Molecules

16 pages, 1240 KiB

Open AccessArticle

Assessment of the Anti-Hyperglycaemic, Anti-Inflammatory and Antioxidant Activities of the Methanol Extract of Moringa Oleifera in Diabetes-Induced Nephrotoxic Male Wistar Rats

by Elizabeth I. Omodanisi¹

, Yapo G. Aboua² and Oluwafemi O. Oguntibeju^1,*

¹ Phytomedicine and Diabetes Research Group, Oxidative Stress Research Centre, Department of Biomedical Sciences, Faculty of Health and Wellness Sciences, Cape Peninsula University of Technology, P.O. Box 1906, Bellville 7535, South Africa

² Faculty of Health and Wellness Sciences, Cape Peninsula University of Technology, P.O. Box 1906, Bellville 7535, South Africa

Molecules 2017, 22(4), 439; https://doi.org/10.3390/molecules22040439 - 23 Mar 2017

Cited by 149 | Viewed by 14306

Abstract

Diabetes mellitus is an endocrine disease of multiple aetiologies in insulin secretion. A deficiency in insulin results in hyperglycemia with metabolic disturbances of biomolecules. Moringa oleifera (MO) is endemic in the tropics with a variety of ethnomedicinal importance. The leaf of this plant [...] Read more.

Diabetes mellitus is an endocrine disease of multiple aetiologies in insulin secretion. A deficiency in insulin results in hyperglycemia with metabolic disturbances of biomolecules. Moringa oleifera (MO) is endemic in the tropics with a variety of ethnomedicinal importance. The leaf of this plant has been reported to possess antioxidant and medicinal properties that may be helpful in the treatment and management of diabetes and its associated complications. Diabetes was induced intraperitoneally in rats by a single dose of streptozotocin (55 mg/kg) and treated with methanolic extract of Moringa oleifera (250 mg/kg b.wt) for six weeks. Forty-eight (48) adult male Wistar strain rats were randomly divided into four groups: normal control (NC), Moringa oleifera treated control rats (NC + MO), diabetic rats (DM) and Moringa oleifera treated diabetic rats (DM + MO). Estimation of antioxidant capacity, total polyphenols, flavonoids and flavonols content of Moringa oleifera extract was performed and serum biochemical markers were evaluated. Antioxidants such as catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD) activities, glutathione (GSH) and inflammatory biomarkers were determined in the kidney. Results showed high antioxidant capacities of MO extract and improved serum biochemical markers, whilst lipid peroxidation (MDA) levels were reduced in non-diabetic and diabetic rats after MO treatment when compared to normal control. Subsequent administration of MO led to an increased concentration of serum albumin, globulin and total protein with a decrease in the level of MDA, and improvements in CAT, SOD, GSH, GPx, (tumour necrosis factor-alpha)TNF-α and (interleukin-6)IL-6. MO contains potent phytochemical constituents that offer protective action against diabetic-induced renal damage, reactive oxygen species (ROS) and inflammation and could therefore play a role in reducing diabetic complications, particularly in developing countries such as in Africa where the majority cannot afford orthodox medicine. Full article

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

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9 pages, 1552 KiB

Open AccessArticle

Determination of Ultra-trace Rhodium in Water Samples by Graphite Furnace Atomic Absorption Spectrometry after Cloud Point Extraction Using 2-(5-Iodo-2-Pyridylazo)-5-Dimethylaminoaniline as a Chelating Agent

by Quan Han^1,2,*, Yanyan Huo¹, Jiangyan Wu², Yaping He¹

, Xiaohui Yang¹ and Longhu Yang²

¹ School of Chemical Engineering, Xi′an University, Xi′an 710065, China

² School of Chemistry and Chemical Engineering, Yan’an Universty, Yan’an 716000, China

Molecules 2017, 22(4), 487; https://doi.org/10.3390/molecules22040487 - 24 Mar 2017

Cited by 9 | Viewed by 4354

Abstract

A highly sensitive method based on cloud point extraction (CPE) separation/preconcentration and graphite furnace atomic absorption spectrometry (GFAAS) detection has been developed for the determination of ultra-trace amounts of rhodium in water samples. A new reagent, 2-(5-iodo-2-pyridylazo)-5-dimethylaminoaniline (5-I-PADMA), was used as the chelating [...] Read more.

A highly sensitive method based on cloud point extraction (CPE) separation/preconcentration and graphite furnace atomic absorption spectrometry (GFAAS) detection has been developed for the determination of ultra-trace amounts of rhodium in water samples. A new reagent, 2-(5-iodo-2-pyridylazo)-5-dimethylaminoaniline (5-I-PADMA), was used as the chelating agent and the nonionic surfactant TritonX-114 was chosen as extractant. In a HAc-NaAc buffer solution at pH 5.5, Rh(III) reacts with 5-I-PADMA to form a stable chelate by heating in a boiling water bath for 10 min. Subsequently, the chelate is extracted into the surfactant phase and separated from bulk water. The factors affecting CPE were investigated. Under the optimized conditions, the calibration graph was linear in the range of 0.1–6.0 ng/mL, the detection limit was 0.023 ng/mL for rhodium and relative standard deviation was 3.67% (c = 1.0 ng/mL, n = 11)．The method has been applied to the determination of trace rhodium in water samples with satisfactory results Full article

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12 pages, 6186 KiB

Open AccessArticle

Metabolic Profile of Skimmianine in Rats Determined by Ultra-Performance Liquid Chromatography Coupled with Quadrupole Time-of-Flight Tandem Mass Spectrometry

by Aihua Huang^1,2, Hui Xu^1,*, Ruoting Zhan¹, Weiwen Chen¹, Jiawei Liu¹, Yuguang Chi², Daidi Chen², Xiaoyu Ji¹ and Chaoquan Luo¹

¹ Key Laboratory of Ministry of Education, Research Center of Chinese Herbal Resources and Engineering, Guangzhou University of Chinese Medicine, Guangzhou 510006, China

² School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou 510006, China

Molecules 2017, 22(4), 489; https://doi.org/10.3390/molecules22040489 - 23 Mar 2017

Cited by 21 | Viewed by 5785

Abstract

Skimmianine is a furoquinoline alkaloid present mainly in the Rutaceae family. It has been reported to have analgesic, antispastic, sedative, anti-inflammatory, and other pharmacologic activities. Despite its critical pharmacological function, its metabolite profiling is still unclear. In this study, the in vivo metabolite [...] Read more.

Skimmianine is a furoquinoline alkaloid present mainly in the Rutaceae family. It has been reported to have analgesic, antispastic, sedative, anti-inflammatory, and other pharmacologic activities. Despite its critical pharmacological function, its metabolite profiling is still unclear. In this study, the in vivo metabolite profiling of skimmianine in rats was investigated using ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC/Q-TOF-MS). The metabolites were predicted using MetabolitePilot^TM software. These predicted metabolites were further analyzed by MS² spectra, and compared with the detailed fragmentation pathway of the skimmianine standard and literature data. A total of 16 metabolites were identified for the first time in rat plasma, urine, and feces samples after oral administration of skimmianine. Skimmianine underwent extensive Phase I and Phase II metabolism in rats. The Phase I biotransformations of skimmianine consist of epoxidation of olefin on its furan ring (M1) followed by the hydrolysis of the epoxide ring (M4), hydroxylation (M2, M3), O-demethylation (M5-M7), didemethylation (M14–M16). The Phase II biotransformations include glucuronide conjugation (M8–M10) and sulfate conjugation (M11–M13). The epoxidation of 2,3-olefinic bond followed by the hydrolysis of the epoxide ring and O-demethylation were the major metabolic pathways of skimmianine. The results provide key information for understanding the biotransformation processes of skimmianine and the related furoquinoline alkaloids. Full article

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

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17 pages, 6049 KiB

Open AccessArticle

Bioassay-Guided Isolation of Anti-Inflammatory Components from the Bulbs of Lilium brownii var. viridulum and Identifying the Underlying Mechanism through Acting on the NF-κB/MAPKs Pathway

by Ting Ma, Zhen Wang, Yang-Mei Zhang, Jian-Guang Luo^* and Ling-Yi Kong^*

State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China

Molecules 2017, 22(4), 506; https://doi.org/10.3390/molecules22040506 - 23 Mar 2017

Cited by 38 | Viewed by 7995

Abstract

The bulbs of Lilium brownii var. viridulum (LB) are commonly used as both traditional Chinese medicines and popular functional food for many centuries in China. Previous studies reported that the extract of lily bulbs exhibited anti-inflammatory activity both in vivo and in vitro, [...] Read more.

The bulbs of Lilium brownii var. viridulum (LB) are commonly used as both traditional Chinese medicines and popular functional food for many centuries in China. Previous studies reported that the extract of lily bulbs exhibited anti-inflammatory activity both in vivo and in vitro, but its active components and associated molecular mechanisms remain elusive. In the present study, using bioassay-guided isolation method, two phenylpropenoid acylglycerols, 1-O-feruloyl-2-O-p-coumaroylglycerol (1) and 1,3-O-diferuloylglycerol (2), were obtained and identified from the chloroform fraction of LB. Both compounds 1 and 2 significantly decreased the production of nitrite oxide (NO) in lipopolysaccharide (LPS)-stimulated mouse macrophage RAW264.7 cells in a dose-dependent manner with half maximal inhibitory concentration (IC₅₀) values of 9.12 ± 0.72 μM and 12.01 ± 1.07 μM, respectively. They also inhibited the production of prostaglandin E2 (PGE2) and several other pro-inflammatory cytokines, such as interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). Furthermore, compounds 1 and 2 downregulated the protein levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). They also inhibited the nuclear translocation of nuclear factor-κB (NF-κB) p65 subunit and suppressed mitogen-activated protein kinases (MAPKs) pathway. Taken these data together, compounds 1 and 2 exhibited anti-inflammatory activities through acting on the NF-κB and MAPKs pathway. This research provides the first evidence on the major bioactive constituents and related molecular mechanisms of LB as an anti-inflammatory agent. Our findings also advanced the understanding of LB as a traditional herbal medicine for the prevention and treatment of inflammation. Full article

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

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22 pages, 1280 KiB

Open AccessArticle

New Benzimidazole-1,2,4-Triazole Hybrid Compounds: Synthesis, Anticandidal Activity and Cytotoxicity Evaluation

by Hülya Karaca Gençer^1,*, Ulviye Acar Çevik^2,3, Serkan Levent^2,3, Begüm Nurpelin Sağlık^2,3, Büşra Korkut⁴, Yusuf Özkay^2,3,*

, Sinem Ilgın⁴ and Yusuf Öztürk^3,5

¹ Department of Pharmaceutical Microbiology, Faculty of Pharmacy, Anadolu University, Eskişehir 26470, Turkey

² Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, Eskişehir 26470, Turkey

³ Doping and Narcotic Compounds Analysis Laboratory, Faculty of Pharmacy, Anadolu University, Eskişehir 26470, Turkey

⁴ Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Anadolu University, Eskişehir 26470, Turkey

⁵ Department of Pharmacology, Faculty of Pharmacy, Anadolu University, Eskişehir 26470, Turkey

Molecules 2017, 22(4), 507; https://doi.org/10.3390/molecules22040507 - 27 Mar 2017

Cited by 49 | Viewed by 8580

Abstract

Owing to the growing need for antifungal agents, we synthesized a new series 2-((5-(4-(5-substituted-1H-benzimidazol-2-yl)phenyl)-4-substituted-4H-1,2,4-triazol-3-yl)thio)-1-(substitutedphenyl)ethan-1-one derivatives, which were tested against Candida species. The synthesized compounds were characterized and elucidated by FT-IR, ¹H-NMR, ¹³C-NMR and HR-MS spectroscopies. The synthesized [...] Read more.

Owing to the growing need for antifungal agents, we synthesized a new series 2-((5-(4-(5-substituted-1H-benzimidazol-2-yl)phenyl)-4-substituted-4H-1,2,4-triazol-3-yl)thio)-1-(substitutedphenyl)ethan-1-one derivatives, which were tested against Candida species. The synthesized compounds were characterized and elucidated by FT-IR, ¹H-NMR, ¹³C-NMR and HR-MS spectroscopies. The synthesized compounds were screened in vitro anticandidal activity against Candida species by broth microdiluation methods. In vitro cytotoxic effects of the final compounds were determined by MTT assay. Microbiological studies revealed that compounds 5m, 5o, 5r, 5t, 5y, 5ab, and 5ad possess a good antifungal profile. Compounds 5w was the most active derivative and showed comparable antifungal activity to those of reference drugs ketoconazole and fluconazole. Cytotoxicity evaluation of compounds 5m, 5o, 5r, 5w, 5y, 5ab and 5ad showed that compounds 5w and 5ad were the least cytotoxic agents. Effects of these two compounds against ergosterol biosynthesis were observed by LC-MS-MS method, which is based on quantification of ergosterol level in C. albicans. Compounds 5w and 5d inhibited ergosterol biosynthesis concentration dependently. A fluorescence microscopy study was performed to visualize effect of compound 5w against C. albicans at cellular level. It was determined that compound 5w has a membrane damaging effect, which may be related with inhibition of biosynthesis of ergosterol. Full article

(This article belongs to the Section Medicinal Chemistry)

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14 pages, 1735 KiB

Open AccessArticle

Molecularly Imprinted Polymers for Selective Extraction of Oblongifolin C from Garcinia yunnanensis Hu

by Liping Wang^1,2, Wenwei Fu^1,2, Yunhui Shen¹, Hongsheng Tan^1,2

and Hongxi Xu^1,2,*

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

² Engineering Research Center of Shanghai Colleges for TCM New Drug Discovery, Shanghai 201203, China

Molecules 2017, 22(4), 508; https://doi.org/10.3390/molecules22040508 - 23 Mar 2017

Cited by 20 | Viewed by 5986

Abstract

Molecularly imprinted polymers (MIPs) were synthesized and applied for the selective extraction of oblongifolin C (OC) from fruit extracts of Garcinia yunnanensis Hu. A series of experiments and computational approaches were employed to improve the efficiency of screening for optimal MIP systems in [...] Read more.

Molecularly imprinted polymers (MIPs) were synthesized and applied for the selective extraction of oblongifolin C (OC) from fruit extracts of Garcinia yunnanensis Hu. A series of experiments and computational approaches were employed to improve the efficiency of screening for optimal MIP systems in the study. The molar ratio (1:4) was eventually chosen based on the comparison of the binding energy of the complexes between the template (OC) and the functional monomers using density functional theory (DFT) at the RI-PBE-D3-gCP/def2-TZVP level of theory. The binding characterization and the molecular recognition mechanism of MIPs were further explained using the molecular modeling method along with NMR and IR spectra data. The reusability of this approach was demonstrated in over 20 batch rebinding experiments. A mass of 140.5 mg of OC (>95% purity) was obtained from the 5 g extracts, with 2 g of MIPs with the best binding properties, through a gradient elution program from 35% to 70% methanol-water solution. At the same time, another structural analog, 46.5 mg of guttiferone K (GK) (>88% purity), was also obtained by the gradient elution procedure. Our results showed that the structural analogs could be separated from the crude extracts by the molecularly imprinted solid-phase extraction (MISPE) using a gradient elution procedure for the first time. Full article

(This article belongs to the Section Natural Products Chemistry)

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11 pages, 589 KiB

Open AccessArticle

Nerolidol and Farnesol Inhibit Some Cytochrome P450 Activities but Did Not Affect Other Xenobiotic-Metabolizing Enzymes in Rat and Human Hepatic Subcellular Fractions

by Alena Špičáková¹

, Barbora Szotáková^2,*

, Diana Dimunová², Zuzana Myslivečková², Vladimír Kubíček³, Martin Ambrož², Kateřina Lněničková², Kristýna Krasulová¹

, Pavel Anzenbacher¹ and Lenka Skálová²

¹ Department of Pharmacology and Institute of Molecular and Translational Medicine, Faculty of Medicine, Palacky University, Hněvotínská 3, 77515 Olomouc, Czech Republic

² Department of Biochemical Sciences, Faculty of Pharmacy, Charles University, Akademika Heyrovského 1203, 50005 Hradec Králové, Czech Republic

³ Department of Biophysics and Physical Chemistry, Faculty of Pharmacy, Charles University, Akademika Heyrovského 1203, 50005 Hradec Králové, Czech Republic

Molecules 2017, 22(4), 509; https://doi.org/10.3390/molecules22040509 - 24 Mar 2017

Cited by 15 | Viewed by 5223

Abstract

Sesquiterpenes, 15-carbon compounds formed from three isoprenoid units, are the main components of plant essential oils. Sesquiterpenes occur in human food, but they are principally taken as components of many folk medicines and dietary supplements. The aim of our study was to test [...] Read more.

Sesquiterpenes, 15-carbon compounds formed from three isoprenoid units, are the main components of plant essential oils. Sesquiterpenes occur in human food, but they are principally taken as components of many folk medicines and dietary supplements. The aim of our study was to test and compare the potential inhibitory effect of acyclic sesquiterpenes, trans-nerolidol, cis-nerolidol and farnesol, on the activities of the main xenobiotic-metabolizing enzymes in rat and human liver in vitro. Rat and human subcellular fractions, relatively specific substrates, corresponding coenzymes and HPLC, spectrophotometric or spectrofluorometric analysis of product formation were used. The results showed significant inhibition of cytochromes P450 (namely CYP1A, CYP2B and CYP3A subfamilies) activities by all tested sesquiterpenes in rat as well as in human hepatic microsomes. On the other hand, all tested sesquiterpenes did not significantly affect the activities of carbonyl-reducing enzymes and conjugation enzymes. The results indicate that acyclic sesquiterpenes might affect CYP1A, CYP2B and CYP3A mediated metabolism of concurrently administered drugs and other xenobiotics. The possible drug–sesquiterpene interactions should be verified in in vivo experiments. Full article

(This article belongs to the Section Natural Products Chemistry)

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10 pages, 523 KiB

Open AccessReview

Solanesol Biosynthesis in Plants

by Ning Yan^*, Yanhua Liu, Hongbo Zhang, Yongmei Du, Xinmin Liu and Zhongfeng Zhang

Tobacco Research Institute of Chinese Academy of Agricultural Sciences, Qingdao 266101, China

Molecules 2017, 22(4), 510; https://doi.org/10.3390/molecules22040510 - 23 Mar 2017

Cited by 23 | Viewed by 8280

Abstract

Solanesol is a non-cyclic terpene alcohol composed of nine isoprene units that mainly accumulates in solanaceous plants. Solanesol plays an important role in the interactions between plants and environmental factors such as pathogen infections and moderate-to-high temperatures. Additionally, it is a key intermediate [...] Read more.

Solanesol is a non-cyclic terpene alcohol composed of nine isoprene units that mainly accumulates in solanaceous plants. Solanesol plays an important role in the interactions between plants and environmental factors such as pathogen infections and moderate-to-high temperatures. Additionally, it is a key intermediate for the pharmaceutical synthesis of ubiquinone-based drugs such as coenzyme Q10 and vitamin K2, and anti-cancer agent synergizers such as N-solanesyl-N,N′-bis(3,4-dimethoxybenzyl) ethylenediamine (SDB). In plants, solanesol is formed by the 2-C-methyl-d-erythritol 4-phosphate (MEP) pathway within plastids. Solanesol’s biosynthetic pathway involves the generation of C5 precursors, followed by the generation of direct precursors, and then the biosynthesis and modification of terpenoids; the first two stages of this pathway are well understood. Based on the current understanding of solanesol biosynthesis, we here review the key enzymes involved, including 1-deoxy-d-xylulose 5-phosphate synthase (DXS), 1-deoxy-d-xylulose 5-phosphate reductoisomerase (DXR), isopentenyl diphosphate isomerase (IPI), geranyl geranyl diphosphate synthase (GGPPS), and solanesyl diphosphate synthase (SPS), as well as their biological functions. Notably, studies on microbial heterologous expression and overexpression of key enzymatic genes in tobacco solanesol biosynthesis are of significant importance for medical uses of tobacco. Full article

(This article belongs to the Special Issue Isoprenoid Biosynthesis)

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14 pages, 6646 KiB

Open AccessArticle

Silane Modified Diopside for Improved Interfacial Adhesion and Bioactivity of Composite Scaffolds

by Cijun Shuai^1,2,3,4, Chenying Shuai¹, Pei Feng^1,2, Youwen Yang^1,4, Yong Xu¹, Tian Qin¹, Sheng Yang⁵, Chengde Gao^1,2,* and Shuping Peng^6,7,*

¹ State Key Laboratory of High Performance Complex Manufacturing, Central South University, Changsha 410083, China

² The State Key Laboratory for Powder Metallurgy, Central South University, Changsha 410083, China

³ Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha 410008, China

⁴ State Key Laboratory of Solidification Processing, Northwestern Polytechnical University, Xi’an 710072, China

⁵ Human Reproduction Center, Shenzhen Hospital of Hongkong University, Shenzhen 518053, China

⁶ The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health, Xiangya Hospital, Central South University, Changsha 410008, China

⁷ The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha 410078, China

Molecules 2017, 22(4), 511; https://doi.org/10.3390/molecules22040511 - 23 Mar 2017

Cited by 19 | Viewed by 5442

Abstract

Diopside (DIOP) was introduced into polyetheretherketone/polyglycolicacid (PEEK/PGA) scaffolds fabricated via selective laser sintering to improve bioactivity. The DIOP surface was then modified using a silane coupling agent, 3-glycidoxypropyltrimethoxysilane (KH570), to reinforce interfacial adhesion. The results showed that the tensile properties and thermal stability [...] Read more.

Diopside (DIOP) was introduced into polyetheretherketone/polyglycolicacid (PEEK/PGA) scaffolds fabricated via selective laser sintering to improve bioactivity. The DIOP surface was then modified using a silane coupling agent, 3-glycidoxypropyltrimethoxysilane (KH570), to reinforce interfacial adhesion. The results showed that the tensile properties and thermal stability of the scaffolds were significantly enhanced. It could be explained that, on the one hand, the hydrophilic group of KH570 formed an organic covalent bond with the hydroxy group on DIOP surface. On the other hand, there existed relatively high compatibility between its hydrophobic group and the biopolymer matrix. Thus, the ameliorated interface interaction led to a homogeneous state of DIOP dispersion in the matrix. More importantly, an in vitro bioactivity study demonstrated that the scaffolds with KH570-modified DIOP (KDIOP) exhibited the capability of forming a layer of apatite. In addition, cell culture experiments revealed that they had good biocompatibility compared to the scaffolds without KDIOP. It indicated that the scaffolds with KDIOP possess potential application in tissue engineering. Full article

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16 pages, 1990 KiB

Open AccessArticle

Design and Synthesis of Novel Pyrazole-Substituted Different Nitrogenous Heterocyclic Ring Systems as Potential Anti-Inflammatory Agents

by Eman S. Nossier¹, Hoda H. Fahmy², Nagy M. Khalifa^2,3,*

, Wafaa I. El-Eraky⁴ and Marawan A. Baset⁴

¹ Department of Pharmaceutical Chemistry, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo 11754, Egypt

² Department of Therapeutical Chemistry, Pharmaceutical and Drug Industries Division, National Research Centre, Giza 12622, Egypt

³ Pharmaceutical Chemistry Department, Drug Exploration & Development Chair (DEDC), College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia

⁴ Pharmacology Department, National Research Centre, Dokki, Cairo 12622, Egypt

Molecules 2017, 22(4), 512; https://doi.org/10.3390/molecules22040512 - 24 Mar 2017

Cited by 58 | Viewed by 6436

Abstract

With the aim of developing novel anti-inflammatory scaffolds, a new series of pyrazole-substituted various nitrogenous heterocyclic ring systems at C-4 position were synthesized through different chemical reactions and validated by means of spectral and elemental data. The new obtained compounds were investigated for [...] Read more.

With the aim of developing novel anti-inflammatory scaffolds, a new series of pyrazole-substituted various nitrogenous heterocyclic ring systems at C-4 position were synthesized through different chemical reactions and validated by means of spectral and elemental data. The new obtained compounds were investigated for their anti-inflammatory activity using the carrageenan-induced paw edema standard technique and revealed that, compound 6b showed increased potency with % inhibition of edema 85.23 ± 1.92 and 85.78 ± 0.99, respectively, higher than the standard reference drugs indomethacin and celebrex (72.99% and 83.76%). Molecular modeling studies were initiated herein to validate the attained pharmacological data and provide understandable evidence for the observed anti-inflammatory behavior. Full article

(This article belongs to the Section Medicinal Chemistry)

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16 pages, 1773 KiB

Open AccessArticle

Isolation, Characterization and Antiproliferative Activity of New Metabolites from the South African Endemic Red Algal Species Laurencia alfredensis

by Godwin A. Dziwornu¹, Mino R. Caira¹, Jo-Anne de la Mare², Adrienne L. Edkins², John J. Bolton^3,4, Denzil R. Beukes⁵ and Suthananda N. Sunassee^1,4,6,*

¹ Department of Chemistry, University of Cape Town, Rondebosch 7701, South Africa

² Biomedical Biotechnology Research Unit, Department of Biochemistry and Microbiology, Rhodes University, Grahamstown 6140, South Africa

³ Department of Biological Sciences, University of Cape Town, Rondebosch 7701, South Africa

⁴ Marine Research (Ma-Re) Institute, University of Cape Town, Rondebosch 7701, South Africa

⁵ School of Pharmacy Department of Pharmaceutical Chemistry, University of the Western Cape, Bellville 7535, South Africa

⁶ South African Medical Research Council Drug Discovery and Development Research Unit, University of Cape Town, Rondebosch 7701, South Africa

Molecules 2017, 22(4), 513; https://doi.org/10.3390/molecules22040513 - 23 Mar 2017

Cited by 20 | Viewed by 6238

Abstract

The marine red algae of the genus Laurencia have been widely studied for their structurally diverse and biologically active secondary metabolites. We report here the natural product investigation of the organic extract of a newly identified South African endemic species, Laurencia alfredensis. [...] Read more.

The marine red algae of the genus Laurencia have been widely studied for their structurally diverse and biologically active secondary metabolites. We report here the natural product investigation of the organic extract of a newly identified South African endemic species, Laurencia alfredensis. A sequence of column chromatography, preparative TLC and normal phase HPLC resulted in the isolation of eleven compounds comprising three labdane-type diterpenes (1–3), four polyether triterpenes (4–7), three cholestane-type ecdysteroids (8–10) and a glycolipid (11). Compounds 1–3, 5–8 and 10 have not previously been reported, while compound 9 is reported here for the first time from a natural source and the known compound 11 isolated for the first time from the genus Laurencia. The structural elucidation and the relative configuration assignments of the compounds were accomplished by extensive use of 1D- and 2D-NMR, HR-ESI-MS, UV and IR spectroscopic techniques, while the absolute configuration of compound 1 was determined by single-crystal X-ray diffraction analysis. All compounds were evaluated against the MDA-MB-231 breast and HeLa cervical cancer cell lines. Compound 2 exhibited low micromolar antiproliferative activity (IC₅₀ = 9.3 µM) against the triple negative breast carcinoma and compound 7 was similarly active (IC₅₀ = 8.8 µM) against the cervical cancer cell line. Full article

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

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14 pages, 2107 KiB

Open AccessArticle

Anti-Melanogenic Properties of Greek Plants. A Novel Depigmenting Agent from Morus alba Wood

by Eliza Chaita¹, George Lambrinidis², Christina Cheimonidi³, Adamantia Agalou⁴, Dimitris Beis⁴

, Ioannis Trougakos³

, Emmanuel Mikros²

, Alexios-Leandros Skaltsounis¹ and Nektarios Aligiannis^1,*

¹ Division of Pharmacognosy and Natural Product Chemistry, Department of Pharmacy, National & Kapodistrian University of Athens, Panepistimiopolis Zografou, GR-15771 Athens, Greece

² Division of Pharmaceutical Chemistry, Department of Pharmacy, National & Kapodistrian University of Athens, Panepistimiopolis Zografou, GR-15771 Athens, Greece

³ Department of Cell Biology and Biophysics, Faculty of Biology, National & Kapodistrian University of GR-15784 Athens, Greece

⁴ Developmental Biology, Biomedical Research Foundation Academy of Athens, Soranou Ephessiou 4, 11527 Athens, Greece

Molecules 2017, 22(4), 514; https://doi.org/10.3390/molecules22040514 - 23 Mar 2017

Cited by 78 | Viewed by 8319

Abstract

In therapeutic interventions associated with melanin hyperpigmentation, tyrosinase is regarded as a target enzyme as it catalyzes the rate-limiting steps in mammalian melanogenesis. Since many known agents have been proven to be toxic, there has been increasing impetus to identify alternative tyrosinase inhibitors, [...] Read more.

In therapeutic interventions associated with melanin hyperpigmentation, tyrosinase is regarded as a target enzyme as it catalyzes the rate-limiting steps in mammalian melanogenesis. Since many known agents have been proven to be toxic, there has been increasing impetus to identify alternative tyrosinase inhibitors, especially from natural sources. In this study, we investigated 900 extracts from Greek plants for potential tyrosinase inhibitive properties. Among the five most potent extracts, the methanol extract of Morus alba wood (MAM) demonstrated a significant reduction in intracellular tyrosinase and melanin content in B16F10 melanoma cells. Bioassay-guided isolation led to the acquisition of twelve compounds: oxyresveratrol (1), kuwanon C (2), mulberroside A (3), resorcinol (4), dihydrooxyresveratol (5), trans-dihydromorin (6), 2,4,3′-trihydroxydihydrostilbene (7), kuwanon H (8), 2,4-dihydroxybenzaldehyde (9), morusin (10), moracin M (11) and kuwanon G (12). Among these, 2,4,3′-trihydroxydihydrostilbene (7) is isolated for the first time from Morus alba and constitutes a novel potent tyrosinase inhibitor (IC50 0.8 ± 0.15). We report here for the first time dihydrooxyresveratrol (5) as a potent natural tyrosinase inhibitor (IC50 0.3 ± 0.05). Computational docking analysis indicated the binding modes of six tyrosinase inhibitors with the aminoacids of the active centre of tyrosinase. Finally, we found both MAM extract and compounds 1, 6 and 7 to significantly suppress in vivo melanogenesis during zebrafish embryogenesis. Full article

(This article belongs to the Collection Bioactive Compounds)

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8 pages, 736 KiB

Open AccessArticle

Phenolic Compounds from the Rhizomes of Smilax china L. and Their Anti-Inflammatory Activity

by Cheng Zhong¹, Deng Hu¹, Lian-Bing Hou², Lu-Yao Song², Ying-Jun Zhang³, Yang Xie^1,* and Li-Wen Tian^1,*

¹ School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China

² Department of Pharmacy, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China

³ State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China

Molecules 2017, 22(4), 515; https://doi.org/10.3390/molecules22040515 - 3 Apr 2017

Cited by 23 | Viewed by 7110

Abstract

A new triflavanoid, kandelin B-5 (1), was isolated from the rhizomes of Smilax china L., together with six known phenylpropanoid substituted flavan-3-ols (2–7), nine flavonoids (8–16), two stilbenoids (17, 18), [...] Read more.

A new triflavanoid, kandelin B-5 (1), was isolated from the rhizomes of Smilax china L., together with six known phenylpropanoid substituted flavan-3-ols (2–7), nine flavonoids (8–16), two stilbenoids (17, 18), and two other compounds (19, 20). The structure of compound 1 was determined on the basis of 1D, 2D NMR and HR-ESI-MS data, as well as chemical method. Compounds 2–5, 8–12, 15, 17, and 19 were evaluated for anti-inflammatory activity. Only compounds 10, 15 and 17 showed slightly IL-1β expression inhibitory activities on LPS induced THP-1 cells, with inhibition rate of 15.8%, 37.3%, and 35.8%, respectively, at concentration of 50 μg/mL. Full article

(This article belongs to the Collection Bioactive Compounds)

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19 pages, 1456 KiB

Open AccessArticle

Synthesis of Novel Saccharin Derivatives

by Gregory M. Rankin and Sally-Ann Poulsen^*

Griffith Institute for Drug Discovery, Griffith University, Don Young Road, Nathan, Queensland 4111 Australia

Molecules 2017, 22(4), 516; https://doi.org/10.3390/molecules22040516 - 23 Mar 2017

Cited by 5 | Viewed by 7988

Abstract

The synthesis of saccharin (1,2-benzisothiazol-3-one-1,1-dioxide) derivatives substituted on the benzene ring has seen limited development despite the longevity of this compound’s use as an artificial sweetener. This type of saccharin derivative would however present attractive properties for the development of new bioactive, drug-like [...] Read more.

The synthesis of saccharin (1,2-benzisothiazol-3-one-1,1-dioxide) derivatives substituted on the benzene ring has seen limited development despite the longevity of this compound’s use as an artificial sweetener. This type of saccharin derivative would however present attractive properties for the development of new bioactive, drug-like small molecule compounds. Here we report the derivatisation of the benzene ring of saccharin using Cu(I)-catalyzed azide alkyne cycloaddition (CuAAC) to synthesise a diverse library of novel saccharin-1,2,3-triazole conjugates. All library compounds retain the capability for interactions with biomolecules via the unmodified sulfonamide and lactam groups of the parent saccharin core heterocycle. The compounds also encompass alternate orientations of the 1,2,3-triazole heterocycle, thus further adding diversity to the potential hydrogen bonding interactions of these compounds with biomolecules of therapeutic interest. Our findings demonstrate that specifically functionalized derivatives of saccharin may be prepared from either saccharin azide or saccharin alkyne building blocks in high yield using CuAAC. Full article

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

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12 pages, 806 KiB

Open AccessArticle

Synthesis and Cytotoxicity of N-Substituted Dibenzo[a,j]xanthene-3,11-dicarboxamide Derivatives

by Yongbin Song¹, Yihui Yang^2,*, Lijun Wu², Naiwei Dong², Shang Gao², Hongrui Ji¹, Xia Du¹, Bo Liu¹ and Guoyou Chen³

¹ School of Chemical and Environmental Engineering, Harbin University of Science and Technology, Harbin 150040, China

² College of Pharmacy, Harbin Medical University, Harbin 150081, China

³ College of Pharmacy, Harbin Medical University Daqing Campus, Daqing 163319, China

Molecules 2017, 22(4), 517; https://doi.org/10.3390/molecules22040517 - 23 Mar 2017

Cited by 17 | Viewed by 4651

Abstract

In order to study the structure-activity relationships of xanthene derivatives, four series of N-substituted 14-aryl-14H-dibenzo[a,j]xanthene-3,11-dicarboxamide derivatives were synthesized. The structures of all compounds were identified by ¹H-NMR, HR-MS and IR spectra, in which compounds 6a–h [...] Read more.

In order to study the structure-activity relationships of xanthene derivatives, four series of N-substituted 14-aryl-14H-dibenzo[a,j]xanthene-3,11-dicarboxamide derivatives were synthesized. The structures of all compounds were identified by ¹H-NMR, HR-MS and IR spectra, in which compounds 6a–h were further identified by ¹³C-NMR spectra. The in vitro antitumor activity of the synthesized compounds was tested by MTT assay. Most of them displayed strong inhibitory activity on human hepatocellular carcinoma cell lines (SK-HEP-1, HepG2 and SMMC-7721 cells) and acute promyelocytic leukemia NB4 cells. Compounds 6c–6e exhibited significant inhibitory activity against NB4 cells with IC₅₀ values of 0.52 μM and 0.76 μM, respectively, much lower than 5.31 μM of the positive control As₂O₃. Full article

(This article belongs to the Section Organic Chemistry)

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14 pages, 3509 KiB

Open AccessArticle

A Study of Intramolecular Hydrogen Bonding in Levoglucosan Derivatives

by Lucas Quiquempoix¹, Elena Bogdan², Neil J. Wells¹, Jean-Yves Le Questel^2,*, Jérôme Graton^2,* and Bruno Linclau^1,*

¹ Chemistry, University of Southampton, Highfield, Southampton SO17 1BJ, UK

² CEISAM UMR CNRS 6230, Faculté des Sciences et des Techniques, Université de Nantes, 2 rue de la Houssinière—BP 92208, 44322 Nantes CEDEX 3, France

Molecules 2017, 22(4), 518; https://doi.org/10.3390/molecules22040518 - 24 Mar 2017

Cited by 16 | Viewed by 7321

Abstract

Organofluorine is a weak hydrogen-bond (HB) acceptor. Bernet et al. have demonstrated its capability to perturb OH···O intramolecular hydrogen bonds (IMHBs), using conformationally rigid carbohydrate scaffolds including levoglucosan derivatives. These investigations are supplemented here by experimental and theoretical studies involving six new levoglucosan [...] Read more.

Organofluorine is a weak hydrogen-bond (HB) acceptor. Bernet et al. have demonstrated its capability to perturb OH···O intramolecular hydrogen bonds (IMHBs), using conformationally rigid carbohydrate scaffolds including levoglucosan derivatives. These investigations are supplemented here by experimental and theoretical studies involving six new levoglucosan derivatives, and complement the findings of Bernet et al. However, it is shown that conformational analysis is instrumental in interpreting the experimental data, due to the occurrence of non-intramolecular hydrogen-bonded populations which, although minor, cannot be neglected and appears surprisingly significant. The DFT conformational analysis, together with the computation of NMR parameters (coupling constants and chemical shifts) and wavefunction analyses (AIM, NBO), provides a full picture. Thus, for all compounds, the most stabilized structures show the OH groups in a conformation allowing IMHB with O5 and O6, when possible. Furthermore, the combined approach points out the occurrence of various IMHBs and the effect of the chemical modulations on their features. Thus, two-center or three-center IMHB interactions are observed in these compounds, depending on the presence or absence of additional HB acceptors, such as methoxy or fluorine. Full article

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

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15 pages, 3045 KiB

Open AccessArticle

(R)-(−)-Aloesaponol III 8-Methyl Ether from Eremurus persicus: A Novel Compound against Leishmaniosis

by Daniela Rossi¹, Karzan Mahmood Ahmed^1,2, Raffaella Gaggeri^1,3, Serena Della Volpe¹, Lauretta Maggi¹, Giuseppe Mazzeo⁴

, Giovanna Longhi⁴

, Sergio Abbate⁴, Federica Corana⁵, Emanuela Martino^6,*

, Marisa Machado^7,8

, Raquel Varandas^9,10, Maria Do Céu Sousa^9,10

and Simona Collina^1,*

¹ Department of Drug Sciences, Medicinal Chemistry and Pharmaceutical Technology Section, University of Pavia, Viale Taramelli 12, 27100 Pavia, Italy

² Department of Science-Chemistry, University of Garmian, Kalar 46021, Kurdistan Region, Iraq

³ Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) Srl—IRCCS Via Piero Maroncelli, 40, 47014 Meldola (FC), Italy

⁴ Dipartimento di Medicina Molecolare e Traslazionale, Università di Brescia, Viale Europa 11, 25123 Brescia, Italy

⁵ Centro Grandi Strumenti, University of Pavia, Via Bassi 21, 27100 Pavia, Italy

⁶ Department of Earth and Environmental Sciences, University of Pavia, Via S. Epifanio 14, 27100 Pavia, Italy

⁷ CESPU, Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde, 4585-116 Gandra PRD, Portugal

⁸ CIBIO-UP, Centro de Investigação em Biodiversidade e Recursos Genéticos, Universidade do Porto, InBIO, 4485-661 Vairão, Portugal

⁹ Faculty of Pharmacy, University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal

¹⁰ CNC—Center for Neurosciences and Cell Biology, University of Coimbra, Rua Larga Faculty of Medicine, Pólo I, 3004-504 Coimbra, Portugal

Molecules 2017, 22(4), 519; https://doi.org/10.3390/molecules22040519 - 24 Mar 2017

Cited by 24 | Viewed by 6281

Abstract

Leishmaniosis is a neglected tropical disease which affects several millions of people worldwide. The current drug therapies are expensive and often lack efficacy, mainly due to the development of parasite resistance. Hence, there is an urgent need for new drugs effective against Leishmania [...] Read more.

Leishmaniosis is a neglected tropical disease which affects several millions of people worldwide. The current drug therapies are expensive and often lack efficacy, mainly due to the development of parasite resistance. Hence, there is an urgent need for new drugs effective against Leishmania infections. As a part of our ongoing study on the phytochemical characterization and biological investigation of plants used in the traditional medicine of western and central Asia, in the present study, we focused on Eremurus persicus root extract in order to evaluate its potential in the treatment of leishmaniosis. As a result of our study, aloesaponol III 8-methyl ether (ASME) was isolated for the first time from Eremurus persicus root extract, its chemical structure elucidated by means of IR and NMR experiments and the (R) configuration assigned by optical activity measurements: chiroptical aspects were investigated with vibrational circular dichroism (VCD) and electronic circular dichroism (ECD) spectroscopies and DFT (density functional theory) quantum mechanical calculations. Concerning biological investigations, our results clearly proved that (R)-ASME inhibits Leishmania infantum promastigotes viability (IC₅₀ 73 µg/mL), inducing morphological alterations and mitochondrial potential deregulation. Moreover, it is not toxic on macrophages at the concentration tested, thus representing a promising molecule against Leishmania infections. Full article

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

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23 pages, 11549 KiB

Open AccessReview

Morphology Analysis and Optimization: Crucial Factor Determining the Performance of Perovskite Solar Cells

by Wenjin Zeng¹

, Xingming Liu¹, Xiangru Guo¹, Qiaoli Niu¹, Jianpeng Yi¹, Ruidong Xia^1,* and Yong Min^1,2

¹ Key Laboratory for Organic Electronics & Information Displays (KLOEID) & Institute of Advanced Materials (IAM), Jiangsu National Synergistic Innovation Center for Advanced Materials (SICAM), Nanjing University of Posts and Telecommunications, 9 Wenyuan Road, Nanjing 210023, China

² The School of Materials and Energy, Guangdong University of Technology, Panyu, Guangzhou 510006, China

Molecules 2017, 22(4), 520; https://doi.org/10.3390/molecules22040520 - 24 Mar 2017

Cited by 29 | Viewed by 9887

Abstract

This review presents an overall discussion on the morphology analysis and optimization for perovskite (PVSK) solar cells. Surface morphology and energy alignment have been proven to play a dominant role in determining the device performance. The effect of the key parameters such as [...] Read more.

This review presents an overall discussion on the morphology analysis and optimization for perovskite (PVSK) solar cells. Surface morphology and energy alignment have been proven to play a dominant role in determining the device performance. The effect of the key parameters such as solution condition and preparation atmosphere on the crystallization of PVSK, the characterization of surface morphology and interface distribution in the perovskite layer is discussed in detail. Furthermore, the analysis of interface energy level alignment by using X-ray photoelectron spectroscopy and ultraviolet photoelectron spectroscopy is presented to reveals the correlation between morphology and charge generation and collection within the perovskite layer, and its influence on the device performance. The techniques including architecture modification, solvent annealing, etc. were reviewed as an efficient approach to improve the morphology of PVSK. It is expected that further progress will be achieved with more efforts devoted to the insight of the mechanism of surface engineering in the field of PVSK solar cells. Full article

(This article belongs to the Special Issue Advances in Organic Nanophotonics)

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5 pages, 1147 KiB

Open AccessCommunication

Revision of the Structure of Acremine P from a Marine-Derived Strain of Acremonium persicinum

by Mary J. Garson^1,*, Warren Hehre², Gregory K. Pierens³ and Suciati⁴

¹ School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane, QLD 4072, Australia

² Wavefunction Inc., Irvine, CA 92612, USA

³ Centre for Advanced Imaging, University of Queensland, Brisbane, QLD 4072, Australia

⁴ Faculty of Pharmacy, Airlangga University, Surabaya, East Java 60286, Indonesia

Molecules 2017, 22(4), 521; https://doi.org/10.3390/molecules22040521 - 24 Mar 2017

Cited by 13 | Viewed by 5525

Abstract

The previously published structure of the fungal metabolite acremine P is revised by re-evaluation of chemical shift values and NOESY data, and by DFT calculations. Full article

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

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37 pages, 8128 KiB

Open AccessArticle

Optimized 4,5-Diarylimidazoles as Potent/Selective Inhibitors of Protein Kinase CK1δ and Their Structural Relation to p38α MAPK

by Jakob Halekotte¹

, Lydia Witt¹, Chiara Ianes², Marc Krüger², Mike Bührmann³, Daniel Rauh³, Christian Pichlo⁴, Elena Brunstein⁴, Andreas Luxenburger⁵

, Ulrich Baumann⁴

, Uwe Knippschild², Joachim Bischof^2,*

and Christian Peifer^1,*

¹ Institute of Pharmacy, Christian-Albrechts-University of Kiel, Gutenbergstraße 76, D-24118 Kiel, Germany

² Department of General and Visceral Surgery, Ulm University Hospital, Albert-Einstein-Allee 23, D-89081 Ulm, Germany

³ Institute of Chemical Biology, Dortmund University of Technology, Otto-Hahn-Straße 4a, D-44227 Dortmund, Germany

⁴ Department for Chemistry, University of Cologne, Otto-Fischer-Straße 12-14, D-50674 Cologne, Germany

⁵ The Ferrier Research Institute, Victoria University of Wellington, Gracefield Research Centre, 69 Gracefield Road, Lower Hutt P.O. Box 33-436, New Zealand

Molecules 2017, 22(4), 522; https://doi.org/10.3390/molecules22040522 - 24 Mar 2017

Cited by 39 | Viewed by 9217

Abstract

The involvement of protein kinase CK1δ in the pathogenesis of severe disorders such as Alzheimer’s disease, amyotrophic lateral sclerosis, familial advanced sleep phase syndrome, and cancer has dramatically increased interest in the development of effective small molecule inhibitors for both therapeutic application and [...] Read more.

The involvement of protein kinase CK1δ in the pathogenesis of severe disorders such as Alzheimer’s disease, amyotrophic lateral sclerosis, familial advanced sleep phase syndrome, and cancer has dramatically increased interest in the development of effective small molecule inhibitors for both therapeutic application and basic research. Unfortunately, the design of CK1 isoform-specific compounds has proved to be highly complicated due to the existence of six evolutionarily conserved human CK1 members that possess similar, different, or even opposite physiological and pathophysiological implications. Consequently, only few potent and selective CK1δ inhibitors have been reported so far and structurally divergent approaches are urgently needed in order to establish SAR that might enable complete discrimination of CK1 isoforms and related p38α MAPK. In this study we report on design and characterization of optimized 4,5-diarylimidazoles as highly effective ATP-competitive inhibitors of CK1δ with compounds 11b (IC₅₀ CK1δ = 4 nM, IC₅₀ CK1ε = 25 nM), 12a (IC₅₀ CK1δ = 19 nM, IC₅₀ CK1ε = 227 nM), and 16b (IC₅₀ CK1δ = 8 nM, IC₅₀ CK1ε = 81 nM) being among the most potent CK1δ-targeting agents published to date. Inhibitor compound 11b, displaying potential as a pharmacological tool, has further been profiled over a panel of 321 protein kinases exhibiting high selectivity. Cellular efficacy has been evaluated in human pancreatic cancer cell lines Colo357 (EC₅₀ = 3.5 µM) and Panc89 (EC₅₀ = 1.5 µM). SAR is substantiated by X-ray crystallographic analysis of 16b in CK1δ and 11b in p38α. Full article

(This article belongs to the Special Issue Kinase Inhibitors)

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34 pages, 5592 KiB

Open AccessReview

Metal-Based PSMA Radioligands

by Eleni Gourni^1,2,* and Gjermund Henriksen^1,2,3

¹ Institute of Basic Medical Sciences, University of Oslo, Oslo 0372, Norway

² Norwegian Medical Cyclotron Centre Ltd., P.O. Box 4950 Nydalen, Oslo 0424, Norway

³ Institute of Physics, University of Oslo, Oslo 0317, Norway

Molecules 2017, 22(4), 523; https://doi.org/10.3390/molecules22040523 - 24 Mar 2017

Cited by 60 | Viewed by 16473

Abstract

Prostate cancer is one of the most common malignancies for which great progress has been made in identifying appropriate molecular targets that would enable efficient in vivo targeting for imaging and therapy. The type II integral membrane protein, prostate specific membrane antigen (PSMA) [...] Read more.

Prostate cancer is one of the most common malignancies for which great progress has been made in identifying appropriate molecular targets that would enable efficient in vivo targeting for imaging and therapy. The type II integral membrane protein, prostate specific membrane antigen (PSMA) is overexpressed on prostate cancer cells in proportion to the stage and grade of the tumor progression, especially in androgen-independent, advanced and metastatic disease, rendering it a promising diagnostic and/or therapeutic target. From the perspective of nuclear medicine, PSMA-based radioligands may significantly impact the management of patients who suffer from prostate cancer. For that purpose, chelating-based PSMA-specific ligands have been labeled with various diagnostic and/or therapeutic radiometals for single-photon-emission tomography (SPECT), positron-emission-tomography (PET), radionuclide targeted therapy as well as intraoperative applications. This review focuses on the development and further applications of metal-based PSMA radioligands. Full article

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

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16 pages, 2960 KiB

Open AccessArticle

Protective Effect of Bicyclol on Anti-Tuberculosis Drug Induced Liver Injury in Rats

by Xin Liu^†, Manman Zhao^†, Jiaqi Mi, Hui Chen, Li Sheng^* and Yan Li^*

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

^† These authors contribute equally to this work.

