Molecules

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Open AccessEditorial

Molecules Best Paper Award 2015

by Derek J. McPhee

Molecules 2015, 20(1), 1751-1754; https://doi.org/10.3390/molecules20011751 - 20 Jan 2015

Viewed by 6123

Molecules instituted some years ago a “Best Paper” award to recognize the most outstanding papers in the area of organic synthesis, natural products, medicinal chemistry and molecular diversity published each year in Molecules. We are pleased to announce the third “Molecules [...] Read more.

Molecules instituted some years ago a “Best Paper” award to recognize the most outstanding papers in the area of organic synthesis, natural products, medicinal chemistry and molecular diversity published each year in Molecules. We are pleased to announce the third “Molecules Best Paper Award” for 2015. The winners were chosen by the Editor-in-Chief and selected editorial board members from among all the papers published in 2011. Reviews and research papers were evaluated separately. We are pleased to announce that the following eight papers have won the Molecules Best Paper Award for 2015:[...] Full article

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Open AccessArticle

Glutathione-Garlic Sulfur Conjugates: Slow Hydrogen Sulfide Releasing Agents for Therapeutic Applications

by Ashif Iqbal Bhuiyan, Vilma Toska Papajani, Maurizio Paci and Sonia Melino

Molecules 2015, 20(1), 1731-1750; https://doi.org/10.3390/molecules20011731 - 20 Jan 2015

Cited by 43 | Viewed by 9979

Abstract

Natural organosulfur compounds (OSCs) from Allium sativum L. display antioxidant and chemo-sensitization properties, including the in vitro inhibition of tumor cell proliferation through the induction of apoptosis. Garlic water- and oil-soluble allyl sulfur compounds show distinct properties and the capability to inhibit the [...] Read more.

Natural organosulfur compounds (OSCs) from Allium sativum L. display antioxidant and chemo-sensitization properties, including the in vitro inhibition of tumor cell proliferation through the induction of apoptosis. Garlic water- and oil-soluble allyl sulfur compounds show distinct properties and the capability to inhibit the proliferation of tumor cells. In the present study, we optimized a new protocol for the extraction of water-soluble compounds from garlic at low temperatures and the production of glutathionyl-OSC conjugates during the extraction. Spontaneously, Cys/GSH-mixed-disulfide conjugates are produced by in vivo metabolism of OSCs and represent active molecules able to affect cellular metabolism. Water-soluble extracts, with (GSGaWS) or without (GaWS) glutathione conjugates, were here produced and tested for their ability to release hydrogen sulfide (H₂S), also in the presence of reductants and of thiosulfate:cyanide sulfurtransferase (TST) enzyme. Thus, the TST catalysis of the H₂S-release from garlic OSCs and their conjugates has been investigated by molecular in vitro experiments. The antiproliferative properties of these extracts on the human T-cell lymphoma cell line, HuT 78, were observed and related to histone hyperacetylation and downregulation of GAPDH expression. Altogether, the results presented here pave the way for the production of a GSGaWS as new, slowly-releasing hydrogen sulfide extract for potential therapeutic applications. Full article

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

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Open AccessArticle

Synthesis and in Silico Evaluation of Novel Compounds for PET-Based Investigations of the Norepinephrine Transporter

by Catharina Neudorfer, Amir Seddik, Karem Shanab, Andreas Jurik, Christina Rami-Mark, Wolfgang Holzer, Gerhard Ecker, Markus Mitterhauser, Wolfgang Wadsak and Helmut Spreitzer

Molecules 2015, 20(1), 1712-1730; https://doi.org/10.3390/molecules20011712 - 20 Jan 2015

Cited by 7 | Viewed by 7131

Abstract

Since the norepinephrine transporter (NET) is involved in a variety of diseases, the investigation of underlying dysregulation-mechanisms of the norepinephrine (NE) system is of major interest. Based on the previously described highly potent and selective NET ligand 1-(3-(methylamino)-1-phenylpropyl)-3-phenyl-1,3-dihydro-2H-benzimidaz- ol-2-one (Me@APPI), this [...] Read more.

