synthesized in the solid state, using a planetary ball mill. Comparison with solution reactions, the solvent-free conditions strongly reduced the reagent hydrolysis and resulted in products of higher degree of substitution (DS) with more homogeneous DS distribution. The synthesis of anionic CD derivatives can be effectively performed under mechanochemical activation without significant changes to the substitution pattern but the DS distributions were considerably different from the products of solution syntheses. Full article

(This article belongs to the Special Issue Cyclodextrin Chemistry)

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13 pages, 3744 KiB

Open AccessArticle

Ginsenoside PPD’s Antitumor Effect via Down-Regulation of mTOR Revealed by Super-Resolution Imaging

by Bo Teng, Junguang Jiang, Lijing Zhao, Jing Gao, Junyu Chen, Zhe Liu, Hongda Wang and Binfeng Lu

Molecules 2017, 22(3), 486; https://doi.org/10.3390/molecules22030486 - 19 Mar 2017

Cited by 16 | Viewed by 6382

Abstract

Derived from Panax ginseng, the natural product 20(S)-Protopanaxadiol (PPD) has been reported for its cytotoxicity against several cancer cell lines. The molecular mechanism is, however, not well understood. Here we show that PPD significantly inhibits proliferation, induces apoptosis and causes [...] Read more.

Derived from Panax ginseng, the natural product 20(S)-Protopanaxadiol (PPD) has been reported for its cytotoxicity against several cancer cell lines. The molecular mechanism is, however, not well understood. Here we show that PPD significantly inhibits proliferation, induces apoptosis and causes G2/M cell cycle arrest in human laryngeal carcinoma cells (Hep-2 cells). PPD also decreases the levels of proteins related to cell proliferation. Moreover, PPD-induced apoptosis is characterized by a dose-dependent down-regulation of Bcl-2 expression and up-regulation of Bax, and is accompanied by the activation of Caspase-3 as well. Further molecular mechanism is revealed by direct stochastic optical reconstruction microscopy (dSTORM)—a novel high-precision localization microscopy which enables effective resolution down to the order of 10 nm. It shows the expression and spatial arrangement of mTOR and its downstream effectors, demonstrating that this ginsenoside exerts its excellent anticancer effects via down-regulation of mTOR signaling pathway in Hep-2 cells. Taken together, our findings elucidate that the antitumor effect of PPD is associated with its regulation of mTOR expression and distribution, which encourages further studies of PPD as a promising therapeutic agent against laryngeal carcinoma. Full article

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

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15 pages, 1264 KiB

Open AccessArticle

Effects of Momordica charantia (Bitter Melon) on Ischemic Diabetic Myocardium

by Attila Czompa, Alexandra Gyongyosi, Kitti Szoke, Istvan Bak, Evelin Csepanyi, David D. Haines, Arpad Tosaki and Istvan Lekli

Molecules 2017, 22(3), 488; https://doi.org/10.3390/molecules22030488 - 20 Mar 2017

Cited by 16 | Viewed by 7358

Abstract

Objective: A rat model is here used to test a hypothesis that Momordica charantia (Bitter melon (BM)) extract favorably alters processes in cardiovascular tissue and is systemically relevant to the pathophysiology of type 2 diabetes (T2DM) and related cardiovascular disease. Methods: [...] Read more.

Objective: A rat model is here used to test a hypothesis that Momordica charantia (Bitter melon (BM)) extract favorably alters processes in cardiovascular tissue and is systemically relevant to the pathophysiology of type 2 diabetes (T2DM) and related cardiovascular disease. Methods: Male Lean and Zucker Obese (ZO) rats were gavage-treated for six weeks with 400 mg/kg body weight bitter melon (BM) extract suspended in mucin–water vehicle, or with vehicle (Control). Animals were segregated into four treatment groups, 10 animals in each group, according to strain (Lean or ZO) and treatment (Control or BM). Following six-week treatment periods, peripheral blood was collected from selected animals, followed by sacrifice, thoracotomy and mounting of isolated working heart setup. Results: Body mass of both Lean and ZO rats was unaffected by treatment, likewise, peripheral blood fasting glucose levels showed no significant treatment-related effects. However, some BM treatment-related improvement was noted in postischemic cardiac functions when Lean, BM-treated animals were compared to vehicle treated Lean control rats. Treatment of Lean, but not ZO, rats significantly reduced the magnitude of infarcted zone in isolated hearts subjected to 30 min of ischemia followed by 2 h of working mode reperfusion. Immunohistochemical demonstration of caspase-3 expression by isolated heart tissues subjected to 30 min of ischemia followed by 2 h of reperfusion, revealed significant correlation between BM treatment and reduced expression of this enzyme in hearts obtained from both Lean and ZO animals. The hierarchy and order of caspase-3 expression from highest to lowest was as follows: ZO rats receiving vehicle > ZO rats receiving BM extract > Lean rats treated receiving vehicle > Lean rats administered BM extract. Outcomes of analyses of peripheral blood content of cardiac-related analytics: with particular relevance to clinical application was a significant elevation in blood of ZO and ZO BM-treated, versus Lean rats of total cholesterol (high density lipoprotein HDL-c + low density lipoprotein LDL-c), with an inferred increase in HDL-c/LDL-c ratio—an outcome associated with decreased risk of atherosclerotic disease. Conclusions: BM extract failed to positively affect T2DM- and cardiovascular-related outcomes at a level suggesting use as a standalone treatment. Nevertheless, the encouraging effects of BM in enhancement of cardiac function, suppression of post-ischemic/reperfused infarct size extent and capacity to modulate serum cholesterol, will likely make it useful as an adjuvant therapy for the management of T2DM and related cardiovascular diseases. Full article

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9 pages, 2505 KiB

Open AccessArticle

[2 + 2] Photodimerization of Naphthylvinylpyridines through Cation-π Interactions in Acidic Solution

by Shinji Yamada and Yuka Nojiri

Molecules 2017, 22(3), 491; https://doi.org/10.3390/molecules22030491 - 20 Mar 2017

Cited by 13 | Viewed by 5263

Abstract

Irradiation of (E)-4-(2-(2-naphthyl)vinyl)pyridine (1a) and (E)-4-(2-(1-naphthyl)vinyl)pyridine (1b) with a 250 W high-pressure mercury lamp in acidic solution afforded synHT dimers in high stereoselectivities. Similar results were obtained by visible light irradiation. On the other [...] Read more.

Irradiation of (E)-4-(2-(2-naphthyl)vinyl)pyridine (1a) and (E)-4-(2-(1-naphthyl)vinyl)pyridine (1b) with a 250 W high-pressure mercury lamp in acidic solution afforded synHT dimers in high stereoselectivities. Similar results were obtained by visible light irradiation. On the other hand, when the reactions were carried out under neutral conditions, the stereoselectivities were very low, and the yields were decreased by visible light irradiation. Comparison of the UV-vis spectra between the acidic and the neutral conditions elucidated that the red shift was observed in acidic solutions. These results show that HCl plays essential roles not only in the preorientation of substrates through cation-π interactions, but also in the changes in the absorption properties of substrates that enable visible light reactions. Full article

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

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15 pages, 2012 KiB

Open AccessArticle

New Chiral Ebselen Analogues with Antioxidant and Cytotoxic Potential

by Agata J. Pacuła, Katarzyna B. Kaczor, Jędrzej Antosiewicz, Anna Janecka, Angelika Długosz, Tomasz Janecki, Andrzej Wojtczak and Jacek Ścianowski

Molecules 2017, 22(3), 492; https://doi.org/10.3390/molecules22030492 - 20 Mar 2017

Cited by 42 | Viewed by 8078

Abstract

New chiral camphane-derived benzisoselenazol-3(2H)-ones and corresponding diselenides have been synthetized using a convenient one-pot procedure. Se-N bond was efficiently converted to an Se-Se bond, which could also be easily re-oxidized to the initial benzisoselenazolone moiety. The antioxidant activity of camphor derivatives [...] Read more.

New chiral camphane-derived benzisoselenazol-3(2H)-ones and corresponding diselenides have been synthetized using a convenient one-pot procedure. Se-N bond was efficiently converted to an Se-Se bond, which could also be easily re-oxidized to the initial benzisoselenazolone moiety. The antioxidant activity of camphor derivatives was evaluated and compared to the reactivity of a series of N-amino acid benzisoselenazol-3(2H)-ones obtained by a modified procedure involving the improved synthesis and isolation of the diseleno bis(dibenzoic) acid. The most efficient peroxide scavengers, N-bornyl and N-leucine methyl ester benzisoselenazol-3(2H)-ones, were further evaluated as cytotoxic agents on four cancer cell lines (MCF-7, HEP G2, HL 6, and DU 145) and normal cell line PNT1A. The highest antiproliferative potential was evaluated for two compounds bearing a 3-methylbutyl carbon chain, N-leucine methyl ester and N-3-methylbutyl benzisoselenazol-3(2H)-ones. 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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24 pages, 7314 KiB

Open AccessArticle

Nonradiative Relaxation Mechanisms of UV Excited Phenylalanine Residues: A Comparative Computational Study

by Momir Mališ and Nađa Došlić

Molecules 2017, 22(3), 493; https://doi.org/10.3390/molecules22030493 - 21 Mar 2017

Cited by 8 | Viewed by 5620

Abstract

The present work is directed toward understanding the mechanisms of excited state deactivation in three neutral model peptides containing the phenylalanine residue. The excited state dynamics of the

γ_{L} (g +)

folded form of N-acetylphenylalaninylamide (NAPA B) and its [...] Read more.

The present work is directed toward understanding the mechanisms of excited state deactivation in three neutral model peptides containing the phenylalanine residue. The excited state dynamics of the

γ_{L} (g +)

folded form of N-acetylphenylalaninylamide (NAPA B) and its amide-N-methylated derivative (NAPMA B) is reviewed and compared to the dynamics of the monohydrated structure of NAPA (NAPAH). The goal is to unravel how the environment, and in particular solvation, impacts the photodynamics of peptides. The systems are investigated using reaction path calculations and surface hopping nonadiabatic dynamics based on the coupled cluster doubles (CC2) method and time-dependent density functional theory. The work emphasizes the role that excitation transfer from the phenyl

π π^{*}

to amide

n π^{*}

state plays in the deactivation of the three systems and shows how the ease of out-of-plane distortions of the amide group determines the rate of population transfer between the two electronic states. The subsequent dynamics on the

n π^{*}

state is barrierless along several pathways and leads to fast deactivation to the ground electronic state. Full article

(This article belongs to the Special Issue Experimental and Computational Photochemistry of Bioorganic Molecules)

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13 pages, 2465 KiB

Open AccessArticle

Profiling and Preparation of Metabolites from Pyragrel in Human Urine by Online Solid-Phase Extraction Coupled with High Performance Liquid Chromatography Tandem Mass Spectrometry Followed by a Macroporous Resin-Based Purification Approach

by Xin Zhao, Jingjing Jiang, Guang Yang, Jie Huang, Guoping Yang, Guangwei He, Zhaoxing Chu, Taijun Hang and Guorong Fan

Molecules 2017, 22(3), 494; https://doi.org/10.3390/molecules22030494 - 21 Mar 2017

Cited by 8 | Viewed by 6031

Abstract

Pyragrel, a new anticoagulant drug, is derived from the molecular combination of ligustrazine and ferulic acid. Pyragrel showed significant inhibitory activity against platelet aggregation induced by adenosine diphosphate (ADP), and had been approved for a phase I clinical trial by CFDA. To characterize [...] Read more.