Molecules 2017, 22(4), 524; https://doi.org/10.3390/molecules22040524 - 7 Apr 2017

Cited by 35 | Viewed by 7680

Abstract

The present study was performed to investigate the effect of bicyclol, a synthetic anti-hepatitis drug with anti-oxidative and anti-inflammatory properties, on anti-tuberculosis (anti-TB) drug-induced liver injury and related mechanisms in rats. Bicyclol was given to rats by gavage 2 h before the oral [...] Read more.

The present study was performed to investigate the effect of bicyclol, a synthetic anti-hepatitis drug with anti-oxidative and anti-inflammatory properties, on anti-tuberculosis (anti-TB) drug-induced liver injury and related mechanisms in rats. Bicyclol was given to rats by gavage 2 h before the oral administration of an anti-TB drug once a day for 30 days. Liver injury was evaluated by biochemical and histopathological examinations. Lipid peroxidation, mitochondrial function, and the activity of antioxidants were measured by spectrophotometric methods. Cytokines expression and CYP2E1 activity were determined by ELISA assay and liquid chromatography–tandem mass spectrometry (LC–MS/MS) analysis. The expressions of hepatic CYP2E1 and hepatocyte growth factor (HGF) were assessed by Western blotting. As a result, bicyclol significantly protected against anti-TB drug-induced liver injury by reducing the elevated serum aminotransferases levels and accumulation of hepatic lipids. Meanwhile, the histopathological changes were also attenuated in rats. The protective effect of bicyclol on anti-TB drug-induced hepatotoxicity was mainly due to its ability to attenuate oxidative stress, suppress the inflammatory cytokines and CYP2E1 expression, up-regulate the expression of HGF, and improve mitochondrial function. Furthermore, administration of bicyclol had no significant effect on the plasma pharmacokinetics of the anti-TB drug in rats. Full article

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16 pages, 13027 KiB

Open AccessArticle

The Effect and Mechanism of Transdermal Penetration Enhancement of Fu’s Cupping Therapy: New Physical Penetration Technology for Transdermal Administration with Traditional Chinese Medicine (TCM) Characteristics

by Wei-Jie Xie¹, Yong-Ping Zhang^1,*, Jian Xu¹, Xiao-Bo Sun²

and Fang-Fang Yang¹

¹ School of Pharmacy, Guiyang College of Traditional Chinese Medicine, No. 50 Shi Dong Road, Guiyang 550002, China

² Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China

Molecules 2017, 22(4), 525; https://doi.org/10.3390/molecules22040525 - 27 Mar 2017

Cited by 22 | Viewed by 8651

Abstract

Background: In this paper, a new type of physical penetration technology for transdermal administration with traditional Chinese medicine (TCM) characteristics is presented. Fu’s cupping therapy (FCT), was established and studied using in vitro and in vivo experiments and the penetration effect and mechanism [...] Read more.

Background: In this paper, a new type of physical penetration technology for transdermal administration with traditional Chinese medicine (TCM) characteristics is presented. Fu’s cupping therapy (FCT), was established and studied using in vitro and in vivo experiments and the penetration effect and mechanism of FCT physical penetration technology was preliminarily discussed. Methods: With 1-(4-chlorobenzoyl)-5-methoxy-2-methylindole-3-ylacetic acid (indomethacin, IM) as a model drug, the establishment of high, medium, and low references was completed for the chemical permeation system via in vitro transdermal tests. Furthermore, using chemical penetration enhancers (CPEs) and iontophoresis as references, the percutaneous penetration effect of FCT for IM patches was evaluated using seven species of in vitro diffusion kinetics models and in vitro drug distribution; the IM quantitative analysis method in vivo was established using ultra-performance liquid chromatography-tandem mass spectrometry technology (UPLC-MS/MS), and pharmacokinetic parameters: area under the zero and first moment curves from 0 to last time t (AUC_0–t, AUMC_0–t), area under the zero and first moment curves from 0 to infinity (AUC_0–∞, AUMC_0–∞), maximum plasma concentration (C_max) and mean residence time (MRT), were used as indicators to evaluate the percutaneous penetration effect of FCT in vivo. Additionally, we used the 3^K factorial design to study the joint synergistic penetration effect on FCT and chemical penetration enhancers. Through scanning electron microscopy (SEM) and transmission electron microscope (TEM) imaging, micro- and ultrastructural changes on the surface of the stratum corneum (SC) were observed to explore the FCT penetration mechanism. Results: In vitro and in vivo skin permeation experiments revealed that both the total cumulative percutaneous amount and in vivo percutaneous absorption amount of IM using FCT were greater than the amount using CPEs and iontophoresis. Firstly, compared with the control group, the indomethacin skin percutaneous rate of the FCT low-intensity group (FCTL) was 35.52%, and the enhancement ratio (ER) at 9 h was 1.76X, roughly equivalent to the penetration enhancing effect of the CPEs and iontophoresis. Secondly, the indomethacin percutaneous ratio of the FCT middle-intensity group (FCTM) and FCT high-intensity group (FCTH) were 47.36% and 54.58%, respectively, while the ERs at 9 h were 3.58X and 8.39X, respectively. Thirdly, pharmacokinetic data showed that in vivo indomethacin percutaneous absorption of the FCT was much higher than that of the control, that of the FCTM was slightly higher than that of the CPE, and that of the FCTM group was significantly higher than all others. Meanwhile, variance analysis indicated that the combination of the FCT penetration enhancement method and the CPE method had beneficial effects in enhancing skin penetration: the significance level of the CPE method was 0.0004, which was lower than 0.001, meaning the difference was markedly significant; the significance level of the FCT was also below 0.0001 and its difference markedly significant. The significance level of factor interaction A × B was lower than 0.0001, indicating that the difference in synergism was markedly significant. Moreover, SEM and TEM images showed that the SC surfaces of Sprague-Dawley rats treated with FCT were damaged, and it was difficult to observe the complete surface structure, with SC pores growing larger and its special “brick structure” becoming looser. This indicated that the barrier function of the skin was broken, thus revealing a potentially major route of skin penetration. Conclusion: FCT, as a new form of transdermal penetration technology, has significant penetration effects with TCM characteristics and is of high clinical value. It is worth promoting its development. Full article

(This article belongs to the Special Issue Transdermal Delivery Systems: Current Landscape and Trends)

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13 pages, 590 KiB

Open AccessFeature PaperArticle

Synthesis and Antitumor Activity of New Group 3 Metallocene Complexes

by Angelamaria Caporale¹, Giuseppe Palma²

, Annaluisa Mariconda³, Vitale Del Vecchio²

, Domenico Iacopetta⁴

, Ortensia Ilaria Parisi⁴

, Maria Stefania Sinicropi⁴

, Francesco Puoci⁴, Claudio Arra^2,*, Pasquale Longo³ and Carmela Saturnino^1,*

¹ Department of Science, University of Basilicata, Viale dell'Ateneo Lucano 10, Potenza 85100, Italy

² SSD Sperimentazione Animale, Istituto Nazionale Tumori, IRCCS, “Fondazione G. Pascale”, Via Mariano Semmola, Napoli 80131, Italy

³ Department of Biology and Chemistry, University of Salerno, Via Giovanni Paolo II, 132, Fisciano 84084, Italy

⁴ Department of Pharmacy, Health and Nutritional Sciences, University Calabria, Via Pietro Bucci, Arcavacata di Rende 87036, Italy

Molecules 2017, 22(4), 526; https://doi.org/10.3390/molecules22040526 - 28 Mar 2017

Cited by 15 | Viewed by 4842

Abstract

The quest for alternative drugs with respect to the well-known cis-platin and its derivatives, which are still used in more than 50% of the treatment regimens for patients suffering from cancer, is highly needed. In this context, organometallic compounds, which are defined [...] Read more.

The quest for alternative drugs with respect to the well-known cis-platin and its derivatives, which are still used in more than 50% of the treatment regimens for patients suffering from cancer, is highly needed. In this context, organometallic compounds, which are defined as metal complexes containing at least one direct covalent metal-carbon bond, have recently been found to be promising anticancer drug candidates. A series of new metallocene complexes with scandium, yttrium, and neodymium have been prepared and characterized. Some of these compounds show a very interesting anti-proliferative activity in triple negative breast cancer cell line (MDA.MB231) and the non-hormone sensitive prostate cancer cell line (DU145). Moreover, the interaction of some of them with biological membranes, evaluated using liposomes as bio-membrane mimetic model systems, seems to be relevant. The biological activity of these compounds, particularly those based on yttrium, already effective at low concentrations on both cancer cell lines, should be taken into account with regard to new therapeutic approaches in anticancer therapy. Full article

(This article belongs to the Section Organometallic Chemistry)

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8 pages, 1222 KiB

Open AccessArticle

The Structure–Antioxidant Activity Relationship of Ferulates

by Magdalena Karamać¹

, Lidiya Koleva², Vessela D. Kancheva² and Ryszard Amarowicz^1,*

¹ Department of Chemical and Physical Properties of Food, Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, Tuwima 10, 10-748 Olsztyn, Poland

² Lipid Chemistry Department, Institute of Organic Chemistry with Centre of Phytochemistry, Bulgarian Academy of Sciences, Sofia 1113, Bulgaria

Molecules 2017, 22(4), 527; https://doi.org/10.3390/molecules22040527 - 25 Mar 2017

Cited by 48 | Viewed by 8018

Abstract

The antioxidant activity of ferulic acid (1), iso-ferulic acid (2), coniferyl aldehyde (3), methyl ferulate (4), and ethyl ferulate (5) were investigated using 2,2′-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and ferric-reducing antioxidant power (FRAP) assays [...] Read more.

The antioxidant activity of ferulic acid (1), iso-ferulic acid (2), coniferyl aldehyde (3), methyl ferulate (4), and ethyl ferulate (5) were investigated using 2,2′-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and ferric-reducing antioxidant power (FRAP) assays and autoxidation of triacylglycerols of commercially available sunflower oil (TGSO). The compounds tested for ability to scavenge ABTS radical cations was in the order of ferulic acid > coniferyl aldehyde ≈ iso-ferulic acid > ethyl ferulate ≈ methyl ferulate. The results of the FRAP assay for ferulic acid, iso-ferulic acid, and coniferyl aldehyde were similar to and higher than those of methyl ferulate and ethyl ferulate. In the lipid system, iso-ferulic acid showed weak antioxidant activity. The other ferulates exhibited much stronger, yet similar, activities. Full article

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

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15 pages, 1191 KiB

Open AccessArticle

Subcritical Fluid Extraction of Chinese Quince Seed: Optimization and Product Characterization

by Li Wang¹, Min Wu¹, Hua-Min Liu^2,*, Yu-Xiang Ma³, Xue-De Wang³ and Guang-Yong Qin^1,*

¹ College of Physics Engineering, Zhengzhou University, Zhengzhou, Henan 450001, China

² Province Key Laboratory of Transformation and Utilization of Cereal Resource, Henan University of Technology, Zhengzhou, Henan 450001, China

³ College of Food Science and Technology, Henan University of Technology, Zhengzhou, Henan 450001, China

Molecules 2017, 22(4), 528; https://doi.org/10.3390/molecules22040528 - 25 Mar 2017

Cited by 32 | Viewed by 6487

Abstract

Chinese quince seed (CQS) is an underutilized oil source and a potential source of unsaturated fatty acids and α-tocopherol-rich oil. Subcritical fluid (SCF) extraction is executed at lower pressures and temperatures than the pressures and temperatures used in supercritical fluid extraction. However, no [...] Read more.

Chinese quince seed (CQS) is an underutilized oil source and a potential source of unsaturated fatty acids and α-tocopherol-rich oil. Subcritical fluid (SCF) extraction is executed at lower pressures and temperatures than the pressures and temperatures used in supercritical fluid extraction. However, no studies on the SCF extraction of CQS oil are reported. Therefore, the objective of this study was to evaluate the use of SCF for the extraction of CQS oil and to compare the use of SCF with the classical Soxhlet (CS) and supercritical CO₂ (SC-CO₂) extraction methods. Response surface methodology (RSM) was used to investigate the extraction conditions: temperature (45–65 °C), time (30–50 min), and solvent/solid ratio (5–15 mL/g). The optimization results showed that the highest yield (27.78%) was obtained at 56.18 °C, 40.20 min, and 12.57 mL/g. The oil extracted by SCF had a higher unsaturated fatty acid content (86.37%–86.75%), higher α-tocopherol content (576.0–847.6 mg/kg), lower acid value (3.97 mg/g), and lower peroxide value (0.02 meq O₂/kg) than extractions using CS and SC-CO₂methods. The SCF-defatted meal of oilseed exhibited the highest nitrogen solubility index (49.64%) and protein dispersibility index (50.80%), demonstrating that SCF extraction was a promising and efficient technique as an alternative to CS and SC-CO₂methods, as very mild operating conditions and an eco-friendly solvent can be used in the process with maximum preservation of the quality of the meal. Full article

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

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7 pages, 2404 KiB

Open AccessArticle

New Acorane-Type Sesquiterpene from Acorus calamus L.

by Juan Li¹, Jianping Zhao², Wei Wang¹, Lin Li³, Lan Zhang³, Xiao-Fang Zhao¹, Qing-Ru Liu¹, Fang Liu¹, Min Yang⁴, Ikhlas A. Khan² and Shun-Xiang Li^1,*

¹ Hunan Province Engineering Research Center of Bioactive Substance Discovery of TCM, Hunan University of Chinese Medicine, Changsha 410208, Hunan, China

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

³ Key Laboratory of Neurodegenerative Diseases of Ministry of Education, Capital Medical University, Beijing 100053, China

⁴ Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China

Molecules 2017, 22(4), 529; https://doi.org/10.3390/molecules22040529 - 26 Mar 2017

Cited by 17 | Viewed by 6761

Abstract

A new sesquiterpene, named neo-acorane A (1), and two known ones, acoric acid (2) and calamusin D (3), were isolated from a 95% ethanol extract of the rhizome parts of Acorus calamus L. Their structures were elucidated [...] Read more.

A new sesquiterpene, named neo-acorane A (1), and two known ones, acoric acid (2) and calamusin D (3), were isolated from a 95% ethanol extract of the rhizome parts of Acorus calamus L. Their structures were elucidated by spectroscopic methods, and the absolute configurations were determined by single-crystal X-ray diffraction analysis. Compounds 1 and 2 are nonisoprenoid sesquiterpenoids, likely biosynthesized from an acorane-type sesquiterpene by oxidative fission of the six- or five-membered ring. Moreover, compounds 1 (10 μM), 2 (5 μM and 10 μM) and 3 (10 μM) showed cell proliferation activity on the SK-N-BE (2) cell line. Full article

(This article belongs to the Section Natural Products Chemistry)

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12 pages, 2190 KiB

Open AccessArticle

Hydrogen Sulphide Production in Healthy and Ulcerated Gastric Mucosa of Rats

by Patrycja Bronowicka-Adamska¹, Maria Wróbel^1,*

, Marcin Magierowski²

, Katarzyna Magierowska², Sławomir Kwiecień² and Tomasz Brzozowski²

¹ Chair of Medical Biochemistry, Jagiellonian University Medical College, Krakow, 7 Kopernika St., 31-034 Cracow, Poland

² Department of Physiology, Jagiellonian University Medical College, 31-530 Krakow, Poland

Molecules 2017, 22(4), 530; https://doi.org/10.3390/molecules22040530 - 27 Mar 2017

Cited by 15 | Viewed by 5311

Abstract

Hydrogen sulphide (H₂S) is produced endogenously via two enzymes dependent on pyridoxal phosphate (PLP): cystathionine beta-synthase (CBS, EC 4.2.1.22), cystathionase γ-liase (CTH, EC 4.4.1.1), and a third, 3-mercaptopyruvate sulfurtransferase (MPST, EC 2.8.1.2). H₂S strengthens the defence mechanisms of the [...] Read more.

Hydrogen sulphide (H₂S) is produced endogenously via two enzymes dependent on pyridoxal phosphate (PLP): cystathionine beta-synthase (CBS, EC 4.2.1.22), cystathionase γ-liase (CTH, EC 4.4.1.1), and a third, 3-mercaptopyruvate sulfurtransferase (MPST, EC 2.8.1.2). H₂S strengthens the defence mechanisms of the gastric mucosal barrier, and plays an important role in gastroprotection, including the increased resistance to damage caused by various irritants and non-steroidal anti-inflammatory drugs. The study was conducted to determine the role of H₂S in ulcerated gastric mucosa of rats caused by immobilization in cold water (WRS). The activity and expression of γ-cystathionase, cystathionine β-synthase, 3-mercaptopyruvate sulfurtransferase, and rhodanese was compared with healthy mucosa, together with H₂S generation, and cysteine, glutathione, and cystathionine levels. The results showed that the defence mechanism against stress is associated with stimulation of the production of H₂S in the tissue and confirmed the observed advantageous effect of H₂S on healing of gastric ulcers. In case of animals pretreated with exogenous sources of H₂S and NaHS, and some changes observed in the ulcerated gastric mucosa tend to return to values found in the healthy tissue, a finding that is in accordance with the previously determined gastroprotective properties of H₂S. The results presented in this paper point to the possible role of rhodanese in H₂S production in the gastric mucosa of rats, together with the earlier mentioned three enzymes, which are all active in this tissue. Full article

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

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10 pages, 979 KiB

Open AccessArticle

Choerosponins A and B, Two New Cytotoxic Bridged-Ring Ketones and the Determination of Their Absolute Configurations

by Chang-Wei Li^1,*, Bing Han², Bing Cai² and Cheng-Bin Cui¹

¹ State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China

² Beijing Institute for Biomedicinal Research, Beijing 100091, China

Molecules 2017, 22(4), 531; https://doi.org/10.3390/molecules22040531 - 27 Mar 2017

Cited by 5 | Viewed by 3575

Abstract

Bioactivity-directed fractionation of antitumor compounds from the stem barks of Choerospondias axillaries (Roxb.) Burtt et Hill (Anacardiaceae) afforded two new cytotoxic bridged-ring ketones, choerosponins A (1) and B (2), and their structures were elucidated by spectroscopic methods; their stereochemistry [...] Read more.

Bioactivity-directed fractionation of antitumor compounds from the stem barks of Choerospondias axillaries (Roxb.) Burtt et Hill (Anacardiaceae) afforded two new cytotoxic bridged-ring ketones, choerosponins A (1) and B (2), and their structures were elucidated by spectroscopic methods; their stereochemistry was determined by NOE difference experiments, CD spectra and the modified Mosher’s method. Compound 1 has a rare dioxatricyclo skeleton. Flow cytometry and SRB methods were employed to evaluate the antitumor activity of the two compounds against tsFT210, HCT-15, HeLa, A2780 and MCF-7 cell lines, and both of them showed strong cytotoxicity. MTT and paper disc methods were also used to evaluate their anti-hypoxia and antibacterial activities, and both of them showed no apparent activities. Full article

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11 pages, 1776 KiB

Open AccessArticle

Constituents of the Roots of Dichapetalum pallidum and Their Anti-Proliferative Activity

by Dorcas Osei-Safo^1,*, Godwin Akpeko Dziwornu^1,4, Regina Appiah-Opong², Mary Anti Chama¹, Isaac Tuffour², Reiner Waibel³, Richard Amewu¹ and Ivan Addae-Mensah¹

¹ Chemistry Department, School of Physical and Mathematical Sciences, College of Basic and Applied Sciences, University of Ghana, P.O. Box LG 56, Legon, Accra, Ghana

² Department of Clinical Pathology, Noguchi Memorial Institute for Medical Research, College of Health Sciences, University of Ghana, P.O. Box LG 581, Legon, Accra, Ghana

³ Department of Chemistry and Pharmacy, Friederich Alexander University of Erlangen-Nurnberg, Schuhstrasse 19, 91052 Erlangen, Germany

⁴ Present address: Department of Chemistry, University of Cape Town, Rondebosch 7701, South Africa.

Molecules 2017, 22(4), 532; https://doi.org/10.3390/molecules22040532 - 27 Mar 2017

Cited by 15 | Viewed by 4800

Abstract

As part of our search for bioactive compounds from the Dichapetalaceae, repeated chromatographic purification of the roots of a hitherto unexamined species, Dichapetalum pallidum, led to the isolation of the newly occurring 7-hydroxydichapetalin P (1) and the known dichapetalins A [...] Read more.

As part of our search for bioactive compounds from the Dichapetalaceae, repeated chromatographic purification of the roots of a hitherto unexamined species, Dichapetalum pallidum, led to the isolation of the newly occurring 7-hydroxydichapetalin P (1) and the known dichapetalins A (2) and X (3). Also isolated were the known compounds friedelin-2,3-lactone (4), friedelan-3-one (6), friedelan-3β-ol (7) and pomolic (8), as well as the dipeptide aurantiamide acetate (5). The compounds were characterized by direct interpretation of their IR, 1D NMR and 2D NMR spectral data and by comparison of their physico-chemical data, including their chromatographic profiles, with the literature and authentic samples in our compound library for the genus Dichapetalum. The compounds were assayed for their anti-proliferative activities against the human T-lymphocytic leukemia (Jurkat), acute promyelocytic leukemia (HL-60) and T-lymphoblast-like leukemia (CEM) cell lines. Overall, dichapetalin X showed the strongest (3.14 μM) and broadest cytotoxic activities against all the leukemic cell lines tested, exhibiting even stronger activities than the standard compound, curcumin. Full article

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

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11 pages, 2896 KiB

Open AccessArticle

Artesunate Enhances the Cytotoxicity of 5-Aminolevulinic Acid-Based Sonodynamic Therapy against Mouse Mammary Tumor Cells In Vitro

by Tomohiro Osaki^1,*, Yoshihiro Uto², Masahiro Ishizuka³, Tohru Tanaka³, Nobuyasu Yamanaka⁴, Tsukasa Kurahashi⁴, Kazuo Azuma¹, Yusuke Murahata¹, Takeshi Tsuka¹, Norihiko Itoh¹, Tomohiro Imagawa¹ and Yoshiharu Okamoto¹

¹ Joint Department of Veterinary Clinical Medicine, Faculty of Agriculture, Tottori University, Tottori 680-8553, Japan

² Faculty of Bioscience and Bioindustry, Tokushima University, Tokushima 770-8506, Japan

³ SBI Pharmaceuticals Co., Ltd., Tokyo 106-6020, Japan

⁴ ITO Co., Ltd., Tokyo 176-0014, Japan

Molecules 2017, 22(4), 533; https://doi.org/10.3390/molecules22040533 - 27 Mar 2017

Cited by 18 | Viewed by 5891

Abstract

Sonodynamic therapy (SDT) kills tumor cells through the synergistic effects of ultrasound (US) and a sonosensitizer agent. 5-Aminolevulinic acid (5-ALA) has been used as a sonodynamic sensitizer for cancer treatment. However, studies have shown that 5-ALA-based SDT has limited efficacy against malignant tumors. [...] Read more.

Sonodynamic therapy (SDT) kills tumor cells through the synergistic effects of ultrasound (US) and a sonosensitizer agent. 5-Aminolevulinic acid (5-ALA) has been used as a sonodynamic sensitizer for cancer treatment. However, studies have shown that 5-ALA-based SDT has limited efficacy against malignant tumors. In this study, we examined whether artesunate (ART) could enhance the cytotoxicity of 5-ALA-based SDT against mouse mammary tumor (EMT-6) cells in vitro. In the ART, ART + US, ART + 5-ALA, and ART + 5-ALA + US groups, the cell survival rate correlated with ART concentration, and decreased with increasing concentrations of ART. Morphologically, many apoptotic and necrotic cells were observed in the ART + 5-ALA + US group. The percentage of reactive oxygen species-positive cells in the ART + 5-ALA + US group was also significantly higher than that in the 5-ALA group (p = 0.0228), and the cell death induced by ART + 5-ALA + US could be inhibited by the antioxidant N-acetylcysteine. These results show that ART offers great potential in enhancing the efficacy of 5-ALA-based SDT for the treatment of cancer. However, these results are only based on in vitro studies, and further in vivo studies are required. Full article

(This article belongs to the Special Issue Artemisinin: Against Malaria, Cancer and Viruses)

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2 pages, 146 KiB

Open AccessErratum

Novel Antihypertensive Peptides Derived from Adlay (Coix larchryma-jobi L. var. ma-yuen Stapf) Glutelin

by Bin Li, Liansheng Qiao, Lingling Li, Yanling Zhang, Kai Li, Lingzhi Wang^* and Yanjiang Qiao^*

Beijing University of Chinese Medicine, 6, South Zhonghuan Road, Wangjing, Chaoyang District,Beijing 100102, China

Molecules 2017, 22(4), 534; https://doi.org/10.3390/molecules22040534 - 27 Mar 2017

Cited by 13 | Viewed by 3347

Abstract

n/a Full article

13 pages, 1484 KiB

Open AccessArticle

Novel Sulfamethoxazole Ureas and Oxalamide as Potential Antimycobacterial Agents

by Martin Krátký^1,*, Jiřina Stolaříková² and Jarmila Vinšová¹

¹ Department of Organic and Bioorganic Chemistry, Faculty of Pharmacy in Hradec Králové, Charles University, Heyrovského 1203, 50005 Hradec Králové, Czech Republic

² Laboratory for Mycobacterial Diagnostics and Tuberculosis, Regional Institute of Public Health in Ostrava, Partyzánské námĕstí 7, 70200 Ostrava, Czech Republic

Molecules 2017, 22(4), 535; https://doi.org/10.3390/molecules22040535 - 28 Mar 2017

Cited by 14 | Viewed by 5912

Abstract

Infections caused by Mycobacterium tuberculosis (Mtb.) and nontuberculous mycobacteria (NTM) are considered to be a global health problem; current therapeutic options are limited. Sulfonamides have exhibited a wide range of biological activities including those against mycobacteria. Based on the activity of [...] Read more.

Infections caused by Mycobacterium tuberculosis (Mtb.) and nontuberculous mycobacteria (NTM) are considered to be a global health problem; current therapeutic options are limited. Sulfonamides have exhibited a wide range of biological activities including those against mycobacteria. Based on the activity of 4-(3-heptylureido)-N-(5-methylisoxazol-3-yl)benzenesulfonamide against NTM, we designed a series of homologous sulfamethoxazole-based n-alkyl ureas (C₁–C₁₂), as well as several related ureas and an oxalamide. Fifteen ureas and one oxalamide were synthesized by five synthetic procedures and characterized. They were screened for their activity against Mtb. and three NTM strains (M. avium, M. kansasii). All of them share antimycobacterial properties with minimum inhibitory concentration (MIC) values starting from 2 µM. The highest activity showed 4,4′-[carbonylbis(azanediyl)]bis[N-(5-methylisoxazol-3-yl)benzenesulfonamide] with MIC of 2–62.5 µM (i.e., 1.07–33.28 µg/mL). Among n-alkyl ureas, methyl group is optimal for the inhibition of both Mtb. and NTM. Generally, longer alkyls led to increased MIC values, heptyl being an exception for NTM. Some of the novel derivatives are superior to parent sulfamethoxazole. Several urea and oxalamide derivatives are promising antimycobacterial agents with low micromolar MIC values. Full article

(This article belongs to the Special Issue Sulfonamides)

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16 pages, 5657 KiB

Open AccessReview

The Mechanism of Room-Temperature Ionic-Liquid-Based Electrochemical CO₂ Reduction: A Review

by Hyung-Kyu Lim^*

and Hyungjun Kim^*

Graduate School of EEWS, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Yuseong-gu, Daejeon 34141, Korea

Molecules 2017, 22(4), 536; https://doi.org/10.3390/molecules22040536 - 28 Mar 2017

Cited by 61 | Viewed by 11696

Abstract

Electrochemical CO₂ conversion technology is becoming indispensable in the development of a sustainable carbon-based economy. While various types of electrocatalytic systems have been designed, those based on room-temperature ionic liquids (RTILs) have attracted considerable attention because of their high efficiencies and selectivities. [...] Read more.

Electrochemical CO₂ conversion technology is becoming indispensable in the development of a sustainable carbon-based economy. While various types of electrocatalytic systems have been designed, those based on room-temperature ionic liquids (RTILs) have attracted considerable attention because of their high efficiencies and selectivities. Furthermore, it should be possible to develop more advanced electrocatalytic systems for commercial use because target-specific characteristics can be fine-tuned using various combinations of RTIL ions. To achieve this goal, we require a systematic understanding of the role of the RTIL components in electrocatalytic systems, however, their role has not yet been clarified by experiment or theory. Thus, the purpose of this short review is to summarize recent experimental and theoretical mechanistic studies to provide insight into and to develop guidelines for the successful development of new CO₂ conversion systems. The results discussed here can be summarized as follows. Complex physical and chemical interactions between the RTIL components and the reaction intermediates, in particular at the electrode surface, are critical for determining the activity and selectivity of the electrocatalytic system, although no single factor dominates. Therefore, more fundamental research is required to understand the physical, chemical, and thermodynamic characteristics of complex RTIL-based electrocatalytic 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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14 pages, 15410 KiB

Open AccessArticle

3,4-Dihydroxybenzalactone Suppresses Human Non-Small Cell Lung Carcinoma Cells Metastasis via Suppression of Epithelial to Mesenchymal Transition, ROS-Mediated PI3K/AKT/MAPK/MMP and NFκB Signaling Pathways

by Wei Chao¹, Jeng-Shyan Deng², Pei-Ying Li³, Yu-Chia Liang¹ and Guan-Jhong Huang^1,*

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

² Department of Health and Nutrition Biotechnology, Asia University, Taichung 404, Taiwan

³ School of Pharmacy, College of Pharmacy, China Medical University, Taichung 404, Taiwan

Molecules 2017, 22(4), 537; https://doi.org/10.3390/molecules22040537 - 28 Mar 2017

Cited by 46 | Viewed by 7010

Abstract

3,4-Dihydroxybenzalactone (DBL) was isolated from Phellinus linteus (PL), which is a folk medicine possessing various physiological effects. In this study, we used highly metastatic A549 cells to investigate efficacy of DBL inhibition of cancer metastasis and possible mechanisms. The results revealed DBL inhibited [...] Read more.

3,4-Dihydroxybenzalactone (DBL) was isolated from Phellinus linteus (PL), which is a folk medicine possessing various physiological effects. In this study, we used highly metastatic A549 cells to investigate efficacy of DBL inhibition of cancer metastasis and possible mechanisms. The results revealed DBL inhibited migratory and invasive abilities of cancer cells at noncytotoxic concentrations. We found DBL suppressed enzymatic activities, protein expression, and RNA levels of matrix metalloproteinase (MMP)-2 and MMP-9. Western blot results showed DBL decreased phosphoinositide 3-kinase (PI3K)/AKT, phosphorylation status of mitogen-activated protein kinases (MAPKs), and focal adhesion kinase (FAK)/paxillin, which correlated with cell migratory ability. DBL also affected epithelial to mesenchymal transition (EMT)-related biomarkers. In addition, DBL enhanced cytoprotective effects through elevated antioxidant enzymes including heme oxygenase 1 (HO-1), catalase, glutathione peroxidase (GPx), and superoxide dismutase (SOD). Moreover, DBL influenced the nuclear translocation of nuclear factor κB (NFκB), nuclear factor erythroid 2-related factor 2 (Nrf2), Snail, and Slug in A549 cells. Taken together, these results suggested that treatment with DBL may act as a potential candidate to inhibit lung cancer metastasis by inhibiting MMP-2 and -9 via affecting PI3K/AKT, MAPKs, FAK/paxillin, EMT/Snail and Slug, Nrf2/antioxidant enzymes, and NFκB signaling pathways. Full article

(This article belongs to the Collection Bioactive Compounds)

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11 pages, 873 KiB

Open AccessArticle

Determination of Vancomycin in Human Serum by Cyclodextrin-Micellar Electrokinetic Capillary Chromatography (CD-MEKC) and Application for PDAP Patients

by Jiajing Wang¹, Yuqing Cao², Shengyuan Wu³, Shuowen Wang¹, Xin Zhao⁴, Tingting Zhou², Yuefen Lou^5,*

and Guorong Fan^1,2,3,*

¹ Department of Clinical Pharmacy, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, No. 100 Haining Road, Shanghai 200080, China

² Shanghai Key Laboratory for Pharmaceutical Metabolite Research, School of Pharmacy, Second Military Medical University, Shanghai 200433, China

³ Laboratory of Drug Metabolism & Pharmacokinetics, School of Medicine, Tongji University, No. 1239 Siping Road, Shanghai 200092, China

⁴ Department of Pharmaceutical Analysis, School of Pharmacy, China Pharmaceutical University, No. 24 Tong Jia Xiang, Nanjing 210009, China

⁵ Department of Pharmacy, Shanghai Fourth People's Hospital, Shanghai 200081, China

Molecules 2017, 22(4), 538; https://doi.org/10.3390/molecules22040538 - 28 Mar 2017

Cited by 17 | Viewed by 4816

Abstract

A simple and sensitive cyclodextrin-micellar electrokinetic capillary chromatography (CD-MEKC) method with UV detection was developed and validated for the determination of vancomycin (VCM) in serum. The separation was achieved in 14 min at 25 °C with a fused-silica capillary column of 40.2 cm [...] Read more.

A simple and sensitive cyclodextrin-micellar electrokinetic capillary chromatography (CD-MEKC) method with UV detection was developed and validated for the determination of vancomycin (VCM) in serum. The separation was achieved in 14 min at 25 °C with a fused-silica capillary column of 40.2 cm × 75 μm i.d. (effective length 30.2 cm) and a run buffer containing 25 mM borate buffer with 50 mM sodium dodecylsulfonate (SDS) (pH 9.5) and 2% sulfobutyl-β-cyclodextrin (sulfobutyl-β-CD). Under optimal conditions for biological samples, good separations with high efficiency and short analysis time were achieved. Several parameters affecting the drug separation from biological matrices were studied, including buffer types, concentrations, and pHs. The methods were validated over the range of 0.9998–99.98 µg/mL. Calibration curves of VCM also showed good linearity (r² > 0.999). Intra- and interday precisions (relative standard deviation, RSD) were less than 5.80% and 7.38%, and lower limit of quantification (LLOQ) were lower than 1.0 μg/mL. The mean recoveries ranged between 84.03% and 91.69%. The method was successfully applied for monitoring VCM concentrations in serum of patients with peritoneal dialysis-associated peritonitis (PDAP). The assay should be applicable to pharmacokinetic studies and routine therapeutic drug monitoring of this drug in serum. Full article

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16 pages, 272 KiB

Open AccessReview

Harnessing Solute Carrier Transporters for Precision Oncology

by Michael D. Nyquist¹, Bhagwat Prasad² and Elahe A. Mostaghel^3,4,*

¹ Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA

² Department of Pharmaceutics, University of Washington, Seattle, WA 98195, USA

³ Division of Oncology, Department of Medicine, University of Washington, Seattle, WA 98195 USA

⁴ Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA

Molecules 2017, 22(4), 539; https://doi.org/10.3390/molecules22040539 - 28 Mar 2017

Cited by 38 | Viewed by 7059

Abstract

Solute Carrier (SLC) transporters are a large superfamily of transmembrane carriers involved in the regulated transport of metabolites, nutrients, ions and drugs across cellular membranes. A subset of these solute carriers play a significant role in the cellular uptake of many cancer therapeutics, [...] Read more.

Solute Carrier (SLC) transporters are a large superfamily of transmembrane carriers involved in the regulated transport of metabolites, nutrients, ions and drugs across cellular membranes. A subset of these solute carriers play a significant role in the cellular uptake of many cancer therapeutics, ranging from chemotherapeutics such as antimetabolites, topoisomerase inhibitors, platinum-based drugs and taxanes to targeted therapies such as tyrosine kinase inhibitors. SLC transporters are co-expressed in groups and patterns across normal tissues, suggesting they may comprise a coordinated regulatory circuit serving to mediate normal tissue functions. In cancer however, there are dramatic changes in expression patterns of SLC transporters. This frequently serves to feed the increased metabolic demands of the tumor cell for amino acids, nucleotides and other metabolites, but also presents a therapeutic opportunity, as increased transporter expression may serve to increase intracellular concentrations of substrate drugs. In this review, we examine the regulation of drug transporters in cancer and how this impacts therapy response, and discuss novel approaches to targeting therapies to specific cancers via tumor-specific aberrations in transporter expression. We propose that among the oncogenic changes in SLC transporter expression there exist emergent vulnerabilities that can be exploited therapeutically, extending the application of precision medicine from tumor-specific drug targets to tumor-specific determinants of drug uptake. Full article

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

11 pages, 1295 KiB

Open AccessArticle

Bioactive Constituents Obtained from the Seeds of Lepidium apetalum Willd

by Sijian Wang¹, Pingping Shi², Lu Qu¹, Jingya Ruan¹, Shengcai Yang², Haiyang Yu¹, Yi Zhang^2,* and Tao Wang^1,*

¹ Tianjin State Key Laboratory of Modern Chinese Medicine, 312 Anshanxi Road, Nankai District, Tianjin 300193, China

² Tianjin Key Laboratory of TCM Chemistry and Analysis, Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, 312 Anshanxi Road, Nankai District, Tianjin 300193, China

Molecules 2017, 22(4), 540; https://doi.org/10.3390/molecules22040540 - 28 Mar 2017

Cited by 17 | Viewed by 4541

Abstract

Three new compounds, apetalumosides C₁ (1), D (2), and 1-thio--d-glucopyranosyl(1→1)-1-thio-α-d-glucopyranoside (3), together with twenty-two known ones (4–25) were obtained from the seeds of Lepidium apetalum Willd. Among the known isolates, 5–8, 10– [...] Read more.

Three new compounds, apetalumosides C₁ (1), D (2), and 1-thio--d-glucopyranosyl(1→1)-1-thio-α-d-glucopyranoside (3), together with twenty-two known ones (4–25) were obtained from the seeds of Lepidium apetalum Willd. Among the known isolates, 5–8, 10–13, 16–20, and 25 were obtained from the genus for the first time; 4, 14, 15, and 21–24 were isolated from the species for the first time. Meanwhile, the NMR data of 16 was first reported here. Their structures were determined by means of chemical and spectroscopic methods. On the other hand, their inhibitory effects on sodium oleate-induced triglyceride (TG) overloading in HepG2 cells were evaluated. As a result, two new compounds (1 and 2), together with known isolates 7–11, 13, 14, 16–18, 20, 21, and 25 possessed significant inhibitory effects in the cells. Full article

(This article belongs to the Section Natural Products Chemistry)

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10 pages, 2812 KiB

Open AccessArticle

Thiazine-2-thiones as Masked 1-Azadienes in Cascade Dimerization Reactions)

by Art Kruithof¹, Christophe M. L. Vande Velde², Eelco Ruijter¹ and Romano V. A. Orru^1,*

¹ Department of Chemistry & Pharmaceutical Sciences and Amsterdam Institute for Molecules, Medicines & Systems, Vrije Universiteit Amsterdam, De Boelelaan 1108, 1081HZ Amsterdam, The Netherlands

² Faculty of Applied Engineering, Advanced eactor Technology, University of Antwerp, Groenenborgerlaan 171, 2018 Antwerpen, Belgium

Molecules 2017, 22(4), 541; https://doi.org/10.3390/molecules22040541 - 28 Mar 2017

Cited by 1 | Viewed by 4365

Abstract

We report the unexpected formation of a 1-azadiene dimer from 4,6-diphenyl-3,6-dihydro-2H-1,3-thiazine-2-thiones under prolonged microwave irradiation. In this manner, thiazine-2-thiones act as “masked” 1-azadiene equivalents, which makes them useful synthetic tools to access complex heterocyclic frameworks. We compare this dimerization with earlier [...] Read more.

We report the unexpected formation of a 1-azadiene dimer from 4,6-diphenyl-3,6-dihydro-2H-1,3-thiazine-2-thiones under prolonged microwave irradiation. In this manner, thiazine-2-thiones act as “masked” 1-azadiene equivalents, which makes them useful synthetic tools to access complex heterocyclic frameworks. We compare this dimerization with earlier approaches and elaborate on the observed diastereoselectivity. Full article

(This article belongs to the Special Issue MCRs and Related One-Pot Organic Synthesis)

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22 pages, 3355 KiB

Open AccessArticle

Bisarylureas Based on 1H-Pyrazolo[3,4-d]pyrimidine Scaffold as Novel Pan-RAF Inhibitors with Potent Anti-Proliferative Activities: Structure-Based Design, Synthesis, Biological Evaluation and Molecular Modelling Studies

by Yu Fu, Yuanyuan Wang, Shanhe Wan, Zhonghuang Li, Guangfa Wang, Jiajie Zhang^* and Xiaoyun Wu^*

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

Molecules 2017, 22(4), 542; https://doi.org/10.3390/molecules22040542 - 29 Mar 2017

Cited by 8 | Viewed by 6376

Abstract

RAF (Ras activating factor) kinases are important and attractive targets for cancer therapy. With the aim of discovering RAF inhibitors that bind to DFG-out inactive conformation created by the movement of Asp-Phe-Gly (DFG), we conducted structure-based drug design using the X-ray cocrystal structures [...] Read more.

RAF (Ras activating factor) kinases are important and attractive targets for cancer therapy. With the aim of discovering RAF inhibitors that bind to DFG-out inactive conformation created by the movement of Asp-Phe-Gly (DFG), we conducted structure-based drug design using the X-ray cocrystal structures of BRAF (v-raf murine sarcoma viral oncogene homolog B1), starting from bisarylurea derivative based on 1H-pyrazolo[3,4-d]pyrimidine scaffold 1a. Most of the synthesized compounds showed good to excellent inhibitory activities against BRAF^V600E kinase, possessed moderate to potent anti-proliferative activities against four tumor cell lines (A375, HT-29, PC-3 and A549) and good selectivity towards cancer cells rather normal cells (Madin-Darby canine kidney, MDCK). The most promising compound, 1v, exhibited potent inhibitory activity against not only BRAF^V600E (half maximal inhibitory concentration, IC₅₀ = 23.6 nM) but also wild-type BRAF (IC₅₀ = 51.5 nM) and C-RAF (IC₅₀ = 8.5 nM), and effective cellular anti-proliferative activities against A375, HT-29, PC-3 and A549 cell lines as well as a very good selectivity profile. Moreover, compound 1v mainly arrested the A375 cell line in the G0/G1 stage, and showed significant suppression of MEK (mitogen-activated protein kinase kinase) phosphorylation in A375 and HT-29 cell lines. Taken together, the optimal compound 1v showed excellent in vitro potency as a pan-RAF inhibitor. In addition, the promise of compound 1v was further confirmed by molecular dynamics simulation and binding free energy calculations. Full article

(This article belongs to the Section Medicinal Chemistry)

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11 pages, 2861 KiB

Open AccessArticle

Attenuation of Bleomycin-Induced Pulmonary Fibrosis in Rats with S-Allyl Cysteine

by Takuma Tsukioka¹, Shigekazu Takemura^2,*

, Yukiko Minamiyama^2,3, Shinjiro Mizuguchi¹, Michihito Toda¹ and Shigeru Okada⁴

¹ Department of Thoracic Surgery, Osaka City University Graduate School of Medicine, Osaka 5458585, Japan

² Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, Osaka 5458585, Japan

³ Food Hygiene and Environmental Health Division of Applied Life Science, Graduate School of Life and Environmental Sciences, Kyoto Prefectural University, Sakyo-ku, Kyoto 6068522, Japan

⁴ Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 7008558, Japan

Molecules 2017, 22(4), 543; https://doi.org/10.3390/molecules22040543 - 29 Mar 2017

Cited by 13 | Viewed by 6905

Abstract

Pulmonary fibrosis is a complex disease with high mortality and morbidity. As there are currently no effective treatments, development of new strategies is essential for improving therapeutic outcomes. S-allyl cysteine (SAC) is a constituent of aged garlic extract that has demonstrated efficacy [...] Read more.

Pulmonary fibrosis is a complex disease with high mortality and morbidity. As there are currently no effective treatments, development of new strategies is essential for improving therapeutic outcomes. S-allyl cysteine (SAC) is a constituent of aged garlic extract that has demonstrated efficacy as an antioxidant and anti-inflammatory agent. The current study examines the effects of SAC on pulmonary fibrosis induced by a single intratracheal instillation of bleomycin (2.5 mg/kg). SAC was administered to rats as 0.15% SAC-containing diet from seven days prior to instillation up until the conclusion of the experiment (14 days post-instillation). SAC significantly reduced collagen mRNA expression and protein deposition (33.3 ± 2.7 μg/mg and 28.2 ± 2.1 μg/mg tissue in vehicle- and SAC-treated rats, respectively), and decreased fibrotic area, as assessed histologically. In the rats’ lungs, SAC also attenuated the increased expression of transforming growth factor-β1 (TGF-β1), a central regulator of myofibroblast recruitment, activation, and differentiation. While bleomycin instillation increased the number of myofibroblasts within the lung mesenchymal area, this change was significantly reduced by SAC treatment. SAC may exert efficacy as an anti-fibrotic by attenuating myofibroblast differentiation through TGF-β1-mediated fibroproliferative processes. Thus, our results indicate SAC may be useful for the prevention or treatment of pulmonary fibrosis. Full article

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

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13 pages, 2011 KiB

Open AccessArticle

A Specific Peptide with Calcium-Binding Capacity from Defatted Schizochytrium sp. Protein Hydrolysates and the Molecular Properties

by Xixi Cai^1,2, Qian Yang^1,2, Jiaping Lin², Nanyan Fu¹ and Shaoyun Wang^2,*

¹ The Key Laboratory of Analysis and Detection Technology for Food Safety of the MOE, College of Chemistry, Fuzhou University, Fuzhou 350108, China

² Institute of Food and Marine Bio-Resources, College of Biological Science and Technology, Fuzhou University, Fuzhou 350108, China

Molecules 2017, 22(4), 544; https://doi.org/10.3390/molecules22040544 - 29 Mar 2017

Cited by 25 | Viewed by 6046

Abstract

Marine microorganisms have been proposed as a new kind of protein source. Efforts are needed in order to transform the protein-rich biological wastes left after lipid extraction into value-added bio-products. Thus, the utilization of protein recovered from defatted Schizochytrium sp. by-products presents an [...] Read more.

Marine microorganisms have been proposed as a new kind of protein source. Efforts are needed in order to transform the protein-rich biological wastes left after lipid extraction into value-added bio-products. Thus, the utilization of protein recovered from defatted Schizochytrium sp. by-products presents an opportunity. A specific peptide Tyr-Leu (YL) with calcium-binding capacity was purified from defatted Schizochytrium sp. protein hydrolysates through gel filtration chromatography and RP-HPLC. The calcium-binding activity of YL reached 126.34 ± 3.40 μg/mg. The calcium-binding mechanism was investigated through ultraviolet, fluorescence and infrared spectroscopy. The results showed that calcium ions could form dative bonds with carboxyl oxygen atoms and amino nitrogen atoms as well as the nitrogen and oxygen atoms of amide bonds. YL-Ca exhibited excellent thermal stability and solubility, which was beneficial for its absorption and transport in the basic intestinal tract of the human body. Moreover, the cellular uptake of calcium in Caco-2 cells showed that YL-Ca could enhance calcium uptake efficiency and protect calcium ions against precipitation caused by dietary inhibitors such as tannic acid, oxalate, phytate and metal ions. The findings indicate that the by-product of Schizochytrium sp. is a promising source for making peptide-calcium bio-products as algae-based functional supplements for human beings. 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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10 pages, 526 KiB

Open AccessArticle

Rapid Determination of 30 Polyphenols in Tongmai Formula, a Combination of Puerariae Lobatae Radix, Salviae Miltiorrhizae Radix et Rhizoma, and Chuanxiong Rhizoma, via Liquid Chromatography-Tandem Mass Spectrometry

by Fu-Rong Wang¹, Ying Zhang², Xin-Bao Yang^2,3, Chun-Xu Liu^2,4, Xiu-Wei Yang^1,*, Wei Xu¹ and Jian-Xun Liu^2,3,*

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

² Institute of Bascic Medical Sciences, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China

³ School of Basic Medical Science, Beijing University of Chinese Medicines, Beijing 100029, China

⁴ Faculty of Traditinal Chinese Medicine, Shenyang Pharmaceutical University, Shenyang 110016, Liaoning, China

Molecules 2017, 22(4), 545; https://doi.org/10.3390/molecules22040545 - 29 Mar 2017

Cited by 14 | Viewed by 8322

Abstract

Tongmai formula (TMF) is a herbal preparation composed of three traditional Chinese medicinal materials: Puerariae Lobatae Radix (Gegen), Salviae Miltiorrhizae Radix et Rhizoma (Danshen) and Chuanxiong Rhizoma (Chuanxiong). It has been used to treat cardiovascular diseases for decades. To develop a reliable and [...] Read more.