Since the norepinephrine transporter (NET) is involved in a variety of diseases, the investigation of underlying dysregulation-mechanisms of the norepinephrine (NE) system is of major interest. Based on the previously described highly potent and selective NET ligand 1-(3-(methylamino)-1-phenylpropyl)-3-phenyl-1,3-dihydro-2H-benzimidaz- ol-2-one (Me@APPI), this paper aims at the development of several fluorinated methylamine-based analogs of this compound. The newly synthesized compounds were computationally evaluated for their interactions with the monoamine transporters and represent reference compounds for PET-based investigation of the NET. Full article

(This article belongs to the Special Issue Preparation of Radiopharmaceuticals and Their Use in Drug Development)

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Open AccessArticle

Hybrids of Salicylalkylamides and Mannich Bases: Control of the Amide Conformation by Hydrogen Bonding in Solution and in the Solid State

by Christian Dank, Barbara Kirchknopf, Matthias Mastalir, Hanspeter Kählig, Susanne Felsinger, Alexander Roller, Vladimir B. Arion and Hubert Gstach

Molecules 2015, 20(1), 1686-1711; https://doi.org/10.3390/molecules20011686 - 20 Jan 2015

Cited by 11 | Viewed by 8313

Abstract

3-Aminomethylation of salicylalkylamides afforded hybrids with a Mannich base. In addition, it triggered the rotation of the amide bond. The observed conformational switch is driven by strong intramolecular hydrogen bonding between the Mannich base and phenolic group. Crystal structure analysis reveals the stabilization [...] Read more.

3-Aminomethylation of salicylalkylamides afforded hybrids with a Mannich base. In addition, it triggered the rotation of the amide bond. The observed conformational switch is driven by strong intramolecular hydrogen bonding between the Mannich base and phenolic group. Crystal structure analysis reveals the stabilization of the hybrid molecules by double hydrogen bonding of the phenolic OH, which acts as an acceptor and donor simultaneously. The molecules contain an amide site and a Mannich base site in an orthogonal spatial arrangement. The intramolecular hydrogen bonds are persistent in a nonpolar solvent (e.g., chloroform). The conformational change can be reversed upon protection or protonation of the Mannich base nitrogen. Full article

(This article belongs to the Section Medicinal Chemistry)

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Open AccessArticle

Contact Toxicity and Repellency of the Essential Oil of Liriope muscari (DECN.) Bailey against Three Insect Tobacco Storage Pests

by Yan Wu, Wen-Juan Zhang, Ping-Juan Wang, Kai Yang, Dong-Ye Huang, Jian-Yu Wei, Zhao-Fu Tian, Jia-Feng Bai and Shu-Shan Du

Molecules 2015, 20(1), 1676-1685; https://doi.org/10.3390/molecules20011676 - 20 Jan 2015

Cited by 26 | Viewed by 8402

Abstract

In order to find and develop new botanical pesticides against tobacco storage pests, bioactivity screening was performed. The essential oil obtained from the aerial parts of Liriope muscari was investigated by GC/MS and GC/FID. A total of 14 components representing 96.12% of the [...] Read more.

In order to find and develop new botanical pesticides against tobacco storage pests, bioactivity screening was performed. The essential oil obtained from the aerial parts of Liriope muscari was investigated by GC/MS and GC/FID. A total of 14 components representing 96.12% of the oil were identified and the main compounds in the oil were found to be methyl eugenol (42.15%) and safrole (17.15%), followed by myristicin (14.18%) and 3,5-dimethoxytoluene (10.60%). After screening, the essential oil exhibit potential insecticidal activity. In the progress of assay, it showed that the essential oil exhibited potent contact toxicity against Tribolium castaneum, Lasioderma serricorne and Liposcelis bostrychophila adults, with LD₅₀ values of 13.36, 11.28 µg/adult and 21.37 µg/cm², respectively. The essential oil also exhibited strong repellency against the three stored product insects. At the same concentrations, the essential oil was more repellent to T. castaneum than to L. serricorne adults. The results indicate that the essential oil of Liriope muscari has potential to be developed into a natural insecticide or repellent for controlling insects in stored tobacco and traditional Chinese medicinal materials. Full article

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

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Open AccessArticle

Deoxypodophyllotoxin Induces G2/M Cell Cycle Arrest and Apoptosis in SGC-7901 Cells and Inhibits Tumor Growth in Vivo

by Yu-Rong Wang, Yuan Xu, Zhen-Zhou Jiang, Mounia Guerram, Bin Wang, Xiong Zhu and Lu-Yong Zhang

Molecules 2015, 20(1), 1661-1675; https://doi.org/10.3390/molecules20011661 - 20 Jan 2015

Cited by 47 | Viewed by 10730

Abstract

Deoxypodophyllotoxin (DPT), a natural microtubule destabilizer, was isolated from Anthriscus sylvestris, and a few studies have reported its anti-cancer effect. However, the in vivo antitumor efficacy of DPT is currently indeterminate. In this study, we investigated the anti-gastric cancer effects of DPT [...] Read more.