Pyragrel, a new anticoagulant drug, is derived from the molecular combination of ligustrazine and ferulic acid. Pyragrel showed significant inhibitory activity against platelet aggregation induced by adenosine diphosphate (ADP), and had been approved for a phase I clinical trial by CFDA. To characterize the metabolites of Pyragrel in human urine after intravenous administration, a reliable online solid-phase extraction couple with high performance liquid chromatography tandem mass spectrometry (online SPE-HPLC-MSⁿ) method was conceived and applied. Five metabolites were detected and tentatively identified, which suggested that the major metabolic pathways of Pyragrel in human were double-bond reduction, double-bond oxidation, and then followed by glucuronide conjugation. Two main metabolites were then prepared using β-glucuronide hydrolysis and macroporous resin purification approach followed by preparative high-performance liquid chromatography (PHPLC) method, with their structures confirmed on the basis of nuclear magnetic resonance (NMR) data. This study provided information for the further study of the metabolism and excretion of Pyragrel. Full article

(This article belongs to the Section Metabolites)

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15 pages, 1086 KiB

Open AccessArticle

3-Substituted N-Benzylpyrazine-2-carboxamide Derivatives: Synthesis, Antimycobacterial and Antibacterial Evaluation

by Lucia Semelková, Ondřej Janďourek, Klára Konečná, Pavla Paterová, Lucie Navrátilová, František Trejtnar, Vladimír Kubíček, Jiří Kuneš, Martin Doležal and Jan Zitko

Molecules 2017, 22(3), 495; https://doi.org/10.3390/molecules22030495 - 21 Mar 2017

Cited by 10 | Viewed by 5016

Abstract

A series of substituted N-benzyl-3-chloropyrazine-2-carboxamides were prepared as positional isomers of 5-chloro and 6-chloro derivatives, prepared previously. During the aminolysis of the acyl chloride, the simultaneous substitution of chlorine with benzylamino moiety gave rise to N-benzyl-3-(benzylamino)pyrazine-2-carboxamides as side products, in some [...] Read more.

A series of substituted N-benzyl-3-chloropyrazine-2-carboxamides were prepared as positional isomers of 5-chloro and 6-chloro derivatives, prepared previously. During the aminolysis of the acyl chloride, the simultaneous substitution of chlorine with benzylamino moiety gave rise to N-benzyl-3-(benzylamino)pyrazine-2-carboxamides as side products, in some cases. Although not initially planned, the reaction conditions were modified to populate this double substituted series. The final compounds were tested against four mycobacterial strains. N-(2-methylbenzyl)-3-((2-methylbenzyl)amino)pyrazine-2-carboxamide (1a) and N-(3,4-dichlorobenzyl)-3-((3,4-dichlorobenzyl)amino)pyrazine-2-carboxamide (9a) proved to be the most effective against Mycobacterium tuberculosis H37Rv, with MIC = 12.5 μg·mL⁻¹. Compounds were screened for antibacterial activity. The most active compound was 3-chloro-N-(2-chlorobenzyl)pyrazine-2-carboxamide (5) against Staphylococcus aureus with MIC = 7.81 μM, and Staphylococcus epidermidis with MIC = 15.62 μM. HepG2 in vitro cytotoxicity was evaluated for the most active compounds; however, no significant toxicity was detected. Compound 9a was docked to several conformations of the enoyl-ACP-reductase of Mycobacterium tuberculosis. In some cases, it was capable of H-bond interactions, typical for most of the known inhibitors. Full article

(This article belongs to the Section Medicinal Chemistry)

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14 pages, 3967 KiB

Open AccessArticle

GC-MS Metabolomic Analysis to Reveal the Metabolites and Biological Pathways Involved in the Developmental Stages and Tissue Response of Panax ginseng

by Jia Liu, Yang Liu, Yu Wang, Ann Abozeid, Yuan-Gang Zu, Xiao-Ning Zhang and Zhong-Hua Tang

Molecules 2017, 22(3), 496; https://doi.org/10.3390/molecules22030496 - 21 Mar 2017

Cited by 35 | Viewed by 7698

Abstract

Ginsenosides, the major compounds present in ginseng, are known to have numerous physiological and pharmacological effects. The physiological processes, enzymes and genes involved in ginsenoside synthesis in P. ginseng have been well characterized. However, relatively little information is known about the dynamic metabolic [...] Read more.

Ginsenosides, the major compounds present in ginseng, are known to have numerous physiological and pharmacological effects. The physiological processes, enzymes and genes involved in ginsenoside synthesis in P. ginseng have been well characterized. However, relatively little information is known about the dynamic metabolic changes that occur during ginsenoside accumulation in ginseng. To explore this topic, we isolated metabolites from different tissues at different growth stages, and identified and characterized them by using gas chromatography coupled with mass spectrometry (GC-MS). The results showed that a total of 30, 16, 20, 36 and 31 metabolites were identified and involved in different developmental stages in leaf, stem, petiole, lateral root and main root, respectively. To investigate the contribution of tissue to the biosynthesis of ginsenosides, we examined the metabolic changes of leaf, stem, petiole, lateral root and main root during five development stages: 1-, 2-, 3-, 4- and 5-years. The score plots of partial least squares-discriminate analysis (PLS-DA) showed clear discrimination between growth stages and tissue samples. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis in the same tissue at different growth stages indicated profound biochemical changes in several pathways, including carbohydrate metabolism and pentose phosphate metabolism, in addition, the tissues displayed significant variations in amino acid metabolism, sugar metabolism and energy metabolism. These results should facilitate further dissection of the metabolic flux regulation of ginsenoside accumulation in different developmental stages or different tissues of ginseng. Full article

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

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12 pages, 5602 KiB

Open AccessArticle

Biosynthesis of Oligomeric Anthocyanins from Grape Skin Extracts

by Jin-Woo Hwang, Sithranga Boopathy Natarajan, Yon-Suk Kim, Eun-Kyung Kim, Jae Woong Lee, Sang-Ho Moon, Byong-Tae Jeon and Pyo-Jam Park

Molecules 2017, 22(3), 497; https://doi.org/10.3390/molecules22030497 - 21 Mar 2017

Cited by 9 | Viewed by 6532

Abstract

We synthesized oligomeric anthocyanins from grape skin-derived monomeric anthocyanins such as anthocyanidin and proanthocyanidin by a fermentation technique using Aspergillus niger, crude enzymes and glucosidase. The biosyntheses of the oligomeric anthocyanins carried out by the conventional method using Aspergillus niger and crude [...] Read more.

We synthesized oligomeric anthocyanins from grape skin-derived monomeric anthocyanins such as anthocyanidin and proanthocyanidin by a fermentation technique using Aspergillus niger, crude enzymes and glucosidase. The biosyntheses of the oligomeric anthocyanins carried out by the conventional method using Aspergillus niger and crude enzymes were confirmed by ESI-MS. The molecular weight of the synthesized anthocyanin oligomers was determined using MALDI-MS. The yield of anthocyanin oligomers using crude enzymes was higher than that of the synthesis using Aspergillus fermentation. Several studies have been demonstrated that oligomeric anthocyanins have higher antioxidant activity than monomeric anthocyanins. Fermentation-based synthesis of oligomeric anthocyanins is an alternative way of producing useful anthocyanins that could support the food industry. Full article

(This article belongs to the Special Issue Green Production of Bioactive Natural Products)

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10 pages, 1051 KiB

Open AccessArticle

The Effects of Sweet Foods on the Pharmacokinetics of Glycyrrhizic Acid by icELISA

by Bingqian Jiang, Huihua Qu, Hui Kong, Yue Zhang, Shuchen Liu, Jinjun Cheng, Xin Yan and Yan Zhao

Molecules 2017, 22(3), 498; https://doi.org/10.3390/molecules22030498 - 21 Mar 2017

Cited by 7 | Viewed by 4659

Abstract

The effect of sweet foods, such as honey, was investigated from the perspective of pharmacokinetics on the absorption of glycyrrhizic acid (GA). Due to the unique properties of indirect competitive enzyme-linked immunosorbent assay (icELISA), namely, its: specificity, sensitivity, repeatability, simple pretreatment of samples, [...] Read more.

The effect of sweet foods, such as honey, was investigated from the perspective of pharmacokinetics on the absorption of glycyrrhizic acid (GA). Due to the unique properties of indirect competitive enzyme-linked immunosorbent assay (icELISA), namely, its: specificity, sensitivity, repeatability, simple pretreatment of samples, fast and simple operation, and because it is economic and non-polluting, it has received increased attention. In this study, we used the advantages of this method to see how honey affected the pharmacokinetics of GA. The effects of honey on the pharmacokinetics of GA by ELISA were investigated for the first time. The results indicate that honey can postpone the peak concentration of GA in mouse blood, and this effect correlates well with fructose. As a representative of sweet foods, the result provides the valuable information that honey, or fructose, may act as sustained-releasing drugs in clinical scenarios; and that sweet foods may have some influences on drugs when taken together. Full article

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

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10 pages, 2311 KiB

Open AccessArticle

Exploring the Antitumor Mechanism of High-Dose Cytarabine through the Metabolic Perturbations of Ribonucleotide and Deoxyribonucleotide in Human Promyelocytic Leukemia HL-60 Cells

by Zheng Li, Jian-Ru Guo, Qian-Qian Chen, Cai-Yun Wang, Wei-Jia Zhang, Mei-Cun Yao and Wei Zhang

Molecules 2017, 22(3), 499; https://doi.org/10.3390/molecules22030499 - 21 Mar 2017

Cited by 34 | Viewed by 12498

Abstract

Despite the apparent clinical benefits of high-dose cytarabine (Ara-C) over lower dose Ara-C in acute myeloid leukemia (AML) therapy, the mechanism behind high-dose Ara-C therapy remains uncertain. In this study, a LC-MS-based method was carried out to investigate the metabolic alteration of ribonucleotide [...] Read more.