Tongmai formula (TMF) is a herbal preparation composed of three traditional Chinese medicinal materials: Puerariae Lobatae Radix (Gegen), Salviae Miltiorrhizae Radix et Rhizoma (Danshen) and Chuanxiong Rhizoma (Chuanxiong). It has been used to treat cardiovascular diseases for decades. To develop a reliable and convenient analytical method for a comprehensive determination of polyphenols in TMF and the ascertainment of their chemical correlations with its herbal components, a method combining high-performance liquid chromatography with electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) was developed and validated for rapid determination of 30 polyphenols in TMF and its three herbal components. The chromatographic separation was carried out on a Chromolith Fastgradient RP-18 endcapped 50-2 column using an optimized gradient elution. Statistical analysis of obtained data demonstrated that the method had a desirable linearity, precision, and accuracy, as well as excellent sensitivity. The obtained results indicated that, among the 30 polyphenols in TMF, 22 originated from Gegen, 6 originated from Danshen, and 2 originated from Chuanxiong. The major polyphenols in TMF have been identified as puerarin, mirificin, salvianolic acid B, salvianic acid A, 3’-hydroxypuerarin, 3’-methoxypuerarin, and salvianolic acid A, with a combined contribution of 19.2% of the preparation. The development and validation of this method will greatly facilitate future pharmacological studies of TMF and its herbal components, as well as polyphenols in cardiovascular therapies. Full article

(This article belongs to the Collection Bioactive Compounds)

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13 pages, 4487 KiB

Open AccessArticle

Volatiles Emitted at Different Flowering Stages of Jasminum sambac and Expression of Genes Related to α-Farnesene Biosynthesis

by Ying Yu¹, Shiheng Lyu^1,2, Dan Chen¹, Yi Lin¹, Jianjun Chen^1,2,*, Guixin Chen^1,* and Naixing Ye^1,*

¹ College of Horticulture, Key Laboratory of Tea Science, Fujian Agriculture and Forestry University, Fuzhou, Fujian 350002, China

² Department of Environmental Horticulrture and Mid-Florida Research and Education Center, University of Florida, IFAS, Apopka, FL 32703, USA

Molecules 2017, 22(4), 546; https://doi.org/10.3390/molecules22040546 - 29 Mar 2017

Cited by 54 | Viewed by 12046

Abstract

Fresh jasmine flowers have been used to make jasmine teas in China, but there has been no complete information about volatile organic compound emissions in relation to flower developmental stages and no science-based knowledge about which floral stage should be used for the [...] Read more.

Fresh jasmine flowers have been used to make jasmine teas in China, but there has been no complete information about volatile organic compound emissions in relation to flower developmental stages and no science-based knowledge about which floral stage should be used for the infusion. This study monitored volatile organic compounds emitted from living flowers of Jasminum sambac (L.) Ait. ‘Bifoliatum’ at five developmental stages and also from excised flowers. Among the compounds identified, α-farnesene, linalool, and benzyl acetate were most abundant. Since α-farnesene is synthesized through the Mevalonate pathway, four genes encoding 3-hydroxy-3-methylglutaryl coenzyme A synthase, 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR), farnesyl pyrophosphate synthase, and terpene synthase were isolated. Their expression patterns in living flowers at the five stages and in excised flowers coincided with the emission patterns of α-farnesene. Application of lovastatin, a HMGR inhibitor, significantly reduced the expression of the genes and greatly decreased the emission of α-farnesene. The sweet scent was diminished from lovastatin-treated flowers as well. These results indicate that α-farnesene is an important compound emitted from jasmine flowers, and its emission patterns suggest that flowers at the opening stage or flower buds 8 h after excision should be used for the infusion of tea leaves. Full article

(This article belongs to the Section Natural Products Chemistry)

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11 pages, 1883 KiB

Open AccessArticle

Metal-Free α-C(sp³)–H Functionalized Oxidative Cyclization of Tertiary N,N-Diaryl Amino Alcohols: Theoretical Approach for Mechanistic Pathway

by Zakir Ullah

and Mihyun Kim^*

Gachon Institute of Pharmaceutical Science & Department of Pharmacy, College of Pharmacy, Gachon University, Yeonsu-gu, Incheon 21936, Korea

Molecules 2017, 22(4), 547; https://doi.org/10.3390/molecules22040547 - 29 Mar 2017

Cited by 10 | Viewed by 7367

Abstract

The mechanistic pathway of TEMPO/I₂-mediated oxidative cyclization of N,N-diaryl amino alcohols 1 was investigated. Based on direct empirical experiments, three key intermediates (aminium radical cation 3, α-aminoalkyl radical 4, and iminium 5), four types of reactive species [...] Read more.

The mechanistic pathway of TEMPO/I₂-mediated oxidative cyclization of N,N-diaryl amino alcohols 1 was investigated. Based on direct empirical experiments, three key intermediates (aminium radical cation 3, α-aminoalkyl radical 4, and iminium 5), four types of reactive species (radical TEMPO, cationic TEMPO, TEMPO-I, and iodo radical), and three types of pathways ((1) SET/PCET mechanism; (2) HAT/1,6-H transfer mechanism; (3) ionic mechanism) were assumed. Under the assumption, nine free energy diagrams were acquired through density functional theory calculations. From the comparison of solution-phase free energy, some possible mechanisms were excluded, and then the chosen plausible mechanisms were concretized using the more stable intermediate 7. Full article

(This article belongs to the Special Issue Reactions of Hydrocarbons and other C‒H Compounds)

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11 pages, 2244 KiB

Open AccessArticle

Black Tea High-Molecular-Weight Polyphenol-Rich Fraction Promotes Hypertrophy during Functional Overload in Mice

by Yuki Aoki¹

, Tetsuo Ozawa¹, Tohru Takemasa² and Osamu Numata^1,*

¹ Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8572, Japan

² Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8574, Japan

Molecules 2017, 22(4), 548; https://doi.org/10.3390/molecules22040548 - 29 Mar 2017

Cited by 14 | Viewed by 9966

Abstract

Mitochondria activation factor (MAF) is a high-molecular-weight polyphenol extracted from black tea that stimulates training-induced 5′ adenosine monophosphate-activated protein kinase (AMPK) activation and improves endurance capacity. Originally, MAF was purified from black tea using butanol and acetone, making it unsuitable for food preparation. [...] Read more.

Mitochondria activation factor (MAF) is a high-molecular-weight polyphenol extracted from black tea that stimulates training-induced 5′ adenosine monophosphate-activated protein kinase (AMPK) activation and improves endurance capacity. Originally, MAF was purified from black tea using butanol and acetone, making it unsuitable for food preparation. Hence, we extracted a MAF-rich sample “E80” from black tea, using ethanol and water only. Here, we examined the effects of E80 on resistance training. Eight-week old C57BL/6 mice were fed with a normal diet or a diet containing 0.5% E80 for 4, 7 and 14 days under conditions of functional overload. It was found that E80 administration promoted overload-induced hypertrophy and induced phosphorylation of the Akt/mammalian target of rapamycin (mTOR) pathway proteins, such as Akt, P70 ribosomal protein S6 kinase (p70S6K), and S6 in the plantaris muscle. Therefore, functional overload and E80 administration accelerated mTOR signaling and increased protein synthesis in the muscle, thereby inducing hypertrophy. Full article

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

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10 pages, 5608 KiB

Open AccessArticle

The ‘Molecule of the Month’ Website—An Extraordinary Chemistry Educational Resource Online for over 20 Years

by Paul W. May^1,*

, Simon A. Cotton², Karl Harrison³ and Henry S. Rzepa⁴

¹ School of Chemistry, University of Bristol, Bristol BS8 1TS, UK

² School of Chemistry, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK

³ Department of Chemistry, University of Oxford, South Parks Road, Oxford OX1 3QZ, UK

⁴ Department of Chemistry, Imperial College, South Kensington Campus, London SW7 2AZ, UK

Molecules 2017, 22(4), 549; https://doi.org/10.3390/molecules22040549 - 29 Mar 2017

Cited by 3 | Viewed by 8236

Abstract

The Molecule of the Month website (http://www.chm.bris.ac.uk/motm/motm.htm) is an educational resource that is celebrating its 20th anniversary. Here we reflect on its pioneering role in promoting new technology for visualizing and presenting chemical information on the web, as well as its achievements, as [...] Read more.

The Molecule of the Month website (http://www.chm.bris.ac.uk/motm/motm.htm) is an educational resource that is celebrating its 20th anniversary. Here we reflect on its pioneering role in promoting new technology for visualizing and presenting chemical information on the web, as well as its achievements, as a free educational resource, both as a teaching aid and as a multi-user, multi-author learning platform. We discuss the legal aspects of such sites, as well as issues around how to make the content permanent. Finally, we look forward to how such sites may evolve in the future. Full article

(This article belongs to the Section Molecular Diversity)

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9 pages, 1244 KiB

Open AccessArticle

Assessment of Lipophilicity Indices Derived from Retention Behavior of Antioxidant Compounds in RP-HPLC

by Ioana Anamaria Sima¹, Agata Kot-Wasik², Andrzej Wasik^2,*, Jacek Namieśnik² and Costel Sârbu¹

¹ Faculty of Chemistry and Chemical Engineering, Babeş-Bolyai University, Arany Janos Str., No. 11, RO-400028 Cluj-Napoca, România

² Faculty of Chemistry, Gdansk University of Technology, 80-233 Gdansk, Poland

Molecules 2017, 22(4), 550; https://doi.org/10.3390/molecules22040550 - 29 Mar 2017

Cited by 22 | Viewed by 6108

Abstract

Reverse phase high pressure liquid chromatography was employed in order to evaluate the lipophilicity of antioxidant compounds from different classes, such as phenolic acids, flavanones, flavanols, flavones, anthocyanins, stilbenes, xantonoids, and proanthocyanidins. The retention time of each compound was measured using five different [...] Read more.

Reverse phase high pressure liquid chromatography was employed in order to evaluate the lipophilicity of antioxidant compounds from different classes, such as phenolic acids, flavanones, flavanols, flavones, anthocyanins, stilbenes, xantonoids, and proanthocyanidins. The retention time of each compound was measured using five different HPLC columns: RP18 (LiChroCART, Purosphere RP-18e), C8 (Zorbax, Eclipse XDBC8), C16-Amide (Discovery RP-Amide C16), CN100 (Saulentechnik, Lichrosphere), and pentafluorophenyl (Phenomenex, Kinetex PFP), and the mobile phase consisted of methanol and water (0.1% formic acid) in different proportions. The measurements were conducted at two different column temperatures, room temperature (22 °C) and, in order to mimic the environment from the human body, 37 °C. Furthermore, principal component analysis (PCA) was used to obtain new lipophilicity indices and holistic lipophilicity charts. Additionally, highly representative depictions of the chromatographic behavior of the investigated compounds and stationary phases at different temperatures were obtained using two new chemometric approaches, namely two-way joining cluster analysis and sum of ranking differences. Full article

(This article belongs to the Collection Bioactive Compounds)

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17 pages, 4703 KiB

Open AccessArticle

Physicochemical Properties of Jatropha Oil-Based Polyol Produced by a Two Steps Method

by Sariah Saalah¹

, Luqman Chuah Abdullah^2,3,*

, Min Min Aung^3,4

, Mek Zah Salleh⁵, Dayang Radiah Awang Biak², Mahiran Basri⁴, Emiliana Rose Jusoh³

and Suhaini Mamat^2,6

¹ Chemical Engineering Programme, Faculty of Engineering, Universiti Malaysia Sabah, Jalan UMS, Kota Kinabalu 88400, Sabah, Malaysia

² Department of Chemical and Environmental Engineering, Faculty of Engineering, Universiti Putra Malaysia, Serdang 43400, Selangor, Malaysia

³ Higher Institution Centre of Excellence Wood and Tropical Fibre (HICoE), Institute of Tropical Forestry and Forest Products, Universiti Putra Malaysia, Serdang 43400, Selangor, Malaysia

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

⁵ Radiation Processing Technology Division, Malaysian Nuclear Agency, Kajang 43000, Selangor, Malaysia

⁶ Universiti Kuala Lumpur, Malaysian Institute of Chemical and Bioengineering Technology (UniKL MICET), Alor Gajah 78000, Melaka, Malaysia

Molecules 2017, 22(4), 551; https://doi.org/10.3390/molecules22040551 - 29 Mar 2017

Cited by 43 | Viewed by 7477

Abstract

A low cost, abundant, and renewable vegetable oil source has been gaining increasing attention due to its potential to be chemically modified to polyol and thence to become an alternative replacement for the petroleum-based polyol in polyurethane production. In this study, jatropha oil-based [...] Read more.

A low cost, abundant, and renewable vegetable oil source has been gaining increasing attention due to its potential to be chemically modified to polyol and thence to become an alternative replacement for the petroleum-based polyol in polyurethane production. In this study, jatropha oil-based polyol (JOL) was synthesised from non-edible jatropha oil by a two steps process, namely epoxidation and oxirane ring opening. In the first step, the effect of the reaction temperature, the molar ratio of the oil double bond to formic acid, and the reaction time on the oxirane oxygen content (OOC) of the epoxidised jatropha oil (EJO) were investigated. It was found that 4.3% OOC could be achieved with a molar ratio of 1:0.6, a reaction temperature of 60 °C, and 4 h of reaction. Consequently, a series of polyols with hydroxyl numbers in the range of 138–217 mgKOH/g were produced by oxirane ring opening of EJOs, and the physicochemical and rheological properties were studied. Both the EJOs and the JOLs are liquid and have a number average molecular weight (M_n) in the range of 834 to 1457 g/mol and 1349 to 2129 g/mol, respectively. The JOLs exhibited Newtonian behaviour, with a low viscosity of 430–970 mPas. Finally, the JOL with a hydroxyl number of 161 mgKOH/g was further used to synthesise aqueous polyurethane dispersion, and the urethane formation was successfully monitored by Fourier Transform Infrared (FTIR). Full article

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21 pages, 5919 KiB

Open AccessReview

NMR and IR Investigations of Strong Intramolecular Hydrogen Bonds

by Poul Erik Hansen^* and Jens Spanget-Larsen^*

Department of Science and Environment, Roskilde University, Universitetsvej 1, P.O. Box 260, DK-4000 Roskilde, Denmark

Molecules 2017, 22(4), 552; https://doi.org/10.3390/molecules22040552 - 29 Mar 2017

Cited by 134 | Viewed by 19120

Abstract

For the purpose of this review, strong hydrogen bonds have been defined on the basis of experimental data, such as OH stretching wavenumbers, ν_OH, and OH chemical shifts, δ_OH (in the latter case, after correction for ring current effects). Limits [...] Read more.

For the purpose of this review, strong hydrogen bonds have been defined on the basis of experimental data, such as OH stretching wavenumbers, ν_OH, and OH chemical shifts, δ_OH (in the latter case, after correction for ring current effects). Limits for O–H···Y systems are taken as 2800 > ν_OH > 1800 cm⁻¹, and 19 ppm > δ_O_H > 15 ppm. Recent results as well as an account of theoretical advances are presented for a series of important classes of compounds such as β-diketone enols, β-thioxoketone enols, Mannich bases, proton sponges, quinoline N-oxides and diacid anions. The O···O distance has long been used as a parameter for hydrogen bond strength in O–H···O systems. On a broad scale, a correlation between OH stretching wavenumbers and O···O distances is observed, as demonstrated experimentally as well as theoretically, but for substituted β-diketone enols this correlation is relatively weak. Full article

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

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13 pages, 1091 KiB

Open AccessArticle

Absorption, Metabolic Stability, and Pharmacokinetics of Ginger Phytochemicals

by Rao Mukkavilli, Chunhua Yang, Reenu Singh Tanwar, Ahmed Ghareeb, Latika Luthra and Ritu Aneja^*

Department of Biology, Georgia State University, Atlanta, GA 30303, USA

Molecules 2017, 22(4), 553; https://doi.org/10.3390/molecules22040553 - 30 Mar 2017

Cited by 54 | Viewed by 11656

Abstract

We have previously demonstrated promising anticancer efficacy of orally-fed whole ginger extract (GE) in preclinical prostate models emphasizing the importance of preservation of the natural “milieu”. Essentially, GE primarily includes active ginger phenolics viz., 6-gingerol (6G), 8-gingerol (8G), 10-gingerol (10G), and 6-shogaol (6S). [...] Read more.

We have previously demonstrated promising anticancer efficacy of orally-fed whole ginger extract (GE) in preclinical prostate models emphasizing the importance of preservation of the natural “milieu”. Essentially, GE primarily includes active ginger phenolics viz., 6-gingerol (6G), 8-gingerol (8G), 10-gingerol (10G), and 6-shogaol (6S). However, the druglikeness properties of active GE phenolics like solubility, stability, and metabolic characteristics are poorly understood. Herein, we determined the physicochemical and biochemical properties of GE phenolics by conducting in vitro assays and mouse pharmacokinetic studies with and without co-administration of ketoconazole (KTZ). GE phenolics showed low to moderate solubility in various pH buffers but were stable in simulated gastric and intestinal fluids, indicating their suitability for oral administration. All GE phenolics were metabolically unstable and showed high intrinsic clearance in mouse, rat, dog, and human liver microsomes. Upon oral administration of 250 mg/kg GE, sub-therapeutic concentrations of GE phenolics were observed. Treatment of plasma samples with β-glucuronidase (βgd) increased the exposure of all GE phenolics by 10 to 700-fold. Co-administration of KTZ with GE increased the exposure of free GE phenolics by 3 to 60-fold. Interestingly, when the same samples were treated with βgd, the exposure of GE phenolics increased by 11 to 60-fold, suggesting inhibition of phase I metabolism by KTZ but little effect on glucuronide conjugation. Correlating the in vitro and in vivo results, it is reasonable to conclude that phase II metabolism seems to be the predominant clearance pathway for GE phenolics. We present evidence that the first-pass metabolism, particularly glucuronide conjugation of GE phenolics, underlies low systemic exposure. Full article

(This article belongs to the Special Issue Cancer Chemoprevention)

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15 pages, 842 KiB

Open AccessArticle

Intestinal Transport Characteristics and Metabolism of C-Glucosyl Dihydrochalcone, Aspalathin

by Sandra Bowles^1,*, Elizabeth Joubert^2,3

, Dalene De Beer^2,3

, Johan Louw^1,4, Christel Brunschwig^5,6,7, Mathew Njoroge^5,6,7, Nina Lawrence⁶, Lubbe Wiesner⁷, Kelly Chibale^5,6,8,9 and Christo Muller^1,4,10

¹ Biomedical Research and Innovation Platform, South African Medical Research Council, Tygerberg, Cape Town 7130, South Africa

² Plant Bioactives Group, Post-Harvest and Wine Technology Division, Agricultural Research Council, Infruitec-Nietvoorbij, Stellenbosch 7600, South Africa

³ Department of Food Science, Stellenbosch University, Stellenbosch 7600, South Africa

⁴ Department of Biochemistry and Microbiology, University of Zululand, Kwa-Dlangezwa 3886, South Africa

⁵ Department of Chemistry, University of Cape Town, Rondebosch 7701, South Africa

⁶ Drug Discovery and Development Centre (H3D), University of Cape Town, Rondebosch 7701, South Africa

⁷ Division of Clinical Pharmacology, University of Cape Town, Observatory, Cape Town 7925, South Africa

⁸ Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Observatory, Cape Town 7925, South Africa

⁹ South African Medical Research Council Drug, Discovery and Development Research Unit, University of Cape Town, Rondebosch 7701, South Africa

¹⁰ Department of Medical Physiology, Stellenbosch University, Tygerberg 7507, South Africa

Molecules 2017, 22(4), 554; https://doi.org/10.3390/molecules22040554 - 30 Mar 2017

Cited by 12 | Viewed by 6732

Abstract

Insight into the mechanisms of intestinal transport and metabolism of aspalathin will provide important information for dose optimisation, in particular for studies using mouse models. Aspalathin transportation across the intestinal barrier (Caco-2 monolayer) tested at 1–150 µM had an apparent rate of permeability [...] Read more.

Insight into the mechanisms of intestinal transport and metabolism of aspalathin will provide important information for dose optimisation, in particular for studies using mouse models. Aspalathin transportation across the intestinal barrier (Caco-2 monolayer) tested at 1–150 µM had an apparent rate of permeability (P_app) typical of poorly absorbed compounds (1.73 × 10⁻⁶ cm/s). Major glucose transporters, sodium glucose linked transporter 1 (SGLT1) and glucose transporter 2 (GLUT2), and efflux protein (P-glycoprotein, PgP) (1.84 × 10⁻⁶ cm/s; efflux ratio: 1.1) were excluded as primary transporters, since the P_app of aspalathin was not affected by the presence of specific inhibitors. The P_app of aspalathin was also not affected by constituents of aspalathin-enriched rooibos extracts, but was affected by high glucose concentration (20.5 mM), which decreased the P_app value to 2.9 × 10⁻⁷ cm/s. Aspalathin metabolites (sulphated, glucuronidated and methylated) were found in mouse urine, but not in blood, following an oral dose of 50 mg/kg body weight of the pure compound. Sulphates were the predominant metabolites. These findings suggest that aspalathin is absorbed and metabolised in mice to mostly sulphate conjugates detected in urine. Mechanistically, we showed that aspalathin is not actively transported by the glucose transporters, but presumably passes the monolayer paracellularly. Full article

(This article belongs to the Collection Bioactive Compounds)

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14 pages, 2095 KiB

Open AccessArticle

Zerumbone Alleviates Neuropathic Pain through the Involvement of l-Arginine-Nitric Oxide-cGMP-K⁺ ATP Channel Pathways in Chronic Constriction Injury in Mice Model

by Nurul Atiqah Zulazmi¹, Banulata Gopalsamy¹, Jasmine Chia Siew Min¹, Ahmad Akira Omar Farouk¹, Mohd Roslan Sulaiman¹, B. Hemabarathy Bharatham² and Enoch Kumar Perimal^1,*

¹ Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, University Putra Malaysia, 43400 Serdang, Selangor, Malaysia

² Department of Biomedical Sciences, School of Diagnostic and Applied Sciences, Faculty of Health Sciences, University Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, 50300 Kuala Lumpur, Malaysia

Molecules 2017, 22(4), 555; https://doi.org/10.3390/molecules22040555 - 30 Mar 2017

Cited by 25 | Viewed by 7385

Abstract

The present study investigates the involvement of the l-arginine-Nitric Oxide-cGMP-K⁺ ATP pathways responsible for the action of anti-allodynic and antihyperalgesic activities of zerumbone in chronic constriction injury (CCI) induced neuropathic pain in mice. The role of l-arginine-NO-cGMP-K⁺ was assessed [...] Read more.

The present study investigates the involvement of the l-arginine-Nitric Oxide-cGMP-K⁺ ATP pathways responsible for the action of anti-allodynic and antihyperalgesic activities of zerumbone in chronic constriction injury (CCI) induced neuropathic pain in mice. The role of l-arginine-NO-cGMP-K⁺ was assessed by the von Frey and the Randall-Selitto tests. Both allodynia and hyperalgesia assessments were carried out on the 14th day post CCI, 30 min after treatments were given for each respective pathway. Anti-allodynic and antihyperalgesic effects of zerumbone (10 mg/kg, i.p) were significantly reversed by the pre-treatment of l-arginine (10 mg/kg), 1H [1,2,4]Oxadiazole[4,3a]quinoxalin-1-one (ODQ), a soluble guanosyl cyclase blocker (2 mg/kg i.p.) and glibenclamide (ATP-sensitive potassium channel blocker) (10 mg/kg i.p.) (p < 0.05). Taken together, these results indicate that systemic administration of zerumbone produces significant anti-allodynic and antihyperalgesic activities in neuropathic pain in mice possibly due to involvement of the l-arginine-NO-cGMP-PKG-K⁺ ATP channel pathways in CCI model. Full article

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

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18 pages, 1821 KiB

Open AccessReview

The Role of Molecular Modeling in TiO₂ Photocatalysis

by Zekiye Cinar

Department of Chemistry, Yildiz Technical University, 34220 Istanbul, Turkey

Molecules 2017, 22(4), 556; https://doi.org/10.3390/molecules22040556 - 30 Mar 2017

Cited by 23 | Viewed by 8006

Abstract

Molecular Modeling methods play a very important role in TiO₂ photocatalysis. Recent advances in TiO₂ photocatalysis have produced a number of interesting surface phenomena, reaction products, and various novel visible light active photocatalysts with improved properties. Quantum mechanical calculations appear promising [...] Read more.

Molecular Modeling methods play a very important role in TiO₂ photocatalysis. Recent advances in TiO₂ photocatalysis have produced a number of interesting surface phenomena, reaction products, and various novel visible light active photocatalysts with improved properties. Quantum mechanical calculations appear promising as a means of describing the mechanisms and the product distributions of the photocatalytic degradation reactions of organic pollutants in both gas and aqueous phases. Since quantum mechanical methods utilize the principles of particle physics, their use may be extended to the design of new photocatalysts. This review introduces molecular modeling methods briefly and emphasizes the use of these methods in TiO₂ photocatalysis. The methods used for obtaining information about the degradabilities of the pollutant molecules, predicting reaction mechanisms, and evaluating the roles of the dopants and surface modifiers are explained. Full article

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

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10 pages, 1444 KiB

Open AccessArticle

Neoantimycins A and B, Two Unusual Benzamido Nine-Membered Dilactones from Marine-Derived Streptomyces antibioticus H12-15

by Chen Hu¹, Shi-Wen Zhou¹, Fang Chen¹, Xin-Heng Zheng¹

, Hui-Fang Shen², Bi-Run Lin² and Guang-Xiong Zhou^1,*

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

² Institute of Plant Protection, Guangdong Academy of Agricultural Sciences, Guangzhou 510632, China

Molecules 2017, 22(4), 557; https://doi.org/10.3390/molecules22040557 - 30 Mar 2017

Cited by 45 | Viewed by 4775

Abstract

An actinomycete strain (H12-15) isolated from a sea sediment in a mangrove district was identified as Streptomyces antibioticus on the basis of 16S rDNA gene sequence analysis as well as the investigation of its morphological, physiological, and biochemical characteristics. Two novel benzamido nonacyclic [...] Read more.

An actinomycete strain (H12-15) isolated from a sea sediment in a mangrove district was identified as Streptomyces antibioticus on the basis of 16S rDNA gene sequence analysis as well as the investigation of its morphological, physiological, and biochemical characteristics. Two novel benzamido nonacyclic dilactones, namely neoantimycins A (1) and B (2), together with the known antimycins A_1ab (3a,b), A_2a (4), and A₉ (5), were isolated from the culture broth of this strain. Compounds 1 and 2 are the first natural modified ATNs with an unusual benzamide unit. The structures of these new compounds, including their absolute configuration, were established on the basis of HRMS, NMR spectroscopic data, and quantum chemical ECD calculations. Their cytotoxicities against human breast adenocarcinoma cell line MCF-7, the human glioblastoma cell line SF-268, and the human lung cancer cell line NCI-H460 were also tested. All compounds exhibited mild cytotoxic activity. However, Compounds 1 and 2 showed no activity against C. albicans at the test concentration of 1 mg/mL via paper disc diffusion, while the known antimycins showed obvious antifungal activity. Full article

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22 pages, 1461 KiB

Open AccessReview

Selenium and Sulfur to Produce Allium Functional Crops

by Susana González-Morales¹, Fabián Pérez-Labrada², Ema Laura García-Enciso², Paola Leija-Martínez²

, Julia Medrano-Macías³, Irma Esther Dávila-Rangel², Antonio Juárez-Maldonado⁴

, Erika Nohemí Rivas-Martínez² and Adalberto Benavides-Mendoza^2,*

¹ CONACYT-Universidad Autónoma Agraria Antonio Narro, Saltillo 25315, Mexico

² Departamento de Horticultura, Universidad Autónoma Agraria Antonio Narro, Saltillo 25315, Mexico

³ Facultad de Ciencias Biológicas, Universidad Autónoma de Nuevo León, Ave. Pedro de Alba s/n, Ciudad Universitaria, San Nicolás de los Garza 66450, Mexico

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

Molecules 2017, 22(4), 558; https://doi.org/10.3390/molecules22040558 - 30 Mar 2017

Cited by 68 | Viewed by 9134

Abstract

Selenium is an element that must be considered in the nutrition of certain crops since its use allows the obtaining of biofortified crops with a positive impact on human health. The objective of this review is to present the information on the use [...] Read more.

Selenium is an element that must be considered in the nutrition of certain crops since its use allows the obtaining of biofortified crops with a positive impact on human health. The objective of this review is to present the information on the use of Se and S in the cultivation of plants of the genus Allium. The main proposal is to use Allium as specialist plants for biofortification with Se and S, considering the natural ability to accumulate both elements in different phytochemicals, which promotes the functional value of Allium. In spite of this, in the agricultural production of these species, the addition of sulfur is not realized to obtain functional foods and plants more resistant; it is only sought to cover the necessary requirements for growth. On the other hand, selenium does not appear in the agronomic management plans of most of the producers. Including S and Se fertilization as part of agronomic management can substantially improve Allium crop production. Allium species may be suitable to carry out biofortification with Se; this practice can be combined with the intensive use of S to obtain crops with higher production and sensory, nutritional, and functional quality. Full article

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

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7 pages, 1262 KiB

Open AccessCommunication

Chemical Synthesis and Characterization of an Equinatoxin II(1–85) Analogue

by John A. Karas, Marc-Antoine Sani

and Frances Separovic^*

School of Chemistry, Bio21 Institute, University of Melbourne, Melbourne, VIC 3010, Australia

Molecules 2017, 22(4), 559; https://doi.org/10.3390/molecules22040559 - 30 Mar 2017

Cited by 2 | Viewed by 5327

Abstract

The chemical synthesis of an 85 residue analogue of the pore-forming protein, Equinatoxin II (EqtII), was achieved. Peptide precursors with over 40 residues were assembled by solid phase synthesis. The EqtII(1–46) fragment was modified to the reactive C-terminal thioester and native chemical ligation [...] Read more.

The chemical synthesis of an 85 residue analogue of the pore-forming protein, Equinatoxin II (EqtII), was achieved. Peptide precursors with over 40 residues were assembled by solid phase synthesis. The EqtII(1–46) fragment was modified to the reactive C-terminal thioester and native chemical ligation was performed with the A47C mutated EqtII(47–85) peptide to form the EqtII(1–85) analogue. Circular dichroism spectroscopy indicated that the N-terminal domain of EqtII(1–46) and EqtII(1–85) maintains predominantly an α-helical structure in solution and also in the presence of lipid micelles. This demonstrates the feasibility of assembling the full 179 residue protein EqtII via chemical means. Site-specific isotopic labels could be incorporated for structural studies in membranes by solid-state NMR spectroscopy. Full article

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

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12 pages, 3544 KiB

Open AccessArticle

Effective Subcritical Butane Extraction of Bifenthrin Residue in Black Tea

by Yating Zhang¹, Lingbiao Gu¹, Fei Wang², Lingjun Kong¹ and Guangyong Qin^1,*

¹ Henan Provincial Key Laboratory of Ion Beam Bio-engineering, and School of Physics and Engineering, Zhengzhou University, 100 Science Avenue, Zhengzhou 450001, China

² School of Chemistry and Molecular Engineering, Zhengzhou University, 100 Science Avenue, Zhengzhou 450001, China

Molecules 2017, 22(4), 560; https://doi.org/10.3390/molecules22040560 - 30 Mar 2017

Cited by 7 | Viewed by 5817

Abstract

As a natural and healthy beverage, tea is widely enjoyed; however, the pesticide residues in tea leaves affect the quality and food safety. To develop a highly selective and efficient method for the facile removal of pesticide residues, the subcritical butane extraction (SBE) [...] Read more.

As a natural and healthy beverage, tea is widely enjoyed; however, the pesticide residues in tea leaves affect the quality and food safety. To develop a highly selective and efficient method for the facile removal of pesticide residues, the subcritical butane extraction (SBE) technique was employed, and three variables involving temperature, time and extraction cycles were studied. The optimum SBE conditions were found to be as follows: extraction temperature 45 °C, extraction time 30 min, number of extraction cycles 1, and in such a condition that the extraction efficiency reached as high as 92%. Further, the catechins, theanine, caffeine and aroma components, which determine the quality of the tea, fluctuated after SBE treatment. Compared with the uncrushed leaves, pesticide residues can more easily be removed from crushed leaves, and the practical extraction efficiency was 97%. These results indicate that SBE is a useful method to efficiently remove the bifenthrin, and as appearance is not relevant in the production process, tea leaves should first be crushed and then extracted in order that residual pesticides are thoroughly removed. Full article

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

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14 pages, 4740 KiB

Open AccessCommunication

Novel Palladium(II) Complexes that Influence Prominin-1/CD133 Expression and Stem Cell Factor Release in Tumor Cells

by Eva Fischer-Fodor^1,2

, Roman Mikláš³, Lucia Rišiaňová³

, Mihai Cenariu⁴

, Ioana Georgeta Grosu⁵

, Piroska Virag¹, Maria Perde-Schrepler¹, Ciprian Tomuleasa^1,2

, Ioana Berindan-Neagoe^1,2, Ferdinand Devínsky³ and Natalia Miklášová^3,*

¹ “I. Chiricuta” Institute of Oncology, Republicii 34-36, RO-400015 Cluj-Napoca, Romania

² Medfuture Research Center for Advanced Medicine “Iuliu Hatieganu”, University of Medicine and Pharmacy, Babes 8, RO-400012 Cluj-Napoca, Romania

³ Department of Chemical Theory of Drugs, Faculty of Pharmacy, Comenius University in Bratislava, Kalinčiakova 8, 83104 Bratislava, Slovakia

⁴ Biotechnology Research Center, University of Agricultural Science and Veterinary Medicine, 400372 Cluj-Napoca, Romania

⁵ National Institute for Research and Development of Isotopic and Molecular Technologies, RO-400293 Cluj-Napoca, Romania

Molecules 2017, 22(4), 561; https://doi.org/10.3390/molecules22040561 - 30 Mar 2017

Cited by 12 | Viewed by 4653

Abstract

New Pd(II) complexes of 1,7-bis(2-methoxyphenyl)hepta-1,6-diene-3,5-dione were synthesized and structurally characterized. The complexes were tested in vitro on human colon and hepatic carcinoma cell lines, normal hepatic cells and hematopoietic progenitor cells. Biological tests proved that Pd(II) complexes 1 and 2 (containing a curcumin [...] Read more.

New Pd(II) complexes of 1,7-bis(2-methoxyphenyl)hepta-1,6-diene-3,5-dione were synthesized and structurally characterized. The complexes were tested in vitro on human colon and hepatic carcinoma cell lines, normal hepatic cells and hematopoietic progenitor cells. Biological tests proved that Pd(II) complexes 1 and 2 (containing a curcumin derivative) exhibit a strong in vitro antitumor effect against the cells derived from human colorectal carcinoma and the hepatic metastasis of a colorectal carcinoma. Complex 1 has an outstanding inhibitory effect against BRAF-mutant colon carcinoma and hepatocarcinoma cell growth; 1 and 2 are both more active than the free ligand and have the capacity to trigger early apoptotic processes. By flow cytometric measurements, an important decrease of prominin-1 (CD133) molecule expression on tumor cells membrane was identified in cell populations subjected to 1 and 2. Quantitative immune enzymatic assay proved restrictions in stem cell factor (SCF) release by treated tumor cells. Although less cytotoxic, the free ligand inhibits the surface marker CD133 expression in hepatocarcinoma cells, and in HT-29 colon carcinoma. The new synthesized Pd(II) complexes 1 and 2 exhibit an important potential through their selective cytotoxic activity and by targeting the stem-like tumor cell populations, which leads to the tumor growth arrest and prevention of metastasis. Full article

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

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17 pages, 3329 KiB

Open AccessReview

Research Progress on ¹⁸F-Labeled Agents for Imaging of Myocardial Perfusion with Positron Emission Tomography

by Tiantian Mou¹ and Xianzhong Zhang^2,*

¹ Department of Nuclear Medicine, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China

² State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics & Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen 361102, China

Molecules 2017, 22(4), 562; https://doi.org/10.3390/molecules22040562 - 30 Mar 2017

Cited by 11 | Viewed by 6765

Abstract

Coronary artery disease (CAD) is the leading cause of death in the world. Myocardial perfusion imaging (MPI) plays a significant role in non-invasive diagnosis and prognosis of CAD. However, neither single-photon emission computed tomography nor positron emission tomography clinical MPI agents can absolutely [...] Read more.

Coronary artery disease (CAD) is the leading cause of death in the world. Myocardial perfusion imaging (MPI) plays a significant role in non-invasive diagnosis and prognosis of CAD. However, neither single-photon emission computed tomography nor positron emission tomography clinical MPI agents can absolutely satisfy the demands of clinical practice. In the past decades, tremendous developments happened in the field of ¹⁸F-labeled MPI tracers. This review summarizes the current state of ¹⁸F-labeled MPI tracers, basic research data of those tracers, and the future direction of MPI tracer research. Full article

(This article belongs to the Section Medicinal Chemistry)

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24 pages, 1915 KiB

Open AccessReview

Antisense Oligonucleotide-Based Therapy for Neuromuscular Disease

by Valentina Sardone¹

, Haiyan Zhou¹, Francesco Muntoni^1,2,*, Alessandra Ferlini^1,3,* and Maria Sofia Falzarano³

¹ Dubowitz Neuromuscular Centre, Molecular Neurosciences Section, Developmental Neuroscience Programme, UCL Great Ormond Street Institute of Child Health, London WC1N 1EH, UK

² MRC Centre for Neuromuscular Diseases, UCL Institute of Neurology, London WC1N 3BG, UK

³ UOL Medical Genetics, University of Ferrara, Ferrara 44121, Italy

Molecules 2017, 22(4), 563; https://doi.org/10.3390/molecules22040563 - 5 Apr 2017

Cited by 76 | Viewed by 16320

Abstract

Neuromuscular disorders such as Duchenne Muscular Dystrophy and Spinal Muscular Atrophy are neurodegenerative genetic diseases characterized primarily by muscle weakness and wasting. Until recently there were no effective therapies for these conditions, but antisense oligonucleotides, a new class of synthetic single stranded molecules [...] Read more.

Neuromuscular disorders such as Duchenne Muscular Dystrophy and Spinal Muscular Atrophy are neurodegenerative genetic diseases characterized primarily by muscle weakness and wasting. Until recently there were no effective therapies for these conditions, but antisense oligonucleotides, a new class of synthetic single stranded molecules of nucleic acids, have demonstrated promising experimental results and are at different stages of regulatory approval. The antisense oligonucleotides can modulate the protein expression via targeting hnRNAs or mRNAs and inducing interference with splicing, mRNA degradation, or arrest of translation, finally, resulting in rescue or reduction of the target protein expression. Different classes of antisense oligonucleotides are being tested in several clinical trials, and limitations of their clinical efficacy and toxicity have been reported for some of these compounds, while more encouraging results have supported the development of others. New generation antisense oligonucleotides are also being tested in preclinical models together with specific delivery systems that could allow some of the limitations of current antisense oligonucleotides to be overcome, to improve the cell penetration, to achieve more robust target engagement, and hopefully also be associated with acceptable toxicity. This review article describes the chemical properties and molecular mechanisms of action of the antisense oligonucleotides and the therapeutic implications these compounds have in neuromuscular diseases. Current strategies and carrier systems available for the oligonucleotides delivery will be also described to provide an overview on the past, present and future of these appealing molecules. Full article

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

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14 pages, 7676 KiB

Open AccessArticle

Self-Organized TiO₂–MnO₂ Nanotube Arrays for Efficient Photocatalytic Degradation of Toluene

by María C. Nevárez-Martínez^1,2

, Marek P. Kobylański³, Paweł Mazierski^3,*

, Jolanta Wółkiewicz⁴, Grzegorz Trykowski⁴

, Anna Malankowska³, Magda Kozak³

, Patricio J. Espinoza-Montero²

and Adriana Zaleska-Medynska^3,*

¹ Facultad de Ingeniería Química y Agroindustria, Escuela Politécnica Nacional, Ladrón de Guevara E11-253, P.O. Box 17-01-2759, Quito 170525, Ecuador

² Centro de Investigación y Control Ambiental “CICAM”, Departamento de Ingeniería Civil y Ambiental, Facultad de Ingeniería Civil y Ambiental, Escuela Politécnica Nacional, Ladrón de Guevara E11-253, P.O. Box 17-01-2759, Quito 170525, Ecuador

³ Department of Environmental Technology, Faculty of Chemistry, University of Gdansk, 80-308 Gdansk, Poland

⁴ Faculty of Chemistry, Nicolaus Copernicus University, 87-100 Torun, Poland

Molecules 2017, 22(4), 564; https://doi.org/10.3390/molecules22040564 - 31 Mar 2017

Cited by 51 | Viewed by 8003

Abstract

Vertically oriented, self-organized TiO₂–MnO₂ nanotube arrays were successfully obtained by one-step anodic oxidation of Ti–Mn alloys in an ethylene glycol-based electrolyte. The as-prepared samples were characterized by scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), UV-Vis absorption, photoluminescence spectroscopy, X-ray [...] Read more.

Vertically oriented, self-organized TiO₂–MnO₂ nanotube arrays were successfully obtained by one-step anodic oxidation of Ti–Mn alloys in an ethylene glycol-based electrolyte. The as-prepared samples were characterized by scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), UV-Vis absorption, photoluminescence spectroscopy, X-ray diffraction (XRD), and micro-Raman spectroscopy. The effect of the applied potential (30–50 V), manganese content in the alloy (5–15 wt. %) and water content in the electrolyte (2–10 vol. %) on the morphology and photocatalytic properties was investigated for the first time. The photoactivity was assessed in the toluene removal reaction under visible light, using low-powered LEDs as an irradiation source (λ_max = 465 nm). Morphology analysis showed that samples consisted of auto-aligned nanotubes over the surface of the alloy, their dimensions were: diameter = 76–118 nm, length = 1.0–3.4 μm and wall thickness = 8–11 nm. It was found that the increase in the applied potential led to increase the dimensions while the increase in the content of manganese in the alloy brought to shorter nanotubes. Notably, all samples were photoactive under the influence of visible light and the highest degradation achieved after 60 min of irradiation was 43%. The excitation mechanism of TiO₂–MnO₂ NTs under visible light was presented, pointing out the importance of MnO₂ species for the generation of e⁻ and h⁺. Full article

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

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13 pages, 1821 KiB

Open AccessArticle

Ergosteryl 2-naphthoate, An Ergosterol Derivative, Exhibits Antidepressant Effects Mediated by the Modification of GABAergic and Glutamatergic Systems

by Mingzhu Lin¹, Haijun Li², Yan Zhao^1,*, Enbo Cai¹, Hongyan Zhu¹, Yugang Gao¹, Shuangli Liu¹, He Yang¹, Lianxue Zhang¹, Guosheng Tang¹ and Ruiqing Wang³

¹ College of Chinese Medicinal Materials, Jilin Agriculture University, Xincheng Street 2888th, Changchun 130118, Jilin, China

² Institute of Translational Medicine, the First Hospital of Jilin University, Xinmin Street 71th, Changchun 130021, Jilin, China

³ Center of Ophthalmology, the Second Hospital of Jilin University, Ziqiang Street 218th, Changchun 130041, Jilin, China

Molecules 2017, 22(4), 565; https://doi.org/10.3390/molecules22040565 - 31 Mar 2017

Cited by 12 | Viewed by 5079

Abstract

Phytosterols are a kind of natural component including sitosterol, campesterol, avenasterol, ergosterol (Er) and others. Their main natural sources are vegetable oils and their processed products, followed by grains, by-products of cereals and nuts, and small amounts of fruits, vegetables and mushrooms. In [...] Read more.

Phytosterols are a kind of natural component including sitosterol, campesterol, avenasterol, ergosterol (Er) and others. Their main natural sources are vegetable oils and their processed products, followed by grains, by-products of cereals and nuts, and small amounts of fruits, vegetables and mushrooms. In this study, three new Er monoester derivatives were obtained from the reflux reaction with Er: organic acids (furoic acid, salicylic acid and 2-naphthoic acid), 1-Ethylethyl-3-(3-dimethyllaminopropyl) carbodiimide hydrochloride (EDCI) and 4-dimethylaminopyridine (DMAP) in dichloromethane. Their chemical structures were defined by IR and NMR. The present study was also undertaken to investigate the antidepressant-like effects of Er and its derivatives in male adult mice models of depression, and their probable involvement of GABAergic and glutamatergic systems by the forced swim test (FST). The results indicated that Er and its derivatives display antidepressant effects. Moreover, one derivative of Er, ergosteryl 2-naphthoate (ErN), exhibited stronger antidepressant activity in vivo compared to Er. Acute administration of ErN (5 mg/kg, i.p.) and a combination of ErN (0.5 mg/kg, i.p.), reboxetine (2.5 mg/kg, i.p.), and tianeptine (15 mg/kg, i.p.) reduced the immobility time in the FST. Pretreatment with bicuculline (a competitive γ-aminobutyric acid (GABA) antagonist, 4 mg/kg, i.p.) and N-methyl-d-aspartic acid (NMDA, an agonist at the glutamate site, 75 mg/kg, i.p.) effectively reversed the antidepressant-like effect of ErN (5 mg/kg, i.p.). However, prazosin (a α1-adrenoceptor antagonist, 1 mg/kg, i.p.) and haloperidol (a non-selective D2 receptor antagonist, 0.2 mg/kg, i.p.) did not eliminate the reduced immobility time. Altogether, these results indicated that ErN produced antidepressant-like activity, which might be mediated by GABAergic and glutamatergic systems. Full article

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12 pages, 4880 KiB

Open AccessArticle

Biodegradable Poly(Amino Ester) with Aromatic Backbone as Efficient Nonviral Gene Delivery Vectors

by Qiang Liu, Rong-Chuan Su, Wen-Jing Yi^* and Zhi-Gang Zhao^*

College of Chemistry and Environmental Protection Engineering, Southwest Minzu University, Chengdu 610041, China

Molecules 2017, 22(4), 566; https://doi.org/10.3390/molecules22040566 - 31 Mar 2017

Cited by 12 | Viewed by 5286

Abstract

The development of gene delivery vectors with high efficiency and biocompatibility is one of the critical points of gene therapy. Two biodegradable poly(amino ester)s were synthesized via ring-opening polymerization between low molecular weight (LMW) PEI and diepoxide. The molecular weights of poly(amino ester)s [...] Read more.

The development of gene delivery vectors with high efficiency and biocompatibility is one of the critical points of gene therapy. Two biodegradable poly(amino ester)s were synthesized via ring-opening polymerization between low molecular weight (LMW) PEI and diepoxide. The molecular weights of poly(amino ester)s were measured by GPC. Agarose gel retardation assays showed that these materials have good DNA-binding ability and can retard the electrophoretic mobility of plasmid DNA (pDNA) at a weight ratio of 1. The formed polyplexes have proper sizes of around 200 nm and zeta-potential values of about 30–40 mV for cellular uptake. In vitro experiments revealed that polymer P2 gave higher transfection efficiency than PEI 25KDa and Lipofectamine 2000 with less toxicity, especially in 293 cells. Results demonstrate that such a type of degradable poly(amino ester) may serve as a promising non-viral gene vector. Full article

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10 pages, 2015 KiB

Open AccessArticle

Optimizing Sample Size to Assess the Genetic Diversity in Common Vetch (Vicia sativa L.) Populations Using Start Codon Targeted (SCoT) Markers

by Xutian Chai, Rui Dong, Wenxian Liu, Yanrong Wang and Zhipeng Liu^*

The State Key Laboratory of Grassland Agro-Ecosystems, College of Pastoral Agriculture Science and Technology, Lanzhou University, Lanzhou 730020, China

Molecules 2017, 22(4), 567; https://doi.org/10.3390/molecules22040567 - 31 Mar 2017

Cited by 34 | Viewed by 5490

Abstract

Common vetch (Vicia sativa subsp. sativa L.) is a self-pollinating annual forage legume with worldwide importance. Here, we investigate the optimal number of individuals that may represent the genetic diversity of a single population, using Start Codon Targeted (SCoT) markers. Two cultivated [...] Read more.