Deoxypodophyllotoxin (DPT), a natural microtubule destabilizer, was isolated from Anthriscus sylvestris, and a few studies have reported its anti-cancer effect. However, the in vivo antitumor efficacy of DPT is currently indeterminate. In this study, we investigated the anti-gastric cancer effects of DPT both in vitro and in vivo. Our data showed that DPT inhibited cancer cell proliferation and induced G2/M cell cycle arrest accompanied by an increase in apoptotic cell death in SGC-7901 cancer cells. In addition, DPT caused cyclin B1, Cdc2 and Cdc25C to accumulate, decreased the expression of Bcl-2 and activated caspase-3 and PARP, suggesting that caspase-mediated pathways were involved in DPT-induced apoptosis. Animal studies revealed that DPT significantly inhibited tumor growth and decreased microvessel density (MVD) in a xenograft model of gastric cancer. Taken together, our findings provide a framework for further exploration of DPT as a novel chemotherapeutic for 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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Open AccessArticle

Stability of the Human Hsp90-p50^Cdc37 Chaperone Complex against Nucleotides and Hsp90 Inhibitors, and the Influence of Phosphorylation by Casein Kinase 2

by Sanne H. Olesen, Donna J. Ingles, Jin-Yi Zhu, Mathew P. Martin, Stephane Betzi, Gunda I. Georg, Joseph S. Tash and Ernst Schönbrunn

Molecules 2015, 20(1), 1643-1660; https://doi.org/10.3390/molecules20011643 - 19 Jan 2015

Cited by 11 | Viewed by 9122

Abstract

The molecular chaperone Hsp90 is regulated by co-chaperones such as p50^Cdc37, which recruits a wide selection of client protein kinases. Targeted disruption of the Hsp90-p50^Cdc37 complex by protein–protein interaction (PPI) inhibitors has emerged as an alternative strategy to treat diseases [...] Read more.

The molecular chaperone Hsp90 is regulated by co-chaperones such as p50^Cdc37, which recruits a wide selection of client protein kinases. Targeted disruption of the Hsp90-p50^Cdc37 complex by protein–protein interaction (PPI) inhibitors has emerged as an alternative strategy to treat diseases characterized by aberrant Hsp90 activity. Using isothermal microcalorimetry, ELISA and GST-pull down assays we evaluated reported Hsp90 inhibitors and nucleotides for their ability to inhibit formation of the human Hsp90β-p50^Cdc37 complex, reconstituted in vitro from full-length proteins. Hsp90 inhibitors, including the proposed PPI inhibitors gedunin and H2-gamendazole, did not affect the interaction of Hsp90 with p50^Cdc37 in vitro. Phosphorylation of Hsp90 and p50^Cdc37 by casein kinase 2 (CK2) did not alter the thermodynamic signature of complex formation. However, the phosphorylated complex was vulnerable to disruption by ADP (IC₅₀ = 32 µM), while ATP, AMPPNP and Hsp90 inhibitors remained largely ineffective. The differential inhibitory activity of ADP suggests that phosphorylation by CK2 primes the complex for dissociation in response to a drop in ATP/ADP levels. The approach applied herein provides robust assays for a comprehensive biochemical evaluation of potential effectors of the Hsp90-p50^Cdc37 complex, such as phosphorylation by a kinase or the interaction with small molecule ligands. Full article

(This article belongs to the Special Issue Design and Study of Kinase Inhibitors)

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Open AccessArticle

Inhibition of Urinary Macromolecule Heparin on Aggregation of Nano-COM and Nano-COD Crystals

by Yan Ou, Jun-Fa Xue, Cai-Yan Tan, Bao-Song Gui, Xin-Yuan Sun and Jian-Ming Ouyang

Molecules 2015, 20(1), 1626-1642; https://doi.org/10.3390/molecules20011626 - 19 Jan 2015

Cited by 17 | Viewed by 9371

Abstract

Purpose: This research aims to study the influences of heparin (HP) on the aggregation of nano calcium oxalate monohydrate (COM) and nano calcium oxalate dihydrate (COD) with mean diameter of about 50 nm. Method: The influences of different concentrations of HP [...] Read more.