Despite the apparent clinical benefits of high-dose cytarabine (Ara-C) over lower dose Ara-C in acute myeloid leukemia (AML) therapy, the mechanism behind high-dose Ara-C therapy remains uncertain. In this study, a LC-MS-based method was carried out to investigate the metabolic alteration of ribonucleotide and deoxyribonucleotide in human promyelocytic leukemia cells (HL-60) after treatment with Ara-C to reveal its antitumor mechanism. The metabolic results revealed that four nucleotides (ATP, ADP, CDP, and dCTP) could be used as potential biomarkers indicating the benefit of high-dose Ara-C over lower dose Ara-C treatment. Combining metabolic perturbation and cell cycle analysis, we conjectured that, apart from the acknowledged mechanism of Ara-C on tumor inhibition, high-dose Ara-C could present a specific action pathway. It was suggested that the pronounced rise in AMP/ATP ratio induced by high-dose Ara-C can trigger AMP-activated protein kinase (AMPK) and subsequently Forkhead Box, class O (FoxO), to promote cell cycle arrest. Moreover, the significant decrease in CDP pool induced by high-dose Ara-C might further accelerate the reduction of dCTP, which then aggravates DNA synthesis disturbance. As a result, all of these alterations led to heightened tumor inhibition. This study provides new insight in the investigation of potential mechanisms in the clinical benefits of high-dose Ara-C in therapy for AML. Full article

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

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11 pages, 1674 KiB

Open AccessArticle

Physicochemical Properties and Microbial Quality of Tremella aurantialba Packed in Antimicrobial Composite Films

by Jian Fan, Zhuangzhuang Chu, Lin Li, Tianrui Zhao, Min Yin and Yuyue Qin

Molecules 2017, 22(3), 500; https://doi.org/10.3390/molecules22030500 - 22 Mar 2017

Cited by 9 | Viewed by 5658

Abstract

The effects of poly(lactic acid) (PLA)-based film with inorganic antimicrobial nano-TiO₂ and nano-Ag on the physicochemical and microbial quality of Tremella aurantialba stored at 4 ± 1 °C for 16 days was investigated. Rosemary essential oil (REO, 9 wt %) was added [...] Read more.

The effects of poly(lactic acid) (PLA)-based film with inorganic antimicrobial nano-TiO₂ and nano-Ag on the physicochemical and microbial quality of Tremella aurantialba stored at 4 ± 1 °C for 16 days was investigated. Rosemary essential oil (REO, 9 wt %) was added into PLA film as plasticizer. Low-density polyethylene (LDPE) and PLA film was used as the controls. The experiment measured physicochemical properties and microbial levels, such as weight loss, firmness, vitamin C, color, microbiological quality, and sensory quality. Although Tremella aurantialba packed by nano-composite films had the highest weight loss (4.96% and 5.17%) at the end of storage, it was still in the vicinity of 5%. Tremella aurantialba packed with nano-composite films were significantly (p < 0.05) firmer than those packed by LDPE, PLA, and PLA/REO films. The nano-composite films were more effective in reducing vitamin C and microbial counts and preserving the color of Tremella aurantialba than the other three groups. The overall acceptability of Tremella aurantialba packed by the nano-composite films still remained good and within the limits of marketability after 12 days of storage. The results suggested that the proposed nano-composite films could maintain the quality of Tremella aurantialba and extend its postharvest life. Full article

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11 pages, 1677 KiB

Open AccessArticle

Synthesis, Characterization, and the Antioxidant Activity of Double Quaternized Chitosan Derivatives

by Lijie Wei, Qing Li, Wenqiang Tan, Fang Dong, Fang Luan and Zhanyong Guo

Molecules 2017, 22(3), 501; https://doi.org/10.3390/molecules22030501 - 22 Mar 2017

Cited by 41 | Viewed by 6399

Abstract

With the specialty of improving the water solubility of chitosan, quaternary ammonium salts have broadened the application of this polysaccharide in food, medicine and pesticides. To identify the effect of quaternary ammonium salts’ quantity, single quaternized chitosan N-phenmethyl-N,N-dimethyl [...] Read more.

With the specialty of improving the water solubility of chitosan, quaternary ammonium salts have broadened the application of this polysaccharide in food, medicine and pesticides. To identify the effect of quaternary ammonium salts’ quantity, single quaternized chitosan N-phenmethyl-N,N-dimethyl chitosan (PDCS), double quaternized chitosan N-(1-pyridylmethyl-2-ylmethyl)-N,N-dimethyl chitosan (MP2MDCS), N-(1-pyridylmethyl-3-ylmethyl)-N,N-dimethyl chitosan (MP3MDCS), and N-(1-pyridylmethyl-4-ylmethyl)-N,N-dimethyl chitosan (MP4MDCS) were designed and synthesized successfully through chemical modification of chitosan. Besides, three kinds of antioxidant activities, including hydroxyl radicals, superoxide radicals, and 1,1-Diphenyl-2-picrylhydrazyl (DPPH) radicals were tested in vitro. As shown in this paper, the scavenging ability was ranking in order of MP3MDC > MP4MDCS > MP2MDCS > PDCS > chitosan at 1.6 mg/mL in all assays. All double quaternary ammonium salts were better than chitosan or the single quaternary ammonium salt. In addition, MP3MDCS could scavenge hydroxyl radicals totally at 1.6 mg/mL. MP2MDCS and MP4MDCS with more than 90% scavenging indices both had great scavenging ability on hydroxyl radicals or DPPH radicals. Furthermore, these data demonstrated that the increasing number of the positive charge would improve the antioxidant property of chitosan derivatives, and the N-pyridinium position would influence the scavenging radical ability. Full article

(This article belongs to the Section Medicinal Chemistry)

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9 pages, 1274 KiB

Open AccessArticle

Carapanosins A–C from Seeds of Andiroba (Carapa guianensis, Meliaceae) and Their Effects on LPS-Activated NO Production

by Keiichiro Higuchi, Teppei Miyake, Shoko Ohmori, Yoshimi Tani, Katsuhiko Minoura, Takashi Kikuchi, Takeshi Yamada and Reiko Tanaka

Molecules 2017, 22(3), 502; https://doi.org/10.3390/molecules22030502 - 22 Mar 2017

Cited by 14 | Viewed by 5003

Abstract

Two new phragmalin-type limonoids, Carapanosins A and B (1 and 2), and a new gedunin-type limonoid, Carapansin C (3), together with five known limonoids (4–8) were isolated from the oil of Carapa guianensis A_UBLET [...] Read more.

Two new phragmalin-type limonoids, Carapanosins A and B (1 and 2), and a new gedunin-type limonoid, Carapansin C (3), together with five known limonoids (4–8) were isolated from the oil of Carapa guianensis A_UBLET (Meliaceae) seeds, a traditional medicine in Brazil and Latin American countries. Their structures were elucidated on the basis of spectroscopic analyses using 1D and 2D NMR techniques and HRFABMS. Compounds 1–8 were evaluated for their effects on the production of NO in LPS-activated mouse peritoneal macrophages. The NO inhibitory assay suggested that Compounds 3, 6, and 8 may be valuable as potential inhibitors of macrophage activation. Full article

(This article belongs to the Section Natural Products Chemistry)

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20 pages, 4684 KiB

Open AccessArticle

Consecutive One-Pot versus Domino Multicomponent Approaches to 3-(Diarylmethylene)oxindoles

by Sunhwa Park, Jiyun Lee, Kye Jung Shin, Euichaul Oh and Jae Hong Seo

Molecules 2017, 22(3), 503; https://doi.org/10.3390/molecules22030503 - 22 Mar 2017

Cited by 15 | Viewed by 5637

Abstract

Based on consecutive one-pot conditions combining three palladium-catalyzed reactions (Sonogashira, Heck and Suzuki-Miyaura reactions), a more efficient domino multicomponent method has been successfully developed to access a wide variety of 3-(diarylmethylene)oxindoles. Microwave irradiation and use of a silver salt were the most important [...] Read more.

Based on consecutive one-pot conditions combining three palladium-catalyzed reactions (Sonogashira, Heck and Suzuki-Miyaura reactions), a more efficient domino multicomponent method has been successfully developed to access a wide variety of 3-(diarylmethylene)oxindoles. Microwave irradiation and use of a silver salt were the most important factors to achieve high yields and stereoselectivity. Full article

(This article belongs to the Collection Heterocyclic Compounds)

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11 pages, 2671 KiB

Open AccessArticle

The Anti-Allergic Rhinitis Effect of Traditional Chinese Medicine of Shenqi by Regulating Mast Cell Degranulation and Th1/Th2 Cytokine Balance

by Yang-Yang Shao, Yi-Ming Zhou, Min Hu, Jin-Ze Li, Cheng-Juan Chen, Yong-Jiang Wang, Xiao-Yun Shi, Wen-Jie Wang and Tian-Tai Zhang

Molecules 2017, 22(3), 504; https://doi.org/10.3390/molecules22030504 - 22 Mar 2017

Cited by 52 | Viewed by 8672

Abstract

Shenqi is a traditional Chinese polyherbal medicine has been widely used for the treatment of allergic rhinitis (AR). The aim of this study was to investigate the anti-allergic rhinitis activity of Shenqi and explore its underlying molecular mechanism. Ovalbumin (OVA)-induced allergic rhinitis rat [...] Read more.

Shenqi is a traditional Chinese polyherbal medicine has been widely used for the treatment of allergic rhinitis (AR). The aim of this study was to investigate the anti-allergic rhinitis activity of Shenqi and explore its underlying molecular mechanism. Ovalbumin (OVA)-induced allergic rhinitis rat model was used to evaluate the anti-allergic rhinitis effect of Shenqi. The effect of Shenqi on IgE-mediated degranulation was measured using rat basophilic leukemia (RBL-2H3) cells. Primary spleen lymphocytes were isolated to investigate the anti-allergic mechanism of Shenqi by detecting the expression of transcription factors via Western blot and the level of cytokines (IL-4 and IFN-γ) via ELISA. In OVA-induced AR rat models, Shenqi relieved the allergic rhinitis symptoms, inhibited the histopathological changes of nasal mucosa, and reduced the levels of IL-4 and IgE. The results from the in vitro study certified that Shenqi inhibited mast cell degranulation. Furthermore, the results of GATA3, T-bet, p-STAT6, and SOCS1 expression and production of IFN-γ and IL-4 demonstrated that Shenqi balanced the ratio of Th1/Th2 (IFN-γ/IL-4) in OVA-stimulated spleen lymphocytes. In conclusion, these results suggest that Shenqi exhibits an obvious anti-allergic effect by suppressing the mast cell-mediated allergic response and by improving the imbalance of Th1/Th2 ratio in allergic rhinitis. Full article

(This article belongs to the Section Natural Products Chemistry)

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Review

Jump to: Editorial, Research, Other

18 pages, 2078 KiB

Open AccessFeature PaperReview

Sphingosine 1-Phosphate Receptor 1 Signaling in Mammalian Cells

by Nigel J. Pyne and Susan Pyne

Molecules 2017, 22(3), 344; https://doi.org/10.3390/molecules22030344 - 23 Feb 2017

Cited by 65 | Viewed by 11823

Abstract

The bioactive lipid, sphingosine 1-phosphate (S1P) binds to a family of G protein-coupled receptors, termed S1P₁-S1P₅. These receptors function in, for example, the cardiovascular system to regulate vascular barrier integrity and tone, the nervous system to regulate neuronal differentiation, [...] Read more.