Common vetch (Vicia sativa subsp. sativa L.) is a self-pollinating annual forage legume with worldwide importance. Here, we investigate the optimal number of individuals that may represent the genetic diversity of a single population, using Start Codon Targeted (SCoT) markers. Two cultivated varieties and two wild accessions were evaluated using five SCoT primers, also testing different sampling sizes: 1, 2, 3, 5, 8, 10, 20, 30, 40, 50, and 60 individuals. The results showed that the number of alleles and the Polymorphism Information Content (PIC) were different among the four accessions. Cluster analysis by Unweighted Pair Group Method with Arithmetic Mean (UPGMA) and STRUCTURE placed the 240 individuals into four distinct clusters. The Expected Heterozygosity (H_E) and PIC increased along with an increase in sampling size from 1 to 10 plants but did not change significantly when the sample sizes exceeded 10 individuals. At least 90% of the genetic variation in the four germplasms was represented when the sample size was 10. Finally, we concluded that 10 individuals could effectively represent the genetic diversity of one vetch population based on the SCoT markers. This study provides theoretical support for genetic diversity, cultivar identification, evolution, and marker-assisted selection breeding in common vetch. Full article

(This article belongs to the Section Molecular Diversity)

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11 pages, 1680 KiB

Open AccessArticle

Barbatic Acid Offers a New Possibility for Control of Biomphalaria Glabrata and Schistosomiasis

by Mônica Cristina Barroso Martins¹

, Monique Costa Silva¹, Hianna Arely Milca Fagundes Silva¹, Luanna Ribeiro Santos Silva², Mônica Camelo Pessoa de Azevedo Albuquerque³, André Lima Aires³, Emerson Peter da Silva Falcão⁴, Eugênia C. Pereira^5,*

, Ana Maria Mendonça Albuquerque De Melo² and Nicácio Henrique Da Silva¹

¹ Departamento de Bioquímica e Fisiologia, Universidade Federal de Pernambuco, Recife, PE 50670-901, Brazil

² Departamento de Radiobiologia, Universidade Federal de Pernambuco, Recife, PE 50670-901, Brazil

³ Laboratório de Imunopatologia Keizo Asami LIKA, Universidade Federal de Pernambuco, Recife, PE 50670-901, Brazil

⁴ Laboratório de Síntese e Isolamento Molecular, Centro Acadêmico de Vitória de Santo Antão, Universidade Federal de Pernambuco, Vitória de Santo Antão, PE 50670-901, Brazil

⁵ Departamento de Ciências Geográficas, Centro de Filosofia e Ciências Humanas, Universidade Federal de Pernambuco, Recife, PE 50670-901, Brazil

Molecules 2017, 22(4), 568; https://doi.org/10.3390/molecules22040568 - 31 Mar 2017

Cited by 17 | Viewed by 6417

Abstract

This study evaluated the biological activity of an ether extract and barbatic acid (BAR) from Cladia aggregata on embryos and adult mollusks of Biomphalaria glabrata, cercariae of Schistosoma mansoni and the microcrustacean Artemia salina. The ether extract and BAR were obtained [...] Read more.

This study evaluated the biological activity of an ether extract and barbatic acid (BAR) from Cladia aggregata on embryos and adult mollusks of Biomphalaria glabrata, cercariae of Schistosoma mansoni and the microcrustacean Artemia salina. The ether extract and BAR were obtained by successive extractions with diethyl ether. The obtained extracts were analyzed using thin-layer chromatography (TLC), high-performance liquid chromatography (HPLC), proton nuclear magnetic resonance (¹H-NMR) and infrared (IR) spectroscopy. The results demonstrated that the ether extract exerted embryotoxic effects at 50 and 100 µg/mL and molluscicidal effects at 20 and 25 µg/mL. BAR exhibited no embryotoxicity, and its molluscicidal concentration was equal to that of the ether extract. However, after 60 min of exposure, 1 µg/mL BAR presented cercaricidal activity against the parasite S. mansoni at the second larval stage. Neither substance induced toxicity against A. salina. These results indicate the potential molluscicidal activities of the ether extract and BAR against B. glabrata and S. mansoni cercariae. In addition to these effects, there was a lack of toxicity against the aquatic environment and no damage to the biota, indicating the potential of these products for large-scale control and/or eradication of schistosomiasis. Full article

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

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20 pages, 2522 KiB

Open AccessArticle

Effect of Temperature on Tolbutamide Binding to Glycated Serum Albumin

by Agnieszka Szkudlarek^1,*

, Danuta Pentak², Anna Ploch¹, Jadwiga Pożycka¹

and Małgorzata Maciążek-Jurczyk¹

¹ Department of Physical Pharmacy, School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia, Jagiellońska 4, 41-200 Sosnowiec, Poland

² Department of Materials Chemistry and Chemical Technology, Institute of Chemistry, University of Silesia, Szkolna 9, 40-006 Katowice, Poland

Molecules 2017, 22(4), 569; https://doi.org/10.3390/molecules22040569 - 31 Mar 2017

Cited by 14 | Viewed by 5799

Abstract

Glycation process occurs in protein and becomes more pronounced in diabetes when an increased amount of reducing sugar is present in bloodstream. Glycation of protein may cause conformational changes resulting in the alterations of its binding properties even though they occur at a [...] Read more.

Glycation process occurs in protein and becomes more pronounced in diabetes when an increased amount of reducing sugar is present in bloodstream. Glycation of protein may cause conformational changes resulting in the alterations of its binding properties even though they occur at a distance from the binding sites. The changes in protein properties could be related to several pathological consequences such as diabetic and nondiabetic cardiovascular diseases, cataract, renal dysfunction and Alzheimer’s disease. The experiment was designed to test the impact of glycation process on sulfonylurea drug tolbutamide-albumin binding under physiological (T = 309 K) and inflammatory (T = 311 K and T = 313 K) states using fluorescence and UV-VIS spectroscopies. It was found in fluorescence analysis experiments that the modification of serum albumin in tryptophanyl and tyrosyl residues environment may affect the tolbutamide (TB) binding to albumin in subdomain IIA and/or IIIA (Sudlow’s site I and/or II), and also in subdomains IB and IIB. We estimated the binding of tolbutamide to albumin described by a mixed nature of interaction (specific and nonspecific). The association constants Ka (L∙mol⁻¹) for tolbutamide at its high affinity sites on non-glycated albumin were in the range of 1.98–7.88 × 10⁴ L∙mol⁻¹ (λ_ex = 275 nm), 1.20–1.64 × 10⁴ L∙mol⁻¹ (λ_ex = 295 nm) and decreased to 1.24–0.42 × 10⁴ L∙mol⁻¹ at λ_ex = 275 nm (T = 309 K and T = 311 K) and increased to 2.79 × 10⁴ L∙mol⁻¹ at λ_ex = 275 nm (T = 313 K) and to 4.43–6.61 × 10⁴ L∙mol⁻¹ at λ_ex = 295 nm due to the glycation process. Temperature dependence suggests the important role of van der Waals forces and hydrogen bonding in hydrophobic interactions between tolbutamide and both glycated and non-glycated albumin. We concluded that the changes in the environment of TB binding of albumin in subdomain IIA and/or IIIA as well as in subdomains IB and IIB influence on therapeutic effect and therefore the studies of the binding of tolbutamide (in diabetes) to transporting protein under glycation that refers to the modification of a protein are of great importance in pharmacology and biochemistry. This information may lead to the development of more effective drug therapy in people with diabetes. Full article

(This article belongs to the Section Medicinal Chemistry)

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18 pages, 1778 KiB

Open AccessReview

Chemical and Biological Properties of S-1-Propenyl-ʟ-Cysteine in Aged Garlic Extract

by Yukihioro Kodera^*, Mitsuyasu Ushijima, Hirotaka Amano, Jun-ichiro Suzuki and Toshiaki Matsutomo

Drug Discovery Laboratory, Wakunaga Pharmaceutical Co., Ltd., Hiroshima 739-1195, Japan

Molecules 2017, 22(4), 570; https://doi.org/10.3390/molecules22040570 - 31 Mar 2017

Cited by 68 | Viewed by 10572

Abstract

S-1-Propenyl-ʟ-cysteine (S1PC) is a stereoisomer of S-1-Propenyl-ʟ-cysteine (SAC), an important sulfur-containing amino acid that plays a role for the beneficial pharmacological effects of aged garlic extract (AGE). The existence of S1PC in garlic preparations has been known since the [...] Read more.

S-1-Propenyl-ʟ-cysteine (S1PC) is a stereoisomer of S-1-Propenyl-ʟ-cysteine (SAC), an important sulfur-containing amino acid that plays a role for the beneficial pharmacological effects of aged garlic extract (AGE). The existence of S1PC in garlic preparations has been known since the 1960’s. However, there was no report regarding the biological and/or pharmacological activity of S1PC until 2016. Recently, we performed a series of studies to examine the chemical, biological, pharmacological and pharmacokinetic properties of S1PC, and obtained some interesting results. S1PC existed only in trace amounts in raw garlic, but its concentration increased almost up to the level similar of SAC through aging process of AGE. S1PC showed immunomodulatory effects in vitro and in vivo, and reduced blood pressure in a hypertensive animal model. A pharmacokinetic study revealed that S1PC was readily absorbed after oral administration in rats and dogs with bioavailability of 88–100%. Additionally, S1PC had little inhibitory influence on human cytochrome P450 activities, even at a concentration of 1 mM. Based on these findings, S1PC was suggested to be another important, pharmacologically active and safe component of AGE similar to SAC. In this review, we highlight some results from recent studies on S1PC and discuss the potential medicinal value of S1PC. Full article

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

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9 pages, 1494 KiB

Open AccessArticle

Distal Proton Shuttle Mechanism of Ribosome Catalysed Peptide Bond Formation—A Theoretical Study

by Xiaotong Zhang¹, Yafei Jiang¹, Qiuyun Mao¹, Hongwei Tan^1,*

, Xichen Li¹, Guangju Chen^1,* and Zongchao Jia²

¹ Key Laboratory of Theoretical and Computational Photochemistry, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing 100875, China

² Department of Biomedical and Molecular Sciences, Queen’s University, Kingston, ON K7N 3L6, Canada jia@queensu.ca

Molecules 2017, 22(4), 571; https://doi.org/10.3390/molecules22040571 - 31 Mar 2017

Cited by 5 | Viewed by 5681

Abstract

In this work, we have investigated a novel distal proton shuttle mechanism of ribosome catalyzed peptide bond formation reaction. The reaction was found to follow a two-step mechanism. A distal water molecule located about 6.1 Å away from the attacking amine plays as [...] Read more.

In this work, we have investigated a novel distal proton shuttle mechanism of ribosome catalyzed peptide bond formation reaction. The reaction was found to follow a two-step mechanism. A distal water molecule located about 6.1 Å away from the attacking amine plays as a proton acceptor and results in a charge-separated intermediate that is stabilized by the N terminus of L27 and the A-site A76 5′-phosphate. The ribose A2451 bridges the proton shuttle pathway, thus plays critical role in the reaction. The calculated 27.64 kcal•mol−1 free energy barrier of the distal proton shuttle mechanism is lower than that of eight-membered ring transition state. The distal proton shuttle mechanism studied in this work can provide new insights into the important biological peptide synthesis process. Full article

(This article belongs to the Special Issue Foldamers: Synthesis and Applications)

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17 pages, 3683 KiB

Open AccessArticle

Sulfur-Doped Carbon Nitride Polymers for Photocatalytic Degradation of Organic Pollutant and Reduction of Cr(VI)

by Yun Zheng¹, Zihao Yu¹, Feng Lin¹, Fangsong Guo¹, Khalid A. Alamry²

, Layla A. Taib², Abdullah M. Asiri^2,3 and Xinchen Wang^1,*

¹ State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University, Fuzhou 350002, China

² Chemistry Department, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia

³ Center of Excellence for Advanced Materials Research (CEAMR), Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia

Molecules 2017, 22(4), 572; https://doi.org/10.3390/molecules22040572 - 1 Apr 2017

Cited by 83 | Viewed by 10760

Abstract

As a promising conjugated polymer, binary carbon nitride has attracted extensive attention as a metal-free and visible-light-responsive photocatalyst in the area of photon-involving purification of water and air. Herein, we report sulfur-doped polymeric carbon nitride microrods that are synthesized through thermal polymerization based [...] Read more.

As a promising conjugated polymer, binary carbon nitride has attracted extensive attention as a metal-free and visible-light-responsive photocatalyst in the area of photon-involving purification of water and air. Herein, we report sulfur-doped polymeric carbon nitride microrods that are synthesized through thermal polymerization based on trithiocyanuric acid and melamine (TM) supramolecular aggregates. By tuning the polymerization temperature, a series of sulfur-doped carbon nitride microrods are prepared. The degradation of Rhodamine B (RhB) and the reduction of hexavalent chromium Cr(VI) are selected as probe reactions to evaluate the photocatalytic activities. Results show that increasing pyrolysis temperature leads to a large specific surface area, strong visible-light absorption, and accelerated electron-hole separation. Compared to bulk carbon nitride, the highly porous sulfur-doped carbon nitride microrods fabricated at 650 °C exhibit remarkably higher photocatalytic activity for degradation of RhB and reduction of Cr(VI). This work highlights the importance of self-assembly approach and temperature-control strategy in the synthesis of photoactive materials for environmental remediation. Full article

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

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15 pages, 5427 KiB

Open AccessArticle

Ugonin M, a Helminthostachys zeylanica Constituent, Prevents LPS-Induced Acute Lung Injury through TLR4-Mediated MAPK and NF-κB Signaling Pathways

by Kun-Chang Wu^1,†, Shyh-Shyun Huang^2,†, Yueh-Hsiung Kuo^1,3,†

, Yu-Ling Ho⁴, Chang-Syun Yang¹

, Yuan-Shiun Chang^1,5,* and Guan-Jhong Huang^1,*

¹ Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, College of Chinese Medicine, China Medical University, Taichung 40402, Taiwan

² School of Pharmacy, China Medical University, Taichung 40402, Taiwan

³ Department of Biotechnology, Asia University, Taichung 41354, Taiwan

⁴ Department of Nursing, Hungkuang University, Taichung 43302, Taiwan

⁵ Chinese Crude Drug Pharmacy, China Medical University Hospital, Taichung 40402, Taiwan

^† These authors contributed equally to this work.

Molecules 2017, 22(4), 573; https://doi.org/10.3390/molecules22040573 - 1 Apr 2017

Cited by 46 | Viewed by 6335

Abstract

Helminthostachys zeylanica (L.) Hook. is plant that has been used in traditional Chinese medicine for centuries for the treatment of inflammation, fever, pneumonia, and various disorders. The aims of the present study are to figure out the possible effectiveness of the component Ugonin [...] Read more.

Helminthostachys zeylanica (L.) Hook. is plant that has been used in traditional Chinese medicine for centuries for the treatment of inflammation, fever, pneumonia, and various disorders. The aims of the present study are to figure out the possible effectiveness of the component Ugonin M, a unique flavonoid isolated from H. zeylanica, and to elucidate the mechanism(s) by which it works in the LPS-induced ALI model. In this study, Ugonin M not only inhibited the production of pro-inflammatory mediators such as NO, TNF-α, IL-1β, and IL-6, as well as infiltrated cellular counts and protein content in the bronchoalveolar lavage fluid (BALF) of lipopolysaccharides (LPS)-induced acute lung injury (ALI) mice, but also ameliorated the severity of pulmonary edemas through the score of a histological examination and the ratio of wet to dry weight of lung. Moreover, Ugonin M was observed to significantly suppress LPS-stimulated protein levels of iNOS and COX-2. In addition, we found that Ugonin M not only obviously suppressed NF-κB and MAPK activation via the degradation of NF-κB and IκB-α as well as ERK and p38MAPK active phosphorylation but also inhibited the protein expression level of TLR4. Further, Ugonin M treatment also suppressed the protein levels of MPO and enhanced the protein expressions of HO-1 and antioxidant enzymes (SOD, GPx, and CAT) in lung tissue of LPS-induced ALI mice. It is anticipated that through our findings, there is strong evidence that Ugonin M may exert a potential effect against LPS-induced ALI mice. Hence, Ugonin M could be one of the major effective components of H. zeylanica in the treatment of inflammatory disorders. Full article

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12 pages, 4732 KiB

Open AccessFeature PaperReview

Direct Substitution of Alcohols in Pure Water by Brønsted Acid Catalysis

by Rosa Ortiz^* and Raquel P. Herrera^*

Laboratorio de Organocatálisis Asimétrica, Departamento de Química Orgánica, Instituto de Síntesis Química y Catálisis Homogénea (ISQCH) CSIC-Universidad de Zaragoza, C/Pedro Cerbuna 12, Zaragoza 50009, Spain

Molecules 2017, 22(4), 574; https://doi.org/10.3390/molecules22040574 - 1 Apr 2017

Cited by 33 | Viewed by 9170

Abstract

With the increasing concern for sustainability, the use of environmentally friendly media to perform chemical processes has attracted the attention of many research groups. Among them, the use of water, as the unique solvent for reactions, is currently an active area of research. [...] Read more.

With the increasing concern for sustainability, the use of environmentally friendly media to perform chemical processes has attracted the attention of many research groups. Among them, the use of water, as the unique solvent for reactions, is currently an active area of research. One process of particular interest is the direct nucleophilic substitution of an alcohol avoiding its preliminary transformation into a good leaving group, since one of the by-products in this approach would be water. The direct substitution of allylic, benzylic, and tertiary alcohols has been achieved through S_N1-type reactions with catalytic amounts of Brønsted or Lewis acids; however, organic solvents are often required. In this review, the pioneering S_N1 approaches performed in pure water and in the absence of a metal based Lewis acid are compiled and discussed. Full article

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

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10 pages, 2195 KiB

Open AccessArticle

Development of a Novel Electrochemical Sensor for Determination of Matrine in Sophora flavescens

by Junping Zhang¹, Yanchun Wang² and Wei Zheng^1,*

¹ Department of Oncology, Henan Academy institute of Traditional Chinese Medicine, Zhengzhou 450000, Henan, China

² Department of Traditional Chinese Medicine, Henan Province People's Hospital, Zhengzhou 450002, Henan, China

Molecules 2017, 22(4), 575; https://doi.org/10.3390/molecules22040575 - 1 Apr 2017

Cited by 11 | Viewed by 4431

Abstract

A simple and sensitive electrochemical sensor fabricated with graphene nanosheets (GNs) and a hydroxyapatite (HA) nanocomposite–modified glassy carbon electrode (GCE) was developed for the determination of matrine (MT). The as-prepared electrode (GNs/HA/GCE) was verified to outperform bare a GCE and GNs-modified electrode with [...] Read more.

A simple and sensitive electrochemical sensor fabricated with graphene nanosheets (GNs) and a hydroxyapatite (HA) nanocomposite–modified glassy carbon electrode (GCE) was developed for the determination of matrine (MT). The as-prepared electrode (GNs/HA/GCE) was verified to outperform bare a GCE and GNs-modified electrode with increased oxidation peak currents and the decreased over-potential in the redox process of MT, indicating the great enhancement of electrocatalytic activity toward the oxidation of MT by the composite of GNs and HA. Under the optimized conditions, the oxidation peak currents were related linearly with the concentration of MT, ranging from 2 μM to 3 mM, and the detection limit (S/N = 3) was 1.2 μM. In addition, the proposed electrochemical sensor can be successfully applied in the quantitative determination of MT in Sophora flavescens extract. Full article

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9 pages, 1462 KiB

Open AccessArticle

The Synthesis of 2-Aminobenzoxazoles Using Reusable Ionic Liquid as a Green Catalyst under Mild Conditions

by Ya Zhou^1,†, Zhiqing Liu^1,†, Tingting Yuan¹, Jianbin Huang¹ and Chenjiang Liu^1,2,*

¹ School of Chemistry and Chemical Engineering, Xinjiang University and Key Laboratory of Oil and Gas Fine Chemicals, Ministry of Education, Urumqi 830046, China

² Physics and Chemistry Detecting Center, Xinjiang University, Urumqi 830046, China

^† The two authors contributed equally to this paper.

Molecules 2017, 22(4), 576; https://doi.org/10.3390/molecules22040576 - 2 Apr 2017

Cited by 10 | Viewed by 7470

Abstract

A facile, green, and efficient method for the direct oxidative amination of benzoxazoles using heterocyclic ionic liquid as catalyst has been developed. The reaction proceeded smoothly at room temperature and gave the desirable 2-aminobenzoxazoles with good to excellent yields (up to 97%). The [...] Read more.

A facile, green, and efficient method for the direct oxidative amination of benzoxazoles using heterocyclic ionic liquid as catalyst has been developed. The reaction proceeded smoothly at room temperature and gave the desirable 2-aminobenzoxazoles with good to excellent yields (up to 97%). The catalyst 1-butylpyridinium iodide can be easily recycled and reused with similar efficacies for at least four cycles. Full article

(This article belongs to the Section Green Chemistry)

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10 pages, 1180 KiB

Open AccessArticle

Experimental and Theoretical Reduction Potentials of Some Biologically Active ortho-Carbonyl para-Quinones

by Maximiliano Martínez-Cifuentes^1,*

, Ricardo Salazar^2,*, Oney Ramírez-Rodríguez^3,4, Boris Weiss-López⁵ and Ramiro Araya-Maturana^6,*

¹ Programa Institucional de Fomento a la Investigación, Desarrollo e Innovación, Universidad Tecnológica Metropolitana, Ignacio Valdivieso 2409, Casilla 9845, Santiago 8940577, Chile

² Laboratorio de Electroquímica del Medio Ambiente, LEQMA, Departamento de Química de los Materiales, Facultad de Química y Biología, Universidad de Santiago de Chile, USACh, Casilla 40, Correo 33, Santiago 9170022, Chile

³ Departamento de Química, Instituto de Ciencias Básicas, Universidad Técnica de Manabí, Av. Urbina y Che Guevara, Portoviejo 130104, Ecuador

⁴ Campus Río Simpson, Universidad de Aysén, Obispo Vielmo 62, Coyhaique 5952039, Chile

⁵ Departamento de Química, Facultad de Ciencias, Universidad de Chile, Las Palmeras 3425, Casilla 653, Santiago 7800003, Chile

⁶ Instituto de Química de Recursos Naturales, Universidad de Talca, Av. Lircay s/n, Casilla 747, Talca 3460000, Chile

Molecules 2017, 22(4), 577; https://doi.org/10.3390/molecules22040577 - 4 Apr 2017

Cited by 25 | Viewed by 5837

Abstract

The rational design of quinones with specific redox properties is an issue of great interest because of their applications in pharmaceutical and material sciences. In this work, the electrochemical behavior of a series of four p-quinones was studied experimentally and theoretically. The [...] Read more.

The rational design of quinones with specific redox properties is an issue of great interest because of their applications in pharmaceutical and material sciences. In this work, the electrochemical behavior of a series of four p-quinones was studied experimentally and theoretically. The first and second one-electron reduction potentials of the quinones were determined using cyclic voltammetry and correlated with those calculated by density functional theory (DFT) using three different functionals, BHandHLYP, M06-2x and PBE0. The differences among the experimental reduction potentials were explained in terms of structural effects on the stabilities of the formed species. DFT calculations accurately reproduced the first one-electron experimental reduction potentials with R² higher than 0.94. The BHandHLYP functional presented the best fit to the experimental values (R² = 0.957), followed by M06-2x (R² = 0.947) and PBE0 (R² = 0.942). Full article

(This article belongs to the Special Issue Organic Electrochemistry)

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18 pages, 1267 KiB

Open AccessReview

Na/K Pump and Beyond: Na/K-ATPase as a Modulator of Apoptosis and Autophagy

by Cassiano Felippe Gonçalves-de-Albuquerque^1,2,†

, Adriana Ribeiro Silva^1,†, Camila Ignácio da Silva³, Hugo Caire Castro-Faria-Neto¹ and Patrícia Burth^3,*

¹ Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro RJ CEP 21040-900, Brazil

² Laboratorio de Imunofarmacologia, Departamento de Bioquímica, Universidade Federal do Estado do Rio de Janeiro, Rio de Janeiro RJ CEP 20211-010, Brazil

³ Laboratório de Enzimologia e Sinalização Celular, Departamento de Biologia Celular e Molecular, Instituto de Biologia, Universidade Federal Fluminense, Niterói RJ CEP 24020-141, Brazil

^† These authors contributed equally to this work.

Molecules 2017, 22(4), 578; https://doi.org/10.3390/molecules22040578 - 21 Apr 2017

Cited by 72 | Viewed by 32443

Abstract

Lung cancer is a leading cause of global cancer deaths. Na/K-ATPase has been studied as a target for cancer treatment. Cardiotonic steroids (CS) trigger intracellular signalling upon binding to Na/K-ATPase. Normal lung and tumour cells frequently express different pump isoforms. Thus, Na/K-ATPase is [...] Read more.

Lung cancer is a leading cause of global cancer deaths. Na/K-ATPase has been studied as a target for cancer treatment. Cardiotonic steroids (CS) trigger intracellular signalling upon binding to Na/K-ATPase. Normal lung and tumour cells frequently express different pump isoforms. Thus, Na/K-ATPase is a powerful target for lung cancer treatment. Drugs targeting Na/K-ATPase may induce apoptosis and autophagy in transformed cells. We argue that Na/K-ATPase has a role as a potential target in chemotherapy in lung cancer treatment. We discuss the effects of Na/K-ATPase ligands and molecular pathways inducing deleterious effects on lung cancer cells, especially those leading to apoptosis and autophagy. Full article

(This article belongs to the Special Issue Cardiotonic Steroids)

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16 pages, 3051 KiB

Open AccessArticle

Design, Synthesis and Biological Evaluation of 2-(2-Amino-5(6)-nitro-1H-benzimidazol-1-yl)-N-arylacetamides as Antiprotozoal Agents

by Emanuel Hernández-Núñez^1,*, Hugo Tlahuext², Rosa Moo-Puc³, Diego Moreno⁴, María Ortencia González-Díaz⁵ and Gabriel Navarrete Vázquez⁶

¹ CONACYT, Departamento de Recursos del Mar, Centro de Investigación y de Estudios Avanzados del IPN, Unidad Mérida, Mérida 97310, Yucatán, Mexico

² Centro de Investigaciones Químicas, Universidad Autónoma del Estado de Morelos, Cuernavaca 62210, Morelos, Mexico

³ Unidad Interinstitucional de Investigación Médica, Instituto Mexicano del Seguro Social/Universidad Autónoma de Yucatán, Mérida 97150, Yucatán, México

⁴ Facultad de Ingeniería, Universidad Autónoma de Yucatán, Mérida 97310, Yucatán, Mexico

⁵ CONACYT, Centro de Investigación Científica de Yucatán, Mérida 97200, Yucatán, Mexico

⁶ Facultad de Farmacia, Universidad Autónoma del Estado de Morelos, Cuernavaca 62209, Morelos, Mexico

Molecules 2017, 22(4), 579; https://doi.org/10.3390/molecules22040579 - 4 Apr 2017

Cited by 9 | Viewed by 6666

Abstract

Parasitic diseases are a public health problem affecting millions of people worldwide. One of the scaffolds used in several drugs for the treatment of parasitic diseases is the benzimidazole moiety, a heterocyclic aromatic compound. This compound is a crucial pharmacophore group and is [...] Read more.

Parasitic diseases are a public health problem affecting millions of people worldwide. One of the scaffolds used in several drugs for the treatment of parasitic diseases is the benzimidazole moiety, a heterocyclic aromatic compound. This compound is a crucial pharmacophore group and is considered a privileged structure in medicinal chemistry. In this study, the benzimidazole core served as a model for the synthesis of a series of 2-(2-amino-5(6)-nitro-1H-benzimidazol-1-yl)-N-arylacetamides 1–8 as benznidazole analogues. The in silico pharmacological results calculated with PASS platform exhibited chemical structures highly similar to known antiprotozoal drugs. Compounds 1–8 when evaluated in silico for acute toxicity by oral dosing, were less toxic than benznidazole. The synthesis of compounds 1–8 were carried out through reaction of 5(6)-nitro-1H-benzimidazol-2-amine (12) with 2-chlroactemides 10a–h, in the presence of K₂CO₃ and acetonitrile as solvent, showing an inseparable mixture of two regioisomers with the -NO₂ group in position 5 or 6 with chemical yields of 60 to 94%. The prediction of the NMR spectra of molecule 1 coincided with the experimental chemical displacements of the regioisomers. Comparisons between the NMR prediction and the experimental data revealed that the regioisomer endo-1,6-NO₂ predominated in the reaction. The in vitro antiparasitic activity of these compounds on intestinal unicellular parasites (Giardia intestinalis and Entamoeba histolytica) and a urogenital tract parasite (Trichomonas vaginalis) were tested. Compound 7 showed an IC₅₀ of 3.95 μM and was 7 time more active against G. intestinalis than benznidazole. Compounds 7 and 8 showed 4 times more activity against T. vaginalis compared with benznidazole. Full article

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

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16 pages, 8868 KiB

Open AccessArticle

Growth, Structure, and Photocatalytic Properties of Hierarchical V₂O₅–TiO₂ Nanotube Arrays Obtained from the One-step Anodic Oxidation of Ti–V Alloys

by María C. Nevárez-Martínez^1,2

, Paweł Mazierski^3,*

, Marek P. Kobylański³, Grażyna Szczepańska⁴, Grzegorz Trykowski⁴, Anna Malankowska³, Magda Kozak³

, Patricio J. Espinoza-Montero²

and Adriana Zaleska-Medynska^3,*

¹ Facultad de Ingeniería Química y Agroindustria, Escuela Politécnica Nacional, Ladrón de Guevara E11-253, P.O. Box 17-01-2759, Quito 170525, Ecuador

² Centro de Investigación y Control Ambiental “CICAM”, Departamento de Ingeniería Civil y Ambiental, Facultad de Ingeniería Civil y Ambiental, Escuela Politécnica Nacional, Ladrón de Guevara E11-253, P.O. Box 17-01-2759, Quito 170525, Ecuador

³ Department of Environmental Technology, Faculty of Chemistry, University of Gdansk, Gdansk 80-308, Poland

⁴ Faculty of Chemistry, Nicolaus Copernicus University, Torun 87-100, Poland

Molecules 2017, 22(4), 580; https://doi.org/10.3390/molecules22040580 - 5 Apr 2017

Cited by 32 | Viewed by 8647

Abstract

V₂O₅-TiO₂ mixed oxide nanotube (NT) layers were successfully prepared via the one-step anodization of Ti-V alloys. The obtained samples were characterized by scanning electron microscopy (SEM), UV-Vis absorption, photoluminescence spectroscopy, energy-dispersive X-ray spectroscopy (EDX), X-ray diffraction (DRX), and [...] Read more.

V₂O₅-TiO₂ mixed oxide nanotube (NT) layers were successfully prepared via the one-step anodization of Ti-V alloys. The obtained samples were characterized by scanning electron microscopy (SEM), UV-Vis absorption, photoluminescence spectroscopy, energy-dispersive X-ray spectroscopy (EDX), X-ray diffraction (DRX), and micro-Raman spectroscopy. The effect of the applied voltage (30–50 V), vanadium content (5–15 wt %) in the alloy, and water content (2–10 vol %) in an ethylene glycol-based electrolyte was studied systematically to determine their influence on the morphology, and for the first-time, on the photocatalytic properties of these nanomaterials. The morphology of the samples varied from sponge-like to highly-organized nanotubular structures. The vanadium content in the alloy was found to have the highest influence on the morphology and the sample with the lowest vanadium content (5 wt %) exhibited the best auto-alignment and self-organization (length = 1 μm, diameter = 86 nm and wall thickness = 11 nm). Additionally, a probable growth mechanism of V₂O₅-TiO₂ nanotubes (NTs) over the Ti-V alloys was presented. Toluene, in the gas phase, was effectively removed through photodegradation under visible light (LEDs, λ_max = 465 nm) in the presence of the modified TiO₂ nanostructures. The highest degradation value was 35% after 60 min of irradiation. V₂O₅ species were ascribed as the main structures responsible for the generation of photoactive e⁻ and h⁺ under Vis light and a possible excitation mechanism was proposed. Full article

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

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12 pages, 3109 KiB

Open AccessArticle

Strengthening Triterpene Saponins Biosynthesis by Over-Expression of Farnesyl Pyrophosphate Synthase Gene and RNA Interference of Cycloartenol Synthase Gene in Panax notoginseng Cells

by Yan Yang^1,2, Feng Ge^1,*, Ying Sun¹, Diqiu Liu¹ and Chaoyin Chen¹

¹ Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming 650500, China

² School of Biotechnology and Engineering, Dianxi Science and Technology Normal University, Lincang 677000, China

Molecules 2017, 22(4), 581; https://doi.org/10.3390/molecules22040581 - 5 Apr 2017

Cited by 28 | Viewed by 7280

Abstract

To conform to the multiple regulations of triterpene biosynthesis, the gene encoding farnesyl pyrophosphate synthase (FPS) was transformed into Panax notoginseng (P. notoginseng) cells in which RNA interference (RNAi) of the cycloartenol synthase (CAS) gene had been accomplished. Transgenic cell lines [...] Read more.

To conform to the multiple regulations of triterpene biosynthesis, the gene encoding farnesyl pyrophosphate synthase (FPS) was transformed into Panax notoginseng (P. notoginseng) cells in which RNA interference (RNAi) of the cycloartenol synthase (CAS) gene had been accomplished. Transgenic cell lines showed both higher expression levels of FPS and lower expression levels of CAS compared to the wild-type (WT) cells. In the triterpene and phytosterol analysis, transgenic cell lines provided a higher accumulation of total triterpene saponins, and a lower amount of phytosterols in comparison with the WT cells. Compared with the cells in which RNAi of the CAS gene was achieved, the cells with simultaneously over-expressed FPS and silenced CAS showed higher triterpene contents. These results demonstrate that over-expression of FPS can break the rate-limiting reaction catalyzed by FPS in the triterpene saponins biosynthetic pathway; and inhibition of CAS expression can decrease the synthesis metabolic flux of the phytosterol branch. Thus, more precursors flow in the direction of triterpene synthesis, and ultimately promote the accumulation of P. notoginseng saponins. Meanwhile, silencing and over-expressing key enzyme genes simultaneously is more effective than just manipulating one gene in the regulation of saponin biosynthesis. Full article

(This article belongs to the Special Issue Isoprenoid Biosynthesis)

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14 pages, 4651 KiB

Open AccessHypothesis

Possible Involvement of Hydrosulfide in B₁₂-Dependent Methyl Group Transfer

by John I. Toohey

Cytoregulation Research, Elgin, ON K0G1E0, Canada

Molecules 2017, 22(4), 582; https://doi.org/10.3390/molecules22040582 - 5 Apr 2017

Cited by 22 | Viewed by 6134

Abstract

Evidence from several fields of investigation lead to the hypothesis that the sulfur atom is involved in vitamin B₁₂-dependent methyl group transfer. To compile the evidence, it is necessary to briefly review the following fields: methylation, the new field of sulfane [...] Read more.

Evidence from several fields of investigation lead to the hypothesis that the sulfur atom is involved in vitamin B₁₂-dependent methyl group transfer. To compile the evidence, it is necessary to briefly review the following fields: methylation, the new field of sulfane sulfur/hydrogen sulfide (S°/H₂S), hydrosulfide derivatives of cobalamins, autoxidation of hydrosulfide radical, radical S-adenosylmethionine methyl transfer (RSMT), and methionine synthase (MS). Then, new reaction mechanisms for B₁₂-dependent methyl group transfer are proposed; the mechanisms are facile and overcome difficulties that existed in previously-accepted mechanisms. Finally, the theory is applied to the effect of S°/H₂S in nerve tissue involving the “hypomethylation theory” that was proposed 50 years ago to explain the neuropathology resulting from deficiency of vitamin B₁₂ or folic acid. The conclusions are consistent with emerging evidence that sulfane sulfur/hydrogen sulfide may be beneficial in treating Alzheimer’s disease. Full article

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

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14 pages, 6360 KiB

Open AccessArticle

Discovery and Biological Evaluation of a Series of Pyrrolo[2,3-b]pyrazines as Novel FGFR Inhibitors

by Yan Zhang^1,2, Hongchun Liu², Zhen Zhang^3,4, Ruifeng Wang^3,4, Tongchao Liu^3,4, Chaoyun Wang¹, Yuchi Ma^3,*, Jing Ai^2,*, Dongmei Zhao⁴, Jingkang Shen³ and Bing Xiong^3,*

¹ School of Pharmaceutical Sciences, Binzhou Medical University, Yantai 264003, Shandong, China

² Division of Anti-Tumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, China

³ Department of Medicinal Chemistry, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, China

⁴ Key Laboratory of Structure-Based Drug Design and Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, China

Molecules 2017, 22(4), 583; https://doi.org/10.3390/molecules22040583 - 5 Apr 2017

Cited by 11 | Viewed by 6115

Abstract

Abnormality of fibroblast growth factor receptor (FGFR)-mediated signaling pathways were frequently found in various human malignancies, making FGFRs hot targets for cancer treatment. To address the consistent need for a new chemotype of FGFR inhibitors, here, we started with a hit structure identified [...] Read more.

Abnormality of fibroblast growth factor receptor (FGFR)-mediated signaling pathways were frequently found in various human malignancies, making FGFRs hot targets for cancer treatment. To address the consistent need for a new chemotype of FGFR inhibitors, here, we started with a hit structure identified from our internal hepatocyte growth factor receptor (also called c-Met) inhibitor project, and conducted a chemical optimization. After exploring three parts of the hit compound, we finally discovered a new series of pyrrolo[2,3-b]pyrazine FGFR inhibitors, which contain a novel scaffold and unique molecular shape. We believe that our findings can help others to further develop selective FGFR inhibitors. Full article

(This article belongs to the Special Issue Kinase Inhibitors)

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17 pages, 1156 KiB

Open AccessArticle

Screening and Analysis of the Marker Components in Ganoderma lucidum by HPLC and HPLC-MSⁿ with the Aid of Chemometrics

by Lingfang Wu, Wenyi Liang, Wenjing Chen, Shi Li, Yaping Cui, Qi Qi and Lanzhen Zhang^*

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

Molecules 2017, 22(4), 584; https://doi.org/10.3390/molecules22040584 - 6 Apr 2017

Cited by 38 | Viewed by 6306

Abstract

Ganoderma triterpenes (GTs) are the major secondary metabolites of Ganoderma lucidum, which is a popularly used traditional Chinese medicine for complementary cancer therapy. The present study was to establish a fingerprint evaluation system based on Similarity Analysis (SA), Cluster Analysis (CA) and [...] Read more.

Ganoderma triterpenes (GTs) are the major secondary metabolites of Ganoderma lucidum, which is a popularly used traditional Chinese medicine for complementary cancer therapy. The present study was to establish a fingerprint evaluation system based on Similarity Analysis (SA), Cluster Analysis (CA) and Principal Component Analysis (PCA) for the identification and quality control of G. lucidum. Fifteen samples from the Chinese provinces of Hainan, Neimeng, Shangdong, Jilin, Anhui, Henan, Yunnan, Guangxi and Fujian were analyzed by HPLC-PAD and HPLC-MSⁿ. Forty-seven compounds were detected by HPLC, of which forty-two compounds were tentatively identified by comparing their retention times and mass spectrometry data with that of reference compounds and reviewing the literature. Ganoderic acid B, 3,7,15-trihydroxy-11,23-dioxolanost-8,16-dien-26-oic acid, lucidenic acid A, ganoderic acid G, and 3,7-oxo-12-acetylganoderic acid DM were deemed to be the marker compounds to distinguish the samples with different quality according to both CA and PCA. This study provides helpful chemical information for further research on the anti-tumor activity and mechanism of action of G. lucidum. The results proved that fingerprints combined with chemometrics are a simple, rapid and effective method for the quality control of G. lucidum. Full article

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17 pages, 3166 KiB

Open AccessArticle

Mechanism of Action of Electrospun Chitosan-Based Nanofibers against Meat Spoilage and Pathogenic Bacteria

by Mounia Arkoun¹, France Daigle²

, Marie-Claude Heuzey^1,* and Abdellah Ajji^1,*

¹ CREPEC Department of Chemical Engineering, École Polytechnique de Montréal, P.O. Box 6079, Station Centre-Ville, Montréal, QC H3C 3A7, Canada

² Department of Microbiology, Infectiology and Immunology, Pavillon Roger-Gaudry, Université de Montréal, C.P. 6128, Centre-ville, Montréal, QC H3C 3J7, Canada

Molecules 2017, 22(4), 585; https://doi.org/10.3390/molecules22040585 - 6 Apr 2017

Cited by 99 | Viewed by 9494

Abstract

This study investigates the antibacterial mechanism of action of electrospun chitosan-based nanofibers (CNFs), against Escherichia coli, Salmonella enterica serovar Typhimurium, Staphylococcus aureus and Listeria innocua, bacteria frequently involved in food contamination and spoilage. CNFs were prepared by electrospinning of chitosan and [...] Read more.

This study investigates the antibacterial mechanism of action of electrospun chitosan-based nanofibers (CNFs), against Escherichia coli, Salmonella enterica serovar Typhimurium, Staphylococcus aureus and Listeria innocua, bacteria frequently involved in food contamination and spoilage. CNFs were prepared by electrospinning of chitosan and poly(ethylene oxide) (PEO) blends. The in vitro antibacterial activity of CNFs was evaluated and the susceptibility/resistance of the selected bacteria toward CNFs was examined. Strain susceptibility was evaluated in terms of bacterial type, cell surface hydrophobicity, and charge density, as well as pathogenicity. The efficiency of CNFs on the preservation and shelf life extension of fresh red meat was also assessed. Our results demonstrate that the antibacterial action of CNFs depends on the protonation of their amino groups, regardless of bacterial type and their mechanism of action was bactericidal rather than bacteriostatic. Results also indicate that bacterial susceptibility was not Gram-dependent but strain-dependent, with non-virulent bacteria showing higher susceptibility at a reduction rate of 99.9%. The susceptibility order was: E. coli > L. innocua > S. aureus > S. Typhimurium. Finally, an extension of one week of the shelf life of fresh meat was successfully achieved. These results are promising and of great utility for the potential use of CNFs as bioactive food packaging materials in the food industry, and more specifically in meat quality preservation. Full article

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

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16 pages, 3092 KiB

Open AccessArticle

Optimization of Ionic Liquid-Assisted Extraction of Biflavonoids from Selaginella doederleinii and Evaluation of Its Antioxidant and Antitumor Activity

by Dan Li, Yan Qian, Yu-Jia Tian, Shi-Meng Yuan, Wei Wei and Gang Wang^*

School of Pharmacy, Zunyi Medical College, Zunyi, Guizhou 563003, China

Molecules 2017, 22(4), 586; https://doi.org/10.3390/molecules22040586 - 7 Apr 2017

Cited by 58 | Viewed by 6861

Abstract

As new green solvents, ionic liquids (ILs) have been generally applied in the extraction and separation of natural product. In this study, microwave assisted extraction based on IL (IL-MAE) was firstly employed to extract total biflavonoids from Selaginella doederleinii. Based on single-factor [...] Read more.

As new green solvents, ionic liquids (ILs) have been generally applied in the extraction and separation of natural product. In this study, microwave assisted extraction based on IL (IL-MAE) was firstly employed to extract total biflavonoids from Selaginella doederleinii. Based on single-factor experiment, microwave power (300–700 W), extract time (30–50 min) and extract temperature (40–60 °C) on total bioflavonoids and antioxidant activities of the extracts were further investigated by a Box-Behnken design of response surface methodology (RSM) selecting total bioflavonoids yields and IC₅₀ of radical scavenging as index. Besides antioxidant activity of the extract was evaluated by a 2,2-diphenyl-1-picrylhydarzyl (DPPH) and 2,2′-azinobis-(3-ethylbenzthiazoline-6-sulphonate (ABTS) radical scavenging assay, ferric reducing power assay and chelation of ferrous ions assay, and then anticaner activity was also researched against A549 cell line and 7721 cell line. The results illustrated that three factors and their interactions could be well suited for second-order polynomial models (p < 0.05). Through process parameters, optimization of the extract (460 W, 40 min, and 45 °C) and detection of bioactivity, the yield of total bioflavonoids was 16.83 mg/g and IC₅₀ value was 56.24 μg/mL, respectively, indicating the extract has better anti-oxidation effect and antitumor activity. Furthermore, IL-MAE was the most efficient extracting method compared with MAE and Soxhlet extraction, which could improve extraction efficiency in a shorter time and at a lower temperature. In general, ILs-MAE was first adopted to establish a novel and green extraction process on the yields of total biflavonoids from S. doederleinii. In addition, the extract of containing biflavones showed potent antioxidant and anticancer capacity as a utilized valuable bioactive source for natural medicine. Full article

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

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13 pages, 2777 KiB

Open AccessArticle

Fraxin Prevents Chemically Induced Hepatotoxicity by Reducing Oxidative Stress

by Bo Yoon Chang^1,†, Young Suk Jung^2,†, Chi-Su Yoon¹, Jun Seok Oh³, Jae Heoi Hong³, Youn-Chul Kim¹ and Sung Yeon Kim^1,*

¹ Institute of Pharmaceutical Research and Development, College of Pharmacy, Wonkwang University, Iksan, Jeonbuk 54538, Korea

² College of Pharmacy, Pusan National University, San 30, Jangjeon-dong, Busan 46241, Korea

³ Dongbu Eastern Herbal Medicine Agricultural Association Corporation, Yeosunro 1679, Sunchun-si, Jeonnam 58019, Korea

^† These authors contributed equally to this work.

Molecules 2017, 22(4), 587; https://doi.org/10.3390/molecules22040587 - 6 Apr 2017

Cited by 30 | Viewed by 5785

Abstract

Fraxin isolated from Acer tegmentosum is reported to exert potent anti-oxidative stress action. However, pharmacological activities of fraxin remain to be elucidated. This study investigated the potential hepatoprotective effects of fraxin and the underlying signaling mechanism involved. Treatment with fraxin significantly lowered the [...] Read more.

Fraxin isolated from Acer tegmentosum is reported to exert potent anti-oxidative stress action. However, pharmacological activities of fraxin remain to be elucidated. This study investigated the potential hepatoprotective effects of fraxin and the underlying signaling mechanism involved. Treatment with fraxin significantly lowered the serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in a CCl₄-induced hepatotoxicity rat model. In the fraxin-treated group, glutathione (GSH) significantly increased, while the malondialdehyde (MDA) in the liver significantly decreased. Fraxin also showed radical-scavenging activity. Furthermore, it significantly reduced the t-BHP-induced cytotoxicity and production of reactive oxygen species (ROS) in Hep G2. Fraxin protected Hep G2 cells through Nrf2 pathway-dependent HO-1 expression. The results of this study indicate that fraxin shows potent hepatoprotective effects in vitro and in vivo, presumably through direct antioxidant activity and the Nrf2-mediated antioxidant enzyme system. Full article

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

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12 pages, 1683 KiB

Open AccessArticle

Antioxidant Properties and Oxidative Transformation of Different Chromone Derivatives

by Evelin Csepanyi^1,2, Peter Szabados-Furjesi^1,2, Attila Kiss-Szikszai³, Lisa M. Frensemeier⁴, Uwe Karst⁴, Istvan Lekli¹

, David D. Haines¹, Arpad Tosaki¹

and Istvan Bak^1,2,*

¹ Department of Pharmacology, Faculty of Pharmacy, University of Debrecen, Debrecen H-4032, Hungary

² Department of Bioanalytical Chemistry, Faculty of Pharmacy, University of Debrecen, Debrecen H-4032, Hungary

³ Department of Organic Chemistry, Faculty of Science and Technology, University of Debrecen, Debrecen H-4032, Hungary

⁴ Institute of Inorganic and Analytical Chemistry, University of Muenster, Muenster D-48149, Germany

Molecules 2017, 22(4), 588; https://doi.org/10.3390/molecules22040588 - 6 Apr 2017

Cited by 30 | Viewed by 5947

Abstract

Nowadays, there is an increase in the application of natural products for the prevention of different disorders or adjuvant substances next to pharmacological treatment. Phytochemicals include different chromone derivatives, which possess a wide spectrum of biological activity. The aim of the present study [...] Read more.

Nowadays, there is an increase in the application of natural products for the prevention of different disorders or adjuvant substances next to pharmacological treatment. Phytochemicals include different chromone derivatives, which possess a wide spectrum of biological activity. The aim of the present study was the investigation of the antioxidant activity, cytotoxicity and oxidative transformation of nine chromone derivatives. First, we investigated the radical scavenging activity (ABTS), the oxygen radical absorption capacity (ORAC) and the ferric reducing antioxidant power (FRAP) of the investigated molecules. The cytotoxic effects of the compounds were tested on H9c2 cell cultures by the MTT assay. Each compound showed a significant ORAC value compared to the reference. However, the compound 865 possess significantly higher FRAP and ABTS activity in comparison with the reference and other tested molecules, respectively. Based on these assays, the compound 865 was selected for further analysis. In these experiments, we investigated the oxidative metabolism of the compound in vitro. The molecule was oxidized by the Fenton reaction, artificial porphyrin and electrochemistry; then, the formed products were identified by mass spectrometry. Four possible metabolites were detected. The results revealed the compound 865 to possess good antioxidant properties and to be stable metabolically; hence, it is worth investigating its effects in vivo. Full article

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

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19 pages, 280 KiB

Open AccessReview

ABC Transport Proteins in Cardiovascular Disease—A Brief Summary

by Toni Schumacher and Ralf A. Benndorf^*

Institute of Pharmacy, Department of Clinical Pharmacy and Pharmacotherapy, Martin-Luther-University Halle-Wittenberg, Wolfgang-Langenbeck-Strasse 4, D-06120 Halle (Saale), Germany

Molecules 2017, 22(4), 589; https://doi.org/10.3390/molecules22040589 - 6 Apr 2017

Cited by 95 | Viewed by 9621

Abstract

Adenosine triphosphate (ATP)-binding cassette (ABC) transporters may play an important role in the pathogenesis of atherosclerotic vascular diseases due to their involvement in cholesterol homeostasis, blood pressure regulation, endothelial function, vascular inflammation, as well as platelet production and aggregation. In this regard, ABC [...] Read more.