The bioactive lipid, sphingosine 1-phosphate (S1P) binds to a family of G protein-coupled receptors, termed S1P₁-S1P₅. These receptors function in, for example, the cardiovascular system to regulate vascular barrier integrity and tone, the nervous system to regulate neuronal differentiation, myelination and oligodendrocyte/glial cell survival and the immune system to regulate T- and B-cell subsets and trafficking. S1P receptors also participate in the pathophysiology of autoimmunity, inflammatory disease, cancer, neurodegeneration and others. In this review, we describe how S1P₁ can form a complex with G-protein and β-arrestin, which function together to regulate effector pathways. We also discuss the role of the S1P₁-Platelet derived growth factor receptor β functional complex (which deploys G-protein/β-arrestin and receptor tyrosine kinase signaling) in regulating cell migration. Possible mechanisms by which different S1P-chaperones, such as Apolipoprotein M-High-Density Lipoprotein induce biological programmes in cells are also described. Finally, the role of S1P₁ in health and disease and as a target for clinical intervention is appraised. Full article

(This article belongs to the Special Issue G-protein Coupled Receptor Structure and Function)

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32 pages, 14605 KiB

Open AccessFeature PaperReview

Synergy Effects in the Chemical Synthesis and Extensions of Multicomponent Reactions (MCRs)—The Low Energy Way to Ultra-Short Syntheses of Tailor-Made Molecules

by Heiner Eckert

Molecules 2017, 22(3), 349; https://doi.org/10.3390/molecules22030349 - 25 Feb 2017

Cited by 11 | Viewed by 10252

Abstract

Several novel methods, catalysts and reagents have been developed to improve organic synthesis. Synergistic effects between reactions, reagents and catalysts can lead to minor heats of reaction and occur as an inherent result of multicomponent reactions (MCRs) and their extensions. They enable syntheses [...] Read more.

Several novel methods, catalysts and reagents have been developed to improve organic synthesis. Synergistic effects between reactions, reagents and catalysts can lead to minor heats of reaction and occur as an inherent result of multicomponent reactions (MCRs) and their extensions. They enable syntheses to be performed at a low energy level and the number of synthesis steps to be drastically reduced in comparison with ‘classical’ two-component reactions, fulfilling the rules of Green Chemistry. The very high potential for variability, diversity and complexity of MCRs additionally generates an extremely diverse range of products, thus bringing us closer to the aim of being able to produce tailor-made and extremely low-cost materials, drugs and compound libraries. Full article

(This article belongs to the Section Organic Chemistry)

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29 pages, 6985 KiB

Open AccessReview

Monoclonal Antibodies and Immunoassay for Medical Plant-Derived Natural Products: A Review

by Xin Yan, Yan Zhao, Yue Zhang and Huihua Qu

Molecules 2017, 22(3), 355; https://doi.org/10.3390/molecules22030355 - 26 Feb 2017

Cited by 24 | Viewed by 7169

Abstract

Owing to the widespread application value, monoclonal antibodies (MAbs) have become a tool of increasing importance in modern bioscience research since their emergence. Recently, some researchers have focused on the production of MAbs against medical plant-derived natural products (MPNP), the secondary metabolites of [...] Read more.

Owing to the widespread application value, monoclonal antibodies (MAbs) have become a tool of increasing importance in modern bioscience research since their emergence. Recently, some researchers have focused on the production of MAbs against medical plant-derived natural products (MPNP), the secondary metabolites of medical plants. At the same time, various immunoassay methods were established on the basis of these MPNP MAbs, and then rapidly developed into a novel technique for medical plant and phytomedicine research in the area of quality control, pharmacological analysis, drug discovery, and so on. Dependent on the research works carried out in recent years, this paper aims to provide a comprehensive review of MAbs against MPNP and the application of various immunoassay methods established on the basis of these MAbs, and conclude with a short section on future prospects and research trends in this area. Full article

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

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20 pages, 1815 KiB

Open AccessReview

Impact of Age and Insulin-Like Growth Factor-1 on DNA Damage Responses in UV-Irradiated Human Skin

by Michael G. Kemp, Dan F Spandau and Jeffrey B. Travers

Molecules 2017, 22(3), 356; https://doi.org/10.3390/molecules22030356 - 26 Feb 2017

Cited by 51 | Viewed by 10142

Abstract

The growing incidence of non-melanoma skin cancer (NMSC) necessitates a thorough understanding of its primary risk factors, which include exposure to ultraviolet (UV) wavelengths of sunlight and age. Whereas UV radiation (UVR) has long been known to generate photoproducts in genomic DNA that [...] Read more.

The growing incidence of non-melanoma skin cancer (NMSC) necessitates a thorough understanding of its primary risk factors, which include exposure to ultraviolet (UV) wavelengths of sunlight and age. Whereas UV radiation (UVR) has long been known to generate photoproducts in genomic DNA that promote genetic mutations that drive skin carcinogenesis, the mechanism by which age contributes to disease pathogenesis is less understood and has not been sufficiently studied. In this review, we highlight studies that have considered age as a variable in examining DNA damage responses in UV-irradiated skin and then discuss emerging evidence that the reduced production of insulin-like growth factor-1 (IGF-1) by senescent fibroblasts in the dermis of geriatric skin creates an environment that negatively impacts how epidermal keratinocytes respond to UVR-induced DNA damage. In particular, recent data suggest that two principle components of the cellular response to DNA damage, including nucleotide excision repair and DNA damage checkpoint signaling, are both partially defective in keratinocytes with inactive IGF-1 receptors. Overcoming these tumor-promoting conditions in aged skin may therefore provide a way to lower aging-associated skin cancer risk, and thus we will consider how dermal wounding and related clinical interventions may work to rejuvenate the skin, re-activate IGF-1 signaling, and prevent the initiation of NMSC. Full article

(This article belongs to the Special Issue Cancer Chemoprevention)

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21 pages, 1177 KiB

Open AccessReview

Chlorogenic Acid: Recent Advances on Its Dual Role as a Food Additive and a Nutraceutical against Metabolic Syndrome

by Jesús Santana-Gálvez, Luis Cisneros-Zevallos and Daniel A. Jacobo-Velázquez

Molecules 2017, 22(3), 358; https://doi.org/10.3390/molecules22030358 - 26 Feb 2017

Cited by 562 | Viewed by 26719

Abstract

Chlorogenic acid (5-O-caffeoylquinic acid) is a phenolic compound from the
hydroxycinnamic acid family. This polyphenol possesses many health-promoting properties, most
of them related to the treatment of metabolic syndrome, including anti-oxidant, anti-inflammatory,
antilipidemic, antidiabetic, and antihypertensive activities. The first part of this review [...] Read more.

Chlorogenic acid (5-O-caffeoylquinic acid) is a phenolic compound from the
hydroxycinnamic acid family. This polyphenol possesses many health-promoting properties, most
of them related to the treatment of metabolic syndrome, including anti-oxidant, anti-inflammatory,
antilipidemic, antidiabetic, and antihypertensive activities. The first part of this review will discuss
the role of chlorogenic acid as a nutraceutical for the prevention and treatment of metabolic
syndrome and associated disorders, including in vivo studies, clinical trials, and mechanisms of
action. The second part of the review will be dealing with the role of chlorogenic acid as a food
additive. Chlorogenic acid has shown antimicrobial activity against a wide range of organisms,
including bacteria, yeasts, molds, viruses, and amoebas. These antimicrobial properties can be
useful for the food industry in its constant search for new and natural molecules for the
preservation of food products. In addition, chlorogenic acid has antioxidant activity, particularly
against lipid oxidation; protective properties against degradation of other bioactive compounds
present in food, and prebiotic activity. The combination of these properties makes chlorogenic acid
an excellent candidate for the formulation of dietary supplements and functional foods. Full article

(This article belongs to the Special Issue Recent Advances in Plant Phenolics)

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16 pages, 2315 KiB

Open AccessReview

Molecular Simulations of Disulfide-Rich Venom Peptides with Ion Channels and Membranes

by Evelyne Deplazes

Molecules 2017, 22(3), 362; https://doi.org/10.3390/molecules22030362 - 27 Feb 2017

Cited by 14 | Viewed by 5909

Abstract

Disulfide-rich peptides isolated from the venom of arthropods and marine animals are a rich source of potent and selective modulators of ion channels. This makes these peptides valuable lead molecules for the development of new drugs to treat neurological disorders. Consequently, much effort [...] Read more.

Disulfide-rich peptides isolated from the venom of arthropods and marine animals are a rich source of potent and selective modulators of ion channels. This makes these peptides valuable lead molecules for the development of new drugs to treat neurological disorders. Consequently, much effort goes into understanding their mechanism of action. This paper presents an overview of how molecular simulations have been used to study the interactions of disulfide-rich venom peptides with ion channels and membranes. The review is focused on the use of docking, molecular dynamics simulations, and free energy calculations to (i) predict the structure of peptide-channel complexes; (ii) calculate binding free energies including the effect of peptide modifications; and (iii) study the membrane-binding properties of disulfide-rich venom peptides. The review concludes with a summary and outlook. Full article

(This article belongs to the Special Issue Biomolecular Simulations)

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14 pages, 550 KiB

Open AccessReview

Effect of Oxidative Stress on ABC Transporters: Contribution to Epilepsy Pharmacoresistance

by Gurpreet Kaur Grewal, Samiksha Kukal, Neha Kanojia, Luciano Saso, Shrikant Kukreti and Ritushree Kukreti

Molecules 2017, 22(3), 365; https://doi.org/10.3390/molecules22030365 - 27 Feb 2017

Cited by 49 | Viewed by 7994

Abstract

Epilepsy is a neurological disorder affecting around 1%–2% of population worldwide and its treatment includes use of antiepileptic drugs to control seizures. Failure to respond to antiepileptic drug therapy is a major clinical problem and over expression of ATP-binding cassette transporters is considered [...] Read more.

Epilepsy is a neurological disorder affecting around 1%–2% of population worldwide and its treatment includes use of antiepileptic drugs to control seizures. Failure to respond to antiepileptic drug therapy is a major clinical problem and over expression of ATP-binding cassette transporters is considered one of the major reasons for pharmacoresistance. In this review, we have summarized the regulation of ABC transporters in response to oxidative stress due to disease and antiepileptic drugs. Further, ketogenic diet and antioxidants were examined for their role in pharmacoresistance. The understanding of signalling pathways and mechanism involved may help in identifying potential therapeutic targets and improving drug response. Full article

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

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6 pages, 1453 KiB

Open AccessReview

The Pharmaceutical Industry in 2016. An Analysis of FDA Drug Approvals from a Perspective of the Molecule Type

by Beatriz G. de la Torre and Fernando Albericio

Molecules 2017, 22(3), 368; https://doi.org/10.3390/molecules22030368 - 27 Feb 2017

Cited by 28 | Viewed by 7777

Abstract

This is an analysis from a chemical point of view of the 22 drugs accepted by the FDA during 2016. The different drugs from the 2016 “harvest” have been classified according to their chemical structure: antibodies; TIDES (oligonucleotides and peptides); amino acids and [...] Read more.

This is an analysis from a chemical point of view of the 22 drugs accepted by the FDA during 2016. The different drugs from the 2016 “harvest” have been classified according to their chemical structure: antibodies; TIDES (oligonucleotides and peptides); amino acids and natural products; drug combination; and small molecules. Full article

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15 pages, 3340 KiB

Open AccessReview

Plasma Membrane Na⁺-Coupled Citrate Transporter (SLC13A5) and Neonatal Epileptic Encephalopathy

by Yangzom D. Bhutia, Jonathan J. Kopel, John J. Lawrence, Volker Neugebauer and Vadivel Ganapathy

Molecules 2017, 22(3), 378; https://doi.org/10.3390/molecules22030378 - 28 Feb 2017

Cited by 65 | Viewed by 11847

Abstract

SLC13A5 is a Na⁺-coupled transporter for citrate that is expressed in the plasma membrane of specific cell types in the liver, testis, and brain. It is an electrogenic transporter with a Na⁺:citrate³⁻ stoichiometry of 4:1. In humans, the [...] Read more.

SLC13A5 is a Na⁺-coupled transporter for citrate that is expressed in the plasma membrane of specific cell types in the liver, testis, and brain. It is an electrogenic transporter with a Na⁺:citrate³⁻ stoichiometry of 4:1. In humans, the Michaelis constant for SLC13A5 to transport citrate is ~600 μM, which is physiologically relevant given that the normal concentration of citrate in plasma is in the range of 150–200 μM. Li⁺ stimulates the transport function of human SLC13A5 at concentrations that are in the therapeutic range in patients on lithium therapy. Human SLC13A5 differs from rodent Slc13a5 in two important aspects: the affinity of the human transporter for citrate is ~30-fold less than that of the rodent transporter, thus making human SLC13A5 a low-affinity/high-capacity transporter and the rodent Slc13a5 a high-affinity/low-capacity transporter. In the liver, SLC13A5 is expressed exclusively in the sinusoidal membrane of the hepatocytes, where it plays a role in the uptake of circulating citrate from the sinusoidal blood for metabolic use. In the testis, the transporter is expressed only in spermatozoa, which is also only in the mid piece where mitochondria are located; the likely function of the transporter in spermatozoa is to mediate the uptake of citrate present at high levels in the seminal fluid for subsequent metabolism in the sperm mitochondria to generate biological energy, thereby supporting sperm motility. In the brain, the transporter is expressed mostly in neurons. As astrocytes secrete citrate into extracellular medium, the potential function of SLC13A5 in neurons is to mediate the uptake of circulating citrate and astrocyte-released citrate for subsequent metabolism. Slc13a5-knockout mice have been generated; these mice do not have any overt phenotype but are resistant to experimentally induced metabolic syndrome. Recently however, loss-of-function mutations in human SLC13A5 have been found to cause severe epilepsy and encephalopathy early in life. Interestingly, there is no evidence of epilepsy or encephalopathy in Slc13a5-knockout mice, underlining the significant differences in clinical consequences of the loss of function of this transporter between humans and mice. The markedly different biochemical features of human SLC13A5 and mouse Slc13a5 likely contribute to these differences between humans and mice with regard to the metabolic consequences of the transporter deficiency. The exact molecular mechanisms by which the functional deficiency of the citrate transporter causes epilepsy and impairs neuronal development and function remain to be elucidated, but available literature implicate both dysfunction of GABA (γ-aminobutyrate) signaling and hyperfunction of NMDA (N-methyl-d-aspartate) receptor signaling. Plausible synaptic mechanisms linking loss-of-function mutations in SLC13A5 to epilepsy are discussed. Full article

(This article belongs to the Special Issue Can Membrane Transporters Contribute to Drug Discovery?)

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13 pages, 2934 KiB

Open AccessReview

Pharmacological Activities and Synthesis of Esculetin and Its Derivatives: A Mini-Review

by Chengyuan Liang, Weihui Ju, Shaomeng Pei, Yonghong Tang and Yadong Xiao

Molecules 2017, 22(3), 387; https://doi.org/10.3390/molecules22030387 - 2 Mar 2017

Cited by 100 | Viewed by 11760

Abstract

Esculetin, synonymous with 6,7-dihydroxycoumarin, is the main active ingredient of the traditional Chinese medicine Cortex Fraxini. The twig skin or trunk bark of Cortex Fraxini are used by herb doctors as a mild, bitter liver and gallbladder meridians’ nontoxic drug as well [...] Read more.

Esculetin, synonymous with 6,7-dihydroxycoumarin, is the main active ingredient of the traditional Chinese medicine Cortex Fraxini. The twig skin or trunk bark of Cortex Fraxini are used by herb doctors as a mild, bitter liver and gallbladder meridians’ nontoxic drug as well as dietary supplement. Recently, with a variety of novel esculetin derivatives being reported, the molecular mechanism research as well as clinical application of Cortex Fraxini and esculetin are becoming more attractive. This mini-review will consolidate what is known about the biological activities, the mechanism of esculetin and its synthetic derivatives over the past decade in addition to providing a brief synopsis of the properties of esculetin. Full article

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

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24 pages, 1005 KiB

Open AccessReview

Cancer Chemoprevention by Phytochemicals: Nature’s Healing Touch

by Haseeb Zubair, Shafquat Azim, Aamir Ahmad, Mohammad Aslam Khan, Girijesh Kumar Patel, Seema Singh and Ajay Pratap Singh

Molecules 2017, 22(3), 395; https://doi.org/10.3390/molecules22030395 - 3 Mar 2017

Cited by 100 | Viewed by 17110

Abstract

Phytochemicals are an important part of traditional medicine and have been investigated in detail for possible inclusion in modern medicine as well. These compounds often serve as the backbone for the synthesis of novel therapeutic agents. For many years, phytochemicals have demonstrated encouraging [...] Read more.

Phytochemicals are an important part of traditional medicine and have been investigated in detail for possible inclusion in modern medicine as well. These compounds often serve as the backbone for the synthesis of novel therapeutic agents. For many years, phytochemicals have demonstrated encouraging activity against various human cancer models in pre-clinical assays. Here, we discuss select phytochemicals—curcumin, epigallocatechin-3-gallate (EGCG), resveratrol, plumbagin and honokiol—in the context of their reported effects on the processes of inflammation and oxidative stress, which play a key role in tumorigenesis. We also discuss the emerging evidence on modulation of tumor microenvironment by these phytochemicals which can possibly define their cancer-specific action. Finally, we provide recent updates on how low bioavailability, a major concern with phytochemicals, is being circumvented and the general efficacy being improved, by synthesis of novel chemical analogs and nanoformulations. Full article

(This article belongs to the Special Issue Cancer Chemoprevention)

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11 pages, 246 KiB

Open AccessReview

Implications of Resveratrol on Glucose Uptake and Metabolism

by David León, Elena Uribe, Angara Zambrano and Mónica Salas

Molecules 2017, 22(3), 398; https://doi.org/10.3390/molecules22030398 - 7 Mar 2017

Cited by 25 | Viewed by 8599

Abstract

Resveratrol—a polyphenol of natural origin—has been the object of massive research in the past decade because of its potential use in cancer therapy. However, resveratrol has shown an extensive range of cellular targets and effects, which hinders the use of the molecule for [...] Read more.

Resveratrol—a polyphenol of natural origin—has been the object of massive research in the past decade because of its potential use in cancer therapy. However, resveratrol has shown an extensive range of cellular targets and effects, which hinders the use of the molecule for medical applications including cancer and type 2 diabetes. Here, we review the latest advances in understanding how resveratrol modulates glucose uptake, regulates cellular metabolism, and how this may be useful to improve current therapies. We discuss challenges and findings regarding the inhibition of glucose uptake by resveratrol and other polyphenols of similar chemical structure. We review alternatives that can be exploited to improve cancer therapies, including the use of other polyphenols, or the combination of resveratrol with other molecules and their impact on glucose homeostasis in cancer and diabetes. Full article

(This article belongs to the Special Issue Improvements for Resveratrol Efficacy)

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25 pages, 6507 KiB

Open AccessReview

Pharmacological Potential and Synthetic Approaches of Imidazo[4,5-b]pyridine and Imidazo[4,5-c]pyridine Derivatives

by Malwina Krause, Henryk Foks and Katarzyna Gobis

Molecules 2017, 22(3), 399; https://doi.org/10.3390/molecules22030399 - 4 Mar 2017

Cited by 54 | Viewed by 15584

Abstract

The structural resemblance between the fused imidazopyridine heterocyclic ring system and purines has prompted biological investigations to assess their potential therapeutic significance. They are known to play a crucial role in numerous disease conditions. The discovery of their first bioactivity as GABA_A [...] Read more.

The structural resemblance between the fused imidazopyridine heterocyclic ring system and purines has prompted biological investigations to assess their potential therapeutic significance. They are known to play a crucial role in numerous disease conditions. The discovery of their first bioactivity as GABA_A receptor positive allosteric modulators divulged their medicinal potential. Proton pump inhibitors, aromatase inhibitors, and NSAIDs were also found in this chemical group. Imidazopyridines have the ability to influence many cellular pathways necessary for the proper functioning of cancerous cells, pathogens, components of the immune system, enzymes involved in carbohydrate metabolism, etc. The collective results of biochemical and biophysical properties foregrounded their medicinal significance in central nervous system, digestive system, cancer, inflammation, etc. In recent years, new preparative methods for the synthesis of imidazopyridines using various catalysts have been described. The present manuscript to the best of our knowledge is the complete compilation on the synthesis and medicinal aspects of imidazo[4,5-b]pyridines and imidazo[4,5-c]pyridines reported from the year 2000 to date, including structure–activity relationships. Full article

(This article belongs to the Section Medicinal Chemistry)

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24 pages, 1095 KiB

Open AccessReview

Pentacyclic Triterpene Bioavailability: An Overview of In Vitro and In Vivo Studies

by Niege A. J. C. Furtado, Laetitia Pirson, Hélène Edelberg, Lisa M. Miranda, Cristina Loira-Pastoriza, Véronique Preat, Yvan Larondelle and Christelle M. André

Molecules 2017, 22(3), 400; https://doi.org/10.3390/molecules22030400 - 4 Mar 2017

Cited by 184 | Viewed by 12656

Abstract

Pentacyclic triterpenes are naturally found in a great variety of fruits, vegetables and medicinal plants and are therefore part of the human diet. The beneficial health effects of edible and medicinal plants have partly been associated with their triterpene content, but the in [...] Read more.