Adenosine triphosphate (ATP)-binding cassette (ABC) transporters may play an important role in the pathogenesis of atherosclerotic vascular diseases due to their involvement in cholesterol homeostasis, blood pressure regulation, endothelial function, vascular inflammation, as well as platelet production and aggregation. In this regard, ABC transporters, such as ABCA1, ABCG5 and ABCG8, were initially found to be responsible for genetically-inherited syndromes like Tangier diseases and sitosterolemia. These findings led to the understanding of those transporter’s function in cellular cholesterol efflux and thereby also linked them to atherosclerosis and cardiovascular diseases (CVD). Subsequently, further ABC transporters, i.e., ABCG1, ABCG4, ABCB6, ABCC1, ABCC6 or ABCC9, have been shown to directly or indirectly affect cellular cholesterol efflux, the inflammatory response in macrophages, megakaryocyte proliferation and thrombus formation, as well as vascular function and blood pressure, and may thereby contribute to the pathogenesis of CVD and its complications. Furthermore, ABC transporters, such as ABCB1, ABCC2 or ABCG2, may affect the safety and efficacy of several drug classes currently in use for CVD treatment. This review will give a brief overview of ABC transporters involved in the process of atherogenesis and CVD pathology. It also aims to briefly summarize the role of ABC transporters in the pharmacokinetics and disposition of drugs frequently used to treat CVD and CVD-related complications. Full article

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

10 pages, 3368 KiB

Open AccessCommunication

Synthesis and Antibacterial Evaluation of Novel 3-Substituted Ocotillol-Type Derivatives as Leads

by Yi Bi^1,†

, Xian-Xuan Liu^1,†, Heng-Yuan Zhang^2,†, Xiao Yang³, Ze-Yun Liu¹, Jing Lu¹, Peter John Lewis⁴, Chong-Zhi Wang^5,6, Jin-Yi Xu^2,*, Qing-Guo Meng^1,*, Cong Ma^7,*

and Chun-Su Yuan^5,6

¹ School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai 264005, China

² State Key Laboratory of Natural Medicines and Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China

³ Department of Microbiology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, China

⁴ Biological Sciences, School of Environmental and Life Sciences, University of Newcastle, Callaghan, NSW 2308, Australia

⁵ Tang Center for Herbal Medicine Research, the University of Chicago, Chicago, IL 60637, USA

⁶ Department of Anesthesia and Critical Care, The University of Chicago, Chicago, IL 60637, USA

⁷ Department of Applied Biology and Chemical Technology, and State Key Laboratory of Chirosciences, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, China

^† These authors contributed equally to this work.

Molecules 2017, 22(4), 590; https://doi.org/10.3390/molecules22040590 - 7 Apr 2017

Cited by 25 | Viewed by 5621

Abstract

Due to the rapidly growing bacterial antibiotic-resistance and the scarcity of novel agents in development, bacterial infection is still a global problem. Therefore, new types of antibacterial agents, which are effective both alone and in combination with traditional antibiotics, are urgently needed. In [...] Read more.

Due to the rapidly growing bacterial antibiotic-resistance and the scarcity of novel agents in development, bacterial infection is still a global problem. Therefore, new types of antibacterial agents, which are effective both alone and in combination with traditional antibiotics, are urgently needed. In this paper, a series of antibacterial ocotillol-type C-24 epimers modified from natural 20(S)-protopanaxadiol were synthesized and evaluated for their antibacterial activity. According to the screening results of Gram-positive bacteria (B. subtilis 168 and MRSA USA300) and Gram-negative bacteria (P. aer PAO1 and A. baum ATCC19606) in vitro, the derivatives exhibited good antibacterial activity, particularly against Gram-positive bacteria with an minimum inhibitory concentrations (MIC) value of 2–16 µg/mL. The subsequent synergistic antibacterial assay showed that derivatives 5c and 6c enhanced the susceptibility of B. subtilis 168 and MRSA USA300 to chloramphenicol (CHL) and kanamycin (KAN) (FICI < 0.5). Our data showed that ocotillol-type derivatives with long-chain amino acid substituents at C-3 were good leads against antibiotic-resistant pathogens MRSA USA300, which could improve the ability of KAN and CHL to exhibit antibacterial activity at much lower concentrations with reduced toxicity. Full article

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

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14 pages, 1921 KiB

Open AccessArticle

The Effect of Citrus Essential Oils and Their Constituents on Growth of Xanthomonas citri subsp. citri

by Hossein Mirzaei-Najafgholi¹, Saeed Tarighi^1,*

, Morteza Golmohammadi² and Parissa Taheri¹

¹ Department of Plant Protection, Faculty of Agriculture, Ferdowsi University of Mashhad, 9177948974 Mashhad, Iran

² Iran Citrus Research Institute, 33546915 Ramsar, Iran

Molecules 2017, 22(4), 591; https://doi.org/10.3390/molecules22040591 - 14 Apr 2017

Cited by 52 | Viewed by 9384

Abstract

Citrus bacterial canker (CBC) caused by Xanthomonas citri subsp. citri (Xcc), is the most devastating of the citrus diseases worldwide. During our study, we found that Essential oils (EOs) of some citrus cultivars are effective on Xcc. Therefore, it prompted [...] Read more.

Citrus bacterial canker (CBC) caused by Xanthomonas citri subsp. citri (Xcc), is the most devastating of the citrus diseases worldwide. During our study, we found that Essential oils (EOs) of some citrus cultivars are effective on Xcc. Therefore, it prompted us to determine the plant metabolites responsible for the antibacterial properties. We obtained EOs from some locally cultivated citrus by using a Clevenger apparatus and their major constituents were identified by gas chromatography/mass spectrometry (GC-MS). The effect of Citrus aurantium, C. aurantifolia, Fortunella sp. EOs and their major constituents were evaluated against Xcc-KVXCC1 using a disk diffusion assay. Minimal inhibitory and bactericidal concentration of the EOs and their constituents were determined using the broth microdilution method. C. aurantium, C. aurantifolia Eos, and their major constituents including citral, linalool, citronellal, geraniol, α-terpineol, and linalyl acetate indicated antibacterial effects against Xcc. The C. aurantifolia EO and citral showed the highest antibacterial activity among the tested EOs and constituents with inhibition zones of 15 ± 0.33 mm and 16.67 ± 0.88 mm, respectively. Synergistic effects of the constituents were observed between α-terpineol-citral, citral-citronellal, citral-geraniol, and citronellal-geraniol by using a microdilution checkerboard assay. Transmission electron microscopy revealed that exposure of Xcc cells to citral caused cell wall damage and altered cytoplasmic density. We introduced C. aurantifolia and C. aurantium EOs, and their constituents citral, α-terpineol, citronellal, geraniol, and linalool as possible control agents for CBC. Full article

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

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9 pages, 822 KiB

Open AccessArticle

Two New Thymol Derivatives from the Roots of Ageratina adenophora

by Li-Mei Dong^1,2,3, Mei Zhang^1,†, Qiao-Lin Xu⁴, Qiang Zhang^1,3, Bi Luo^1,3, Qing-Wen Luo^1,3, Wen-Bin Liu^1,3 and Jian-Wen Tan^1,2,*

¹ Guangdong Provincial Key Laboratory of Applied Botany, South China Botanical Garden, Chinese Academy of Sciences, Guangzhou 510650, China

² State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources/Guangdong Key Laboratory for Innovative Development and Utilization of Forest Plant Germplasm, College of Forestry and Landscape Architecture, South China Agricultural University, Guangzhou 510642, China

³ College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China

⁴ Guangdong Provincial Key Laboratory of Bio-Control for the Forest Disease and Pest, Guangdong Academy of Forestry, Guangzhou 510520, China

^† Presently work at Beijing Center for Physical and Chemical Analysis, Beijing Key Laboratory of Organic Materials Testing Technology & Quality Evaluation, Beijing 100089, China.

Molecules 2017, 22(4), 592; https://doi.org/10.3390/molecules22040592 - 8 Apr 2017

Cited by 22 | Viewed by 5091

Abstract

Two new thymol derivatives, 7,9-diisobutyryloxy-8-ethoxythymol (1) and 7-acetoxy-8-methoxy-9-isobutyryloxythymol (2), were isolated from fresh roots of Ageratina adenophora, together with four known compounds, 7,9-di-isobutyryloxy-8-methoxythymol (3), 9-oxoageraphorone (4), (−)-isochaminic acid (5) and (1α,6α)-10-hydroxycar-3-ene-2-one ( [...] Read more.

Two new thymol derivatives, 7,9-diisobutyryloxy-8-ethoxythymol (1) and 7-acetoxy-8-methoxy-9-isobutyryloxythymol (2), were isolated from fresh roots of Ageratina adenophora, together with four known compounds, 7,9-di-isobutyryloxy-8-methoxythymol (3), 9-oxoageraphorone (4), (−)-isochaminic acid (5) and (1α,6α)-10-hydroxycar-3-ene-2-one (6). Their structures were established on the basis of detailed spectroscopic analysis, and they were all isolated from the roots of A. adenophora for the first time. All the compounds were tested for their in vitro antibacterial activity toward three Gram-positive and two Gram-negative bacterial strains. Thymol derivatives 1–3 only selectively showed slight in vitro bacteriostatic activity toward three Gram-positive bacteria. The two known carene-type monoterpenes 5 and 6 were found to show moderate in vitro antibacterial activity against all five tested bacterial strains, with MIC values from 15.6 to 62.5 μg/mL. In addition, compounds 5 and 6 were further revealed to show in vitro cytotoxicity against human tumor A549, HeLa and HepG2 cell lines, with IC₅₀ values ranging from 18.36 to 41.87 μM. However, their cytotoxic activities were inferior to those of reference compound adriamycin. Full article

(This article belongs to the Section Natural Products Chemistry)

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15 pages, 7474 KiB

Open AccessArticle

A Study about Regioisomeric Hydroquinones with Multiple Intramolecular Hydrogen Bonding

by Maximiliano Martínez-Cifuentes^1,*

, Wilson Cardona², Claudio Saitz³, Boris Weiss-López⁴ and Ramiro Araya-Maturana^5,*

¹ Programa Institucional de Fomento a la Investigación, Desarrollo e Innovación, Universidad Tecnológica Metropolitana, Ignacio Valdivieso 2409, Casilla 9845, Santiago 8940577, Chile

² Departamento de Ciencias Químicas, Facultad de Ciencias Exactas, Universidad Andrés Bello, Autopista Concepción-Talcahuano 7100, Talcahuano 4300866, Chile

³ Departamento de Química Orgánica y Fisicoquímica, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santos Dumont 964, Casilla 233, Santiago 8380494, Chile

⁴ Departamento de Química, Facultad de Ciencias, Universidad de Chile, Las Palmeras 3425, Casilla 653, Santiago 7800003, Chile

⁵ Instituto de Química de Recursos Naturales, Universidad de Talca, Av. Lircay s/n, Casilla 747, Talca 3460000, Chile

Molecules 2017, 22(4), 593; https://doi.org/10.3390/molecules22040593 - 7 Apr 2017

Cited by 13 | Viewed by 4789

Abstract

A theoretical exploration about hydrogen bonding in a series of synthetic regioisomeric antitumor tricyclic hydroquinones is presented. The stabilization energy for the intramolecular hydrogen bond (IHB) formation in four structurally different situations were evaluated: (a) IHB between the proton of a phenolic hydroxyl [...] Read more.

A theoretical exploration about hydrogen bonding in a series of synthetic regioisomeric antitumor tricyclic hydroquinones is presented. The stabilization energy for the intramolecular hydrogen bond (IHB) formation in four structurally different situations were evaluated: (a) IHB between the proton of a phenolic hydroxyl group and an ortho-carbonyl group (forming a six-membered ring); (b) between the oxygen atom of a phenolic hydroxyl group and the proton of an hydroxyalkyl group (seven membered ring); (c) between the proton of a phenolic hydroxyl group with the oxygen atom of the hydroxyl group of a hydroxyalkyl moiety (seven-membered ring); and (d) between the proton of a phenolic hydroxyl group and an oxygen atom directly bonded to the aromatic ring in ortho position (five-membered ring). A conformational analysis for the rotation around the hydroxyalkyl substituent is also performed. It is observed that there is a correspondence between the conformational energies and the IHB. The strongest intramolecular hydrogen bonds are those involving a phenolic proton and a carbonyl oxygen atom, forming a six-membered ring, and the weakest are those involving a phenolic proton with the oxygen atom of the chromenone, forming five-membered rings. Additionally, the synthesis and structural assignment of two pairs of regioisomeric hydroquinones, by 2D-NMR experiments, are reported. These results can be useful in the design of biologically-active molecules. Full article

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

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31 pages, 1703 KiB

Open AccessReview

Engineering of Syndiotactic and Isotactic Polystyrene-Based Copolymers via Stereoselective Catalytic Polymerization

by Eva Laur, Evgueni Kirillov^* and Jean-François Carpentier^*

Université de Rennes 1, CNRS, Institut des Sciences Chimiques de Rennes, UMR 6226, F-35042 Rennes CEDEX, France

Molecules 2017, 22(4), 594; https://doi.org/10.3390/molecules22040594 - 7 Apr 2017

Cited by 21 | Viewed by 10358

Abstract

This contribution presents an updated overview of the different copolymers containing stereoregular polystyrene blocks. Special emphasis is placed on syndiospecific and isospecific copolymerization of styrene with co-monomers (ethylene and α-olefins, conjugated and non-conjugated dienes, styrene derivatives, etc.). The catalytic systems involved are described [...] Read more.

This contribution presents an updated overview of the different copolymers containing stereoregular polystyrene blocks. Special emphasis is placed on syndiospecific and isospecific copolymerization of styrene with co-monomers (ethylene and α-olefins, conjugated and non-conjugated dienes, styrene derivatives, etc.). The catalytic systems involved are described and the polymerization mechanisms are discussed. Alternative approaches (simultaneous, living, chain-transfer and graft copolymerization) and the resulting detailed structures and characteristics of the copolymers are also reported. Full article

(This article belongs to the Special Issue Organometallic Catalysis for Olefin Polymerization/Oligomerization)

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14 pages, 4560 KiB

Open AccessArticle

TCS2 Increases Olaquindox-Induced Apoptosis by Upregulation of ROS Production and Downregulation of Autophagy in HEK293 Cells

by Daowen Li, Kena Zhao, Xiayun Yang, Xilong Xiao and Shusheng Tang^*

College of Veterinary Medicine, China Agricultural University, Yuanmingyuan West Road No. 2, Haidian District, Beijing 100193, China

Molecules 2017, 22(4), 595; https://doi.org/10.3390/molecules22040595 - 7 Apr 2017

Cited by 7 | Viewed by 4921

Abstract

Olaquindox, a feed additive, has drawn public attention due to its potential mutagenicity, genotoxicity, hepatoxicity and nephrotoxicity. The purpose of this study was to investigate the role of tuberous sclerosis complex (TSC2) pathways in olaquindox-induced autophagy in human embryonic kidney 293 (HEK293) cells. [...] Read more.

Olaquindox, a feed additive, has drawn public attention due to its potential mutagenicity, genotoxicity, hepatoxicity and nephrotoxicity. The purpose of this study was to investigate the role of tuberous sclerosis complex (TSC2) pathways in olaquindox-induced autophagy in human embryonic kidney 293 (HEK293) cells. The results revealed that olaquindox treatment reduced the cell viability of HEK293 cells and downregulated the expression of TSC2 in a dose- and time-dependent manner. Meanwhile, olaquindox treatment markedly induced the production of reactive oxygen species (ROS), cascaded to autophagy, oxidative stress, and apoptotic cell death, which was effectively eliminated by the antioxidant N-acetylcysteine (NAC). Furthermore, overexpression of TSC2 attenuated olaquindox-induced autophagy in contrast to inducing the production of ROS, oxidative stress and apoptosis. Consistently, knockdown of TSC2 upregulated autophagy, and decreased olaquindox-induced cell apoptosis. In conclusion, our findings indicate that TSC2 partly participates in olaquindox-induced autophagy, oxidative stress and apoptosis, and demonstrate that TSC2 has a negative regulation role in olaquindox-induced autophagy in HEK293 cells. Full article

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

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26 pages, 6029 KiB

Open AccessReview

Neutron Crystallography for the Study of Hydrogen Bonds in Macromolecules

by Esko Oksanen^1,2

, Julian C.-H. Chen³ and Suzanne Zoë Fisher^1,4,*

¹ Science Directorate, European Spallation Source ERIC, Tunavägen 24, 22100 Lund, Sweden

² Department of Biochemistry and Structural Biology, Lund University, Sölvegatan 39, 22362 Lund, Sweden

³ Bioscience Division, Los Alamos National Laboratory, Los Alamos, NM 87545, USA

⁴ Department of Biology, Lund University, Sölvegatan 35, 22362 Lund, Sweden

Molecules 2017, 22(4), 596; https://doi.org/10.3390/molecules22040596 - 7 Apr 2017

Cited by 41 | Viewed by 8884

Abstract

Abstract: The hydrogen bond (H bond) is one of the most important interactions that form the foundation of secondary and tertiary protein structure. Beyond holding protein structures together, H bonds are also intimately involved in solvent coordination, ligand binding, and enzyme catalysis. [...] Read more.

Abstract: The hydrogen bond (H bond) is one of the most important interactions that form the foundation of secondary and tertiary protein structure. Beyond holding protein structures together, H bonds are also intimately involved in solvent coordination, ligand binding, and enzyme catalysis. The H bond by definition involves the light atom, H, and it is very difficult to study directly, especially with X-ray crystallographic techniques, due to the poor scattering power of H atoms. Neutron protein crystallography provides a powerful, complementary tool that can give unambiguous information to structural biologists on solvent organization and coordination, the electrostatics of ligand binding, the protonation states of amino acid side chains and catalytic water species. The method is complementary to X-ray crystallography and the dynamic data obtainable with NMR spectroscopy. Also, as it gives explicit H atom positions, it can be very valuable to computational chemistry where exact knowledge of protonation and solvent orientation can make a large difference in modeling. This article gives general information about neutron crystallography and shows specific examples of how the method has contributed to structural biology, structure-based drug design; and the understanding of fundamental questions of reaction mechanisms. Full article

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

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9 pages, 383 KiB

Open AccessFeature PaperArticle

Anti-Trypanosomatid Elemanolide Sesquiterpene Lactones from Vernonia lasiopus O. Hoffm

by Njogu M. Kimani¹

, Josphat C. Matasyoh², Marcel Kaiser^3,4, Reto Brun^3,4 and Thomas J. Schmidt^1,*

¹ Institute of Pharmaceutical Biology and Phytochemistry (IPBP), University of Münster, PharmaCampus Corrensstraße 48, D-48149 Münster, Germany

² Department of Chemistry, Egerton University, P.O. Box 536, Egerton, Nairobi 20115, Kenya

³ Swiss Tropical and Public Health Institute (Swiss TPH), Socinstr. 57, CH-4051 Basel, Switzerland

⁴ University of Basel, Petersplatz 1, CH-4003 Basel, Switzerland

Molecules 2017, 22(4), 597; https://doi.org/10.3390/molecules22040597 - 8 Apr 2017

Cited by 24 | Viewed by 6186

Abstract

Sleeping sickness or human African trypanosomiasis (HAT) is a neglected tropical disease (NTD) threatening millions of peoples’ lives with thousands infected. The disease is endemic in poorly developed regions of sub-Saharan Africa and is caused by the kinetoplastid “protozoan” parasite Trypanosoma brucei. [...] Read more.

Sleeping sickness or human African trypanosomiasis (HAT) is a neglected tropical disease (NTD) threatening millions of peoples’ lives with thousands infected. The disease is endemic in poorly developed regions of sub-Saharan Africa and is caused by the kinetoplastid “protozoan” parasite Trypanosoma brucei. The parasites are transmitted to humans through bites of infected tsetse flies of the genus Glossina. The few available drugs for treatment of this disease are highly toxic, difficult to administer, costly and unavailable to poor rural communities bearing the major burden of this infection. Therefore, the search for new efficacious, safe and affordable drugs is of high importance. Vernonia lasiopus O. Hoffm., an indigenous African plant of the Asteraceae family, has been extensively reported to be used ethno-medicinally as a treatment for malaria. Its crude extracts obtained with solvents of different polarity were screened in vitro for anti-protozoal activity and the dichloromethane extract was found to be particularly active against Trypanosoma brucei rhodesiense (IC₅₀ = 0.17 µg/mL). Bioassay-guided chromatographic fractionation of the dichloromethane extract led to the isolation and identification of six elemanolide type sesquiterpene lactones: 8-desacylvernolide, vernolepin, vernomenin, vernodalol, vernodalin and 11,13-dihydrovernodalin. All these elemanolide sesquiterpene lactones showed in vitro anti-trypanosomal activity. They were also tested for cytotoxicity against mammalian cells (L6 cell line). Vernolepin, the main component in the extract, was also the most potent with an IC₅₀ value of 0.05 µg/mL against T.b. rhodesiense trypomastigotes. This compound showed a selectivity index of 14.5, which makes it an interesting candidate for in vivo tests and determination of its mechanism of action. Full article

(This article belongs to the Special Issue Special Issue in Honor of Professor Nikolaus (Klaus) Fischer on the Occasion of His 80th Birthday)

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9 pages, 1257 KiB

Open AccessReview

Non-Anticoagulant Heparins Are Hepcidin Antagonists for the Treatment of Anemia

by Maura Poli¹, Michela Asperti¹, Paola Ruzzenenti¹, Annamaria Naggi²

and Paolo Arosio^1,*

¹ Department of Molecular and Translational Medicine, University of Brescia, Viale Europa 11, 25123 Brescia, Italy

² G. Ronzoni Institute for Chemical and Biochemical Research, Milan 20133, Italy

Molecules 2017, 22(4), 598; https://doi.org/10.3390/molecules22040598 - 8 Apr 2017

Cited by 18 | Viewed by 7410

Abstract

The peptide hormone hepcidin is a key controller of systemic iron homeostasis, and its expression in the liver is mainly regulated by bone morphogenetic proteins (BMPs), which are heparin binding proteins. In fact, heparins are strong suppressors of hepcidin expression in hepatic cell [...] Read more.

The peptide hormone hepcidin is a key controller of systemic iron homeostasis, and its expression in the liver is mainly regulated by bone morphogenetic proteins (BMPs), which are heparin binding proteins. In fact, heparins are strong suppressors of hepcidin expression in hepatic cell lines that act by inhibiting the phosphorylation of SMAD1/5/8 proteins elicited by the BMPs. The inhibitory effect of heparins has been demonstrated in cells and in mice, where subcutaneous injections of non-anticoagulant heparins inhibited liver hepcidin expression and increased iron bioavailability. The chemical characteristics for high anti-hepcidin activity in vitro and in vivo include the 2O-and 6O-sulfation and a molecular weight above 7 kDa. The most potent heparins have been found to be the super-sulfated ones, active in hepcidin suppression with a molecular weight as low as 4 kDa. Moreover, the alteration of endogenous heparan sulfates has been found to cause a reduction in hepcidin expression in vitro and in vivo, indicating that heparins act by interfering with the interaction between BMPs and components of the complex involved in the activation of the BMP/SMAD1/5/8 pathway. This review summarizes recent findings on the anti-hepcidin activity of heparins and their possible use for the treatment of anemia caused by hepcidin excess, including the anemia of chronic diseases. Full article

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

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13 pages, 1487 KiB

Open AccessArticle

Acute Hypoglycemic and Antidiabetic Effect of Teuhetenone A Isolated from Turnera diffusa

by Aída Parra-Naranjo^1,†, Cecilia Delgado-Montemayor^1,†, Alejandra Fraga-López¹, Gabriela Castañeda-Corral², Ricardo Salazar-Aranda¹, Juan José Acevedo-Fernández²

and Noemi Waksman^1,*

¹ Departmento de Química Analítica, Facultad de Medicina, Universidad Autónoma de Nuevo León, Monterrey, N.L., C.P. 64460, Mexico

² Depto. de Fisiología y Fisiopatología, Facultad de Medicina, Universidad Autónoma del Estado de Morelos, Calle Leñeros s/n, Col. Los Volcanes, Cuernavaca Mor. C.P. 62350, Mexico

^† Both authors contributed equally.

Molecules 2017, 22(4), 599; https://doi.org/10.3390/molecules22040599 - 8 Apr 2017

Cited by 27 | Viewed by 7517

Abstract

Diabetes mellitus is a chronic degenerative disease that causes long-term complications and represents a serious public health problem. Turnera diffusa (damiana) is a shrub that grows throughout Mexico and is traditionally used for many illnesses including diabetes. Although a large number of plant [...] Read more.

Diabetes mellitus is a chronic degenerative disease that causes long-term complications and represents a serious public health problem. Turnera diffusa (damiana) is a shrub that grows throughout Mexico and is traditionally used for many illnesses including diabetes. Although a large number of plant metabolites are known, there are no reports indicating which of these are responsible for this activity, and this identification was the objective of the present work. Through bioassay-guided fractionation of a methanolic extract obtained from the aerial part of T. diffusa, teuhetenone A was isolated and identified as the main metabolite responsible for the plant’s hypoglycemic activity. Alpha-glucosidase inhibitory activity and cytotoxicity of this metabolite were determined. Hypoglycemic and antidiabetic activities were evaluated in a murine model of diabetes in vivo, by monitoring glucose levels for six hours and comparing them with levels after administering various controls. Teuhetenone A was not cytotoxic at the tested concentrations, and did not show inhibitory activity in the glucosidase test, and the in vivo assays showed a gradual reduction in glucose levels in normoglycemic and diabetic mice. Considering these results, we suggest that teuhetenone A has potential as an antidiabetic compound, which could be further submitted to preclinical assays. Full article

(This article belongs to the Section Natural Products Chemistry)

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48 pages, 3051 KiB

Open AccessFeature PaperReview

Cellular Models and In Vitro Assays for the Screening of modulators of P-gp, MRP1 and BCRP

by Mariline Gameiro, Renata Silva^*

, Carolina Rocha-Pereira^*, Helena Carmo, Félix Carvalho

, Maria De Lourdes Bastos and Fernando Remião

UCIBIO/REQUIMTE, Laboratório de Toxicologia, Departamento de Ciências Biológicas, Faculdade de Farmácia, Universidade do Porto, Rua Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal

Molecules 2017, 22(4), 600; https://doi.org/10.3390/molecules22040600 - 8 Apr 2017

Cited by 100 | Viewed by 13752

Abstract

Adenosine triphosphate (ATP)-binding cassette (ABC) transporters are highly expressed in tumor cells, as well as in organs involved in absorption and secretion processes, mediating the ATP-dependent efflux of compounds, both endogenous substances and xenobiotics, including drugs. Their expression and activity levels are modulated [...] Read more.

Adenosine triphosphate (ATP)-binding cassette (ABC) transporters are highly expressed in tumor cells, as well as in organs involved in absorption and secretion processes, mediating the ATP-dependent efflux of compounds, both endogenous substances and xenobiotics, including drugs. Their expression and activity levels are modulated by the presence of inhibitors, inducers and/or activators. In vitro, ex vivo and in vivo studies with both known and newly synthesized P-glycoprotein (P-gp) inducers and/or activators have shown the usefulness of these transport mechanisms in reducing the systemic exposure and specific tissue access of potentially harmful compounds. This article focuses on the main ABC transporters involved in multidrug resistance [P-gp, multidrug resistance-associated protein 1 (MRP1) and breast cancer resistance protein (BCRP)] expressed in tissues of toxicological relevance, such as the blood-brain barrier, cardiovascular system, liver, kidney and intestine. Moreover, it provides a review of the available cellular models, in vitro and ex vivo assays for the screening and selection of safe and specific inducers and activators of these membrane transporters. The available cellular models and in vitro assays have been proposed as high throughput and low-cost alternatives to excessive animal testing, allowing the evaluation of a large number of compounds. Full article

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

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5 pages, 176 KiB

Open AccessEditorial

Special Issue: Enzyme Immobilization 2016

by Roberto Fernandez-Lafuente

Departamento de Biocatálisis, Instituto de Catálisis-CSIC, C/Marie Curie 2, Campus UAM-CSIC, Cantoblanco, 28049 Madrid, Spain

Molecules 2017, 22(4), 601; https://doi.org/10.3390/molecules22040601 - 8 Apr 2017

Cited by 10 | Viewed by 5126

Abstract

The use of enzymes as industrial biocatalysts is currently a solution for many problems of modern organic chemistry, which tries to carry out the most complex reactions under the rules of green chemistry [1].[...] Full article

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

10 pages, 1058 KiB

Open AccessArticle

Screening, Purification and Characterization of Anionic Antimicrobial Proteins from Foeniculum Vulgare

by Raid Al Akeel¹, Ayesha Mateen¹, Rabbani Syed^1,*, Abdullah A. Alyousef¹ and Mohammed Rafi Shaik^2,*

¹ Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud University, Riyadh 11451, Saudi Arabia

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

Molecules 2017, 22(4), 602; https://doi.org/10.3390/molecules22040602 - 8 Apr 2017

Cited by 13 | Viewed by 6565

Abstract

Foeniculum vulgare Mill., commonly called fennel, is a medicinal plant belonging to the Umbelliferae (Apiaceae) family, and is used in traditional medicine. Antibacterial peptides were isolated using sodium phosphate citrate buffer and, for extraction, cetyltrimethyl ammonium bromide (CTAB) buffer with pH 6, have [...] Read more.

Foeniculum vulgare Mill., commonly called fennel, is a medicinal plant belonging to the Umbelliferae (Apiaceae) family, and is used in traditional medicine. Antibacterial peptides were isolated using sodium phosphate citrate buffer and, for extraction, cetyltrimethyl ammonium bromide (CTAB) buffer with pH 6, have been employed and antimicrobial activity tested against four reference strains. The extracted protein was subjected to 3 kDa dialysis and separation was carried out by DEAE-ion exchange chromatography and further proteins were identified by 2D gel electrophoresis. The results of Foeniculum vulgare elutes obtained from DEAE-ion exchange chromatography were tested for antibacterial activity. Elute 3 shows the highest antibacterial activity on Pseudomonas aeruginosa with a diameter of a zone of inhibition of 16 mm and IC₅₀ value 25.02 (mcg/mL). Based on the findings of the wide usage in treatment of various ailments and day-to-day life, Foeniculum vulgare seeds were used in the present research and have shown promising antibacterial effects, which requires further proteomic research to authenticate the role of the anticipated proteins. Full article

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

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12 pages, 3225 KiB

Open AccessFeature PaperArticle

Gold Nanoparticles Deposited on Surface Modified Carbon Xerogels as Reusable Catalysts for Cyclohexane C-H Activation in the Presence of CO and Water

by Ana Paula da Costa Ribeiro¹

, Luísa Margarida Dias Ribeiro de Sousa Martins^1,2,*

, Sónia Alexandra Correia Carabineiro^3,*

, José Luís Figueiredo³

and Armando José Latourrette Pombeiro¹

¹ Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal

² Chemical Engineering Department, Instituto Superior de Engenharia de Lisboa, Instituto Politécnico de Lisboa, R. Conselheiro Emídio Navarro, 1959-007 Lisboa, Portugal

³ Laboratório de Catálise e Materiais, Laboratório Associado LSRE-LCM, Faculdade de Engenharia, Universidade do Porto, Rua Dr. Roberto Frias, 4200-465 Porto, Portugal

Molecules 2017, 22(4), 603; https://doi.org/10.3390/molecules22040603 - 9 Apr 2017

Cited by 21 | Viewed by 5655

Abstract

The use of gold as a promotor of alkane hydrocarboxylation is reported for the first time. Cyclohexane hydrocarboxylation to cyclohexanecarboxylic acid (up to 55% yield) with CO, water, and peroxodisulfate in a water/acetonitrile medium at circa 50 °C has been achieved in the [...] Read more.

The use of gold as a promotor of alkane hydrocarboxylation is reported for the first time. Cyclohexane hydrocarboxylation to cyclohexanecarboxylic acid (up to 55% yield) with CO, water, and peroxodisulfate in a water/acetonitrile medium at circa 50 °C has been achieved in the presence of gold nanoparticles deposited by a colloidal method on a carbon xerogel in its original form (CX), after oxidation with HNO₃ (-ox), or after oxidation with HNO₃ and subsequent treatment with NaOH (-ox-Na). Au/CX-ox-Na behaves as re-usable catalyst maintaining its initial activity and selectivity for at least seven consecutive cycles. Green metric values of atom economy or carbon efficiency also attest to the improvement brought by this novel catalytic system to the hydrocarboxylation of cyclohexane. Full article

(This article belongs to the Special Issue Reactions of Hydrocarbons and other C‒H Compounds)

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13 pages, 16915 KiB

Open AccessArticle

Structural Characterization and Antifungal Studies of Zinc-Doped Hydroxyapatite Coatings

by Simona Liliana Iconaru¹

, Alina Mihaela Prodan^2,3, Nicolas Buton⁴ and Daniela Predoi^1,*

¹ National Institute of Materials Physics, Atomistilor Street, No. 105 bis, P.O. Box MG 07, 077125 Magurele, Romania

² Emergency Hospital Floreasca Bucharest, 8 Calea Floresca, Sector 1, 014461 Bucharest, Romania

³ Surgery Department, Carol Davila University of Medicine and Pharmacy, 8 Eroii Sanitari, Sector 5, 050474 Bucharest, Romania

⁴ HORIBA Jobin Yvon S.A.S., 6-18, rue du Canal, 91165 Longjumeau CEDEX, France

Molecules 2017, 22(4), 604; https://doi.org/10.3390/molecules22040604 - 9 Apr 2017

Cited by 60 | Viewed by 6537

Abstract

The present study is focused on the synthesis, characterization and antifungal evaluation of zinc-doped hydroxyapatite (Zn:HAp) coatings. The Zn:HAp coatings were deposited on a pure Si (Zn:HAp_Si) and Ti (Zn:HAp_Ti) substrate by a sol-gel dip coating method using a zinc-doped hydroxyapatite nanogel. The [...] Read more.

The present study is focused on the synthesis, characterization and antifungal evaluation of zinc-doped hydroxyapatite (Zn:HAp) coatings. The Zn:HAp coatings were deposited on a pure Si (Zn:HAp_Si) and Ti (Zn:HAp_Ti) substrate by a sol-gel dip coating method using a zinc-doped hydroxyapatite nanogel. The nature of the crystal phase was determined by X-ray diffraction (XRD). The crystalline phase of the prepared Zn:HAp composite was assigned to hexagonal hydroxyapatite in the P6_3/m space group. The colloidal properties of the resulting Zn:HAp (x_Zn = 0.1) nanogel were analyzed by Dynamic Light Scattering (DLS) and zeta potential. Scanning Electron Microscopy (SEM) was used to investigate the morphology of the zinc-doped hydroxyapatite (Zn:HAp) nanogel composite and Zn:HAp coatings. The elements Ca, P, O and Zn were found in the Zn:HAp composite. According to the EDX results, the degree of Zn substitution in the structure of Zn:HAp composite was 1.67 wt%. Moreover, the antifungal activity of Zn:HAp_Si and Zn:HAp_Ti against Candida albicans (C. albicans) was evaluated. A decrease in the number of surviving cells was not observed under dark conditions, whereas under daylight and UV light illumination a major decrease in the number of surviving cells was observed. Full article

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

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14 pages, 2289 KiB

Open AccessArticle

An Efficient One-Pot Protocol for the Synthesis of Substituted 3,4-Dihydropyrimidin-2(1H)-ones Using Metallophthalocyanines (MPcs) as Potent Heterogeneous Catalysts: Synthesis, Characterization, Aggregation and Antimicrobial Activity

by Naceur Hamdi^1,2,*

, Rawdha Medyouni¹, Hallouma Bilel¹, Lamjed Mansour³

and Antonio Romerosa⁴

¹ Research Laboratory of Environmental Sciences and Technologies (LR16ES09), Higher Institute of Environmental Sciences and Technology, University of Carthage, Hammam-Lif 2050, Tunisia

² Chemistry Department, College of Science and Arts, Qassim University, Al-Rass 51921, Saudi Arabia

³ Zoology Department, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia

⁴ Área de Química Inorgánica-CIESOL, Universidad de Almería, 04120, Almería, Spain

Molecules 2017, 22(4), 605; https://doi.org/10.3390/molecules22040605 - 9 Apr 2017

Cited by 10 | Viewed by 6034

Abstract

In this study, novel phthalonitrile 3 and their corresponding metal-free 4 and metallophthalocyanine derivatives 5–7 bearing 2-isopropenyl-4-methoxy-1-methylbenzene groups were synthesized and characterized. 3,4-Dihydropyrimidinones have been synthesized by a modified Biginelli-type reaction with various metallophthalocyanines 5–7 as catalysts. Compared to [...] Read more.

In this study, novel phthalonitrile 3 and their corresponding metal-free 4 and metallophthalocyanine derivatives 5–7 bearing 2-isopropenyl-4-methoxy-1-methylbenzene groups were synthesized and characterized. 3,4-Dihydropyrimidinones have been synthesized by a modified Biginelli-type reaction with various metallophthalocyanines 5–7 as catalysts. Compared to the classical Biginielli reaction, the new method has the advantages of good yield and short reaction time. Among the various metallophthalocyanines studied, cobalt (II)-phthalocyanine was found to be most active for this transformation. The newly prepared compounds were characterized using elemental analyses, MS, IR, ¹H/¹³C-NMR and UV-Vis spectroscopy. In addition; the 3,4-dihydropyrimidinones (DHPMs) 8–12 were investigated for antimicrobial activities and revealed good activity. The minimum inhibitory concentration (MIC) was determined by the microdilution technique in Mueller-Hinton broth. The MICs were recorded after 24 hours of incubation at 37 °C. These results are promising, showing these compounds are biologically active. Full article

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

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15 pages, 1653 KiB

Open AccessArticle

Thermo-Oxidative Stability Evaluation of Bullfrog (Rana catesbeiana Shaw) Oil

by Renata Rutckeviski¹, Francisco H. Xavier-Júnior¹, Andreza R.V. Morais¹, Éverton N. Alencar¹

, Lucas Amaral-Machado^1,2, Julieta Genre¹, Amanda D. Gondim³

and Eryvaldo S.T. Egito^1,2,*

¹ Disperse Systems Laboratory (LaSiD), Pharmacy Department, Federal University of Rio Grande do Norte (UFRN), Av. General Gustavo de Cordeiro-SN-Petropolis, Natal 59010-180, Brazil

² Graduate Program in Health Sciences, LaSiD, UFRN, Av. General Gustavo de Cordeiro-SN-Petrópolis, Natal 59010-180, Brazil

³ Chemistry Department, Federal University of Rio Grande do Norte, Av. Senador Salgado Filho-3000-Lagoa Nova, Natal 59072-970, Brazil

Molecules 2017, 22(4), 606; https://doi.org/10.3390/molecules22040606 - 10 Apr 2017

Cited by 16 | Viewed by 6322

Abstract

Bullfrog oil (BO), a natural product obtained from recycling of adipose tissue from the amphibian Rana catesbeiana Shaw, has been recently evaluated as a therapeutic activity ingredient. This work aimed to evaluate the long-term and accelerated thermal oxidative stabilities of this product, which [...] Read more.

Bullfrog oil (BO), a natural product obtained from recycling of adipose tissue from the amphibian Rana catesbeiana Shaw, has been recently evaluated as a therapeutic activity ingredient. This work aimed to evaluate the long-term and accelerated thermal oxidative stabilities of this product, which is a promising raw material for emulsion technology development. BO was extracted from amphibian adipose tissue at 70 °C with a yield of 60% ± 0.9%. Its main fatty acid compounds were oleic (30.0%) and eicosapentaenoic (17.6%) acids. Using titration techniques, BO showed peroxide, acid, iodine and saponification indices of 1.92 mEq·O₂/kg, 2.95 mg·KOH/g oil, 104.2 g I₂/100 g oil and 171.2 mg·KOH/g oil, respectively. In order to improve the accelerated oxidative stability of BO, synthetic antioxidants butylhydroxytoluene (BHT) and buthylhydroxyanisole (BHA) were used. The addition of BHT increased the oxidation induction time compared to the pure oil, or the oil containing BHA. From the results, the best oil-antioxidant mixture and concentration to increase the oxidative stability and allow the oil to be a stable raw material for formulation purposes was derived. Full article

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

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21 pages, 11964 KiB

Open AccessArticle

Computational Identification of Antibody Epitopes on the Dengue Virus NS1 Protein

by Martina L. Jones^1,2

, Fiona S. Legge³, Kebaneilwe Lebani¹, Stephen M. Mahler^1,2, Paul R. Young^2,4,5, Daniel Watterson^4,5, Herbert R. Treutlein^3,6,* and Jun Zeng^3,6,*

¹ Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, St. Lucia, QLD 4072, Australia

² ARC Training Centre for Biopharmaceutical Innovation, The University of Queensland, St. Lucia, QLD 4072, Australia

³ Computist Bio-Nanotech, 1 Dalmore Drive, Scoresby, VIC 3179, Australia

⁴ School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, QLD 4072, Australia

⁵ Australian Infectious Diseases Research Centre, The University of Queensland, St. Lucia, QLD 4072, Australia

⁶ School of Medical Sciences, RMIT University, P.O. Box 71, Bundoora, VIC 3083, Australia

Molecules 2017, 22(4), 607; https://doi.org/10.3390/molecules22040607 - 10 Apr 2017

Cited by 11 | Viewed by 6587

Abstract

We have previously described a method to predict antigenic epitopes on proteins recognized by specific antibodies. Here we have applied this method to identify epitopes on the NS1 proteins of the four Dengue virus serotypes (DENV1–4) that are bound by a small panel [...] Read more.

We have previously described a method to predict antigenic epitopes on proteins recognized by specific antibodies. Here we have applied this method to identify epitopes on the NS1 proteins of the four Dengue virus serotypes (DENV1–4) that are bound by a small panel of monoclonal antibodies 1H7.4, 1G5.3 and Gus2. Several epitope regions were predicted for these antibodies and these were found to reflect the experimentally observed reactivities. The known binding epitopes on DENV2 for the antibodies 1H7.4 and 1G5.3 were identified, revealing the reasons for the serotype specificity of 1H7.4 and 1G5.3, and the non-selectivity of Gus2. As DENV NS1 is critical for virus replication and a key vaccine candidate, epitope prediction will be valuable in designing appropriate vaccine control strategies. The ability to predict potential epitopes by computational methods significantly reduces the amount of experimental work required to screen peptide libraries for epitope mapping. Full article

(This article belongs to the Special Issue Biomolecular Simulations)

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15 pages, 1386 KiB

Open AccessArticle

Structure-Activity and Lipophilicity Relationships of Selected Antibacterial Natural Flavones and Flavanones of Chilean Flora

by Javier Echeverría^*

, Julia Opazo, Leonora Mendoza, Alejandro Urzúa^*

and Marcela Wilkens^*

Facultad de Química y Biología, Universidad de Santiago de Chile, Santiago 9170022, Chile

Molecules 2017, 22(4), 608; https://doi.org/10.3390/molecules22040608 - 10 Apr 2017

Cited by 121 | Viewed by 8544

Abstract

In this study, we tested eight naturally-occurring flavonoids—three flavanones and five flavones—for their possible antibacterial properties against four Gram-positive and four Gram-negative bacteria. Flavonoids are known for their antimicrobial properties, and due their structural diversity; these plant-derived compounds are a good model to [...] Read more.

In this study, we tested eight naturally-occurring flavonoids—three flavanones and five flavones—for their possible antibacterial properties against four Gram-positive and four Gram-negative bacteria. Flavonoids are known for their antimicrobial properties, and due their structural diversity; these plant-derived compounds are a good model to study potential novel antibacterial mechanisms. The lipophilicity and the interaction of antibacterial compounds with the cell membrane define the success or failure to access its target. Therefore, through the determination of partition coefficients in a non-polar/aqueous phase, lipophilicity estimation and the quantification of the antibacterial activity of different flavonoids, flavanones, and flavones, a relationship between these parameters was assessed. Active flavonoids presented diffusion coefficients between 9.4 × 10⁻¹⁰ and 12.3 × 10⁻¹⁰ m²/s and lipophilicity range between 2.0 to 3.3. Active flavonoids against Gram-negative bacteria showed a narrower range of lipophilicity values, compared to active flavonoids against Gram-positive bacteria, which showed a wide range of lipophilicity and cell lysis. Galangin was the most active flavonoid, whose structural features are the presence of two hydroxyl groups located strategically on ring A and the absence of polar groups on ring B. Methylation of one hydroxyl group decreases the activity in 3-O-methylgalangin, and methylation of both hydroxyl groups caused inactivation, as shown for 3,7-O-dimethylgalangin. In conclusion, the amphipathic features of flavonoids play a crucial role in the antibacterial activity. In these compounds, hydrophilic and hydrophobic moieties must be present and could be predicted by lipophilicity analysis. Full article

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

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16 pages, 2075 KiB

Open AccessArticle

Anti-Inflammatory and Antioxidant Properties of Casein Hydrolysate Produced Using High Hydrostatic Pressure Combined with Proteolytic Enzymes

by Fatemeh Bamdad¹, Seulki Hazel Shin¹, Joo-Won Suh^2,*, Chamila Nimalaratne¹ and Hoon Sunwoo^1,*

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

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

Molecules 2017, 22(4), 609; https://doi.org/10.3390/molecules22040609 - 10 Apr 2017

Cited by 93 | Viewed by 9343

Abstract

Casein-derived peptides are shown to possess radical scavenging and metal chelating properties. The objective of this study was to evaluate novel anti-inflammatory properties of casein hydrolysates (CH) produced by an eco-friendly process that combines high hydrostatic pressure with enzymatic hydrolysis (HHP-EH). Casein was [...] Read more.

Casein-derived peptides are shown to possess radical scavenging and metal chelating properties. The objective of this study was to evaluate novel anti-inflammatory properties of casein hydrolysates (CH) produced by an eco-friendly process that combines high hydrostatic pressure with enzymatic hydrolysis (HHP-EH). Casein was hydrolysed by different proteases, including flavourzyme (Fla), savinase (Sav), thermolysin (Ther), trypsin (Try), and elastase (Ela) at 0.1, 50, 100, and 200 MPa pressure levels under various enzyme-to-substrate ratios and incubation times. Casein hydrolysates were evaluated for the degree of hydrolysis (DH), molecular weight distribution patterns, and anti-inflammatory properties in chemical and cellular models. Hydrolysates produced using HHP-EH exhibited higher DH values and proportions of smaller peptides compared to atmospheric pressure-enzymatic hydrolysis (AP-EH). Among five enzymes, Fla-digested HHP-EH-CH (HHP-Fla-CH) showed significantly higher antioxidant properties than AP-Fla-CH. The anti-inflammatory properties of HHP-Fla-CH were also observed by significantly reduced nitric oxide and by the suppression of the synthesis of pro-inflammatory cytokines in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells. Liquid chromatography with tandem mass spectrometry (LC-MS/MS) revealed that 59% of the amino acids of the peptides in HHP-Fla-CH were composed of proline, valine, and leucine, indicating the potential anti-inflammatory properties. In conclusion, the HHP-EH method provides a promising technology to produce bioactive peptides from casein in an eco-friendly process. Full article

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

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22 pages, 708 KiB

Open AccessReview

The Pharmacological Effects of Lutein and Zeaxanthin on Visual Disorders and Cognition Diseases

by Yu-Ping Jia^1,†

, Lei Sun^1,†, He-Shui Yu¹, Li-Peng Liang¹, Wei Li¹, Hui Ding², Xin-Bo Song^1,2 and Li-Juan Zhang^1,*

¹ College of Pharmaceutical Engineering of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China

² Tianjin Zhongyi Pharmaceutical Co., Ltd., Tianjin 300193, China

^† These authors contribute equally to this work.

Molecules 2017, 22(4), 610; https://doi.org/10.3390/molecules22040610 - 20 Apr 2017

Cited by 105 | Viewed by 25993

Abstract

Lutein (L) and zeaxanthin (Z) are dietary carotenoids derived from dark green leafy vegetables, orange and yellow fruits that form the macular pigment of the human eyes. It was hypothesized that they protect against visual disorders and cognition diseases, such as age-related macular [...] Read more.

Lutein (L) and zeaxanthin (Z) are dietary carotenoids derived from dark green leafy vegetables, orange and yellow fruits that form the macular pigment of the human eyes. It was hypothesized that they protect against visual disorders and cognition diseases, such as age-related macular degeneration (AMD), age-related cataract (ARC), cognition diseases, ischemic/hypoxia induced retinopathy, light damage of the retina, retinitis pigmentosa, retinal detachment, uveitis and diabetic retinopathy. The mechanism by which they are involved in the prevention of eye diseases may be due their physical blue light filtration properties and local antioxidant activity. In addition to their protective roles against light-induced oxidative damage, there are increasing evidences that L and Z may also improve normal ocular function by enhancing contrast sensitivity and by reducing glare disability. Surveys about L and Z supplementation have indicated that moderate intakes of L and Z are associated with decreased AMD risk and less visual impairment. Furthermore, this review discusses the appropriate consumption quantities, the consumption safety of L, side effects and future research directions. Full article

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10 pages, 1693 KiB

Open AccessArticle

Structural Analysis and Immuno-Stimulating Activity of an Acidic Polysaccharide from the Stems of Dendrobium nobile Lindl.

by Jun-Hui Wang^*, Shu-Rong Zuo and Jian-Ping Luo^*

School of Food Science and Engineering, Hefei University of Technology, Hefei 230009, China

Molecules 2017, 22(4), 611; https://doi.org/10.3390/molecules22040611 - 10 Apr 2017

Cited by 34 | Viewed by 5500

Abstract

Dendrobium nobile Lindl., an epiphytic herb distributed in the Southeast Asia, is used as a tonic and antipyretic herbal medicine in China. In this study, a water-soluble acidic heteropolysaccharide, DNP-W4, containing mannose, glucose, galactose, xylose, rhamnose, and galacturonic acid, in the molar ratios [...] Read more.