Pentacyclic triterpenes are naturally found in a great variety of fruits, vegetables and medicinal plants and are therefore part of the human diet. The beneficial health effects of edible and medicinal plants have partly been associated with their triterpene content, but the in vivo efficacy in humans depends on many factors, including absorption and metabolism. This review presents an overview of in vitro and in vivo studies that were carried out to determine the bioavailability of pentacyclic triterpenes and highlights the efforts that have been performed to improve the dissolution properties and absorption of these compounds. As plant matrices play a critical role in triterpene bioaccessibility, this review covers literature data on the bioavailability of pentacyclic triterpenes ingested either from foods and medicinal plants or in their free form. Full article

(This article belongs to the Collection Bioactive Compounds)

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21 pages, 5198 KiB

Open AccessReview

The Role of Sub- and Supercritical CO₂ as “Processing Solvent” for the Recycling and Sample Preparation of Lithium Ion Battery Electrolytes

by Sascha Nowak and Martin Winter

Molecules 2017, 22(3), 403; https://doi.org/10.3390/molecules22030403 - 6 Mar 2017

Cited by 87 | Viewed by 15986

Abstract

Quantitative electrolyte extraction from lithium ion batteries (LIB) is of great interest for recycling processes. Following the generally valid EU legal guidelines for the recycling of batteries, 50 wt % of a LIB cell has to be recovered, which cannot be achieved without [...] Read more.

Quantitative electrolyte extraction from lithium ion batteries (LIB) is of great interest for recycling processes. Following the generally valid EU legal guidelines for the recycling of batteries, 50 wt % of a LIB cell has to be recovered, which cannot be achieved without the electrolyte; hence, the electrolyte represents a target component for the recycling of LIBs. Additionally, fluoride or fluorinated compounds, as inevitably present in LIB electrolytes, can hamper or even damage recycling processes in industry and have to be removed from the solid LIB parts, as well. Finally, extraction is a necessary tool for LIB electrolyte aging analysis as well as for post-mortem investigations in general, because a qualitative overview can already be achieved after a few minutes of extraction for well-aged, apparently “dry” LIB cells, where the electrolyte is deeply penetrated or even gellified in the solid battery materials. Full article

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

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32 pages, 6225 KiB

Open AccessReview

Hydrogen Atomic Positions of O–H···O Hydrogen Bonds in Solution and in the Solid State: The Synergy of Quantum Chemical Calculations with ¹H-NMR Chemical Shifts and X-ray Diffraction Methods

by Michael G. Siskos, M. Iqbal Choudhary and Ioannis P. Gerothanassis

Molecules 2017, 22(3), 415; https://doi.org/10.3390/molecules22030415 - 7 Mar 2017

Cited by 61 | Viewed by 9263

Abstract

The exact knowledge of hydrogen atomic positions of O–H···O hydrogen bonds in solution and in the solid state has been a major challenge in structural and physical organic chemistry. The objective of this review article is to summarize recent developments in the refinement [...] Read more.

The exact knowledge of hydrogen atomic positions of O–H···O hydrogen bonds in solution and in the solid state has been a major challenge in structural and physical organic chemistry. The objective of this review article is to summarize recent developments in the refinement of labile hydrogen positions with the use of: (i) density functional theory (DFT) calculations after a structure has been determined by X-ray from single crystals or from powders; (ii) ¹H-NMR chemical shifts as constraints in DFT calculations, and (iii) use of root-mean-square deviation between experimentally determined and DFT calculated ¹H-NMR chemical shifts considering the great sensitivity of ¹H-NMR shielding to hydrogen bonding properties. Full article

(This article belongs to the Special Issue Intramolecular Hydrogen Bonding 2017)

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29 pages, 872 KiB

Open AccessReview

What Is New in the miRNA World Regarding Osteosarcoma and Chondrosarcoma?

by Gaia Palmini, Francesca Marini and Maria Luisa Brandi

Molecules 2017, 22(3), 417; https://doi.org/10.3390/molecules22030417 - 7 Mar 2017

Cited by 67 | Viewed by 8710

Abstract

Despite the availability of multimodal and aggressive therapies, currently patients with skeletal sarcomas, including osteosarcoma and chondrosarcoma, often have a poor prognosis. In recent decades, advances in sequencing technology have revealed the presence of RNAs without coding potential known as non-coding RNAs (ncRNAs), [...] Read more.

Despite the availability of multimodal and aggressive therapies, currently patients with skeletal sarcomas, including osteosarcoma and chondrosarcoma, often have a poor prognosis. In recent decades, advances in sequencing technology have revealed the presence of RNAs without coding potential known as non-coding RNAs (ncRNAs), which provides evidence that protein-coding genes account for only a small percentage of the entire genome. This has suggested the influence of ncRNAs during development, apoptosis and cell proliferation. The discovery of microRNAs (miRNAs) in 1993 underscored the importance of these molecules in pathological diseases such as cancer. Increasing interest in this field has allowed researchers to study the role of miRNAs in cancer progression. Regarding skeletal sarcomas, the research surrounding which miRNAs are involved in the tumourigenesis of osteosarcoma and chondrosarcoma has rapidly gained traction, including the identification of which miRNAs act as tumour suppressors and which act as oncogenes. In this review, we will summarize what is new regarding the roles of miRNAs in chondrosarcoma as well as the latest discoveries of identified miRNAs in osteosarcoma. Full article

(This article belongs to the Special Issue Nucleic Acid-based Drug)

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15 pages, 266 KiB

Open AccessReview

Spotlight on Biomimetic Systems Based on Lyotropic Liquid Crystal

by Juliana F. De Souza, Katiusca Da S. Pontes, Thais F. R. Alves, Venâncio A. Amaral, Márcia De A. Rebelo, Moema A. Hausen and Marco V. Chaud

Molecules 2017, 22(3), 419; https://doi.org/10.3390/molecules22030419 - 7 Mar 2017

Cited by 36 | Viewed by 8995

Abstract

The behavior of lyotropic biomimetic systems in drug delivery was reviewed. These behaviors are influenced by drug properties, the initial water content, type of lyotropic liquid crystals (LLC), swell ability, drug loading rate, the presence of ions with higher or less kosmotropic or [...] Read more.

The behavior of lyotropic biomimetic systems in drug delivery was reviewed. These behaviors are influenced by drug properties, the initial water content, type of lyotropic liquid crystals (LLC), swell ability, drug loading rate, the presence of ions with higher or less kosmotropic or chaotropic force, and the electrostatic interaction between the drug and the lipid bilayers. The in vivo interaction between LCC—drugs, and the impact on the bioavailability of drugs, was reviewed. The LLC with a different architecture can be formed by the self-assembly of lipids in aqueous medium, and can be tuned by the structures and physical properties of the emulsion. These LLC lamellar phase, cubic phase, and hexagonal phase, possess fascinating viscoelastic properties, which make them useful as a dispersion technology, and a highly ordered, thermodynamically stable internal nanostructure, thereby offering the potential as a sustained drug release matrix for drug delivery. In addition, the biodegradable and biocompatible nature of lipids demonstrates a minimum toxicity and thus, they are used for various routes of administration. This review is not intended to provide a comprehensive overview, but focuses on the advantages over non modified conventional materials and LLC biomimetic properties. Full article

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11 pages, 433 KiB

Open AccessReview

How Open Data Shapes In Silico Transporter Modeling

by Floriane Montanari and Barbara Zdrazil

Molecules 2017, 22(3), 422; https://doi.org/10.3390/molecules22030422 - 7 Mar 2017

Cited by 4 | Viewed by 5219

Abstract

Chemical compound bioactivity and related data are nowadays easily available from open data sources and the open medicinal chemistry literature for many transmembrane proteins. Computational ligand-based modeling of transporters has therefore experienced a shift from local (quantitative) models to more global, qualitative, predictive [...] Read more.

Chemical compound bioactivity and related data are nowadays easily available from open data sources and the open medicinal chemistry literature for many transmembrane proteins. Computational ligand-based modeling of transporters has therefore experienced a shift from local (quantitative) models to more global, qualitative, predictive models. As the size and heterogeneity of the data set rises, careful data curation becomes even more important. This includes, for example, not only a tailored cutoff setting for the generation of binary classes, but also the proper assessment of the applicability domain. Powerful machine learning algorithms (such as multi-label classification) now allow the simultaneous prediction of multiple related targets. However, the more complex, the less interpretable these models will get. We emphasize that transmembrane transporters are very peculiar, some of which act as off-targets rather than as real drug targets. Thus, careful selection of the right modeling technique is important, as well as cautious interpretation of results. We hope that, as more and more data will become available, we will be able to ameliorate and specify our models, coming closer towards function elucidation and the development of safer medicine. Full article

(This article belongs to the Special Issue Can Membrane Transporters Contribute to Drug Discovery?)

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44 pages, 13620 KiB

Open AccessReview

Intramolecular Hydrogen Bonding Involving Organic Fluorine: NMR Investigations Corroborated by DFT-Based Theoretical Calculations

by Sandeep Kumar Mishra and N. Suryaprakash

Molecules 2017, 22(3), 423; https://doi.org/10.3390/molecules22030423 - 7 Mar 2017

Cited by 61 | Viewed by 15380 | Correction

Abstract

The combined utility of many one and two dimensional NMR methodologies and DFT-based theoretical calculations have been exploited to detect the intramolecular hydrogen bond (HB) in number of different organic fluorine-containing derivatives of molecules, viz. benzanilides, hydrazides, imides, benzamides, and diphenyloxamides. The existence [...] Read more.

The combined utility of many one and two dimensional NMR methodologies and DFT-based theoretical calculations have been exploited to detect the intramolecular hydrogen bond (HB) in number of different organic fluorine-containing derivatives of molecules, viz. benzanilides, hydrazides, imides, benzamides, and diphenyloxamides. The existence of two and three centered hydrogen bonds has been convincingly established in the investigated molecules. The NMR spectral parameters, viz., coupling mediated through hydrogen bond, one-bond NH scalar couplings, physical parameter dependent variation of chemical shifts of NH protons have paved the way for understanding the presence of hydrogen bond involving organic fluorine in all the investigated molecules. The experimental NMR findings are further corroborated by DFT-based theoretical calculations including NCI, QTAIM, MD simulations and NBO analysis. The monitoring of H/D exchange with NMR spectroscopy established the effect of intramolecular HB and the influence of electronegativity of various substituents on the chemical kinetics in the number of organic building blocks. The utility of DQ-SQ technique in determining the information about HB in various fluorine substituted molecules has been convincingly established. Full article

(This article belongs to the Special Issue Intramolecular Hydrogen Bonding 2017)

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17 pages, 1032 KiB

Open AccessReview

β-Defensins in the Fight against Helicobacter pylori

by Raffaela Pero, Lorena Coretti, Ersilia Nigro, Francesca Lembo, Sonia Laneri, Barbara Lombardo, Aurora Daniele and Olga Scudiero

Molecules 2017, 22(3), 424; https://doi.org/10.3390/molecules22030424 - 7 Mar 2017

Cited by 49 | Viewed by 9012

Abstract

Antimicrobial peptides (AMPs) play a pivotal role in the innate immune responses to Helicobacter pylori (Hp) in humans. β-Defensins, a class of cationic arginine-rich AMPs, are small peptides secreted by immune cells and epithelial cells that exert antimicrobial activity against a broad spectrum [...] Read more.