Dendrobium nobile Lindl., an epiphytic herb distributed in the Southeast Asia, is used as a tonic and antipyretic herbal medicine in China. In this study, a water-soluble acidic heteropolysaccharide, DNP-W4, containing mannose, glucose, galactose, xylose, rhamnose, and galacturonic acid, in the molar ratios of 1.0:4.9:2.5:0.5:1.0:0.9, was obtained from the stems of Dendrobium nobile Lindl. Using methylation analysis, partial acid hydrolysis, pectolyase treatment, NMR, and ESI-MS, the structure of DNP-W4 was elucidated. The obtained data indicated that DNP-W4 was a complex heteropolysaccharide and possessed a backbone composed of (1→4)-linked β-d-Glcp, (1→6)-linked β-d-Glcp, and (1→6)-linked β-d-Galp, with substitutes at O-4/6 of Glcp residues and O-3 of Galp. The branches of DNP-W4 were composed of terminal Manp, (1→6)-linked β-d-Manp, (1→3)-linked β-d-Glcp, β-d-Glcp, β-d-Galp, (1→4)-linked α-d-GalAp, (1→2)-linked α-L-Rhap, and Xylp. DNP-W4 had little immunological activities, but its derivatives had immuno-stimulating activities to some extent. Full article

(This article belongs to the Special Issue Natural Polysaccharides)

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11 pages, 1644 KiB

Open AccessArticle

c-Jun Contributes to Transcriptional Control of GNA12 Expression in Prostate Cancer Cells

by Udhaya Kumari Udayappan¹ and Patrick J. Casey^1,2,*

¹ Program in Cancer and Stem Cell Biology, Duke-NUS Medical School, 8 College Road, Singapore 169857, Singapore

² Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA

Molecules 2017, 22(4), 612; https://doi.org/10.3390/molecules22040612 - 10 Apr 2017

Cited by 15 | Viewed by 5824

Abstract

Abstract: GNA12 is the α subunit of a heterotrimeric G protein that possesses oncogenic potential. Activated GNA12 also promotes prostate and breast cancer cell invasion in vitro and in vivo, and its expression is up-regulated in many tumors, particularly metastatic tissues. In [...] Read more.

Abstract: GNA12 is the α subunit of a heterotrimeric G protein that possesses oncogenic potential. Activated GNA12 also promotes prostate and breast cancer cell invasion in vitro and in vivo, and its expression is up-regulated in many tumors, particularly metastatic tissues. In this study, we explored the control of expression of GNA12 in prostate cancer cells. Initial studies on LnCAP (low metastatic potential, containing low levels of GNA12) and PC3 (high metastatic potential, containing high GNA12 levels) cells revealed that GNA12 mRNA levels correlated with protein levels, suggesting control at the transcriptional level. To identify potential factors controlling GNA12 transcription, we cloned the upstream 5′ regulatory region of the human GNA12 gene and examined its activity using reporter assays. Deletion analysis revealed the highest level of promoter activity in a 784 bp region, and subsequent in silico analysis indicated the presence of transcription factor binding sites for C/EBP (CCAAT/enhancer binding protein), CREB1 (cAMP-response-element-binding protein 1), and c-Jun in this minimal element for transcriptional control. A small interfering RNA (siRNA) knockdown approach revealed that silencing of c-Jun expression significantly reduced GNA12 5′ regulatory region reporter activity. In addition, chromatin immunoprecipitation assays confirmed that c-Jun binds to the GNA12 5′ regulatory region in PC3 cells. Silencing of c-Jun expression reduced mRNA and protein levels of GNA12, but not the closely-related GNA13, in prostate cancer cells. Understanding the mechanisms by which GNA12 expression is controlled may aid in the development of therapies that target key elements responsible for GNA12-mediated tumor progression. Full article

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

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13 pages, 1910 KiB

Open AccessArticle

Synthesis of Pyrrolo[1,2-a]pyrimidine Enantiomers via Domino Ring-Closure followed by Retro Diels-Alder Protocol

by Beáta Fekete¹, Márta Palkó¹, Matti Haukka² and Ferenc Fülöp^1,3,*

¹ Institute of Pharmaceutical Chemistry, University of Szeged, Eötvös utca 6, Szeged H-6720, Hungary

² Department of Chemistry, University of Jyväskylä, FIN-40014 Turku, Finland

³ MTA-SZTE Stereochemistry Research Group, Hungarian Academy of Sciences, Eötvös utca 6, Szeged H-6720, Hungary

Molecules 2017, 22(4), 613; https://doi.org/10.3390/molecules22040613 - 13 Apr 2017

Cited by 10 | Viewed by 5611

Abstract

From 2-aminonorbornene hydroxamic acids, a simple and efficient method for the preparation of pyrrolo[1,2-a]pyrimidine enantiomers is reported. The synthesis is based on domino ring-closure followed by microwave-induced retro Diels-Alder (RDA) protocols, where the chirality of the desired products is transferred from [...] Read more.

From 2-aminonorbornene hydroxamic acids, a simple and efficient method for the preparation of pyrrolo[1,2-a]pyrimidine enantiomers is reported. The synthesis is based on domino ring-closure followed by microwave-induced retro Diels-Alder (RDA) protocols, where the chirality of the desired products is transferred from norbornene derivatives. The stereochemistry of the synthesized compounds was proven by X-ray crystallography. The absolute configuration of the product is determined by the configuration of the starting amino hydroxamic acid. Full article

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

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11 pages, 5185 KiB

Open AccessArticle

Bergamot Essential Oil Attenuates Anxiety-Like Behaviour in Rats

by Laura Rombolà¹

, Laura Tridico¹

, Damiana Scuteri¹, Tsukasa Sakurada², Shinobu Sakurada³, Hirokazu Mizoguchi³, Pinarosa Avato⁴, Maria Tiziana Corasaniti⁵

, Giacinto Bagetta¹

and Luigi Antonio Morrone^1,*

¹ Department of Pharmacy, Health and Nutritional Sciences, Section of Preclinical and Translational Pharmacology, University of Calabria, 87036 Rende, Italy

² First Department of Pharmacology, Daiichi College of Pharmaceutical Sciences, 815-8511 Fukuoka, Japan

³ Department of Physiology and Anatomy, Tohoku Pharmaceutical University, 981-8558 Sendai, Japan

⁴ Department of Pharmacy-Drug Sciences, University of Bari Aldo Moro, IT-70125 Bari, Italy

⁵ Department of Health Sciences, University “Magna Graecia” of Catanzaro, 88100 Catanzaro, Italy

Molecules 2017, 22(4), 614; https://doi.org/10.3390/molecules22040614 - 11 Apr 2017

Cited by 71 | Viewed by 17092

Abstract

Preclinical studies have recently highlighted that bergamot essential oil (BEO) is endowed with remarkable neurobiolological effects. BEO can affect synaptic transmission, modulate electroencephalographic activity and it showed neuroprotective and analgesic properties. The phytocomplex, along with other essential oils, is also widely used in [...] Read more.

Preclinical studies have recently highlighted that bergamot essential oil (BEO) is endowed with remarkable neurobiolological effects. BEO can affect synaptic transmission, modulate electroencephalographic activity and it showed neuroprotective and analgesic properties. The phytocomplex, along with other essential oils, is also widely used in aromatherapy to minimize symptoms of stress-induced anxiety and mild mood disorders. However, only limited preclinical evidences are actually available. This study examined the anxiolytic/sedative-like effects of BEO using an open field task (OFT), an elevated plus-maze task (EPM), and a forced swimming task (FST) in rats. This study further compared behavioural effects of BEO to those of the benzodiazepine diazepam. Analysis of data suggests that BEO induces anxiolytic-like/relaxant effects in animal behavioural tasks not superimposable to those of the DZP. The present observations provide further insight to the pharmacological profile of BEO and support its rational use in aromatherapy. Full article

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

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28 pages, 6174 KiB

Open AccessReview

Recent Advances in Cyanamide Chemistry: Synthesis and Applications

by M. R. Ranga Prabhath, Luke Williams, Shreesha V. Bhat and Pallavi Sharma^*

School of Chemistry, Joseph Banks Laboratories, University of Lincoln, Lincoln LN6 7DL, UK

Molecules 2017, 22(4), 615; https://doi.org/10.3390/molecules22040615 - 12 Apr 2017

Cited by 62 | Viewed by 14915

Abstract

The application of alkyl and aryl substituted cyanamides in synthetic chemistry has diversified multi-fold in recent years. In this review, we discuss recent advances (since 2012) in the chemistry of cyanamides and detail their application in cycloaddition chemistry, aminocyanation reactions, as well as [...] Read more.

The application of alkyl and aryl substituted cyanamides in synthetic chemistry has diversified multi-fold in recent years. In this review, we discuss recent advances (since 2012) in the chemistry of cyanamides and detail their application in cycloaddition chemistry, aminocyanation reactions, as well as electrophilic cyanide-transfer agents and their unique radical and coordination chemistry. Full article

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

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11 pages, 4884 KiB

Open AccessArticle

Anti-Inflammatory, Antioxidant and Crystallographic Studies of N-Palmitoyl-ethanol Amine (PEA) Derivatives

by Carmela Saturnino^1,†, Ada Popolo^2,†

, Anna Ramunno², Simona Adesso², Michela Pecoraro², Maria Rosaria Plutino^3,*, Silvia Rizzato⁴, Alberto Albinati⁴, Stefania Marzocco^2,*

, Marina Sala², Domenico Iacopetta⁵

and Maria Stefania Sinicropi⁵

¹ Department of Science, University of Basilicata, Viale dell′Ateneo Lucano 10, Potenza 85100, Italy

² Department of Pharmacy, University of Salerno, Via Giovanni Paolo II n 132, Fisciano (SA) 84084, Italy

³ Institute for the Study of Nanostructured Materials, ISMN-CNR, Palermo, c/o Department of ChiBioFarAm, University of Messina, Vill. S. Agata, Viale F. Stagno d’Alcontres 31, Messina 98166, Italy

⁴ Department of Chemistry, University of Milano, Via Golgi 19, Milano 20133, Italy

⁵ Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Via Pietro Bucci, Arcavacata di Rende (CS) 87036, Italy

^† These authors contributed equally to the paper.

Molecules 2017, 22(4), 616; https://doi.org/10.3390/molecules22040616 - 11 Apr 2017

Cited by 17 | Viewed by 5810

Abstract

N-Palmitoyl-ethanolamine (PEA) is an anti-inflammatory component of egg yolk that is usually employed for the prevention of respiratory apparatus virus infection and then frequently used for its efficient anti-inflammatory and analgesic effects in experimental models of visceral, neuropathic, and inflammatory diseases. Nevertheless, [...] Read more.

N-Palmitoyl-ethanolamine (PEA) is an anti-inflammatory component of egg yolk that is usually employed for the prevention of respiratory apparatus virus infection and then frequently used for its efficient anti-inflammatory and analgesic effects in experimental models of visceral, neuropathic, and inflammatory diseases. Nevertheless, data of its use in animal or human therapy are still scarce and further studies are needed. Herein, we report the biological evaluation of a small library of N-palmitoyl-ethanolamine analogues or derivatives, characterized by a protected acid function (either as palmitoyl amides or hexadecyl esters), useful to decrease their hydrolysis rate in vitro and prolong their biological activity. Two of these compounds—namely phenyl-carbamic acid hexadecyl ester (4) and 2-methyl-pentadecanoic acid (4-nitro-phenyl)-amide (5)—have shown good anti-inflammatory and antioxidant properties, without affecting the viability of J774A.1 macrophages. Finally, crystals suitable for X-ray analysis of compound 4 have been obtained, and its solved crystal structure is here reported. Our outcomes may be helpful for a rational drug design based on new PEA analogues/derivatives with improved biological properties. Full article

(This article belongs to the Section Medicinal Chemistry)

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24 pages, 724 KiB

Open AccessReview

Functional Assays in the Diagnosis of Heparin-Induced Thrombocytopenia: A Review

by Valentine Minet^1,*, Jean-Michel Dogné¹ and François Mullier²

¹ Department of Pharmacy, Namur Thrombosis and Hemostasis Center (NTHC), Namur Research Institute for LIfe Sciences (NARILIS), University of Namur, Namur 5000, Belgium

² CHU UCL Namur, Namur Thrombosis and Hemostasis Center (NTHC), Hematology Laboratory, Université catholique de Louvain, Yvoir 5530, Belgium

Molecules 2017, 22(4), 617; https://doi.org/10.3390/molecules22040617 - 11 Apr 2017

Cited by 75 | Viewed by 10536

Abstract

A rapid and accurate diagnosis in patients with suspected heparin-induced thrombocytopenia (HIT) is essential for patient management but remains challenging. Current HIT diagnosis ideally relies on a combination of clinical information, immunoassay and functional assay results. Platelet activation assays or functional assays detect [...] Read more.

A rapid and accurate diagnosis in patients with suspected heparin-induced thrombocytopenia (HIT) is essential for patient management but remains challenging. Current HIT diagnosis ideally relies on a combination of clinical information, immunoassay and functional assay results. Platelet activation assays or functional assays detect HIT antibodies that are more clinically significant. Several functional assays have been developed and evaluated in the literature. They differ in the activation endpoint studied; the technique or technology used; the platelet donor selection; the platelet suspension (washed platelets, platelet rich plasma or whole blood); the patient sample (serum or plasma); and the heparin used (type and concentrations). Inconsistencies in controls performed and associated results interpretation are common. Thresholds and performances are determined differently among papers. Functional assays suffer from interlaboratory variability. This lack of standardization limits the evaluation and the accessibility of functional assays in laboratories. In the present article, we review all the current activation endpoints, techniques and methodologies of functional assays developed for HIT diagnosis. 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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7 pages, 334 KiB

Open AccessArticle

Effects of Schiff Base Formation and Aldol Condensation on the Determination of Aldehydes in Rice Wine Using GC-MS

by Ji Hye Han, Sang Mi Lee and Young-Suk Kim^*

Department of Food Science and Engineering, Ewha Womans University, Seoul 120-750, Korea

Molecules 2017, 22(4), 618; https://doi.org/10.3390/molecules22040618 - 11 Apr 2017

Cited by 5 | Viewed by 9860

Abstract

The Schiff base reaction and aldol condensation that occur during sample preparation can lead to the reduction of aldehyde content in the analysis of traditional Korean rice wine, makgeolli. The contents of aldehydes were decreased, whereas those of hydroxy carbonyl compounds were [...] Read more.

The Schiff base reaction and aldol condensation that occur during sample preparation can lead to the reduction of aldehyde content in the analysis of traditional Korean rice wine, makgeolli. The contents of aldehydes were decreased, whereas those of hydroxy carbonyl compounds were increased by increasing the pH. In the presence of added amino acids, the levels of aldehydes in makgeolli were reduced as the amount of the amino acid alanine increased. Also, the contents of hydroxyl carbonyl compounds were reduced by alanine addition as compared to the control. Therefore, the determination of aldehydes can be affected by pH and the amount of amino acids, which can vary during fermentation and storage of alcoholic beverages because pH and amino acids affect Schiff base formation and aldol condensation. Full article

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15 pages, 3836 KiB

Open AccessArticle

Degradation of Methyl 2-Aminobenzoate (Methyl Anthranilate) by H₂O₂/UV: Effect of Inorganic Anions and Derived Radicals

by Grazia Maria Lanzafame^1,2,†, Mohamed Sarakha¹, Debora Fabbri²

and Davide Vione^2,3,*

¹ Institut de Chimie de Clermont-Ferrand, Clermont Université, Université Blaise Pascal, F-63177 Aubière, France

² Dipartimento di Chimica, Università di Torino, Via Pietro Giuria 5, 10125 Torino, Italy

³ Centro Interdipartimentale NatRisk, Università di Torino, Largo Paolo Braccini 2, 10095 Grugliasco (TO), Italy

^† Present address: Institut National de l'environnement Industriel et des Risques (INERIS), Rue Jacques Taffanel, F-60550 Verneuil-en-Halatte, France

Molecules 2017, 22(4), 619; https://doi.org/10.3390/molecules22040619 - 12 Apr 2017

Cited by 30 | Viewed by 8311

Abstract

This study shows that methyl 2-aminobenzoate (also known as methyl anthranilate, hereafter MA) undergoes direct photolysis under UVC and UVB irradiation and that its photodegradation is further accelerated in the presence of H₂O₂. Hydrogen peroxide acts as a source [...] Read more.

This study shows that methyl 2-aminobenzoate (also known as methyl anthranilate, hereafter MA) undergoes direct photolysis under UVC and UVB irradiation and that its photodegradation is further accelerated in the presence of H₂O₂. Hydrogen peroxide acts as a source of hydroxyl radicals (·OH) under photochemical conditions and yields MA hydroxyderivatives. The trend of MA photodegradation rate vs. H₂O₂ concentration reaches a plateau because of the combined effects of H₂O₂ absorption saturation and ·OH scavenging by H₂O₂. The addition of chloride ions causes scavenging of ·OH, yielding Cl₂·⁻ as the most likely reactive species, and it increases the MA photodegradation rate at high H₂O₂ concentration values. The reaction between Cl₂·⁻ and MA, which has second-order rate constant

k_{C l_{2}^{• -} + M A}

= (4.0 ± 0.3) × 10⁸ M⁻¹·s⁻¹ (determined by laser flash photolysis), appears to be more selective than the ·OH process in the presence of H₂O₂, because Cl₂·⁻ undergoes more limited scavenging by H₂O₂ compared to ·OH. While the addition of carbonate causes ·OH scavenging to produce CO₃·⁻ (

k_{C O_{3}^{• -} + M A}

= (3.1 ± 0.2) × 10⁸ M⁻¹·s⁻¹), carbonate considerably inhibits the photodegradation of MA. A possible explanation is that the elevated pH values of the carbonate solutions make H₂O₂ to partially occur as HO₂⁻, which reacts very quickly with either ·OH or CO₃·⁻ to produce O₂·⁻. The superoxide anion could reduce partially oxidised MA back to the initial substrate, with consequent inhibition of MA photodegradation. Fast MA photodegradation is also observed in the presence of persulphate/UV, which yields SO₄·⁻ that reacts effectively with MA (

k_{S O_{4}^{• -} + M A}

= (5.6 ± 0.4) × 10⁹ M⁻¹·s⁻¹). Irradiated H₂O₂ is effective in photodegrading MA, but the resulting MA hydroxyderivatives are predicted to be about as toxic as the parent compound for aquatic organisms (most notably, fish and crustaceans). Full article

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

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15 pages, 5717 KiB

Open AccessArticle

Uncaria tomentosa Leaves Decoction Modulates Differently ROS Production in Cancer and Normal Cells, and Effects Cisplatin Cytotoxicity

by Anita Kośmider^1,*, Edyta Czepielewska², Mieczysław Kuraś³, Krzysztof Gulewicz⁴, Wioleta Pietrzak⁵, Renata Nowak⁵ and Grażyna Nowicka¹

¹ Department of Biochemistry and Pharmacogenomics, Faculty of Pharmacy with the Laboratory Medicine Division, and Center for Preclinical Studies, Medical University of Warsaw, 02097 Warsaw, Poland

² Department of Clinical Pharmacy and Pharmaceutical Care, Faculty of Pharmacy with the Laboratory Medicine Division, Medical University of Warsaw, 02097 Warsaw, Poland

³ Department of Molecular Plant Physiology, Faculty of Biology, University of Warsaw, 02096 Warsaw, Poland

⁴ Institute of Bioorganic Chemistry Polish Academy of Science, Poznań, 61704 Poznań, Poland

⁵ Chair and Department of Pharmaceutical Botany, Medical University of Lublin, 20093 Lublin, Poland

Molecules 2017, 22(4), 620; https://doi.org/10.3390/molecules22040620 - 12 Apr 2017

Cited by 25 | Viewed by 7136

Abstract

Uncaria tomentosa is a woody vine with a long history of use in traditional Peruvian medicine and nowadays supplements containing this vine as ingredient are available. Immunomodulating, anti-inflammatory and anticancer properties of Uncaria tomentosa have been suggested and attributed mainly to the presence [...] Read more.

Uncaria tomentosa is a woody vine with a long history of use in traditional Peruvian medicine and nowadays supplements containing this vine as ingredient are available. Immunomodulating, anti-inflammatory and anticancer properties of Uncaria tomentosa have been suggested and attributed mainly to the presence of tetracyclic or pentacyclic oxindole alkaloids. However, the synergic action of different compounds occurring in extracts and modulation of redox processes may significantly influence the anticancer activity of Uncaria tomentosa. The aim of the present study was to investigate for the first time the cytotoxic effects of the tetracyclic alkaloids free aqueous extract (decoction) of dried Uncaria tomentosa leaf blades in normal and cancer cells, and to assess the effect of the tested extract on cisplatin (CDDP) cytotoxicity. Tested Uncaria tomentosa extract was not cytotoxic for NHDF cells, but demonstrated cytotoxic effect against HepG2 cells. The extract increased ROS production in HepG2 cells, which resulted in decreased GSH level, leading to apoptosis of these cells through activation of caspase-3 and caspase-7. A reduction of NF-κB active form was observed in cancer cells. In normal cells the extract did not affect ROS production, GSH level and NF-κB activity, and maintained cell viability. HepG2 cells incubation with Uncaria tomentosa decoction and simultaneously with CDDP resulted in an increase in CDPP cytotoxic activity against HepG2, while under the same conditions Uncaria tomentosa prevents NHDF cell viability reduction due to CDDP. The results indicate that Uncaria tomentosa leaves decoction modulates differently cancer and normal cells oxidative metabolism and, enhanced cytotoxicity of CDDP against cancer cells and at the same time increased normal healthy cells resistance to cisplatin. Further studies are needed to confirm our observations and to describe underlying molecular mechanism, and the potential usefulness of Uncaria tomentosa decoction in adjuvant therapy for cancer. Full article

(This article belongs to the Section Natural Products Chemistry)

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13 pages, 1245 KiB

Open AccessArticle

Essential Oils of Hyptis pectinata Chemotypes: Isolation, Binary Mixtures and Acute Toxicity on Leaf-Cutting Ants

by Rosana B. Feitosa-Alcantara¹, Leandro Bacci¹, Arie F. Blank¹

, Péricles B. Alves², Indira Morgana de A. Silva¹, Caroline A. Soares¹, Taís S. Sampaio², Paulo Cesar de L. Nogueira² and Maria De Fátima Arrigoni-Blank^1,*

¹ Departamento de Engenharia Agronômica, Universidade Federal de Sergipe, São Cristóvão, SE 49100-000, Brazil

² Departamento de Química, Universidade Federal de Sergipe, São Cristóvão, SE 49100-000, Brazil

Molecules 2017, 22(4), 621; https://doi.org/10.3390/molecules22040621 - 12 Apr 2017

Cited by 23 | Viewed by 6592

Abstract

Leaf-cutting ants are pests of great economic importance due to the damage they cause to agricultural and forest crops. The use of organosynthetic insecticides is the main form of control of these insects. In order to develop safer technology, the objective of this [...] Read more.

Leaf-cutting ants are pests of great economic importance due to the damage they cause to agricultural and forest crops. The use of organosynthetic insecticides is the main form of control of these insects. In order to develop safer technology, the objective of this work was to evaluate the formicidal activity of the essential oils of two Hyptis pectinata genotypes (chemotypes) and their major compounds on the leaf-cutting ants Acromyrmex balzani Emery and Atta sexdens rubropilosa Forel. Bioassays of exposure pathways (contact and fumigation) and binary mixtures of the major compounds were performed. The major compounds identified in the essential oils of H. pectinata were β-caryophyllene, caryophyllene oxide and calamusenone. The essential oils of H. pectinata were toxic to the ants in both exposure pathways. Essential oils were more toxic than their major compounds alone. The chemotype calamusenone was more toxic to A. balzani in both exposure pathways. A. sexdens rubropilosa was more susceptible to the essential oil of the chemotype β-caryophyllene in both exposure pathways. In general, the binary mixtures of the major compounds resulted in additive effect of toxicity. The essential oils of H. pectinata is a raw material of great potential for the development of new insecticides. Full article

(This article belongs to the Collection Bioactive Compounds)

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10 pages, 3615 KiB

Open AccessArticle

Synthesis and Self-Assembly of Shape Amphiphiles Based on POSS-Dendron Conjugates

by Yu Shao¹

, Minyuan Ding², Yujie Xu², Fangjia Zhao², Hui Dai², Xia-Ran Miao³, Shuguang Yang^1,* and Hui Li^1,2,*

¹ State Key Laboratory for Modification of Chemical Fibers and Polymer Materials and College of Material Science and Engineering, Center for Advanced Low-Dimension Materials, Donghua University, Shanghai 201620, China

² School of Materials Science and Engineering, East China University of Science and Technology, Shanghai 200237, China

³ Shanghai Institute of Applied Physics, Chinese Academy of Science, Shanghai 201204, China

Molecules 2017, 22(4), 622; https://doi.org/10.3390/molecules22040622 - 21 Apr 2017

Cited by 9 | Viewed by 8497

Abstract

Shape has been increasingly recognized as an important factor for self-assembly. In this paper, a series of shape amphiphiles have been built by linking polyhedral oligomeric silsesquioxane (POSS) and a dendron via linkers of different lengths. Three conjugates of octahedral silsesquioxanes (T₈ [...] Read more.

Shape has been increasingly recognized as an important factor for self-assembly. In this paper, a series of shape amphiphiles have been built by linking polyhedral oligomeric silsesquioxane (POSS) and a dendron via linkers of different lengths. Three conjugates of octahedral silsesquioxanes (T₈-POSS) and dendron are designed and synthesized and are referred to as isobutyl T₈-POSS gallic acid derivatives (BPOSS-GAD-1, BPOSS-GAD-2, BPOSS-GAD-3). These samples have been fully characterized by ¹H-NMR, ¹³C-NMR, Fourier transform infrared (FT-IR) spectroscopy and matrix-assisted laser desorption/ionization time of flight (MALDI-TOF) mass spectrometry to establish their chemical identity and purity. Driven by different interactions between POSS and dendron, ordered superstructure can be found upon self-assembly. The stabilities and structures of these samples are further studied by using differential scanning calorimetry (DSC), small-angle X-ray scattering (SAXS), wide-angle X-ray diffraction (WAXD), and molecular simulations. The results show that their melting points range from 74 °C to 143 °C and the molecular packing schemes in the assemblies can form lamellar structure of BPOSS-GAD-3 as determined by the different linkers. Full article

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15 pages, 3195 KiB

Open AccessArticle

Bioavailable Citrus sinensis Extract: Polyphenolic Composition and Biological Activity

by Giacomo Pepe^1,2, Francesco Pagano^1,2, Simona Adesso¹, Eduardo Sommella^1,2, Carmine Ostacolo³

, Michele Manfra⁴, Marcello Chieppa^1,5, Marina Sala¹, Mariateresa Russo², Stefania Marzocco¹

and Pietro Campiglia^1,6,*

¹ Department of Pharmacy, School of Pharmacy, University of Salerno, Via Giovanni Paolo II 132, I-84084 Fisciano, Italy

² Department of Agriculture, Laboratory of Food Chemistry, University of Reggio Calabria, Via Melissari stecca n°4, I-89122 Reggio Calabria, Italy

³ Department of Pharmacy, University of Naples Federico II, Via D. Montesano 49, I-80131 Napoli, Italy

⁴ Department of Science, University of Basilicata, Viale dell’Ateneo Lucano 10, I-85100 Potenza, Italy

⁵ National Institute of Gastroenterology “S. de Bellis”, Institute of Research, I-70013 Castellana Grotte, Italy

⁶ European Biomedical Research Institute of Salerno, Via De Renzi 3, I-84125 Salerno, Italy

Molecules 2017, 22(4), 623; https://doi.org/10.3390/molecules22040623 - 15 Apr 2017

Cited by 38 | Viewed by 8536

Abstract

Citrus plants contain large amounts of flavonoids with beneficial effects on human health. In the present study, the antioxidant and anti-inflammatory potential of bioavailable polyphenols from Citrus sinensis was evaluated in vitro and ex vivo, using the murine macrophages cell line J774A.1 and [...] Read more.

Citrus plants contain large amounts of flavonoids with beneficial effects on human health. In the present study, the antioxidant and anti-inflammatory potential of bioavailable polyphenols from Citrus sinensis was evaluated in vitro and ex vivo, using the murine macrophages cell line J774A.1 and primary peritoneal macrophages. Following simulated gastro-intestinal digestion, the in vitro bioavailability of Citrus sinensis polyphenolic extract was assessed using the human cell line Caco-2 grown as monolayers on a transwell membrane. Data demonstrated a relative permeation of its compounds (8.3%). Thus, the antioxidant and anti-inflammatory effect of polyphenolic Citrus sinensis fraction (Cs) was compared to the bioavailable one (CsB). Results revealed that Citrus extract were able to reduce macrophages pro-inflammatory mediators, including nitric oxide, iNOS, COX-2 and different cytokines. Moreover, the effect of Citrus sinensis polyphenols was associated with antioxidant effects, such as a reduction of reactive oxygen species (ROS) and heme-oxygenase-1 (HO-1) increased expression. Our results provide evidence that the bioavailable polyphenolic constituents of the Citrus sinensis extract accumulate prevalently at intestinal level and could reach systemic circulation exerting their effect. The bioavailable fraction showed a higher anti-inflammatory and antioxidant potential compared to the initial extract, thus highlighting its potential nutraceutical value. Full article

(This article belongs to the Section Natural Products Chemistry)

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15 pages, 1496 KiB

Open AccessArticle

LC-ESI-MS/MS Identification of Biologically Active Phenolic Compounds in Mistletoe Berry Extracts from Different Host Trees

by Wioleta Pietrzak¹

, Renata Nowak^1,*, Urszula Gawlik-Dziki²

, Marta Kinga Lemieszek³ and Wojciech Rzeski^3,4

¹ Department of Pharmaceutical Botany, Medical University of Lublin, Chodźki 1 Str., 20-093 Lublin, Poland

² Department of Biochemistry and Food Chemistry, University of Life Sciences, Skromna 8 Str., 20-704 Lublin, Poland

³ Department of Medical Biology, Institute of Rural Health in Lublin, Jaczewskiego 2, 20-090 Lublin, Poland

⁴ Department of Virology and Immunology, Maria Curie Skłodowska University, Akademicka 19, 20-033 Lublin, Poland

Molecules 2017, 22(4), 624; https://doi.org/10.3390/molecules22040624 - 12 Apr 2017

Cited by 55 | Viewed by 7491

Abstract

A new, rapid, sensitive and selective liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) method was developed to determine the content of flavonoid aglycones and phenolic acids in mistletoe berries (Viscum album L.) harvested from six different Polish host trees. Additionally, the total phenolic [...] Read more.

A new, rapid, sensitive and selective liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) method was developed to determine the content of flavonoid aglycones and phenolic acids in mistletoe berries (Viscum album L.) harvested from six different Polish host trees. Additionally, the total phenolic content (TPC) and total flavonoid content (TFC) as well as an antioxidant and antiproliferative activity were evaluated for the first time. The plant material was selectively extracted using ultrasound assisted maceration with methanol/water (8:2) solution. The obtained TPC and TFC results varied from 7.146 to 9.345 mg GA g⁻¹ and from 1.888 to 2.888 mg Q g⁻¹ of dry extracts, respectively. The LC-ESI-MS/MS analysis demonstrated the highest content of phenolic acids in mistletoe berries from Populus nigra ‘Italica’ L. and flavonoid aglycones in mistletoe berries from Tilia cordata Mill. (354.45 µg and 5.955 µg per g dry extract, respectively). The moderate antioxidant activity of investigated extracts was obtained. The studies revealed that the examined extracts decreased the proliferation of human colon adenocarcinoma cells line LS180 in a dose-dependent manner without cytotoxicity in the human colon epithelial cell line CCD 841 CoTr. Moreover, the obtained results suggest considerable impact of polyphenols on the anticancer activity of these extracts. Full article

(This article belongs to the Collection Bioactive Compounds)

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12 pages, 1259 KiB

Open AccessArticle

Expression of Adenosine A_2B Receptor and Adenosine Deaminase in Rabbit Gastric Mucosa ECL Cells

by Rosa María Arin^*, Ana Isabel Vallejo, Yuri Rueda, Olatz Fresnedo

and Begoña Ochoa

Department of Physiology, Faculty of Medicine and Nursing, University of the Basque Country UPV/EHU, Sarriena s/n, 48940 Leioa, Bizkaia, Spain

Molecules 2017, 22(4), 625; https://doi.org/10.3390/molecules22040625 - 12 Apr 2017

Cited by 9 | Viewed by 9027

Abstract

Adenosine is readily available to the glandular epithelium of the stomach. Formed continuously in intracellular and extracellular locations, it is notably produced from ATP released in enteric cotransmission. Adenosine analogs modulate chloride secretion in gastric glands and activate acid secretion in isolated parietal [...] Read more.

Adenosine is readily available to the glandular epithelium of the stomach. Formed continuously in intracellular and extracellular locations, it is notably produced from ATP released in enteric cotransmission. Adenosine analogs modulate chloride secretion in gastric glands and activate acid secretion in isolated parietal cells through A_2B adenosine receptor (A2BR) binding. A functional link between surface A2BR and adenosine deaminase (ADA) was found in parietal cells, but whether this connection is a general feature of gastric mucosa cells is unknown. Here we examine whether A2BR is expressed at the membrane of histamine-producing enterochromaffin-like (ECL) cells, the major endocrine cell type in the oxyntic mucosa, and if so, whether it has a vicinity relationship with ADA. We used a highly homogeneous population of rabbit ECL cells (size 7.5–10 µm) after purification by elutriation centrifugation. The surface expression of A2BR and ADA proteins was assessed by flow cytometry and confocal microscopy. Our findings demonstrate that A2BR and ADA are partially coexpressed at the gastric ECL cell surface and that A2BR is functional, with regard to binding of adenosine analogs and adenylate cyclase activation. The physiological relevance of A2BR and ADA association in regulating histamine release is yet to be explained. Full article

(This article belongs to the Special Issue Adenosine Receptors)

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13 pages, 3315 KiB

Open AccessArticle

One–Pot Phosphate-Mediated Synthesis of Novel 1,3,5-Trisubstituted Pyridinium Salts: A New Family of S. aureus Inhibitors

by Thomas Pesnot¹, Markus C. Gershater², Martin Edwards², John M. Ward² and Helen C. Hailes^1,*

¹ Department of Chemistry, University College London, Christopher Ingold Laboratories, 20 Gordon Street, London WC1H 0AJ, UK

² The Advanced Centre for Biochemical Engineering, Department of Biochemical Engineering, University College London, Bernard Katz Building, Gower Street, London WC1E 6BT, UK

Molecules 2017, 22(4), 626; https://doi.org/10.3390/molecules22040626 - 12 Apr 2017

Cited by 7 | Viewed by 5708

Abstract

Polysubstituted pyridinium salts are valuable pharmacophores found in many biologically active molecules. Their synthesis typically involves the use of multistep procedures or harsh reaction conditions. Here, we report water-based phosphate mediated reaction conditions that promote the condensation of arylacetaldehydes with amines to give [...] Read more.

Polysubstituted pyridinium salts are valuable pharmacophores found in many biologically active molecules. Their synthesis typically involves the use of multistep procedures or harsh reaction conditions. Here, we report water-based phosphate mediated reaction conditions that promote the condensation of arylacetaldehydes with amines to give 1,3,5-pyridinium salts. The reaction, carried out at pH 6, provides conditions suitable for the use of less stable aldehydes and amines in this Chichibabin pyridine condensation. The evaluation of selected 1,3,5-trisubstituted pyridinium salts highlighted that they can inhibit the growth of S. aureus in the low μg/mL range. The synthetic accessibility of these compounds and preliminary growth inhibition data may pave the way towards the discovery of new anti-bacterials based on the 1,3,5-trisubstituted pyridinium scaffold. Full article

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

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13 pages, 2479 KiB

Open AccessArticle

Pro-Angiogenic Effects of Low Dose Ethoxidine in a Murine Model of Ischemic Hindlimb: Correlation between Ethoxidine Levels and Increased Activation of the Nitric Oxide Pathway

by Nicolas Clere^1,2,*,†

, Kim Hung Thien To^2,3,†, Samuel Legeay^1,2

, Samuel Bertrand^4,5, Jean Jacques Helesbeux⁶

, Olivier Duval⁶ and Sébastien Faure^1,2

¹ MINT, Univ Angers, INSERM, CNRS, Université Bretagne Loire, IBS-CHU, 4 rue Larrey, F-49933 Angers, France

² Department of Pharmaceutical Pharmacology and Physiology, UFR Santé-School of Pharmacy, University of Angers, F-49045 Angers, France

³ Department of Medical Pharmacology and Physiology, University of Missouri, Columbia, MO 65212, USA

⁴ EA 2160, Univ Nantes, Université Bretagne Loire, F-44200 Nantes, France

⁵ School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Quai Ernest-Ansermet 30, CH-1211 Geneva 4, Switzerland

⁶ SONAS, SFR QUASAV 4207, UPRES EA921, Univ Angers, Université Bretagne Loire, F-49035 Angers, France

^† These authors contributed equally to this work.

Molecules 2017, 22(4), 627; https://doi.org/10.3390/molecules22040627 - 12 Apr 2017

Cited by 1 | Viewed by 3989

Abstract

Ethoxidine, a benzo[c]phenanthridine derivative, has been identified as a potent inhibitor of topoisomerase I in cancer cell lines. Our group has reported paradoxical properties of ethoxidine in cellular processes leading to angiogenesis on endothelial cells. Because low concentration ethoxidine is able to favor [...] Read more.

Ethoxidine, a benzo[c]phenanthridine derivative, has been identified as a potent inhibitor of topoisomerase I in cancer cell lines. Our group has reported paradoxical properties of ethoxidine in cellular processes leading to angiogenesis on endothelial cells. Because low concentration ethoxidine is able to favor angiogenesis, the present study aimed to investigate the ability of 10⁻⁹ M ethoxidine to modulate neovascularization in a model of mouse hindlimb ischemia. After inducing unilateral hindlimb ischemia, mice were treated for 21 days with glucose 5% or with ethoxidine, to reach plasma concentrations equivalent to 10^–9 M. Laser Doppler analysis showed that recovery of blood flow was 1.5 fold higher in ethoxidine-treated mice in comparison with control mice. Furthermore, CD31 staining and angiographic studies confirmed an increase of vascular density in ethoxidine-treated mice. This ethoxidine-induced recovery was associated with an increase of NO production through an enhancement of eNOS phosphorylation on its activator site in skeletal muscle from ischemic hindlimb. Moreover, real-time RT-PCR and western blots have highlighted that ethoxidine has pro-angiogenic properties by inducing a significant enhancement in vegf transcripts and VEGF expression, respectively. These findings suggest that ethoxidine could contribute to favor neovascularization after an ischemic injury by promoting the NO pathway and VEGF expression. Full article

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12 pages, 6893 KiB

Open AccessArticle

Synthesis and Antiproliferative Activity of Novel All-Trans-Retinoic Acid-Podophyllotoxin Conjugate towards Human Gastric Cancer Cells

by Lei Zhang^*, Jing Wang^*, Lai Liu, Chengyue Zheng and Yang Wang

School of Pharmacy, Zunyi Medical University, 201 Dalian Road, Zunyi 563003, Guizhou, China

Molecules 2017, 22(4), 628; https://doi.org/10.3390/molecules22040628 - 17 Apr 2017

Cited by 20 | Viewed by 6402

Abstract

With the purpose of creating a multifunctional drug for gastric cancer treatment, a novel all-trans-retinoic acid (ATRA) conjugate with podophyllotoxin (PPT) was designed and synthesized, and its in vitro antiproliferative activity was evaluated against human gastric cancer cell [...] Read more.

With the purpose of creating a multifunctional drug for gastric cancer treatment, a novel all-trans-retinoic acid (ATRA) conjugate with podophyllotoxin (PPT) was designed and synthesized, and its in vitro antiproliferative activity was evaluated against human gastric cancer cell lines using CCK-8 assay. The conjugate, P-A, exhibited significant anticancer activity against MKN-45 and BGC-823 cells with IC₅₀ values of 0.419 ± 0.032 and 0.202 ± 0.055 μM, respectively. Moreover, P-A efficiently triggered cell cycle arrest and induced apoptosis in MKN-45 and BGC-823 cells due to modulation of cell cycle arrest- (CDK1, CDK2, CyclinA and CyclinB1) and apoptosis- (cleaved caspase-3, -8 and -9) related proteins, respectively. Further mechanism studies revealed that P-A could increase the expression levels of RARα and RARβ, and decrease the level of RARγ in MKN-45 and BGC-823 cells. Finally, P-A inhibited the ERK1/2 and AKT signaling in the above two cancer cell lines. More importantly, the underlying mechanisms of P-A were similar to those of precursor PPT but different with the other precursor ATRA. Together, the conjugate P-A was a promising candidate for the potential treatment of human gastric cancer. Full article

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

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15 pages, 3486 KiB

Open AccessArticle

Metronomic Cordycepin Therapy Prolongs Survival of Oral Cancer-Bearing Mice and Inhibits Epithelial-Mesenchymal Transition

by Nai-Wen Su^1,2, Shu-Hua Wu³, Chih-Wen Chi³, Chung-Ji Liu^4,5

, Tung-Hu Tsai^2,6,*

and Yu-Jen Chen^2,3,7,8,*

¹ Division of Medical Oncology and Hematology, Department of Internal Medicine, Mackay Memorial Hospital, Taipei 11094, Taiwan

² Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, Taipei 11221, Taiwan

³ Department of Medical Research, Mackay Memorial Hospital, Taipei 25160, Taiwan

⁴ Department of Oral and Maxillofacial Surgery, Mackay Memorial Hospital, Taipei 11094, Taiwan

⁵ Institute of Oral Biology, School of Dentistry, National Yang-Ming University, Taipei 11221, Taiwan

⁶ Department of Chemical Engineering, National United University, Miaoli 36063, Taiwan

⁷ Department of Radiation Oncology, Mackay Memorial Hospital, Taipei 25160, Taiwan

⁸ Research Center for Chinese Medicine and Acupuncture, China Medical University, Taichung 404, Taiwan

Molecules 2017, 22(4), 629; https://doi.org/10.3390/molecules22040629 - 13 Apr 2017

Cited by 29 | Viewed by 5844

Abstract

Cordycepin (3′-deoxyadenosine) is a natural compound abundantly found in Cordyceps sinesis in natural and fermented sources. In this study, we examined the effects of cordycepin in a human oral squamous cell carcinoma (OSCC) xenograft model. Cordycepin was administered in a regular, low-dose and [...] Read more.

Cordycepin (3′-deoxyadenosine) is a natural compound abundantly found in Cordyceps sinesis in natural and fermented sources. In this study, we examined the effects of cordycepin in a human oral squamous cell carcinoma (OSCC) xenograft model. Cordycepin was administered in a regular, low-dose and prolonged schedule metronomic therapy. Two doses of cordycepin (25 mg/kg, 50 mg/kg) were administrated five days a week for eight consecutive weeks. The tumor volumes were reduced and survival time was significantly prolonged from 30.3 ± 0.9 days (control group) to 56 days (50 mg/kg group, the day of tumor-bearing mice were sacrificed for welfare consideration). The weights of mice did not change and liver, renal, and hematologic functions were not compromised. Cordycepin inhibited the OSCC cell viability in vitro (IC₅₀ 122.4–125.2 μM). Furthermore, morphological characteristics of apoptosis, increased caspase-3 activity and G2/M cell cycle arrest were observed. In wound healing assay, cordycepin restrained the OSCC cell migration. Cordycepin upregulated E-cadherin and downregulated N-cadherin protein expression, implying inhibition of epithelial-mesenchymal transition (EMT). The immunohistochemical staining of xenograft tumor with E-cadherin and vimentin validated in vitro results. In conclusion, metronomic cordycepin therapy showed effective tumor control, prolonged survival and low toxicities. Cytotoxicity against cancer cells with apoptotic features and EMT inhibition were observed. 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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9 pages, 574 KiB

Open AccessArticle

N-(2,2-Dimethyl-1-(quinolin-2-yl)propylidene) arylaminonickel Complexes and Their Ethylene Oligomerization

by Hongyi Suo^1,2

, Tong Zhao³, Yiqing Wang¹, Qing Ban^3,* and Wen-Hua Sun^1,2,*

¹ Key Laboratory of Engineering Plastics and Beijing National Laboratory for Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China

² CAS Research/Education Center for Excellence in Molecular Sciences, University of Chinese Academy of Sciences, Beijing 100049, China

³ School of Materials Science and Engineering, Qilu University of Technology, Jinan 250353, China

Molecules 2017, 22(4), 630; https://doi.org/10.3390/molecules22040630 - 13 Apr 2017

Cited by 12 | Viewed by 4751

Abstract

A series of N-(2,2-dimethyl-1-(quinolin-2-yl)propylidene) arylamines was sophisticatedly synthesized and reacted with nickel(II) bromine for the formation of the corresponding nickel complexes. All the organic compounds were characterized by IR, NMR spectra and elemental analysis, while all the nickel complexes were characterized by [...] Read more.

A series of N-(2,2-dimethyl-1-(quinolin-2-yl)propylidene) arylamines was sophisticatedly synthesized and reacted with nickel(II) bromine for the formation of the corresponding nickel complexes. All the organic compounds were characterized by IR, NMR spectra and elemental analysis, while all the nickel complexes were characterized by IR spectra and elemental analysis. On activation with ethylaluminium sesquichloride (EASC) and modified methylaluminoxane (MMAO), all nickel precatalysts exhibited good activities toward ethylene oligomerization, indicating the positive efficiency of gem-dimethyl substitutents; in which major hexenes were obtained with MMAO. The catalytic parameters were verified, and the steric and electronic influences of substituents with ligands were observed, with a slight change of activities under different ethylene pressures. Full article

(This article belongs to the Special Issue Organometallic Catalysis for Olefin Polymerization/Oligomerization)

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13 pages, 2562 KiB

Open AccessArticle

Loss of the Phenolic Hydroxyl Group and Aromaticity from the Side Chain of Anti-Proliferative 10-Methyl-aplog-1, a Simplified Analog of Aplysiatoxin, Enhances Its Tumor-Promoting and Proinflammatory Activities

by Yusuke Hanaki¹, Masayuki Kikumori¹, Harukuni Tokuda¹, Mutsumi Okamura², Shingo Dan², Naoko Adachi³, Naoaki Saito³, Ryo C. Yanagita⁴

and Kazuhiro Irie^1,*

¹ Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto 606-8502, Japan

² Division of Molecular Pharmacology, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo 135-8550, Japan

³ Laboratory of Molecular Pharmacology, Biosignal Research Center, Kobe University, Kobe 657-8501, Japan

⁴ Department of Applied Biological Science, Faculty of Agriculture, Kagawa University, Kagawa 761-0795, Japan

Molecules 2017, 22(4), 631; https://doi.org/10.3390/molecules22040631 - 13 Apr 2017

Cited by 7 | Viewed by 5730

Abstract

Aplysiatoxin (ATX) is a protein kinase C (PKC) activator with potent tumor-promoting activity. In contrast, 10-methyl-aplog-1 (1), a simplified analog of ATX, was anti-proliferative towards several cancer cell lines without significant tumor-promoting and proinflammatory activities. To determine the effects of the [...] Read more.

Aplysiatoxin (ATX) is a protein kinase C (PKC) activator with potent tumor-promoting activity. In contrast, 10-methyl-aplog-1 (1), a simplified analog of ATX, was anti-proliferative towards several cancer cell lines without significant tumor-promoting and proinflammatory activities. To determine the effects of the phenolic group on the biological activities of 1, we synthesized new derivatives (2, 3) that lack the phenolic hydroxyl group and/or the aromatic ring. Compound 2, like 1, showed potent anti-proliferative activity against several cancer cell lines, but little with respect to tumor-promoting and proinflammatory activities. In contrast, 3 exhibited weaker growth inhibitory activity, and promoted inflammation and tumorigenesis. The binding affinity of 3 for PKCδ, which is involved in growth inhibition and apoptosis, was several times lower than those of 1 and 2, possibly due to the absence of the hydrogen bond and CH/π interaction between its side chain and either Met-239 or Pro-241 in the PKCδ-C1B domain. These results suggest that both the aromatic ring and phenolic hydroxyl group can suppress the proinflammatory and tumor-promoting activities of 1 and, therefore, at least the aromatic ring in the side chain of 1 is indispensable for developing anti-cancer leads with potent anti-proliferative activity and limited side effects. In accordance with the binding affinity, the concentration of 3 necessary to induce PKCδ-GFP translocation to the plasma membrane and perinuclear regions in HEK293 cells was higher than that of 1 and 2. However, the translocation profiles for PKCδ-GFP due to induction by 1–3 were similar. Full article

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

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14 pages, 1636 KiB

Open AccessArticle

A Network-Based Pharmacology Study of the Herb-Induced Liver Injury Potential of Traditional Hepatoprotective Chinese Herbal Medicines

by Ming Hong¹, Sha Li¹, Hor Yue Tan¹, Fan Cheung¹, Ning Wang¹, Jihan Huang²

and Yibin Feng^1,*

¹ School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China

² Shanghai University of Traditional Chinese Medicine, Shanghai, China

Molecules 2017, 22(4), 632; https://doi.org/10.3390/molecules22040632 - 14 Apr 2017

Cited by 62 | Viewed by 10288

Abstract

Herbal medicines are widely used for treating liver diseases and generally regarded as safe due to their extensive use in Traditional Chinese Medicine practice for thousands of years. However, in recent years, there have been increased concerns regarding the long-term risk of Herb-Induced [...] Read more.

Herbal medicines are widely used for treating liver diseases and generally regarded as safe due to their extensive use in Traditional Chinese Medicine practice for thousands of years. However, in recent years, there have been increased concerns regarding the long-term risk of Herb-Induced Liver Injury (HILI) in patients with liver dysfunction. Herein, two representative Chinese herbal medicines: one—Xiao-Chai-Hu-Tang (XCHT)—a composite formula, and the other—Radix Polygoni Multiflori (Heshouwu)—a single herb, were analyzed by network pharmacology study. Based on the network pharmacology framework, we exploited the potential HILI effects of XCHT and Heshouwu by predicting the molecular mechanisms of HILI and identified the potential hepatotoxic ingredients in XCHT and Heshouwu. According to our network results, kaempferol and thymol in XCHT and rhein in Heshouwu exhibit the largest number of liver injury target connections, whereby CASP3, PPARG and MCL1 may be potential liver injury targets for these herbal medicines. This network pharmacology assay might serve as a useful tool to explore the underlying molecular mechanism of HILI. Based on the theoretical predictions, further experimental verification should be performed to validate the accuracy of the predicted interactions between herbal ingredients and protein targets in the future. Full article

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

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12 pages, 651 KiB

Open AccessArticle

Synthesis of Curcuminoids and Evaluation of Their Cytotoxic and Antioxidant Properties

by María Concepción Lozada-García^1,‡, Raúl G. Enríquez², Teresa O. Ramírez-Apán², Antonio Nieto-Camacho², Juan Francisco Palacios-Espinosa¹, Zeltzin Custodio-Galván¹, Olivia Soria-Arteche^1,*,† and Jaime Pérez-Villanueva^1,*,†

¹ Departamento de Sistemas Biológicos, División de Ciencias Biológicas y de la Salud, Universidad Autónoma Metropolitana-Xochimilco (UAM-X.), Ciudad de México 04960, Mexico

² Instituto de Química, Universidad Nacional Autónoma de México (UNAM), Ciudad de México 04510, Mexico

^† These authors contributed equally to this work.

^‡ This paper was written in memory of Dra. María Concepción Lozada-García.

Molecules 2017, 22(4), 633; https://doi.org/10.3390/molecules22040633 - 14 Apr 2017

Cited by 36 | Viewed by 7862

Abstract

Curcumin (1) and ten derivatives (2–11) were synthesized and evaluated as cytotoxic and antioxidant agents. The results of primary screening by Sulforhodamine B assay against five human cancer cell lines (U-251 MG, glioblastoma; PC-3, human prostatic; HCT-15, [...] Read more.

Curcumin (1) and ten derivatives (2–11) were synthesized and evaluated as cytotoxic and antioxidant agents. The results of primary screening by Sulforhodamine B assay against five human cancer cell lines (U-251 MG, glioblastoma; PC-3, human prostatic; HCT-15, human colorectal; K562, human chronic myelogenous leukemia; and SKLU-1, non-small cell lung cancer) allowed us to calculate the half maximal inhibitory concentration (IC₅₀) values for the more active compounds against HCT-15 and K562 cell lines. Compounds 2 and 10 were the most active against both cell lines and were more active than curcumin itself. Thiobarbituric acid reactive substances (TBARS) assay showed that 7 has potent activity; even stronger than curcumin, α-tocopherol, and quercetin. Full article

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

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32 pages, 4276 KiB

Open AccessArticle

Synthesis and Spectral Properties of meso-Arylbacteriochlorins, Including Insights into Essential Motifs of their Hydrodipyrrin Precursors

by Muthyala Nagarjuna Reddy¹, Shaofei Zhang¹, Han-Je Kim^2,*, Olga Mass¹, Masahiko Taniguchi¹ and Jonathan S. Lindsey^1,*

¹ Department of Chemistry, North Carolina State University, Raleigh, NC 27695-8204, USA

² Department of Science Education, Gongju National University of Education, Gongju 314-701, Korea

Molecules 2017, 22(4), 634; https://doi.org/10.3390/molecules22040634 - 14 Apr 2017

Cited by 7 | Viewed by 5788

Abstract

Synthetic bacteriochlorins—analogues of bacteriochlorophylls, Nature’s near-infrared absorbers—are attractive for diverse photochemical studies. meso-Arylbacteriochlorins have been prepared by the self-condensation of a dihydrodipyrrin–carbinol or dihydrodipyrrin–acetal following an Eastern-Western (E-W) or Northern-Southern (N-S) joining process. The bacteriochlorins bear a gem-dimethyl group in each pyrroline [...] Read more.

Synthetic bacteriochlorins—analogues of bacteriochlorophylls, Nature’s near-infrared absorbers—are attractive for diverse photochemical studies. meso-Arylbacteriochlorins have been prepared by the self-condensation of a dihydrodipyrrin–carbinol or dihydrodipyrrin–acetal following an Eastern-Western (E-W) or Northern-Southern (N-S) joining process. The bacteriochlorins bear a gem-dimethyl group in each pyrroline ring to ensure stability toward oxidation. The two routes differ in the location of the gem-dimethyl group at the respective 3- or 2-position in the dihydrodipyrrin, and the method of synthesis of the dihydrodipyrrin. Treatment of a known 3,3-dimethyldihydrodipyrrin-1-carboxaldehyde with an aryl Grignard reagent afforded the dihydrodipyrrin-1-(aryl)carbinol, and upon subsequent acetylation, the corresponding dihydrodipyrrin-1-methyl acetate (dihydrodipyrrin–acetate). Self-condensation of the dihydrodipyrrin–acetate gave a meso-diarylbacteriochlorin (E-W route). A 2,2-dimethyl-5-aryldihydrodipyrrin-1-(aryl)carbinol underwent self-condensation to give a trans-A₂B₂-type meso-tetraarylbacteriochlorin (N-S route). In each case, the aromatization process entails a 2e⁻/2H⁺ (aerobic) dehydrogenative oxidation following the dihydrodipyrrin self-condensation. Comparison of a tetrahydrodipyrrin–acetal (0%) versus a dihydrodipyrrin–acetal (41%) in bacteriochlorin formation and results with various 1-substituted dihydrodipyrrins revealed the importance of resonance stabilization of the reactive hydrodipyrrin intermediate. Altogether 10 new dihydrodipyrrins and five new bacteriochlorins have been prepared. The bacteriochlorins exhibit characteristic bacteriochlorophyll-like absorption spectra, including a Q_y band in the region 726–743 nm. Full article

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

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27 pages, 2910 KiB

Open AccessReview

Na⁺_i,K⁺_i-Dependent and -Independent Signaling Triggered by Cardiotonic Steroids: Facts and Artifacts

by Sergei N. Orlov^1,2,3,*, Elizaveta A. Klimanova¹, Artem M. Tverskoi¹, Elizaveta A. Vladychenskaya¹, Larisa V. Smolyaninova¹ and Olga D. Lopina¹

¹ Laboratory of Biological Membranes, Faculty of Biology, M.V. Lomonosov Moscow State University, 1/12 Leninskie Gory, Moscow 119234, Russia

² Department of Medical Biology, Siberian Medical State University, Tomsk 634055, Russia

³ Department of Sports Tourism Sports Physiology and Medicine, National Research Tomsk State University, Tomsk 634050, Russia

Molecules 2017, 22(4), 635; https://doi.org/10.3390/molecules22040635 - 14 Apr 2017

Cited by 29 | Viewed by 6677

Abstract

Na⁺,K⁺-ATPase is the only known receptor of cardiotonic steroids (CTS) whose interaction with catalytic α-subunits leads to inhibition of this enzyme. As predicted, CTS affect numerous cellular functions related to the maintenance of the transmembrane gradient of monovalent cations, [...] Read more.

Na⁺,K⁺-ATPase is the only known receptor of cardiotonic steroids (CTS) whose interaction with catalytic α-subunits leads to inhibition of this enzyme. As predicted, CTS affect numerous cellular functions related to the maintenance of the transmembrane gradient of monovalent cations, such as electrical membrane potential, cell volume, transepithelial movement of salt and osmotically-obliged water, symport of Na⁺ with inorganic phosphate, glucose, amino acids, nucleotides, etc. During the last two decades, it was shown that side-by-side with these canonical Na⁺_i/K⁺_i-dependent cellular responses, long-term exposure to CTS affects transcription, translation, tight junction, cell adhesion and exhibits tissue-specific impact on cell survival and death. It was also shown that CTS trigger diverse signaling cascades via conformational transitions of the Na⁺,K⁺-ATPase α-subunit that, in turn, results in the activation of membrane-associated non-receptor tyrosine kinase Src, phosphatidylinositol 3-kinase and the inositol 1,4,5-triphosphate receptor. These findings allowed researchers to propose that endogenous CTS might be considered as a novel class of steroid hormones. We focus our review on the analysis of the relative impact Na⁺_i,K⁺_i-mediated and -independent pathways in cellular responses evoked by CTS. Full article

(This article belongs to the Special Issue Cardiotonic Steroids)

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15 pages, 1463 KiB

Open AccessArticle

Stability of Bioactive Compounds in Broccoli as Affected by Cutting Styles and Storage Time

by Ana Mariel Torres-Contreras¹, Vimal Nair²

, Luis Cisneros-Zevallos² and Daniel A. Jacobo-Velázquez^1,*

¹ Tecnológico de Monterrey, Escuela de Ingeniería y Ciencias, Centro de Biotecnología FEMSA, Av. Eugenio Garza Sada 2501 Sur, Monterrey 64849, Mexico

² Department of Horticultural Sciences, Texas A&M University, College Station, TX 77843-2133, USA

Molecules 2017, 22(4), 636; https://doi.org/10.3390/molecules22040636 - 15 Apr 2017

Cited by 63 | Viewed by 9341

Abstract

Broccoli contains bioactive molecules and thus its consumption is related with the prevention of chronic and degenerative diseases. The application of wounding stress to horticultural crops is a common practice, since it is the basis for the fresh-cut produce industry. In this study, [...] Read more.

Broccoli contains bioactive molecules and thus its consumption is related with the prevention of chronic and degenerative diseases. The application of wounding stress to horticultural crops is a common practice, since it is the basis for the fresh-cut produce industry. In this study, the effect of four different cutting styles (CSs) (florets (CS1), florets cut into two even pieces (CS2), florets cut into four even pieces (CS3), and florets processed into chops (CS4)) and storage time (0 and 24 h at 20 °C) on the content of bioactive compounds in broccoli was evaluated. Immediately after cutting, 5-O-caffeoylquinic acid and caffeic acid content increased by 122.4% and 41.6% in CS4 and CS2, respectively. Likewise, after storage, 3-O-caffeoylquinic acid and 5-O-caffeoylquinic acid increased by 46.7% and 98.2%, respectively in CS1. Glucoerucin and gluconasturtiin content decreased by 62% and 50%, respectively in CS3; whereas after storage most glucosinolates increased in CS1. Total isothiocyanates, increased by 133% immediately in CS4, and after storage CS1 showed 65% higher levels of sulforaphane. Total ascorbic acid increased 35% after cutting in CS2, and remained stable after storage. Results presented herein would allow broccoli producers to select proper cutting styles that preserve or increase the content of bioactive molecules. Full article

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

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8 pages, 2498 KiB

Open AccessCommunication

Discovery of an Octahedral Silicon Complex as a Potent Antifungal Agent

by Chen Fu^*, Bin Fu, Xixi Peng and Guojian Liao^*

College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, China

Molecules 2017, 22(4), 637; https://doi.org/10.3390/molecules22040637 - 15 Apr 2017

Cited by 2 | Viewed by 5295

Abstract

Octahedral transition metal complexes have been shown to have tremendous applications in chemical biology and medicinal chemistry. Meanwhile, structural transition metals can be replaced by inert octahedral silicon in a proof-of-principle study. We here introduce the first example of octahedral silicon complexes, which [...] Read more.

Octahedral transition metal complexes have been shown to have tremendous applications in chemical biology and medicinal chemistry. Meanwhile, structural transition metals can be replaced by inert octahedral silicon in a proof-of-principle study. We here introduce the first example of octahedral silicon complexes, which can very well serve as an efficient antimicrobial agent. The typical silicon arenediolate complex 1 {[(phen)₂Si(OO)](PF₆)₂, with phen = 1,10-phenanthroline, OO = 9,10-phenanthrenediolate} exhibited significant inhibition towards the growth of Cryptococcus neoformans with MIC and MFC values of 4.5 and 11.3 μM, respectively. Moreover, it was fungicidal against both proliferative and quiescent Cryptococcus cells. This work may set the stage for the development of novel antifungal drugs based upon hexacoodinate silicon scaffolds. Full article

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

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13 pages, 1064 KiB

Open AccessArticle

Optimization of Ultrasound-Assisted Extraction of Antioxidants from the Mung Bean Coat

by Yue Zhou^1,†, Jie Zheng^1,†, Ren-You Gan²

, Tong Zhou¹, Dong-Ping Xu¹ and Hua-Bin Li^1,3,*

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

² School of Biological Sciences, The University of Hong Kong, Hong Kong 999077, China

³ South China Sea Bioresource Exploitation and Utilization Collaborative Innovation Center, Sun Yat-Sen University, Guangzhou 510006, China

^† These authors equally contributed to this paper.

Molecules 2017, 22(4), 638; https://doi.org/10.3390/molecules22040638 - 15 Apr 2017

Cited by 74 | Viewed by 6871

Abstract

Mung bean (Vigna radiata) sprout is commonly consumed as a vegetable, while the coat of the germinated mung bean is a waste. In this paper, an ultrasound-assisted extraction method has been developed to extract natural antioxidants from the seed coat of [...] Read more.

Mung bean (Vigna radiata) sprout is commonly consumed as a vegetable, while the coat of the germinated mung bean is a waste. In this paper, an ultrasound-assisted extraction method has been developed to extract natural antioxidants from the seed coat of mung bean. Several experimental parameters—which included ethanol concentration, solvent/material ratio, ultrasound extraction time, temperature, and power—were studied in single-factor experiments. The interaction of three key experimental parameters (ethanol concentration, solvent/material ratio, and ultrasonic extraction time) was further investigated by response surface method. Besides, traditional extracting methods, including maceration and Soxhlet extraction methods, were also carried out for comparison. The results suggested that the best extracting condition was 37.6% (v/v) of ethanol concentration, 35.1:1 mL/g of solvent/material ratio and ultrasonic extraction of 46.1 min at 70 °C under 500 W ultrasonic irradiation. The antioxidant capacity (178.28 ± 7.39 µmol Trolox/g DW) was much stronger than those obtained by the maceration extraction process (158.66 ± 4.73 µmol Trolox/g DW) and the Soxhlet extraction process (138.42 ± 3.63 µmol Trolox/g DW). In addition, several antioxidant components in the extract were identified and quantified. This study is helpful for value-added utilization of the waste from germinated mung bean. Full article

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

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14 pages, 1646 KiB

Open AccessArticle

Evaluation of Polyphenolic Content, Antioxidant and Diuretic Activities of Six Fumaria Species

by Ramona Păltinean^1,†, Andrei Mocan^1,2,†, Laurian Vlase^3,*

, Ana-Maria Gheldiu³, Gianina Crișan¹, Irina Ielciu¹

, Oliviu Voștinaru⁴ and Ovidiu Crișan⁵

¹ Department of Pharmaceutical Botany, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400337 Cluj-Napoca, Romania

² ICHAT and Institute for Life Sciences, University of Agricultural Sciences and Veterinary Medicine, Calea Mănăştur 3-5, 400372 Cluj-Napoca, Romania

³ Department of Pharmaceutical Technology and Biopharmaceutics, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400010 Cluj-Napoca, Romania

⁴ Department of Pharmacology, Physiology and Physiopathology, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400349 Cluj-Napoca, Romania

⁵ Department of Organic Chemistry, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400010 Cluj-Napoca, Romania

^† These authors have equal contributions

Molecules 2017, 22(4), 639; https://doi.org/10.3390/molecules22040639 - 15 Apr 2017

Cited by 50 | Viewed by 7075

Abstract

Romanian traditional medicine describes the use of aerial parts of Fumaria species to treat hepatobiliary diseases as well as diuretic agents. The present study aims to investigate the chemical composition, antioxidant properties, and diuretic effects of several Fumaria species. LC/MS analysis revealed that [...] Read more.

Romanian traditional medicine describes the use of aerial parts of Fumaria species to treat hepatobiliary diseases as well as diuretic agents. The present study aims to investigate the chemical composition, antioxidant properties, and diuretic effects of several Fumaria species. LC/MS analysis revealed that Fumaria species contain phenolic acids and high amounts of flavonoids with rutin and isoquercitrin as main compounds. Concerning antioxidant capacity, the most significant results were obtained for F. capreolata and F. vailantii. Both species showed a good correlation between the antioxidant capacity and a high amount of flavonoids. Furthermore, the extracts of F. officinalis and F. schleicheri produced a strong increase in urinary volumetric excretion of saline-loaded rats, 24 h after the oral administration of a single dose of 250 mg/kg bw. Moreover, both extracts of F. officinalis and F. schleicheri increased the urinary excretion of Na⁺ and K⁺. Results from the present study offer a new perspective concerning the chemical composition and bioactivities of traditionally used fumitory species. Full article

(This article belongs to the Section Natural Products Chemistry)

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9 pages, 1955 KiB

Open AccessArticle

Expeditious Synthesis of Dianionic-Headed 4-Sulfoalkanoic Acid Surfactants

by Jianhui Jiang^1,2 and Jiaxi Xu^1,*

¹ State Key Laboratory of Chemical Resource Engineering, Department of Organic Chemistry, Faculty of Science, Beijing University of Chemical Technology, Beijing 100029, China

² Engineering Laboratory of Chemical Resources Utilization in South Xinjiang of Xinjiang Production and Construction Corps, College of Life Sciences, Tarim University, Alar, Xinjiang 843300, China

Molecules 2017, 22(4), 640; https://doi.org/10.3390/molecules22040640 - 16 Apr 2017

Cited by 2 | Viewed by 4340

Abstract

4-Sulfoalkanoic acids are a class of important dianionic-headed surfactants. Various 4-sulfoalkanoic acids with straight C8, C10, C12, C14, C16, and C18 chains were synthesized expeditiously through the radical addition of methyl 2-((ethoxycarbonothioyl)thio)acetate to linear terminal olefins and subsequent oxidation with peroxyformic acid. This [...] Read more.

4-Sulfoalkanoic acids are a class of important dianionic-headed surfactants. Various 4-sulfoalkanoic acids with straight C8, C10, C12, C14, C16, and C18 chains were synthesized expeditiously through the radical addition of methyl 2-((ethoxycarbonothioyl)thio)acetate to linear terminal olefins and subsequent oxidation with peroxyformic acid. This is a useful and convenient strategy for the synthesis of dianionic-headed surfactants with a carboxylic acid and sulfonic acid functionalities in the head group region. Full article

(This article belongs to the Section Organic Chemistry)

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10 pages, 6177 KiB

Open AccessArticle

Establishing Reliable Cu-64 Production Process: From Target Plating to Molecular Specific Tumor Micro-PET Imaging

by Qinghua Xie^1,2,†, Hua Zhu^2,†, Feng Wang², Xiangxi Meng³

, Qiushi Ren³, Chuanqin Xia^1,* and Zhi Yang^2,*

¹ College of Chemistry, Sichuan University, Chengdu 610064, China

² Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Nuclear Medicine, Peking University Cancer Hospital & Institute, Beijing 100142, China

³ Department of Biomedical Engineering, College of Engineering, Peking University, Beijing 100871, China

^† These authors contributed equally to this work.

Molecules 2017, 22(4), 641; https://doi.org/10.3390/molecules22040641 - 17 Apr 2017

Cited by 45 | Viewed by 8964

Abstract

Copper-64 is a useful radioisotope for positron emission tomography (PET). Due to the wide range of applications, the demand of ⁶⁴Cu with low metallic impurities is increasing. Here we report a simple method for the efficient production of high specific activity ⁶⁴ [...] Read more.

Copper-64 is a useful radioisotope for positron emission tomography (PET). Due to the wide range of applications, the demand of ⁶⁴Cu with low metallic impurities is increasing. Here we report a simple method for the efficient production of high specific activity ⁶⁴Cu using a cyclotron for biomedical application. We designed new equipment based on the plating of enriched ⁶⁴Ni as the target, and used automated ion exchange chromatography to purify copper-64 efficiently after irradiation and dissolution of the target in good radiochemical and chemical yield and purity. The ⁶⁴Cu radionuclide produced using 99.32% enriched ⁶⁴Ni with a density of 61.4 ± 5.0 mg/cm², reaching a total radioactivity greater than 200 mCi, with specific activity up to 5.6 GBq/μmoL. It was further incorporated into modified monoclonal antibody DOTA-rituximab to synthesize ⁶⁴Cu-DOTA-rituximab, which was used successfully for micro-PET imaging. Full article

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8 pages, 2128 KiB

Open AccessArticle

Anti-Proliferative Effect of Triterpenoidal Glycosides from the Roots of Anemone vitifolia through a Pro-Apoptotic Way

by Changcai Bai^1,*,†

, Yunyun Ye^1,2,†, Xiao Feng^2,†, Ruifeng Bai², Lu Han¹, Xiuping Zhou¹, Xinyao Yang², Pengfei Tu² and Xingyun Chai^2,*

¹ Key Laboratory of Hui Medicine Modernization, Ministry of Education, Ningxia Medical University Pharmacy College, Yinchuan 750004, China

² Modern Research Center for Traditional Chinese Medicine, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, China

^† These authors contributed to the paper equally.

Molecules 2017, 22(4), 642; https://doi.org/10.3390/molecules22040642 - 17 Apr 2017

Cited by 10 | Viewed by 4529

Abstract

A cytotoxicity-guided phytochemical investigation of Anemone vitifolia roots led to the isolation of six oleanane saponins (1–6), which were reported from the species for the first time. Their structures were determined by comparing its MS and NMR data with [...] Read more.

A cytotoxicity-guided phytochemical investigation of Anemone vitifolia roots led to the isolation of six oleanane saponins (1–6), which were reported from the species for the first time. Their structures were determined by comparing its MS and NMR data with those in literature. Compounds 1–4 showed significant inhibitory effects on the proliferation of hepatocellular carcinoma HepG2 cells with IC₅₀ values ranging from 2.0 to 8.5 μM, compared to positive control methotrexate with IC₅₀ value of 15.8 μM. Flow cytometry analysis revealed that compounds 1–4 exerted anti-proliferative effects through a pro-apoptotic way of hepatocellular carcinoma cells. Full article

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8 pages, 1257 KiB

Open AccessCommunication

An Expedient Total Synthesis of Triciribine

by Chen Hu, Zhizhong Ruan, Haixin Ding, Yirong Zhou and Qiang Xiao^*

Jiangxi Key Laboratory of Organic Chemistry, Jiangxi Science & Technology Normal University, Nanchang 330013, China

Molecules 2017, 22(4), 643; https://doi.org/10.3390/molecules22040643 - 17 Apr 2017

Cited by 7 | Viewed by 4594

Abstract

In the present paper, we report an expedient total synthesis of triciribine, a tricyclic 7-deazapurine nucleoside and protein kinase B (AKT ) inhibitor, in 35% overall yield. Our synthesis route features a highly regioselective substitution of 1-N-Boc-2-methylhydrazine and a trifluoroacetic acid [...] Read more.

In the present paper, we report an expedient total synthesis of triciribine, a tricyclic 7-deazapurine nucleoside and protein kinase B (AKT ) inhibitor, in 35% overall yield. Our synthesis route features a highly regioselective substitution of 1-N-Boc-2-methylhydrazine and a trifluoroacetic acid catalyzed one-pot transformation which combined the deprotection of the tert-butylcarbonyl (Boc) group and ring closure reaction together to give a tricyclic nucleobase motif. Full article

(This article belongs to the Section Organic Chemistry)

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10 pages, 1859 KiB

Open AccessArticle

Systematic Understanding of the Mechanism of Salvianolic Acid A via Computational Target Fishing

by Shao-Jun Chen^* and Ming-Chao Cui

Department of Traditional Chinese Medicine, Zhejiang Pharmaceutical College, 888 Yinxian Avenue Eastern Section, Ningbo 315100, China

Molecules 2017, 22(4), 644; https://doi.org/10.3390/molecules22040644 - 17 Apr 2017

Cited by 35 | Viewed by 7443

Abstract

Salvianolic acid A (SAA) is one of the most abundant water-soluble and potent anti-oxidative compounds isolated from Danshen, a traditional Chinese medicine. A systematic overview of its mechanism of action is yet to be performed. In the present study, the druggability of SAA [...] Read more.

Salvianolic acid A (SAA) is one of the most abundant water-soluble and potent anti-oxidative compounds isolated from Danshen, a traditional Chinese medicine. A systematic overview of its mechanism of action is yet to be performed. In the present study, the druggability of SAA was measured using the TCMSP server, and potential targets of SAA were identified by PharmMapper and DRAR-CPI. Intersecting targets were then assessed by GeneMANIA and GO pathway analysis, and drug-target-pathway networks were constructed to give a visual view. The results showed that SAA has good druggability, and 13 putative protein targets were identified. Network analysis showed that these targets were associated with cancer, metabolism and other physiological processes. In summary, SAA is predicted to target multiple proteins and pathways to form a network that exerts systematic pharmacological effects. Full article

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27 pages, 9131 KiB

Open AccessArticle

Molecular Hybridization-Guided One-Pot Multicomponent Synthesis of Turmerone Motif-Fused 3,3′-Pyrrolidinyl-dispirooxindoles via a 1,3-Dipolar Cycloaddition Reaction

by Bing Lin^1,†, Gen Zhou^1,†, Yi Gong¹, Qi-Di Wei¹, Min-Yi Tian¹, Xiong-Li Liu^1,*, Ting-Ting Feng¹, Ying Zhou^1,* and Wei-Cheng Yuan²

¹ Guizhou Medicine Edicine Edible Plant Resources Research and Development Center, College of Pharmacy, Guizhou University, Guiyang 550025, China

² Key Laboratory for Asymmetric Synthesis & Chirotechnology of Sichuan Province, Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences, Chengdu 610041, China

^† These two authors contributed equally to this work.

Molecules 2017, 22(4), 645; https://doi.org/10.3390/molecules22040645 - 17 Apr 2017

Cited by 9 | Viewed by 5587

Abstract

Described herein is the development of a facile and efficient methodology for the synthesis of novel turmerone motif-fused 3,3′-pyrrolidinyl-dispirooxindoles 3–5 via a multicomponent 1,3-dipolar cycloaddition of dienones 2 with azomethine ylides (thermally generated in situfrom isatins and proline or thioproline or sarcosine). Products [...] Read more.

Described herein is the development of a facile and efficient methodology for the synthesis of novel turmerone motif-fused 3,3′-pyrrolidinyl-dispirooxindoles 3–5 via a multicomponent 1,3-dipolar cycloaddition of dienones 2 with azomethine ylides (thermally generated in situfrom isatins and proline or thioproline or sarcosine). Products bearing four or three consecutive stereocenters consist of two oxindole moieties and a pyrrolidinyl core, including vicinal spiroquaternary stereocenters fused in one ring structure were smoothly obtained in high yields (up to 93% yield) with good diastereoselectivity (up to >20:1). Another valuable application of this method was for the design of new hybrid architectures for biological screening through the adequate fusion of these sub-units of turmerone and 3,3′-pyrrolidinyl-dispirooxindole, generating drug-like molecules. Full article

(This article belongs to the Collection Heterocyclic Compounds)

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8 pages, 1220 KiB

Open AccessArticle

Metajapogenins A–C, Pregnane Steroids from Shells of Metaplexis japonica

by Hui-Li Yao, Yang Liu, Xiao-Hong Liu, Hua Gao, Kun Liu, Yan-Lin Shao, Xin-Yu Fang and Wei Wang^*

School of Pharmacy, Qingdao University, Qingdao 266021, Shandong, China

Molecules 2017, 22(4), 646; https://doi.org/10.3390/molecules22040646 - 17 Apr 2017

Cited by 5 | Viewed by 4054

Abstract

Phytochemical investigation of the shells of Metaplexis japonica (Thunb.) Makino, belonging to the family of Apocynaceae, afforded three new pregnane steroids, metajapogenins A–C, along with three known compounds. The structures of the new compounds were elucidated as 12β,14β,17β-trihydroxypregna-3,5-dien-7,20-dione, 12β,14β,17β,20β-tetrahydroxypregna-3,5-dien-7-one; 3β,12β,14β,17β-tetrahydroxypregn-5-ene-7,20-dione on the basis [...] Read more.

Phytochemical investigation of the shells of Metaplexis japonica (Thunb.) Makino, belonging to the family of Apocynaceae, afforded three new pregnane steroids, metajapogenins A–C, along with three known compounds. The structures of the new compounds were elucidated as 12β,14β,17β-trihydroxypregna-3,5-dien-7,20-dione, 12β,14β,17β,20β-tetrahydroxypregna-3,5-dien-7-one; 3β,12β,14β,17β-tetrahydroxypregn-5-ene-7,20-dione on the basis of extensive spectroscopic evidence derived from 1D; 2D-NMR experiments and mass spectrometry. The known compounds included pergularin; 12-O-acetylpergularin; and pergularin-3-O-β-d-oleandropyranose; which were identified for the first time in the shells of M. japonica. Full article

(This article belongs to the Section Natural Products Chemistry)

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12 pages, 556 KiB

Open AccessArticle

Chemical Constituents of Supercritical Extracts from Alpinia officinarum and the Feeding Deterrent Activity against Tribolium castaneum

by Mintong Xin¹, Shanshan Guo¹, Wenjuan Zhang¹

, Zhufeng Geng^1,2, Junyu Liang¹, Shushan Du^1,*, Zhiwei Deng² and Yongyan Wang¹

¹ Beijing Key Laboratory of Traditional Chinese Medicine Protection and Utilization, Faculty of Geographical Science, Beijing Normal University, Beijing 100875, China

² Analytical and Testing Center, Beijing Normal University, Beijing 100875, China

Molecules 2017, 22(4), 647; https://doi.org/10.3390/molecules22040647 - 18 Apr 2017

Cited by 20 | Viewed by 6467

Abstract

Alpinia officinarum has been confirmed to possess bioactivities against some pests. In this work, a sample was obtained from A. officinarum rhizomes by supercritical fluid CO₂ extraction (SFE). According to GC-MS analysis, the main chemical components for SFE-sample included benzylacetone (26.77%), 1,7-diphenyl-5-hydroxy-3-heptanone [...] Read more.

Alpinia officinarum has been confirmed to possess bioactivities against some pests. In this work, a sample was obtained from A. officinarum rhizomes by supercritical fluid CO₂ extraction (SFE). According to GC-MS analysis, the main chemical components for SFE-sample included benzylacetone (26.77%), 1,7-diphenyl-5-hydroxy-3-heptanone (17.78%), guaiacylacetone (10.03%) and benzenepropanal (7.42%). The essential oil of A. officinarum rhizomes (LD₅₀ = 20.71 μg/adult) exhibited more contact toxicity than SFE extract (LD₅₀ = 82.72 μg/adult) against Tribolium castaneum. From SFE extracts, one new compound, 1-phenyl-4-(16,17-dimethyl-9,13-octadiene)-5-isopentenyl-7-(4”-methoxyl-3”-hydroxyl-phenyl)-3-heptanone (3), together with five known compounds identified as 5-hydroxy-1,7-diphenyl-3-heptanone (1), 1,7-diphenyl-4-hepten-3-one (2), galangin (4), galangin-3-methyl ether (5) and pinocembrin (6), were isolated and their feeding deterrent activities against T. castaneum adults were assessed. It was found that compounds 1–6 had feeding deterrent activities against T. castaneum with feeding deterrent indices of 18.21%, 18.94%, 19.79%, 26.99%, 20.34%, and 35.81%, respectively, at the concentration of 1500 ppm. Hence, the essential oil and SFE extracts/compounds of A. officinarum rhizomes represent promising alternatives in the control of T. castaneum adults. Full article

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10 pages, 423 KiB

Open AccessArticle

Growth Inhibition of Sulfate-Reducing Bacteria in Produced Water from the Petroleum Industry Using Essential Oils

by Pamella Macedo de Souza¹, Fátima Regina de Vasconcelos Goulart¹, Joana Montezano Marques^1,2, Humberto Ribeiro Bizzo³

, Arie Fitzgerald Blank⁴

, Claudia Groposo⁵, Maíra Paula de Sousa⁵, Vanessa Vólaro⁶, Celuta Sales Alviano¹, Daniela Sales Alviano Moreno¹ and Lucy Seldin^1,*

¹ Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-590, Brazil

² Instituto de Ciências Biológicas, Universidade Federal do Pará, Pará 66075-900, Brazil

³ Embrapa, Agroindústria de Alimentos, Rio de Janeiro 23020-470 Brazil

⁴ Departamento de Engenharia Agronômica, Universidade Federal de Sergipe, Sergipe 49.100-000, Brazil

⁵ CENPES/Petrobras, Rio de Janeiro 21941-915, Brazil

⁶ Grupo Falcão Bauer, São Paulo 05036-070, Brazil

Molecules 2017, 22(4), 648; https://doi.org/10.3390/molecules22040648 - 19 Apr 2017

Cited by 22 | Viewed by 7183

Abstract

Strategies for the control of sulfate-reducing bacteria (SRB) in the oil industry involve the use of high concentrations of biocides, but these may induce bacterial resistance and/or be harmful to public health and the environment. Essential oils (EO) produced by plants inhibit the [...] Read more.

Strategies for the control of sulfate-reducing bacteria (SRB) in the oil industry involve the use of high concentrations of biocides, but these may induce bacterial resistance and/or be harmful to public health and the environment. Essential oils (EO) produced by plants inhibit the growth of different microorganisms and are a possible alternative for controlling SRB. We aimed to characterize the bacterial community of produced water obtained from a Brazilian petroleum facility using molecular methods, as well as to evaluate the antimicrobial activity of EO from different plants and their major components against Desulfovibrio alaskensis NCIMB 13491 and against SRB growth directly in the produced water. Denaturing gradient gel electrophoresis revealed the presence of the genera Pelobacter and Marinobacterium, Geotoga petraea, and the SRB Desulfoplanes formicivorans in our produced water samples. Sequencing of dsrA insert-containing clones confirmed the presence of sequences related to D. formicivorans. EO obtained from Citrus aurantifolia, Lippia alba LA44 and Cymbopogon citratus, as well as citral, linalool, eugenol and geraniol, greatly inhibited (minimum inhibitory concentration (MIC) = 78 µg/mL) the growth of D. alaskensis in a liquid medium. The same MIC was obtained directly in the produced water with EO from L. alba LA44 (containing 82% citral) and with pure citral. These findings may help to control detrimental bacteria in the oil industry. Full article

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

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17 pages, 6326 KiB

Open AccessArticle

Inhibitory Effect of Triterpenoids from Panax ginseng on Coagulation Factor X

by Lingxin Xiong^1,2,3, Zeng Qi^1,2, Bingzhen Zheng^1,2, Zhuo Li^1,2, Fang Wang³, Jinping Liu^1,2,*

and Pingya Li^1,2,*

¹ School of Pharmaceutical Sciences, Jilin University, Fujin Road 1266, Changchun 130021, China

² National and Local Joint Engineering Research Center for Ginseng Innovative Drugs Development, Western Chaoyang Road 45, Changchun 130021, China

³ Department of Pathogen Biology, Basic Medical College, Jilin University, Changchun 130021, China

Molecules 2017, 22(4), 649; https://doi.org/10.3390/molecules22040649 - 24 Apr 2017

Cited by 28 | Viewed by 6790

Abstract

Enzymes involved in the coagulation process have received great attention as potential targets for the development of oral anti-coagulants. Among these enzymes, coagulation factor Xa (FXa) has remained the center of attention in the last decade. In this study, 16 ginsenosides and two [...] Read more.

Enzymes involved in the coagulation process have received great attention as potential targets for the development of oral anti-coagulants. Among these enzymes, coagulation factor Xa (FXa) has remained the center of attention in the last decade. In this study, 16 ginsenosides and two sapogenins were isolated, identified and quantified. To determine the inhibitory potential on FXa, the chromogenic substrates method was used. The assay suggested that compounds 5, 13 and 18 were mainly responsible for the anti-coagulant effect. Furthermore, these three compounds also possessed high thrombin selectivity in the thrombin inhibition assay. Furthermore, Glide XP from Schrödinger was employed for molecular docking to clarify the interaction between the bioactive compounds and FXa. Therefore, the chemical and biological results indicate that compounds 5 (ginsenoside Rg2), 13 (ginsenoside Rg3) and 18 (protopanaxtriol, PPT) are potential natural inhibitors against FXa. Full article

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

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17 pages, 1342 KiB

Open AccessArticle

Synthesis, Characterization, Antimicrobial and Antiproliferative Activity Evaluation of Cu(II), Co(II), Zn(II), Ni(II) and Pt(II) Complexes with Isoniazid-Derived Compound

by Elena Pahonțu^1,*, Diana-Carolina Ilieș^2,*, Sergiu Shova³, Camelia Oprean^4,5, Virgil Păunescu^5,6, Octavian Tudorel Olaru⁷

, Flavian Ștefan Rădulescu⁸, Aurelian Gulea⁹, Tudor Roșu¹⁰ and Doina Drăgănescu¹¹

¹ Inorganic Chemistry Department, Faculty of Pharmacy, University of Medicine and Pharmacy “Carol Davila”, 6 Traian Vuia Street, 020956 Bucharest, Romania

² Organic Chemistry Department, Faculty of Pharmacy, University of Medicine and Pharmacy “Carol Davila”, 6 Traian Vuia Street, 020956 Bucharest, Romania

³ Institute of Macromolecular Chemistry “Petru Poni”, 41A Grigore Ghica Voda Alley, 700487 Iasi, Romania

⁴ Environmental and Food Chemistry Department, Faculty of Pharmacy, University of Medicine and Pharmacy “Victor Babeş”, 2nd Eftimie Murgu Sq., 300041 Timişoara, Romania

⁵ “Pius Brinzeu” Timișoara County Emergency Clinical Hospital, Oncogen Institute, 156 Liviu Rebreanu, 300723 Timişoara, Romania

⁶ Functional Sciences Department, Faculty of Medicine, University of Medicine and Pharmacy “Victor Babeş”, 2 Eftimie Murgu Square, 300041 Timişoara, Romania

⁷ Pharmaceutical Botany and Cell Biology Department, Faculty of Pharmacy, University of Medicine and Pharmacy “Carol Davila”, 6 Traian Vuia Street, 020956 Bucharest, Romania

⁸ Pharmaceutical Biotechnology Department, Faculty of Pharmacy, University of Medicine and Pharmacy “Carol Davila”, 6 Traian Vuia Street, 020956 Bucharest, Romania

⁹ Coordination Chemistry Department, Moldova State University, 60 Mateevici Street, 2009 Chisinau, Moldova

¹⁰ Inorganic Chemistry Department, Faculty of Chemistry, University of Bucharest, 23 Dumbrava Rosie Street, 020462 Bucharest, Romania

¹¹ Pharmaceutical Physics Department, Faculty of Pharmacy, University of and Pharmacy “Carol Davila”, 6 Traian Vuia Street, 020956 Bucharest, Romania

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Molecules 2017, 22(4), 650; https://doi.org/10.3390/molecules22040650 - 19 Apr 2017

Cited by 58 | Viewed by 6666

Abstract

Hydrazone complexes of Cu(II), Co(II), Zn(II), Ni(II) and Pt(II) with N-isonicotinoyl-N′-(3-metoxy-2 hydroxybenzaldehyde)-hydrazone (HL) were synthesized and characterized by different physico-chemical techniques including elemental and thermal analysis, magnetic susceptibility measurements, molar electric conductivity, as well as IR (infrared), ¹ [...] Read more.

Hydrazone complexes of Cu(II), Co(II), Zn(II), Ni(II) and Pt(II) with N-isonicotinoyl-N′-(3-metoxy-2 hydroxybenzaldehyde)-hydrazone (HL) were synthesized and characterized by different physico-chemical techniques including elemental and thermal analysis, magnetic susceptibility measurements, molar electric conductivity, as well as IR (infrared), ¹H-NMR and ¹³C-NMR (hydrogen and carbon nuclear magnetic resonance, UV-Vis (ultraviolet-visible), FAB (fast atom bombardment), EPR (electron paramagnetic resonance), and mass spectroscopies. The crystal structure of ligand was determined by single crystal X-ray diffraction studies. Spectral data showed that hydrazone behaves as an ONO tridentate ligand through the azomethine nitrogen, phenolate and keto oxygen atoms. For the copper(II) complexes, metal–ligand bonding parameters were evaluated from the EPR spectra. These parameters indicate the presence of in-plane π bonding. In addition, the f values of complexes 1–4 indicate small distortion from planarity. The effect of these complexes on proliferation of human breast cancer (MCF-7 and SKBR-3), human melanoma (A375), lung adenocarcinoma cells (NCI-H1573) and their antibacterial activity against Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus and Candida albicans strains were studied and compared with those of free ligand. The ligand and complexes 1–3 showed significant antimicrobial activity against the Gram-positive bacteria Staphylococcus aureus and Candida albicans in comparison to the control drugs. The complexes 2–4 could be potential antitumor agents, leading to a significant improvement of the cytotoxic activity when compared with HL. Full article

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

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11 pages, 251 KiB

Open AccessArticle

Antifungal and Anti-Biofilm Activities of Acetone Lichen Extracts against Candida albicans

by Marion Millot^1,*,†, Marion Girardot^2,†, Lucile Dutreix², Lengo Mambu¹ and Christine Imbert²

¹ Laboratoire de Chimie des Substances Naturelles, Faculté de Pharmacie, 2 rue du Dr Marcland, 87025 Limoges, France

² Laboratoire Ecologie et Biologie des Interactions, Equipe Microbiologie de l’Eau, Université de Poitiers, UMR CNRS 7267, F-86073 Poitiers, France

^† These authors contributed equally to this work.

Molecules 2017, 22(4), 651; https://doi.org/10.3390/molecules22040651 - 19 Apr 2017

Cited by 44 | Viewed by 8681

Abstract

Candida albicans is a commensal coloniser of the human gastrointestinal tract and an opportunistic pathogen, especially thanks to its capacity to form biofilms. This lifestyle is frequently involved in infections and increases the yeast resistance to antimicrobials and immune defenses. In this context, [...] Read more.

Candida albicans is a commensal coloniser of the human gastrointestinal tract and an opportunistic pathogen, especially thanks to its capacity to form biofilms. This lifestyle is frequently involved in infections and increases the yeast resistance to antimicrobials and immune defenses. In this context, 38 lichen acetone extracts have been prepared and evaluated for their activity against C. albicans planktonic and sessile cells. Minimum inhibitory concentrations of extracts (MICs) were determined using the broth microdilution method. Anti-biofilm activity was evaluated using tetrazolium salt (XTT) assay as the ability to inhibit the maturation phase (anti-maturation) or to eradicate a preformed 24 h old biofilm (anti-biofilm). While none of the extracts were active against planktonic cells, biofilm maturation was limited by 11 of the tested extracts. Seven extracts displayed both anti-maturation and anti-biofilm activities (half maximal inhibitory concentrations IC_{50_mat} and IC_{50_biof} ≤ 100 µg/mL); Evernia prunastri and Ramalina fastigiata were the most promising lichens (IC_{50_mat} < 4 µg/mL and IC_{50_biof} < 10 µg/mL). Chemical profiles of the active extracts performed by thin layer chromatography (TLC) and high performance liquid chromatography (HPLC) have been analyzed. Depsides, which were present in large amounts in the most active extracts, could be involved in anti-biofilm activities. This work confirmed that lichens represent a reservoir of compounds with anti-biofilm potential. Full article

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

17 pages, 4022 KiB

Open AccessArticle

Modification of Natural Eudesmane Scaffolds via Mizoroki-Heck Reactions

by Mohamed Zaki^1,2, Mohamed Akssira² and Sabine Berteina-Raboin^1,*

¹ Institut de Chimie Organique et Analytique, University d’Orléans, UMR CNRS 7311, B.P. 6759, 45067 Orléans CEDEX 2, France

² Laboratoire de Chimie Physique & Chimie Bioorganique, Département de chimie, URA C 22, Pôle RéPAM, F. S. T. University Hassan II de Casablanca, B.P. 146 Yasmina, 28800 Mohammedia, Morocco

Molecules 2017, 22(4), 652; https://doi.org/10.3390/molecules22040652 - 20 Apr 2017

Viewed by 5504

Abstract

The Mizoroki-Heck reaction was applied to substrates derived from isocostic and ilicic acids, important sesquiterpene components of Dittrichia viscosa L. Greuter that were extracted directly from plant material collected in Morocco. After optimization of the metallo-catalysis conditions, various aryl-groups were successfully introduced on [...] Read more.

The Mizoroki-Heck reaction was applied to substrates derived from isocostic and ilicic acids, important sesquiterpene components of Dittrichia viscosa L. Greuter that were extracted directly from plant material collected in Morocco. After optimization of the metallo-catalysis conditions, various aryl-groups were successfully introduced on the exocyclic double bond with an exclusive E-configuration and without racemization. Full article

(This article belongs to the Collection Bioactive Compounds)

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12 pages, 8629 KiB

Open AccessArticle

Gamma-Aminobutyric Acid Increases the Production of Short-Chain Fatty Acids and Decreases pH Values in Mouse Colon

by Min Xie, Hai-Hong Chen, Shao-Ping Nie, Jun-Yi Yin^* and Ming-Yong Xie^*

State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047, China

Molecules 2017, 22(4), 653; https://doi.org/10.3390/molecules22040653 - 20 Apr 2017

Cited by 31 | Viewed by 6847

Abstract

Gamma-Aminobutyric acid (GABA) could regulate physiological functions in the gastrointestinal tract. The present study aimed to investigate the effect of GABA on colon health in mice. The female Kunming mice were given GABA at doses of 5, 10, 20 and 40 mg/kg/d for [...] Read more.

Gamma-Aminobutyric acid (GABA) could regulate physiological functions in the gastrointestinal tract. The present study aimed to investigate the effect of GABA on colon health in mice. The female Kunming mice were given GABA at doses of 5, 10, 20 and 40 mg/kg/d for 14 days. Afterwards, the short-chain fatty acids (SCFAs) concentrations, pH values, colon index, colon length and weight of colonic and cecal contents were determined to evaluate the effects of GABA on colon health. The results showed that intake of GABA could increase the concentrations of acetate, propionate, butyrate and total SCFAs in colonic and cecal contents, as well as the weight of colonic and cecal contents. The colon index and length of the 40 mg/kg/d GABA-treated group were significantly higher than those of the control group (p < 0.05). In addition, decrease of pH values in colonic and cecal contents was also observed. These results suggest that GABA may improve colon health. Full article

(This article belongs to the Section Medicinal Chemistry)

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15 pages, 10429 KiB

Open AccessArticle

Study on the Rationality for Antiviral Activity of Flos Lonicerae Japonicae-Fructus Forsythiae Herb Couple Preparations Improved by Chito-Oligosaccharide via Integral Pharmacokinetics

by Wei Zhou^1,2,3,4, Ailing Yin⁵, Jinjun Shan⁶, Shouchuan Wang⁶, Baochang Cai¹ and Liuqing Di^1,2,3,*

¹ College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China

² Jiangsu Engineering Research Center for Efficient Delivery System of TCM, Nanjing 210023, China

³ Nanjing Engineering Research Center for Industrialization of Chinese Medicine Pellets, Nanjing 210023, China

⁴ Faculty of Health Sciences, University of Macau, Macau SAR, China

⁵ Department of Pharmacy, Third Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210023, China

⁶ Jiangsu Key Laboratory of Pediatric Respiratory Disease, Institute of Paediatrics, Nanjing University of Chinese Medicine, Nanjing 210021, China

Molecules 2017, 22(4), 654; https://doi.org/10.3390/molecules22040654 - 20 Apr 2017

Cited by 33 | Viewed by 6436

Abstract

In the present study, the rationality for the antiviral effect (H1N1 virus) of Flos Lonicerae Japonicae (FLJ, named JinYinHua)-Fructus forsythiae (FF, named LianQiao) herb couple preparations improved by chito-oligosaccharide (COS) was investigated. We found that the improvement of antiviral activity for four preparations [...] Read more.