Antimicrobial peptides (AMPs) play a pivotal role in the innate immune responses to Helicobacter pylori (Hp) in humans. β-Defensins, a class of cationic arginine-rich AMPs, are small peptides secreted by immune cells and epithelial cells that exert antimicrobial activity against a broad spectrum of microorganisms, including Gram-positive and Gram-negative bacteria and fungi. During Hp infections, AMP expression is able to eradicate the bacteria, thereby preventing Hp infections in gastrointestinal tract. It is likely that gastric β-defensins expression is increased during Hp infection. The aim of this review is to focus on increased knowledge of the role of β-defensins in response to Hp infection. We also briefly discuss the potential use of AMPs, either alone or in combination with conventional antibiotics, for the treatment of Hp infection. Full article

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

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18 pages, 3222 KiB

Open AccessReview

N-Pyrrylarylsulfones with High Therapeutic Potential

by Valeria Famiglini, Sabrina Castellano and Romano Silvestri

Molecules 2017, 22(3), 434; https://doi.org/10.3390/molecules22030434 - 9 Mar 2017

Cited by 8 | Viewed by 6098

Abstract

This review illustrates the various studies made to investigate the activity of N-pyrrylarylsulfone containing compounds as potential antiviral, anticancer and SNC drugs. A number of synthetic approaches to obtain tetracyclic, tricyclic and non-cyclic compounds, and their biological activity with regard to structure–activity [...] Read more.

This review illustrates the various studies made to investigate the activity of N-pyrrylarylsulfone containing compounds as potential antiviral, anticancer and SNC drugs. A number of synthetic approaches to obtain tetracyclic, tricyclic and non-cyclic compounds, and their biological activity with regard to structure–activity relationships (SARs) have been reviewed. The literature reviewed here may provide useful information on the potential of N-pyrrylarylsulfone pharmacophore as well as suggest concepts for the design and synthesis of new N-pyrrylarylsulfone based agents. Full article

(This article belongs to the Special Issue Sulfonamides)

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22 pages, 6127 KiB

Open AccessReview

Conservation of the Keap1-Nrf2 System: An Evolutionary Journey through Stressful Space and Time

by Yuji Fuse and Makoto Kobayashi

Molecules 2017, 22(3), 436; https://doi.org/10.3390/molecules22030436 - 9 Mar 2017

Cited by 140 | Viewed by 12569

Abstract

The Keap1-Nrf2 system is an evolutionarily conserved defense mechanism against oxidative and xenobiotic stress. Its regulatory mechanisms, e.g., stress-sensing mechanism, proteasome-based regulation of Nrf2 activity and selection of target genes, have been elucidated mainly in mammals. In addition, emerging model animals, such as [...] Read more.

The Keap1-Nrf2 system is an evolutionarily conserved defense mechanism against oxidative and xenobiotic stress. Its regulatory mechanisms, e.g., stress-sensing mechanism, proteasome-based regulation of Nrf2 activity and selection of target genes, have been elucidated mainly in mammals. In addition, emerging model animals, such as zebrafish, fruit fly and Caenorhabditis elegans, have been shown to have similar anti-stress systems to mammals, suggesting that analogous defense systems are widely conserved throughout the animal kingdom. Experimental evidence in lower animals provides important information beyond mere laboratory-confined utility, such as regarding how these systems transformed during evolution, which may help characterize the mammalian system in greater detail. Recent advances in genome projects of both model and non-model animals have provided a great deal of useful information toward this end. We herein review the research on Keap1-Nrf2 and its analogous systems in both mammals and lower model animals. In addition, by comparing the amino acid sequences of Nrf2 and Keap1 proteins from various species, we can deduce the evolutionary history of the anti-stress system. This combinatorial approach using both experimental and genetic data will suggest perspectives of approach for researchers studying the stress response. Full article

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

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17 pages, 2382 KiB

Open AccessReview

Structural Probing and Molecular Modeling of the A₃ Adenosine Receptor: A Focus on Agonist Binding

by Antonella Ciancetta and Kenneth A. Jacobson

Molecules 2017, 22(3), 449; https://doi.org/10.3390/molecules22030449 - 11 Mar 2017

Cited by 33 | Viewed by 9727

Abstract

Adenosine is an endogenous modulator exerting its functions through the activation of four adenosine receptor (AR) subtypes, termed A₁, A_2A, A_2B and A₃, which belong to the G protein-coupled receptor (GPCR) superfamily. The human A₃ [...] Read more.

Adenosine is an endogenous modulator exerting its functions through the activation of four adenosine receptor (AR) subtypes, termed A₁, A_2A, A_2B and A₃, which belong to the G protein-coupled receptor (GPCR) superfamily. The human A₃AR (hA₃AR) subtype is implicated in several cytoprotective functions. Therefore, hA₃AR modulators, and in particular agonists, are sought for their potential application as anti-inflammatory, anticancer, and cardioprotective agents. Structure-based molecular modeling techniques have been applied over the years to rationalize the structure–activity relationships (SARs) of newly emerged A₃AR ligands, guide the subsequent lead optimization, and interpret site-directed mutagenesis (SDM) data from a molecular perspective. In this review, we showcase selected modeling-based and guided strategies that were applied to elucidate the binding of agonists to the A₃AR and discuss the challenges associated with an accurate prediction of the receptor extracellular vestibule through homology modeling from the available X-ray templates. Full article

(This article belongs to the Special Issue Adenosine Receptors)

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33 pages, 4877 KiB

Open AccessReview

The Formyl Peptide Receptors: Diversity of Ligands and Mechanism for Recognition

by Hui-Qiong He and Richard D. Ye

Molecules 2017, 22(3), 455; https://doi.org/10.3390/molecules22030455 - 13 Mar 2017

Cited by 222 | Viewed by 16458

Abstract

The formyl peptide receptors (FPRs) are G protein-coupled receptors that transduce chemotactic signals in phagocytes and mediate host-defense as well as inflammatory responses including cell adhesion, directed migration, granule release and superoxide production. In recent years, the cellular distribution and biological functions of [...] Read more.

The formyl peptide receptors (FPRs) are G protein-coupled receptors that transduce chemotactic signals in phagocytes and mediate host-defense as well as inflammatory responses including cell adhesion, directed migration, granule release and superoxide production. In recent years, the cellular distribution and biological functions of FPRs have expanded to include additional roles in homeostasis of organ functions and modulation of inflammation. In a prototype, FPRs recognize peptides containing N-formylated methionine such as those produced in bacteria and mitochondria, thereby serving as pattern recognition receptors. The repertoire of FPR ligands, however, has expanded rapidly to include not only N-formyl peptides from microbes but also non-formyl peptides of microbial and host origins, synthetic small molecules and an eicosanoid. How these chemically diverse ligands are recognized by the three human FPRs (FPR1, FPR2 and FPR3) and their murine equivalents is largely unclear. In the absence of crystal structures for the FPRs, site-directed mutagenesis, computer-aided ligand docking and structural simulation have led to the identification of amino acids within FPR1 and FPR2 that interact with several formyl peptides. This review article summarizes the progress made in the understanding of FPR ligand diversity as well as ligand recognition mechanisms used by these receptors. Full article

(This article belongs to the Special Issue G-protein Coupled Receptor Structure and Function)

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25 pages, 3949 KiB

Open AccessReview

Emerging Anti-Mitotic Activities and Other Bioactivities of Sesquiterpene Compounds upon Human Cells

by Alessandra Bosco and Roy M. Golsteyn

Molecules 2017, 22(3), 459; https://doi.org/10.3390/molecules22030459 - 13 Mar 2017

Cited by 30 | Viewed by 9333

Abstract

We review the bio-activities of natural product sesquiterpenes and present the first description of their effects upon mitosis. This type of biological effect upon cells is unexpected because sesquiterpenes are believed to inactivate proteins through Michael-type additions that cause non-specific cytotoxicity. Yet, certain [...] Read more.

We review the bio-activities of natural product sesquiterpenes and present the first description of their effects upon mitosis. This type of biological effect upon cells is unexpected because sesquiterpenes are believed to inactivate proteins through Michael-type additions that cause non-specific cytotoxicity. Yet, certain types of sesquiterpenes can arrest cells in mitosis as measured by cell biology, biochemical and imaging techniques. We have listed the sesquiterpenes that arrest cells in mitosis and analyzed the biological data that support those observations. In view of the biochemical complexity of mitosis, we propose that a subset of sesquiterpenes have a unique chemical structure that can target a precise protein(s) required for mitosis. Since the process of mitotic arrest precedes that of cell death, it is possible that some sesquiterpenes that are currently classified as cytotoxic might also induce a mitotic arrest. Our analysis provides a new perspective of sesquiterpene chemical biology Full article

(This article belongs to the Collection Bioactive Compounds)

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25 pages, 1379 KiB

Open AccessReview

New Roads Leading to Old Destinations: Efflux Pumps as Targets to Reverse Multidrug Resistance in Bacteria

by Gabriella Spengler, Annamária Kincses, Márió Gajdács and Leonard Amaral

Molecules 2017, 22(3), 468; https://doi.org/10.3390/molecules22030468 - 15 Mar 2017

Cited by 158 | Viewed by 17940

Abstract

Multidrug resistance (MDR) has appeared in response to selective pressures resulting from the incorrect use of antibiotics and other antimicrobials. This inappropriate application and mismanagement of antibiotics have led to serious problems in the therapy of infectious diseases. Bacteria can develop resistance by [...] Read more.

Multidrug resistance (MDR) has appeared in response to selective pressures resulting from the incorrect use of antibiotics and other antimicrobials. This inappropriate application and mismanagement of antibiotics have led to serious problems in the therapy of infectious diseases. Bacteria can develop resistance by various mechanisms and one of the most important factors resulting in MDR is efflux pump-mediated resistance. Because of the importance of the efflux-related multidrug resistance the development of new therapeutic approaches aiming to inhibit bacterial efflux pumps is a promising way to combat bacteria having over-expressed MDR efflux systems. The definition of an efflux pump inhibitor (EPI) includes the ability to render the bacterium increasingly more sensitive to a given antibiotic or even reverse the multidrug resistant phenotype. In the recent years numerous EPIs have been developed, although so far their clinical application has not yet been achieved due to their in vivo toxicity and side effects. In this review, we aim to give a short overview of efflux mediated resistance in bacteria, EPI compounds of plant and synthetic origin, and the possible methods to investigate and screen EPI compounds in bacterial systems. Full article

(This article belongs to the Special Issue Can Membrane Transporters Contribute to Drug Discovery?)

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7 pages, 569 KiB

Open AccessReview

On the Emerging Role of the Taste Receptor Type 1 (T1R) Family of Nutrient-Sensors in the Musculoskeletal System

by Shoichiro Kokabu, Jonathan W. Lowery, Takashi Toyono, Tsuyoshi Sato and Tetsuya Yoda

Molecules 2017, 22(3), 469; https://doi.org/10.3390/molecules22030469 - 15 Mar 2017

Cited by 13 | Viewed by 7922

Abstract

The special sense of taste guides and guards food intake and is essential for body maintenance. Salty and sour tastes are sensed via ion channels or gated ion channels while G protein-coupled receptors (GPCRs) of the taste receptor type 1 (T1R) family sense [...] Read more.