In the present study, the rationality for the antiviral effect (H1N1 virus) of Flos Lonicerae Japonicae (FLJ, named JinYinHua)-Fructus forsythiae (FF, named LianQiao) herb couple preparations improved by chito-oligosaccharide (COS) was investigated. We found that the improvement of antiviral activity for four preparations attributed to the enhancement of bioavailability for the FLJ-FF herb couple in vivo, and that caffeic acid derivatives are the most important type of components for antiviral activity. The anti-Influenza virus activity-half maximal inhibitory concentration (IC₅₀), not area under concentration (AUC) was considered as the weighting factor for integrating the pharmacokinetics of caffeic acid derivatives. It was found that the integral absorption, both in vitro and in vivo, especially that in Shuang-Huang-Lian, can be improved significantly by COS, an absorption enhancer based on tight junction. The results indicated that the antiviral activity in four preparations improved by COS was mainly attributed to the integral absorption enhancement of caffeic acid derivatives. Full article

(This article belongs to the Section Natural Products Chemistry)

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18 pages, 20087 KiB

Open AccessArticle

Protein Stability and Unfolding Following Glycine Radical Formation

by Michael C. Owen,^1,*, Imre G. Csizmadia^2,3, Béla Viskolcz²

and Birgit Strodel^1,4

¹ Institute of Complex Systems: Structural Biochemistry (ICS-6) Forschungszentrum Jülich, 52425 Jülich, Germany

² Institute of Chemistry, Faculty of Material Science, University of Miskolc, Egyetemváros 1, H-3529 Miskolc, Hungary

³ Department of Chemistry, University of Toronto, Toronto, ON M5S 3H6, Canada

⁴ Institute of Theoretical and Computational Chemistry, Heinrich Heine University Düsseldorf, Universitätsstrasse 1, 40225 Düsseldorf, Germany

Molecules 2017, 22(4), 655; https://doi.org/10.3390/molecules22040655 - 19 Apr 2017

Cited by 6 | Viewed by 6499

Abstract

Glycine (Gly) residues are particularly susceptible to hydrogen abstraction; which results in the formation of the capto-dative stabilized C_α-centered Gly radical (GLR) on the protein backbone. We examined the effect of GLR formation on the structure of the Trp cage; tryptophan [...] Read more.

Glycine (Gly) residues are particularly susceptible to hydrogen abstraction; which results in the formation of the capto-dative stabilized C_α-centered Gly radical (GLR) on the protein backbone. We examined the effect of GLR formation on the structure of the Trp cage; tryptophan zipper; and the villin headpiece; three fast-folding and stable miniproteins; using all-atom (OPLS-AA) molecular dynamics simulations. Radicalization changes the conformation of the GLR residue and affects both neighboring residues but did not affect the stability of the Trp zipper. The stability of helices away from the radical center in villin were also affected by radicalization; and GLR in place of Gly15 caused the Trp cage to unfold within 1 µs. These results provide new evidence on the destabilizing effects of protein oxidation by reactive oxygen species. Full article

(This article belongs to the Special Issue Biomolecular Simulations)

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12 pages, 5249 KiB

Open AccessArticle

Synthetic Fluororutaecarpine Inhibits Inflammatory Stimuli and Activates Endothelial Transient Receptor Potential Vanilloid-Type 1

by Chi-Ming Lee¹, Jiun-An Gu², Tin-Gan Rau², Chi Wang¹, Chiao-Han Yen¹, Shih-Hao Huang³, Feng-Yen Lin⁴, Chun-Mao Lin^5,*,† and Sheng-Tung Huang^6,*,†

¹ Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan

² Institute of Chemical Engineering, College of Engineering, National Taipei University of Technology, Taipei 10608, Taiwan

³ Department of Food and Beverage Management, Taipei College of Maritime Technology, Taipei 11174, Taiwan

⁴ Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan

⁵ Department of Biochemistry, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan

⁶ Institute of Biochemical and Biomedical Engineering, College of Engineering, National Taipei University of Technology, Taipei 10608, Taiwan

^† These authors contributed equally to this work.

Molecules 2017, 22(4), 656; https://doi.org/10.3390/molecules22040656 - 19 Apr 2017

Cited by 11 | Viewed by 5075

Abstract

The natural product, rutaecarpine (RUT), is the main effective component of Evodia rutaecarpa which is a widely used traditional Chinese medicine. It has vasodilation, anticoagulation, and anti-inflammatory activities. However, further therapeutic applications are limited by its cytotoxicity. Thus, a derivative of RUT, 10-fluoro-2-methoxyrutaecarpine [...] Read more.

The natural product, rutaecarpine (RUT), is the main effective component of Evodia rutaecarpa which is a widely used traditional Chinese medicine. It has vasodilation, anticoagulation, and anti-inflammatory activities. However, further therapeutic applications are limited by its cytotoxicity. Thus, a derivative of RUT, 10-fluoro-2-methoxyrutaecarpine (F-RUT), was designed and synthesized that showed no cytotoxicity toward RAW264.7 macrophages at 20 μM. In an anti-inflammation experiment, it inhibited the production of nitric oxide (NO) and tumor necrosis factor (TNF)-α in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages; cyclooxygenase (COX)-2 and inducible NO synthase (iNOS) induced by LPS were also downregulated. After 24 h of treatment, F-RUT significantly inhibited cell migration and invasion of ovarian A2780 cells. Furthermore, F-RUT promoted expressions of transient receptor potential vanilloid type 1 (TRPV1) and endothelial (e)NOS in human aortic endothelial cells, and predominantly reduced the inflammation in ovalbumin/alum-challenged mice. These results suggest that the novel synthetic F-RUT exerts activities against inflammation and vasodilation, while displaying less toxicity than its lead compound. Full article

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20 pages, 3885 KiB

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Diversity Analysis and Bioresource Characterization of Halophilic Bacteria Isolated from a South African Saltpan

by Ramganesh Selvarajan^1,*

, Timothy Sibanda¹, Memory Tekere¹, Hlengilizwe Nyoni² and Stephen Meddows-Taylor³

¹ Department of Environmental Sciences, College of Agriculture and Environmental Sciences, UNISA Science Campus, P.O. Box X6, Florida 1710, South Africa

² Department of Nanotechnology and Water Sustainability, College of Science, Engineering and Technology, UNISA Science Campus, P.O. Box X6, Florida 1710, South Africa

³ College of Agriculture and Environmental Sciences Laboratories, UNISA Science Campus, P.O. Box X6, Florida 1710, South Africa

Molecules 2017, 22(4), 657; https://doi.org/10.3390/molecules22040657 - 20 Apr 2017

Cited by 41 | Viewed by 10254

Abstract

Though intensive research has been channeled towards the biotechnological applications of halophiles and other extremophilic microbes, these studies have not been, by any means, exhaustive. Saline environments still offer a vast diversity of microbes with potential to produce an array of natural products [...] Read more.

Though intensive research has been channeled towards the biotechnological applications of halophiles and other extremophilic microbes, these studies have not been, by any means, exhaustive. Saline environments still offer a vast diversity of microbes with potential to produce an array of natural products which can only be unlocked by concerted research efforts. In this study, a combination of culture and molecular approaches were employed to characterize halophilic bacteria from saltpan water samples and profile their potential biotechnological applications. Physicochemical analysis of the water samples showed that pH was alkaline (pH 8.8), with a salinity of 12.8%. 16S rRNA gene targeted amplicon analysis produced 10 bacterial phyla constituting of Bacteroidetes (30.57%), Proteobacteria (15.27%), Actinobacteria (9.05%), Planctomycetes (5.52%) and Cyanobacteria (3.18%). Eighteen strains were identified using sequencing analysis of the culturable bacterial strains. From these, the strains SP7 and SP9 were positive for cellulase production while the strains SP4, SP8 and SP22 were positive for lipase production. Quantitative enzyme assays showed moderate extracellular cellulase activity (1.95 U/mL) and lipase activity (3.71 U/mL) by the isolate SP9 and SP4 respectively. Further, of the six isolates, the isolate SP9 exhibited exploitable potential in the bioremediation of hydrocarbon pollution as demonstrated by its fairly high activity against benzanthracene (70% DCPIP reduction). Elucidation of the isolates secondary metabolites showed the production of the molecules 2,3-butanediol, hexahydro-3-(2-methylpropyl)pyrrole[1,2a]pyrazine-1,4-dione, aziridine, dimethylamine and ethyl acetate (GC-MS) and oxypurinol and 5-hydroxydecanoic acid (LC-MS), particularly by the isolate Salinivibrio sp. SP9. Overall, the study showed that the isolated halophiles can produce secondary metabolites with potential industrial and pharmaceutical application. Full article

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

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9 pages, 521 KiB

Open AccessArticle

Synthesis and Antiviral Activity of Novel 1,4-Pentadien-3-one Derivatives Containing a 1,3,4-Thiadiazole Moiety

by Lu Yu^†, Xiuhai Gan^†, Dagui Zhou, Fangcheng He, Song Zeng and Deyu Hu^*

¹ State Key Laboratory Breeding Base of Green Pesticide and Agricultural Bioengineering, Key Laboratory of Green Pesticide and Agriculture Bioengineering, Ministry of Education, Guizhou University, Guiyang 550025, Guizhou, China

^† These authors contributed equally to this work.

Molecules 2017, 22(4), 658; https://doi.org/10.3390/molecules22040658 - 21 Apr 2017

Cited by 54 | Viewed by 6681

Abstract

1,4-Pentadien-3-one derivatives derived from curcumin possess excellent inhibitory activity against plant viruses. On the basis of this finding, a series of novel 1,4-pentadien-3-one derivatives containing a 1,3,4-thiadiazole moiety were designed and synthesized, and their structures confirmed by IR, ¹H-NMR, and ¹³C-NMR [...] Read more.

1,4-Pentadien-3-one derivatives derived from curcumin possess excellent inhibitory activity against plant viruses. On the basis of this finding, a series of novel 1,4-pentadien-3-one derivatives containing a 1,3,4-thiadiazole moiety were designed and synthesized, and their structures confirmed by IR, ¹H-NMR, and ¹³C-NMR spectroscopy and elemental analysis. The antiviral activities of the title compounds were evaluated against tobacco mosaic virus (TMV) and cucumber mosaic virus (CMV) in vivo. The assay results showed that most of compounds had remarkable antiviral activities against TMV and CMV, among which compounds 4b, 4h, 4i, 4k, 4o, and 4q exhibited good curative, protection, and inactivation activity against TMV. Compounds 4h, 4i, 4k, 4l, 4o, and 4q exhibited excellent protection activity against TMV, with EC₅₀ values of 105.01, 254.77, 135.38, 297.40, 248.18, and 129.87 μg/mL, respectively, which were superior to that of ribavirin (457.25 µg/mL). In addition, preliminary SARs indicated that small electron-withdrawing groups on the aromatic ring were favorable for anti-TMV activity. This finding suggests that 1,4-pentadien-3-one derivatives containing a 1,3,4-thiadiazole moiety may be considered as potential lead structures for discovering new antiviral agents. Full article

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

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11 pages, 3158 KiB

Open AccessArticle

Synthesis, Biological Evaluation, and Molecular Docking Studies of Novel Isatin-Thiazole Derivatives as α-Glucosidase Inhibitors

by Zhenzhen Xie, Guangcheng Wang^*, Jing Wang, Ming Chen, Yaping Peng, Luyao Li, Bing Deng, Shan Chen and Wenbiao Li

College of Chemistry and Chemical Engineering, Hunan Engineering Laboratory for Analyse and Drugs Development of Ethnomedicine in Wuling Mountains, Jishou University, Jishou 416000, China

Molecules 2017, 22(4), 659; https://doi.org/10.3390/molecules22040659 - 20 Apr 2017

Cited by 53 | Viewed by 6782

Abstract

A series of novel isatin-thiazole derivatives were synthesized and screened for their in vitro α-glucosidase inhibitory activity. These compounds displayed a varying degree of α-glucosidase inhibitory activity with IC₅₀ ranging from 5.36 ± 0.13 to 35.76 ± 0.31 μm as compared to [...] Read more.

A series of novel isatin-thiazole derivatives were synthesized and screened for their in vitro α-glucosidase inhibitory activity. These compounds displayed a varying degree of α-glucosidase inhibitory activity with IC₅₀ ranging from 5.36 ± 0.13 to 35.76 ± 0.31 μm as compared to the standard drug acarbose (IC₅₀ = 817.38 ± 6.27 μm). Among the series, compound 6p bearing a hydroxyl group at the 4-position of the right phenyl and 2-fluorobenzyl substituent at the N1-positions of the 5-methylisatin displayed the highest inhibitory activity with an IC₅₀ value of 5.36 ± 0.13 μm. Molecular docking studies revealed the existence of hydrophobic interaction, CH-π interaction, arene-anion interaction, arene-cation interaction, and hydrogen bond between these compounds and α-glucosidase enzyme. Full article

(This article belongs to the Section Medicinal Chemistry)

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8 pages, 4159 KiB

Open AccessArticle

Evaluation of Tanshinone IIA Developmental Toxicity in Zebrafish Embryos

by Tao Wang¹

, Chengxi Wang², Qiong Wu², Kangdi Zheng², Jiaojiao Chen³, Yutao Lan^3,*, Yao Qin⁴, Wenjie Mei^2,* and Baoguo Wang^1,*

¹ School of Public Health, Guangdong Pharmaceutical University, Guangzhou 510310, Guangdong, China

² School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, Guangdong, China

³ School of Nursing, Guangdong Pharmaceutical University, Guangzhou 510310, Guangdong, China

⁴ Chn-Alternative Biotech Co. Ltd., Guangzhou 510432, Guangdong, China

Molecules 2017, 22(4), 660; https://doi.org/10.3390/molecules22040660 - 21 Apr 2017

Cited by 49 | Viewed by 6985

Abstract

Tanshinone IIA (Tan-IIA) is derived from the dried roots of Salvia miltiorrhiza Bunge, a traditional Chinese medicine. Although Salvia miltiorrhiza has been applied for many years, the toxicity of the mono-constituent of Salvia miltiorrhiza, tanshinone IIA, is still understudied. This study evaluated [...] Read more.

Tanshinone IIA (Tan-IIA) is derived from the dried roots of Salvia miltiorrhiza Bunge, a traditional Chinese medicine. Although Salvia miltiorrhiza has been applied for many years, the toxicity of the mono-constituent of Salvia miltiorrhiza, tanshinone IIA, is still understudied. This study evaluated the cardiotoxicity and developmental malformations of Tan-IIA by using zebrafish normal embryos and dechorionated embryos. After treatment with Tan-IIA in different concentrations for four-day periods, obvious pericardial edema, spinal curvature, and even missing tails were observed in zebrafish embryos. The LC₅₀ values in the dechorionated embryo group at 72 h post-fertilization (hpf) and 96 hpf were 18.5 μM and 12.8 μM, respectively, and the teratogenicity was manifested at a concentration of about 1 µM. The main endpoints of teratogenicity were scoliosis, malformation of tail, and pericardium edema. Our findings displayed the potential cardiotoxicity and severe impact on the abnormal development of Tan-IIA in zebrafish embryo at high concentrations, which may help avoid the risk of its clinical application. Full article

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

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10 pages, 1082 KiB

Open AccessArticle

Reactions of 5-Indolizyl Lithium Compounds with Some Bielectrophiles

by Sergey A. Rzhevskii^1,2, Victor B. Rybakov², Victor N. Khrustalev³

and Eugene V. Babaev^1,2,*

¹ Life Sciences Center, Moscow Institute of Physics and Technology, Institutskii per. 9/7, Dolgoprudniy, Moscow Region 141701, Russia

² Chemistry Department, Moscow State University, Moscow 119991, Russia

³ Peoples’ Friendship University of Russia (RUDN University), Miklukho-Maklaya str. 6, Moscow 117198, Russia

Molecules 2017, 22(4), 661; https://doi.org/10.3390/molecules22040661 - 20 Apr 2017

Cited by 4 | Viewed by 6382

Abstract

Abstract: Indolizyl-5-lithium anions react with succinic and phtalic anhidrides giving 1,4-keto acids, with oxallyl chloride giving 1,2-diketone, and with ethyl pyruvate giving 1,2-hydroxyacid. However, with α-halocarbonyl compounds, they react in different ways, forming the products of selective bromination at C-5 (with α-bromo [...] Read more.

Abstract: Indolizyl-5-lithium anions react with succinic and phtalic anhidrides giving 1,4-keto acids, with oxallyl chloride giving 1,2-diketone, and with ethyl pyruvate giving 1,2-hydroxyacid. However, with α-halocarbonyl compounds, they react in different ways, forming the products of selective bromination at C-5 (with α-bromo ketones and esters of α-bromo acids) and 5-chloroacetyl indolizines. Full article

(This article belongs to the Collection Heterocyclic Compounds)

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11 pages, 9169 KiB

Open AccessArticle

Improved Synthesis of 1-O-Acyl-β-d-Glucopyranose Tetraacetates

by Yu Chen¹, Huan Lu², Yanyu Chen¹, Wansheng Yu², Hui Dai² and Xianhua Pan^1,2,*

¹ School of Perfume and Aroma Technology, Shanghai Institute of Technology, 100 Haiquan Rd., Shanghai 201418, China

² Shanghai Research Institute of Fragrance and Flavor Industry, 480 Nanning Rd., Shanghai 200232, China

Molecules 2017, 22(4), 662; https://doi.org/10.3390/molecules22040662 - 21 Apr 2017

Cited by 2 | Viewed by 4728

Abstract

An improved synthesis of 1-O-acyl glucosyl esters that avoids the use of expensive Ag reagents as well as the hydrolysis of unstable glucosyl bromides is reported. Notably, β-configuration products were obtained exclusively in good yields. Full article

(This article belongs to the Section Organic Chemistry)

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12 pages, 42147 KiB

Open AccessArticle

On the Morphology of Group II Metal Fluoride Nanocrystals at Finite Temperature and Partial Pressure of HF

by Zeinab Kaawar¹, Stefan Mahn², Erhard Kemnitz²

and Beate Paulus^1,*

¹ Institut für Chemie und Biochemie, Freie Universität Berlin, Takustr. 3, 14195 Berlin, Germany

² Institut für Chemie, Humboldt-Universität zu Berlin, Brook-Taylor-Str. 2, 12489 Berlin, Germany

Molecules 2017, 22(4), 663; https://doi.org/10.3390/molecules22040663 - 21 Apr 2017

Cited by 4 | Viewed by 4970

Abstract

We have investigated the bulk and surface properties of the group II metal fluorides CaF

_{2}

, SrF

_{2}

and BaF

_{2}

using periodic density functional theory (DFT) calculations and surface thermodynamics. Our bulk results show that the best agreement with experiment is [...] Read more.

We have investigated the bulk and surface properties of the group II metal fluorides CaF

_{2}

, SrF

_{2}

and BaF

_{2}

using periodic density functional theory (DFT) calculations and surface thermodynamics. Our bulk results show that the best agreement with experiment is achieved with the B3LYP and PBE functionals. We determined the relative importance of the low index surfaces in vacuum and found that an fluoride microcrystal exposes only the (111) surface in which the undercoordinated cations are sevenfold coordinated. With methods of ab initio surface thermodynamics, we analyzed the stability of different surfaces under hydrogen fluoride (HF) pressure and determined the presumable shape of the crystals with respect to different HF concentrations and temperatures. In the case of CaF

_{2}

and SrF

_{2}

, the calculated shapes of the crystals agree well with TEM images of fluorolytic sol-gel synthesized nanocrystals at room temperature and high HF concentration. Full article

(This article belongs to the Special Issue Nano-sized Metal Fluorides: Novel Approaches to Lewis Acid Catalysts)

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16 pages, 4311 KiB

Open AccessArticle

Ameliorative Effects and Possible Molecular Mechanism of Action of Black Ginseng (Panax ginseng) on Acetaminophen-Mediated Liver Injury

by Jun-Nan Hu, Zhi Liu, Zi Wang, Xin-Dian Li, Lian-Xue Zhang, Wei Li^*

and Ying-Ping Wang^*

College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, China

Molecules 2017, 22(4), 664; https://doi.org/10.3390/molecules22040664 - 21 Apr 2017

Cited by 56 | Viewed by 8754

Abstract

Background: Frequent overdosing of acetaminophen (APAP) has become the major cause of acute liver injury (ALI). The present study aimed to evaluate the potential hepatoprotective effects of black ginseng (BG) on APAP-induced mice liver injuries and the underlying mechanisms of action were [...] Read more.

Background: Frequent overdosing of acetaminophen (APAP) has become the major cause of acute liver injury (ALI). The present study aimed to evaluate the potential hepatoprotective effects of black ginseng (BG) on APAP-induced mice liver injuries and the underlying mechanisms of action were further investigated for the first time. Methods: Mice were treated with BG (300, 600 mg/kg) by oral gavage once a day for seven days. On the 7th day, all mice were treated with 250 mg/kg APAP which caused severe liver injury after 24 h and hepatotoxicity was assessed. Results: Our results showed that pretreatment with BG significantly decreased the levels of serum alanine aminotransferase (ALT) and aspartate transaminase (AST) compared with the APAP group. Meanwhile, hepatic antioxidant including glutathione (GSH) was elevated compared with the APAP group. In contrast, a significant decrease of the levels of the lipid peroxidation product malondialdehyde (MDA) was observed in the BG-treated groups compared with the APAP group. These effects were associated with significant increases of cytochrome P450 E1 (CYP2E1) and 4-hydroxynonenal (4-HNE) levels in liver tissues. Moreover, BG supplementation suppressed activation of apoptotic pathways through increasing Bcl-2 and decreasing Bax protein expression levels according to western blotting analysis. Histopathological examination revealed that BG pretreatment significantly inhibited APAP-induced necrosis and inflammatory infiltration in liver tissues. Biological indicators of nitrative stress like 3-nitrotyrosine (3-NT) were also inhibited after pretreatment with BG, compared with the APAP group. Conclusions: The results clearly suggest that the underlying molecular mechanisms of action of BG-mediated alleviation of APAP-induced hepatotoxicity may involve its anti-oxidant, anti-apoptotic, anti-inflammatory and anti-nitrative effects. Full article

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

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12 pages, 3229 KiB

Open AccessArticle

Development of User-Friendly Method to Distinguish Subspecies of the Korean Medicinal Herb Perilla frutescens Using Multiplex-PCR

by Yonguk Kim¹

, Ah-Young Kim², Ara Jo¹, Hakjoon Choi¹, Seung-Sik Cho³

and Chulyung Choi^1,*

¹ Jeonnam Institute of Natural Resources Research, Jangheung-gun, Jeollanamdo 59338, Korea

² School of Biological Sciences and Technology, Chonnam National University, Gwangju 61186, Korea

³ Department of Pharmacy, College of Pharmacy, Mokpo National University, Muan, Jeonnam 58554, Korea

Molecules 2017, 22(4), 665; https://doi.org/10.3390/molecules22040665 - 21 Apr 2017

Cited by 9 | Viewed by 5718

Abstract

Perilla (Perilla frutescens) is an economically and culturally important plant in East Asia. Plant breeding between cultivars has enhanced the genetic diversity of perilla overall, but means that functionally diverse subspecies are more difficult to identify and distinguish. In this study, [...] Read more.

Perilla (Perilla frutescens) is an economically and culturally important plant in East Asia. Plant breeding between cultivars has enhanced the genetic diversity of perilla overall, but means that functionally diverse subspecies are more difficult to identify and distinguish. In this study, we developed gene-based DNA markers to distinguish between the Korean herbal medicinal perilla varieties. We identified informative simple sequence repeat (SSR) regions on the promoter regions of the Myb-P1 and dihydroflavonol 4-reductase (DFR) genes, as well as a large insertion-deletion (indel) region in the limonene synthase (LS) gene, and developed markers to characterize the distinct subspecies differences (PfMyb-P1pro, PfDFRpro, and PfLS, respectively). Using the PfLS primers, a 430-bp region could be amplified from P. frutescens var. acuta, crispa, and f. viridis (known as Jasoyeop, Jureum-soyeop, and Chungsoyeop, respectively), but not from P. frutescens var. japonica (Dlggae). The PfMybpro primers resulted in PCR products of 314 or 316, 330, 322, and 315 bp from Dlggae, Jasoyeop, Jureum-soyeop, and Chungsoyeop, respectively, and the PfDFRpro primers resulted in products of 189 or 202, 187 or 189, 185 or 189, and 193bp, respectively, for the four perilla subspecies. Combining these three reactions into a single multiplex PCR approach resulted in subspecies-specific PCR band patterns for six common types of commercial perilla, distinguishing between three varieties of Dlggae (Cham-Dlggae, Ip-Dlggae, and Bora-Dlggae), as well as identifying Jasoyeop, Jureum-soyeop, and Chungsoyeop. These user-friendly markers will be valuable as a simple and efficient method for identifying the Korean medicinal herb Jasoyeop, as well as distinguishing between other functionally distinct subspecies, which may have broad applications in the Korean herbal industry. Full article

(This article belongs to the Section Molecular Diversity)

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14 pages, 3169 KiB

Open AccessArticle

Phenolic Compounds Isolated from Caesalpinia coriaria Induce S and G2/M Phase Cell Cycle Arrest Differentially and Trigger Cell Death by Interfering with Microtubule Dynamics in Cancer Cell Lines

by Jessica Nayelli Sánchez-Carranza¹, Laura Alvarez², Silvia Marquina-Bahena², Enrique Salas-Vidal³, Verónica Cuevas¹, Elizabeth W. Jiménez¹, Rafael A. Veloz G.⁴, Maelle Carraz^5,*

and Leticia González-Maya^1,*

¹ Facultad de Farmacia, Universidad Autónoma del Estado de Morelos, Av. Universidad 1001, Col. Chamilpa, C.P. 62209 Cuernavaca, Mexico

² Centro de Investigaciones Químicas-IICBA, Universidad Autónoma del Estado de Morelos, Av. Universidad 1001, Col. Chamilpa, C.P. 62209 Cuernavaca, Mexico

³ Departamento de Genética del Desarrollo y Fisiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, C.P. 62209 Morelos, Mexico

⁴ Departamento de Ingenieria Agroindustrial, Universidad de Guanajuato, Salvatierra, C.P. 38000 Guanajuato, Mexico

⁵ UMR152 Pharma Dev, Université de Toulouse, IRD, UPS, 31062 Toulouse, France

Molecules 2017, 22(4), 666; https://doi.org/10.3390/molecules22040666 - 22 Apr 2017

Cited by 38 | Viewed by 8073

Abstract

Caesalpinia coriaria (C. coriaria), also named cascalote, has been known traditionally in México for having cicatrizing and inflammatory properties. Phytochemical reports on Caesalpinia species have identified a high content of phenolic compounds and shown antineoplastic effects against cancer cells. The aim [...] Read more.

Caesalpinia coriaria (C. coriaria), also named cascalote, has been known traditionally in México for having cicatrizing and inflammatory properties. Phytochemical reports on Caesalpinia species have identified a high content of phenolic compounds and shown antineoplastic effects against cancer cells. The aim of this study was to isolate and identify the active compounds of a water:acetone:ethanol (WAE) extract of C. coriaria pods and characterize their cytotoxic effect and cell death induction in different cancer cell lines. The compounds isolated and identified by chromatography and spectroscopic analysis were stigmasterol, ethyl gallate and gallic acid. Cytotoxic assays on cancer cells showed different ranges of activities. A differential effect on cell cycle progression was observed by flow cytometry. In particular, ethyl gallate and tannic acid induced G2/M phase cell cycle arrest and showed interesting effect on microtubule stabilization in Hep3B cells observed by immunofluorescence. The induction of apoptosis was characterized by morphological characteristic changes, and was supported by increases in the ratio of Bax/Bcl-2 expression and activation of caspase 3/7. This work constitutes the first phytochemical and cytotoxic study of C. coriaria and showed the action of its phenolic constituents on cell cycle, cell death and microtubules organization. Full article

(This article belongs to the Section Natural Products Chemistry)

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13 pages, 2092 KiB

Open AccessArticle

UVA, UVB and UVC Light Enhances the Biosynthesis of Phenolic Antioxidants in Fresh-Cut Carrot through a Synergistic Effect with Wounding

by Bernadeth B. Surjadinata¹, Daniel A. Jacobo-Velázquez²

and Luis Cisneros-Zevallos^1,*

¹ Department of Horticultural Sciences, Texas A&M University, College Station, TX 778432-133, USA

² Tecnológico de Monterrey, Escuela de Ingeniería y Ciencias, Centro de Biotecnología FEMSA, Av. Eugenio Garza Sada 2501 Sur, C.P. 64849 Monterrey, N.L., Mexico

Molecules 2017, 22(4), 668; https://doi.org/10.3390/molecules22040668 - 24 Apr 2017

Cited by 111 | Viewed by 11876

Abstract

Previously, we found that phenolic content and antioxidant capacity (AOX) in carrots increased with wounding intensity. It was also reported that UV radiation may trigger the phenylpropanoid metabolism in plant tissues. Here, we determined the combined effect of wounding intensity and UV radiation [...] Read more.

Previously, we found that phenolic content and antioxidant capacity (AOX) in carrots increased with wounding intensity. It was also reported that UV radiation may trigger the phenylpropanoid metabolism in plant tissues. Here, we determined the combined effect of wounding intensity and UV radiation on phenolic compounds, AOX, and the phenylalanine ammonia-lyase (PAL) activity of carrots. Accordingly, phenolic content, AOX, and PAL activity increased in cut carrots with the duration of UVC radiation, whereas whole carrots showed no increase. Carrot pies showed a higher increase compared to slices and shreds. Phenolics, AOX, and PAL activity also increased in cut carrots exposed to UVA or UVB. The major phenolics were chlorogenic acid and its isomers, ferulic acid, and isocoumarin. The type of UV radiation affected phenolic profiles. Chlorogenic acid was induced by all UV radiations but mostly by UVB and UVC, ferulic acid was induced by all UV lights to comparable levels, while isocoumarin and 4,5-diCQA was induced mainly by UVB and UVC compared to UVA. In general, total phenolics correlated linearly with AOX for all treatments. A reactive oxygen species (ROS) mediated hypothetical mechanism explaining the synergistic effect of wounding and different UV radiation stresses on phenolics accumulation in plants is herein proposed. Full article

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

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24 pages, 1419 KiB

Open AccessReview

Polyphenolic Compounds and Digestive Enzymes: In Vitro Non-Covalent Interactions

by Alejandra I. Martinez-Gonzalez¹, Ángel G. Díaz-Sánchez¹

, Laura A. de la Rosa¹, Claudia L. Vargas-Requena¹, Ismael Bustos-Jaimes²

and And Emilio Alvarez-Parrilla^1,*

¹ Departamento de Ciencias Químico Biológicas, Instituto de Ciencias Biomédicas, Universidad Autónoma de Ciudad Juárez, Ciudad Juárez (32310), Mexico

² Departamento de Bioquímica, Facultad de Medicina, Universidad Nacional Autónoma de México, México D.F. (04510), Mexico

Molecules 2017, 22(4), 669; https://doi.org/10.3390/molecules22040669 - 22 Apr 2017

Cited by 215 | Viewed by 14769

Abstract

The digestive enzymes–polyphenolic compounds (PCs) interactions behind the inhibition of these enzymes have not been completely studied. The existing studies have mainly analyzed polyphenolic extracts and reported inhibition percentages of catalytic activities determined by UV-Vis spectroscopy techniques. Recently, pure PCs and new methods [...] Read more.

The digestive enzymes–polyphenolic compounds (PCs) interactions behind the inhibition of these enzymes have not been completely studied. The existing studies have mainly analyzed polyphenolic extracts and reported inhibition percentages of catalytic activities determined by UV-Vis spectroscopy techniques. Recently, pure PCs and new methods such as isothermal titration calorimetry and circular dichroism have been applied to describe these interactions. The present review focuses on PCs structural characteristics behind the inhibition of digestive enzymes, and progress of the used methods. Some characteristics such as molecular weight, number and position of substitution, and glycosylation of flavonoids seem to be related to the inhibitory effect of PCs; also, this effect seems to be different for carbohydrate-hydrolyzing enzymes and proteases. The digestive enzyme–PCs molecular interactions have shown that non-covalent binding, mostly by van der Waals forces, hydrogen binding, hydrophobic binding, and other electrostatic forces regulate them. These interactions were mainly associated to non-competitive type inhibitions of the enzymatic activities. The present review emphasizes on the digestive enzymes such as α-glycosidase (AG), α-amylase (PA), lipase (PL), pepsin (PE), trypsin (TP), and chymotrypsin (CT). Existing studies conducted in vitro allow one to elucidate the characteristics of the structure–function relationships, where differences between the structures of PCs might be the reason for different in vivo effects. Full article

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16 pages, 3774 KiB

Open AccessArticle

Multiple UDP-Glucuronosyltransferase and Sulfotransferase Enzymes are Responsible for the Metabolism of Verproside in Human Liver Preparations

by Ju-Hyun Kim¹, Deok-Kyu Hwang¹, Ju-Yeon Moon¹, Yongnam Lee², Ji Seok Yoo², Dae Hee Shin² and Hye Suk Lee^1,*

¹ Drug Metabolism & Bioanalysis Laboratory, College of Pharmacy, The Catholic University of Korea, Bucheon 14462, Korea

² Central R&D Institute, YUNGJIN PHARM. CO., LTD., Suwon 16229, Korea

Molecules 2017, 22(4), 670; https://doi.org/10.3390/molecules22040670 - 22 Apr 2017

Cited by 6 | Viewed by 5330

Abstract

Verproside, an active iridoid glycoside component of Veronica species, such as Pseudolysimachion rotundum var. subintegrum and Veronica anagallis-aquatica, possesses anti-asthma, anti-inflammatory, anti-nociceptive, antioxidant, and cytostatic activities. Verproside is metabolized into nine metabolites in human hepatocytes: verproside glucuronides (M1, M2) [...] Read more.

Verproside, an active iridoid glycoside component of Veronica species, such as Pseudolysimachion rotundum var. subintegrum and Veronica anagallis-aquatica, possesses anti-asthma, anti-inflammatory, anti-nociceptive, antioxidant, and cytostatic activities. Verproside is metabolized into nine metabolites in human hepatocytes: verproside glucuronides (M1, M2) via glucuronidation, verproside sulfate (M3) via sulfation, picroside II (M4) and isovanilloylcatalpol (M5) via O-methylation, M4 glucuronide (M6) and M4 sulfate (M8) via further glucuronidation and sulfation of M4, and M5 glucuronide (M7) and M5 sulfate (M9) via further glucuronidation and sulfation of M5. Drug-metabolizing enzymes responsible for verproside metabolism, including sulfotransferase (SULT) and UDP-glucuronosyltransferase (UGT), were characterized. The formation of verproside glucuronides (M1, M2), isovanilloylcatalpol glucuronide (M7), and picroside II glucuronide (M6) was catalyzed by commonly expressed UGT1A1 and UGT1A9 and gastrointestinal-specific UGT1A7, UGT1A8, and UGT1A10, consistent with the higher intrinsic clearance values for the formation of M1, M2, M6, and M7 in human intestinal microsomes compared with those in liver microsomes. The formation of verproside sulfate (M3) and M5 sulfate (M9) from verproside and isovanilloylcatalpol (M5), respectively, was catalyzed by SULT1A1. Metabolism of picroside II (M4) into M4 sulfate (M8) was catalyzed by SULT1A1, SULT1E1, SULT1A2, SULT1A3, and SULT1C4. Based on these results, the pharmacokinetics of verproside may be affected by the co-administration of relevant UGT and SULT inhibitors or inducers. Full article

(This article belongs to the Section Medicinal Chemistry)

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14 pages, 2486 KiB

Open AccessArticle

Effects of Flavonoids and Triterpene Analogues from Leaves of Eleutherococcus sieboldianus (Makino) Koidz. ‘Himeukogi’ in 3T3-L1 Preadipocytes

by Atsuyoshi Nishina^1,*, Masaya Itagaki¹, Yuusuke Suzuki¹, Mamoru Koketsu², Masayuki Ninomiya², Daisuke Sato³, Takashi Suzuki⁴, Satoshi Hayakawa⁵

, Makoto Kuroda⁶ and Hirokazu Kimura⁶

¹ College of Science and Technology, Nihon University, 1-5-1 Kandasurugadai, Chiyoda, Tokyo 101-0062, Japan

² Department of Chemistry and Biomolecular Science, Faculty of Engineering, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan

³ Department of Biomedical Information Engineering, Graduate School of Medical Science, Yamagata University, 2-2-2 Iidanishi, Yamagata 990-9585, Japan

⁴ School of Pharmacy, Nihon University, 7-7-1 Narashinodai, Funabashi, Chiba 274-8555, Japan

⁵ Department of Pathology and Microbiology ,School of Medicine, Nihon University, 30-1 Ohotaniguchi-kamicho, Itabashi, Tokyo 173-8610, Japan

⁶ National Institute of Infectious Diseases, 4-7-1 Gakuen, Musashimurayama, Tokyo 208-0011, Japan

Molecules 2017, 22(4), 671; https://doi.org/10.3390/molecules22040671 - 22 Apr 2017

Cited by 16 | Viewed by 5964

Abstract

Eleutherococcus sieboldianus (Makino) Koidz. is a local product from the area in and around Yonezawa City in Yamagata Prefecture, Japan. It has been used as a medicinal plant for a long time. We isolated and identified four types of flavonoid glycosides [astragalin ( [...] Read more.

Eleutherococcus sieboldianus (Makino) Koidz. is a local product from the area in and around Yonezawa City in Yamagata Prefecture, Japan. It has been used as a medicinal plant for a long time. We isolated and identified four types of flavonoid glycosides [astragalin (1), isoquercetin (2), rhamnocitrin 3-O-glucoside (3), and nicotiflorin (4)], a triterpene [methyl hederagenin (5)], and three types of triterpene glycosides [δ-hederin (6), echinocystic acid 3-O-arabinoside (7), and cauloside B (8)] from the methanol extract of E. sieboldianus, which regulates lipid accumulation in 3T3-L1 preadipocytes. Among the compounds isolated, 2 and 8 up- and down-regulated lipid accumulation and insulin induced adipocyte differentiation in 3T3-L1 preadipocytes. Compound 2 induced up-regulation of lipid accumulation and decreased adipocyte size, while 8 down-regulated lipid accumulations without decreasing cell size. Additionally, 2 increased adipogenic proteins [peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer-binding protein alpha (C/EBPα), and fatty-acid-binding protein 4 (FABP4)]. In contrast, 8 decreased the levels of all adipogenic proteins and glucose transporter type 4 (GLUT4), but increased adiponectin. Full article

(This article belongs to the Special Issue Plant Polyphenols as Potential Therapeutic Agents for Diabetes and Obesity)

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16 pages, 1773 KiB

Open AccessCommunication

Modified Nucleotides as Substrates of Terminal Deoxynucleotidyl Transferase

by Daiva Tauraitė^1,*,†, Jevgenija Jakubovska^1,†, Julija Dabužinskaitė¹, Maksim Bratchikov²

and Rolandas Meškys¹

¹ Department of Molecular Microbiology and Biotechnology, Institute of Biochemistry, Life Sciences Center, Vilnius University, Sauletekio al. 7, Vilnius LT-10257, Lithuania

² Department of Physiology, Biochemistry, Microbiology and Laboratory Medicine, Faculty of Medicine, Vilnius University, M. K. Čiurlionio g. 21, Vilnius LT-03101, Lithuania

^† These authors contributed equally to this work.

Molecules 2017, 22(4), 672; https://doi.org/10.3390/molecules22040672 - 22 Apr 2017

Cited by 23 | Viewed by 10753

Abstract

The synthesis of novel modified nucleotides and their incorporation into DNA sequences opens many possibilities to change the chemical properties of oligonucleotides (ONs), and, therefore, broaden the field of practical applications of modified DNA. The chemical synthesis of nucleotide derivatives, including ones bearing [...] Read more.

The synthesis of novel modified nucleotides and their incorporation into DNA sequences opens many possibilities to change the chemical properties of oligonucleotides (ONs), and, therefore, broaden the field of practical applications of modified DNA. The chemical synthesis of nucleotide derivatives, including ones bearing thio-, hydrazino-, cyano- and carboxy groups as well as 2-pyridone nucleobase-containing nucleotides was carried out. The prepared compounds were tested as substrates of terminal deoxynucleotidyl transferase (TdT). The nucleotides containing N⁴-aminocytosine, 4-thiouracil as well as 2-pyridone, 4-chloro- and 4-bromo-2-pyridone as a nucleobase were accepted by TdT, thus allowing enzymatic synthesis of 3’-terminally modified ONs. The successful UV-induced cross-linking of 4-thiouracil-containing ONs to TdT was carried out. Enzymatic post-synthetic 3’-modification of ONs with various photo- and chemically-reactive groups opens novel possibilities for future applications, especially in analysis of the mechanisms of polymerases and the development of photo-labels, sensors, and self-assembling structures. Full article

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

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16 pages, 2684 KiB

Open AccessArticle

Production of Laccase by a New Myrothecium verrucaria MD-R-16 Isolated from Pigeon Pea [Cajanus cajan (L.) Millsp.] and its Application on Dye Decolorization

by Jiao Sun^1,2,†, Na Guo^1,2,†, Li-Li Niu^1,2, Qing-Fang Wang^1,2, Yu-Ping Zang^1,2, Yuan-Gang Zu^1,2 and Yu-Jie Fu^1,2,*

¹ Key Laboratory of Forest Plant Ecology, Ministry of Education, Northeast Forestry University, Harbin 150040, China

² Engineering Research Center of Forest Bio-Preparation, Ministry of Education, Northeast Forestry University, Harbin 150040, China

^† These authors contributed equally to the work.

Molecules 2017, 22(4), 673; https://doi.org/10.3390/molecules22040673 - 23 Apr 2017

Cited by 38 | Viewed by 6756

Abstract

The present study was conducted to screen a laccase-producing fungal endophyte, optimize fermentation conditions, and evaluate the decolorization ability of the laccase. A new fungal endophyte capable of laccase-producing was firstly isolated from pigeon pea and identified as Myrothecium verrucaria based on a [...] Read more.

The present study was conducted to screen a laccase-producing fungal endophyte, optimize fermentation conditions, and evaluate the decolorization ability of the laccase. A new fungal endophyte capable of laccase-producing was firstly isolated from pigeon pea and identified as Myrothecium verrucaria based on a ITS-rRNA sequences analysis. Meanwhile, various fermentation parameters on the laccase production were optimized via response surface methodology (RSM). The optimal fermentation conditions were a fermentation time of five days, temperature 30 °C and pH 6.22. Laccase activity reached 16.52 ± 0.18 U/mL under the above conditions. Furthermore, the laccase showed effective decolorization capability toward synthetic dyes (Congo red, Methyl orange, Methyl red, and Crystal violet) in the presence of the redox mediator ABTS, with more than 70% of dyes decolorizing after 24 h of incubation. Additionally, the activity of laccase was relatively stable with pH (4.5–6.5) and a temperature range of 35–55 °C. Therefore, the high laccase production of the strain and the new fungal laccase could provide a promising alterative approach for industrial and environmental applications. Full article

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10 pages, 2839 KiB

Open AccessArticle

High-Performance Prediction of Human Estrogen Receptor Agonists Based on Chemical Structures

by Yuki Asako and Yoshihiro Uesawa^*

Department of Clinical Pharmaceutics Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Tokyo 204-8588, Japan

Molecules 2017, 22(4), 675; https://doi.org/10.3390/molecules22040675 - 23 Apr 2017

Cited by 9 | Viewed by 5753

Abstract

Many agonists for the estrogen receptor are known to disrupt endocrine functioning. We have developed a computational model that predicts agonists for the estrogen receptor ligand-binding domain in an assay system. Our model was entered into the Tox21 Data Challenge 2014, a computational [...] Read more.

Many agonists for the estrogen receptor are known to disrupt endocrine functioning. We have developed a computational model that predicts agonists for the estrogen receptor ligand-binding domain in an assay system. Our model was entered into the Tox21 Data Challenge 2014, a computational toxicology competition organized by the National Center for Advancing Translational Sciences. This competition aims to find high-performance predictive models for various adverse-outcome pathways, including the estrogen receptor. Our predictive model, which is based on the random forest method, delivered the best performance in its competition category. In the current study, the predictive performance of the random forest models was improved by strictly adjusting the hyperparameters to avoid overfitting. The random forest models were optimized from 4000 descriptors simultaneously applied to 10,000 activity assay results for the estrogen receptor ligand-binding domain, which have been measured and compiled by Tox21. Owing to the correlation between our model’s and the challenge’s results, we consider that our model currently possesses the highest predictive power on agonist activity of the estrogen receptor ligand-binding domain. Furthermore, analysis of the optimized model revealed some important features of the agonists, such as the number of hydroxyl groups in the molecules. Full article

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

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18 pages, 5360 KiB

Open AccessReview

Adenosine A1 and A2A Receptors in the Brain: Current Research and Their Role in Neurodegeneration

by Jocelyn Stockwell

, Elisabet Jakova and Francisco S. Cayabyab^*

Department of Surgery, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada

Molecules 2017, 22(4), 676; https://doi.org/10.3390/molecules22040676 - 23 Apr 2017

Cited by 166 | Viewed by 19842

Abstract

The inhibitory adenosine A1 receptor (A1R) and excitatory A2A receptor (A2AR) are predominantly expressed in the brain. Whereas the A2AR has been implicated in normal aging and enhancing neurotoxicity in multiple neurodegenerative diseases, the inhibitory A1R has traditionally been ascribed to have a [...] Read more.

The inhibitory adenosine A1 receptor (A1R) and excitatory A2A receptor (A2AR) are predominantly expressed in the brain. Whereas the A2AR has been implicated in normal aging and enhancing neurotoxicity in multiple neurodegenerative diseases, the inhibitory A1R has traditionally been ascribed to have a neuroprotective function in various brain insults. This review provides a summary of the emerging role of prolonged A1R signaling and its potential cross-talk with A2AR in the cellular basis for increased neurotoxicity in neurodegenerative disorders. This A1R signaling enhances A2AR-mediated neurodegeneration, and provides a platform for future development of neuroprotective agents in stroke, Parkinson’s disease and epilepsy. Full article

(This article belongs to the Special Issue Adenosine Receptors)

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19 pages, 4173 KiB

Open AccessFeature PaperArticle

Photocatalytic and Adsorption Performances of Faceted Cuprous Oxide (Cu₂O) Particles for the Removal of Methyl Orange (MO) from Aqueous Media

by Weng Chye Jeffrey Ho^1,*, Qiuling Tay¹, Huan Qi¹, Zhaohong Huang², Jiao Li³ and Zhong Chen^1,*

¹ School of Materials Science and Engineering, Nanyang Technological University, Singapore 639798, Singapore

² Singapore Institute of Manufacturing Technology, 71 Nanyang Drive, Singapore 638075, Singapore

³ School of Materials Science and Engineering, Shandong University of Technology, Zibo 255049, Shandong Province, China

Molecules 2017, 22(4), 677; https://doi.org/10.3390/molecules22040677 - 23 Apr 2017

Cited by 109 | Viewed by 10465

Abstract

Particles of sub-micron size possess significant capacity to adsorb organic molecules from aqueous media. Semiconductor photocatalysts in particle form could potentially be utilized for dye removal through either physical adsorption or photo-induced chemical process. The photocatalytic and adsorption capabilities of Cu₂O [...] Read more.

Particles of sub-micron size possess significant capacity to adsorb organic molecules from aqueous media. Semiconductor photocatalysts in particle form could potentially be utilized for dye removal through either physical adsorption or photo-induced chemical process. The photocatalytic and adsorption capabilities of Cu₂O particles with various exposed crystal facets have been studied through separate adsorption capacity test and photocatalytic degradation test. These crystals display unique cubic, octahedral, rhombic dodecahedral, and truncated polyhedral shapes due to specifically exposed crystal facet(s). For comparison, Cu₂O particles with no clear exposed facets were also prepared. The current work confirms that the surface charge critically affects the adsorption performance of the synthesized Cu₂O particles. The octahedral shaped Cu₂O particles, with exposed {111} facets, possess the best adsorption capability of methyl orange (MO) dye due to the strongest positive surface charge among the different types of particles. In addition, we also found that the adsorption of MO follows the Langmuir monolayer mechanism. The octahedral particles also performed the best in photocatalytic dye degradation of MO under visible light irradiation because of the assistance from dye absorption. On top of the photocatalytic study, the stability of these Cu₂O particles during the photocatalytic processes was also investigated. Cu(OH)₂ and CuO are the likely corrosion products found on the particle surface after the photocorrosion in MO solution. By adding hole scavengers in the solution, the photocorrosion of Cu₂O was greatly reduced. This observation confirms that the photocatalytically generated holes were responsible for the photocorrosion of Cu₂O. Full article

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

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Molecules, Volume 22, Issue 4 (April 2017) – 174 articles

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