The special sense of taste guides and guards food intake and is essential for body maintenance. Salty and sour tastes are sensed via ion channels or gated ion channels while G protein-coupled receptors (GPCRs) of the taste receptor type 1 (T1R) family sense sweet and umami tastes and GPCRs of the taste receptor type 2 (T2R) family sense bitter tastes. T1R and T2R receptors share similar downstream signaling pathways that result in the stimulation of phospholipase-C-β2. The T1R family includes three members that form heterodimeric complexes to recognize either amino acids or sweet molecules such as glucose. Although these functions were originally described in gustatory tissue, T1R family members are expressed in numerous non-gustatory tissues and are now viewed as nutrient sensors that play important roles in monitoring global glucose and amino acid status. Here, we highlight emerging evidence detailing the function of T1R family members in the musculoskeletal system and review these findings in the context of the musculoskeletal diseases sarcopenia and osteoporosis, which are major public health problems among the elderly that affect locomotion, activities of daily living, and quality of life. These studies raise the possibility that T1R family member function may be modulated for therapeutic benefit. Full article

(This article belongs to the Special Issue G-protein Coupled Receptor Structure and Function)

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18 pages, 283 KiB

Open AccessReview

Therapeutic Potentials of Microalgae in the Treatment of Alzheimer’s Disease

by Tosin A. Olasehinde, Ademola O. Olaniran and Anthony I. Okoh

Molecules 2017, 22(3), 480; https://doi.org/10.3390/molecules22030480 - 18 Mar 2017

Cited by 108 | Viewed by 12587

Abstract

Current research is geared towards the discovery of new compounds with strong neuroprotective potential and few or no side effects compared to synthetic drugs. This review focuses on the potentials of extracts and biologically active compounds derived from microalgal biomass for the treatment [...] Read more.

Current research is geared towards the discovery of new compounds with strong neuroprotective potential and few or no side effects compared to synthetic drugs. This review focuses on the potentials of extracts and biologically active compounds derived from microalgal biomass for the treatment and management of Alzheimer’s disease (AD). Microalgal research has gained much attention recently due to its contribution to the production of renewable fuels and the ability of alga cells to produce several secondary metabolites such as carotenoids, polyphenols, sterols, polyunsaturated fatty acids and polysaccharides. These compounds exhibit several pharmacological activities and possess neuroprotective potential. The pathogenesis of Alzheimer’s disease (AD) involves complex mechanisms that are associated with oxidative stress, cholinergic dysfunction, neuronal damage, protein misfolding and aggregation. The antioxidant, anticholinesterase activities as well as the inhibitory effects of some bioactive compounds from microalgae extracts on β-amyloid aggregation and neuronal death are discussed extensively. Phytochemical compounds from microalgae are used as pharmaceuticals, nutraceuticals and food supplements, and may possess neuroprotective potentials that are relevant to the management and/or treatment of AD. Full article

(This article belongs to the Collection Neuroprotection Mediated by Natural Products and Their Chemical Derivatives)

22 pages, 817 KiB

Open AccessFeature PaperReview

Synthesis of Substituted α-Trifluoromethyl Piperidinic Derivatives

by Sarah Rioton, Domingo Gomez Pardo and Janine Cossy

Molecules 2017, 22(3), 483; https://doi.org/10.3390/molecules22030483 - 19 Mar 2017

Cited by 8 | Viewed by 8500

Abstract

A comprehensive survey of pathways leading to the generation of α-trifluoromethyl monocyclic piperidinic derivatives is provided (65 references). These compounds have been synthesized either from 6-membered rings e.g., pipecolic acid or lactam derivatives by introduction a trifluoromethyl group, from pyridine or pyridinone derivatives [...] Read more.

A comprehensive survey of pathways leading to the generation of α-trifluoromethyl monocyclic piperidinic derivatives is provided (65 references). These compounds have been synthesized either from 6-membered rings e.g., pipecolic acid or lactam derivatives by introduction a trifluoromethyl group, from pyridine or pyridinone derivatives by reduction, and from 5-membered rings e.g., prolinol derivatives by ring expansion, from linear amines by cyclization or from dienes/dienophiles by [4 + 2]-cycloaddition. Full article

(This article belongs to the Special Issue Women in Organic Chemistry)

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29 pages, 4122 KiB

Open AccessReview

Catechins and Their Therapeutic Benefits to Inflammatory Bowel Disease

by Fei-Yan Fan, Li-Xuan Sang and Min Jiang

Molecules 2017, 22(3), 484; https://doi.org/10.3390/molecules22030484 - 19 Mar 2017

Cited by 282 | Viewed by 17470

Abstract

Catechins are natural polyphenolic phytochemicals that exist in food and medicinal plants, such as tea, legume and rubiaceae. An increasing number of studies have associated the intake of catechins-rich foods with the prevention and treatment of chronic diseases in humans, such as inflammatory [...] Read more.

Catechins are natural polyphenolic phytochemicals that exist in food and medicinal plants, such as tea, legume and rubiaceae. An increasing number of studies have associated the intake of catechins-rich foods with the prevention and treatment of chronic diseases in humans, such as inflammatory bowel disease (IBD). Some studies have demonstrated that catechins could significantly inhibit the excessive oxidative stress through direct or indirect antioxidant effects and promote the activation of the antioxidative substances such as glutathione peroxidases (GPO) and glutathione (GSH), reducing the oxidative damages to the colon. In addition, catechins can also regulate the infiltration and proliferation of immune related-cells, such as neutrophils, colonic epithelial cells, macrophages, and T lymphocytes, helping reduce the inflammatory relations and provide benefits to IBD. Perhaps catechins can further inhibit the deterioration of intestinal lesions through regulating the cell gap junctions. Furthermore, catechins can exert their significant anti-inflammatory properties by regulating the activation or deactivation of inflammation-related oxidative stress-related cell signaling pathways, such as nuclear factor-kappa B (NF-κB), mitogen activated protein kinases (MAPKs), transcription factor nuclear factor (erythroid-derived 2)-like 2 (Nrf2), signal transducer and the activator of transcription 1/3 (STAT1/3) pathways. Finally, catechins can also stabilize the structure of the gastrointestinal micro-ecological environment via promoting the proliferation of beneficial intestinal bacteria and regulating the balance of intestinal flora, so as to relieve the IBD. Furthermore, catechins may regulate the tight junctions (TJ) in the epithelium. This paper elaborates the currently known possible molecular mechanisms of catechins in favor of IBD. Full article

(This article belongs to the Special Issue Catechins and Human Health: Current State of the Science)

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24 pages, 1830 KiB

Open AccessReview

Pretreatment of Lignocellulosic Biomass with Ionic Liquids and Ionic Liquid-Based Solvent Systems

by Qidong Hou, Meiting Ju, Weizun Li, Le Liu, Yu Chen and Qian Yang

Molecules 2017, 22(3), 490; https://doi.org/10.3390/molecules22030490 - 20 Mar 2017

Cited by 158 | Viewed by 14617

Abstract

Pretreatment is very important for the efficient production of value-added products from lignocellulosic biomass. However, traditional pretreatment methods have several disadvantages, including low efficiency and high pollution. This article gives an overview on the applications of ionic liquids (ILs) and IL-based solvent systems [...] Read more.

Pretreatment is very important for the efficient production of value-added products from lignocellulosic biomass. However, traditional pretreatment methods have several disadvantages, including low efficiency and high pollution. This article gives an overview on the applications of ionic liquids (ILs) and IL-based solvent systems in the pretreatment of lignocellulosic biomass. It is divided into three parts: the first deals with the dissolution of biomass in ILs and IL-based solvent systems; the second focuses on the fractionation of biomass using ILs and IL-based solvent systems as solvents; the third emphasizes the enzymatic saccharification of biomass after pretreatment with ILs and IL-based solvent systems. Full article

(This article belongs to the Special Issue Ionic Liquids and Deep Eutectic Solvents for Synthesis, Materials and Energy)

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20 pages, 2720 KiB

Open AccessReview

Potential Antivirals: Natural Products Targeting Replication Enzymes of Dengue and Chikungunya Viruses

by Ana Flávia Costa da Silveira Oliveira, Róbson Ricardo Teixeira, André Silva de Oliveira, Ana Paula Martins de Souza, Milene Lopes da Silva and Sérgio Oliveira de Paula

Molecules 2017, 22(3), 505; https://doi.org/10.3390/molecules22030505 - 22 Mar 2017

Cited by 65 | Viewed by 11117

Abstract

Dengue virus (DENV) and chikungunya virus (CHIKV) are reemergent arboviruses that are transmitted by mosquitoes of the Aedes genus. During the last several decades, these viruses have been responsible for millions of cases of infection and thousands of deaths worldwide. Therefore, several investigations [...] Read more.

Dengue virus (DENV) and chikungunya virus (CHIKV) are reemergent arboviruses that are transmitted by mosquitoes of the Aedes genus. During the last several decades, these viruses have been responsible for millions of cases of infection and thousands of deaths worldwide. Therefore, several investigations were conducted over the past few years to find antiviral compounds for the treatment of DENV and CHIKV infections. One attractive strategy is the screening of compounds that target enzymes involved in the replication of both DENV and CHIKV. In this review, we describe advances in the evaluation of natural products targeting the enzymes involved in the replication of these viruses. Full article

(This article belongs to the Collection Natural Products as Leads or Drugs against Neglected Tropical Diseases)

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8 pages, 656 KiB

Open AccessPerspective

Under-Reported Aspects of Platinum Drug Pharmacology

by Dirk Theile

Molecules 2017, 22(3), 382; https://doi.org/10.3390/molecules22030382 - 28 Feb 2017

Cited by 18 | Viewed by 5950

Abstract

Platinum drugs remain the backbone of many antineoplastic regimens. Among the numerous chemical or pharmacological effects of platinum drugs, some aspects tend to be under-reported. Thus, this perspective paper intends to stress some neglected properties of platinum drugs: first, the physico-chemical characteristics (aquation [...] Read more.

Platinum drugs remain the backbone of many antineoplastic regimens. Among the numerous chemical or pharmacological effects of platinum drugs, some aspects tend to be under-reported. Thus, this perspective paper intends to stress some neglected properties of platinum drugs: first, the physico-chemical characteristics (aquation reaction kinetics) that determine site-specific toxicity; second, the impact on RNA molecules. Knowledge of the ‘RNA world’ has dramatically changed our understanding of cellular and molecular biology. The inherent RNA-crosslinking properties should make platinum-based drugs interact with coding and non-coding RNAs. Third, we will discuss the impact on the immune system, which is now recognized to substantially contribute to chemotherapy efficacy. Together, platinum drugs are in fact old drugs, but are worth re-focusing on. Many aspects are still mysterious but can pave the way to new drugs or an improved application of the already existing compounds. Full article

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

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