Purpose: This research aims to study the influences of heparin (HP) on the aggregation of nano calcium oxalate monohydrate (COM) and nano calcium oxalate dihydrate (COD) with mean diameter of about 50 nm. Method: The influences of different concentrations of HP on the mean diameter and Zeta potential of nano COM and nano COD were investigated using a nanoparticle size Zeta potential analyzer. Results: HP could be adsorbed on the surface of nano COM and nano COD crystals, leading to an increase in the absolute value of Zeta potential on the crystals and an increase in the electrostatic repulsion force between crystals. Consequently, the aggregation of the crystals is reduced and the stability of the system is improved. The strong adsorption ability of HP was closely related to the -OSO₃⁻ and -COO⁻ groups contained in the HP molecules. X-ray photoelectron spectroscopy confirmed the coordination of HP with Ca²⁺ ions of COM and COD crystals. Conclusion: HP could inhibit the aggregation of nano COM and nano COD crystals and increase their stability in aqueous solution, which is conducive in inhibiting the formation of calcium oxalate stones. Full article

(This article belongs to the Special Issue Glycosaminoglycans and Their Mimetics)

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Open AccessReview

Triterpenes as Potentially Cytotoxic Compounds

by Malwina Chudzik, Ilona Korzonek-Szlacheta and Wojciech Król

Molecules 2015, 20(1), 1610-1625; https://doi.org/10.3390/molecules20011610 - 19 Jan 2015

Cited by 159 | Viewed by 11348

Abstract

Triterpenes are compounds of natural origin, which have numerously biological activities: anti-cancer properties, anti-inflammatory, anti-oxidative, anti-viral, anti-bacterial and anti-fungal. These substances can be isolated from plants, animals or fungi. Nowadays, when neoplasms are main cause of death, triterpenes can become an alternative method [...] Read more.

Triterpenes are compounds of natural origin, which have numerously biological activities: anti-cancer properties, anti-inflammatory, anti-oxidative, anti-viral, anti-bacterial and anti-fungal. These substances can be isolated from plants, animals or fungi. Nowadays, when neoplasms are main cause of death, triterpenes can become an alternative method for treating cancer because of their cytotoxic properties and chemopreventive activities. Full article

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

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Open AccessArticle

Identification and Quantitative Characterization of PSORI-CM01, a Chinese Medicine Formula for Psoriasis Therapy, by Liquid Chromatography Coupled with an LTQ Orbitrap Mass Spectrometer

by Shao-Dan Chen, Chuan-Jian Lu and Rui-Zhi Zhao

Molecules 2015, 20(1), 1594-1609; https://doi.org/10.3390/molecules20011594 - 19 Jan 2015

Cited by 28 | Viewed by 7012

Abstract

PSORI-CM01 is a Chinese medicine formula prepared from medicinal herbs and used in China for the treatment of psoriasis. However, the chemical constituents in PSORI-CM01 have not been clarified yet. In order to quickly define the chemical profiles and control the quality of [...] Read more.

PSORI-CM01 is a Chinese medicine formula prepared from medicinal herbs and used in China for the treatment of psoriasis. However, the chemical constituents in PSORI-CM01 have not been clarified yet. In order to quickly define the chemical profiles and control the quality of PSORI-CM01 preparations, ultra-high liquid chromatography coupled with electrospray ionization hybrid linear trap quadrupole Orbitrap mass spectrometry (UHPLC-ESI-LTQ/Orbitrap-MS) was applied for simultaneous identification and quantification of multiple constituents. A total of 108 compounds, including organic acids, phenolic acids, flavonoids, and terpenoids, were identified or tentatively deduced on the base of their retention behaviors, MS and MSⁿ data, or by comparing with reference substances and literature data. In addition, an optimized UHPLC-ESI-MS method was established for the quantitative determination of 14 marker compounds in different dosage forms of PSORI-CM01 preparations. The validation of the method, including spike recoveries, linearity, sensitivity (LOQ), precision, and repeatability, was carried out and demonstrated to be satisfied the requirements of quantitative analysis. This is the first report on the comprehensive determination of chemical constituents in PSORI-CM01 preparations by UHPLC-ESI-LTQ/Orbitrap mass spectrometry. The results suggested that the established methods would be a powerful and reliable analytical tool for the characterization of multi-constituents in complex chemical system and quality control of TCM preparations. Full article

(This article belongs to the Section Natural Products Chemistry)

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Open AccessArticle

Synergistic Effects of Nucleating Agents and Plasticizers on the Crystallization Behavior of Poly(lactic acid)

by Xuetao Shi, Guangcheng Zhang, Thanh Vu Phuong and Andrea Lazzeri

Molecules 2015, 20(1), 1579-1593; https://doi.org/10.3390/molecules20011579 - 19 Jan 2015

Cited by 113 | Viewed by 9748

Abstract

The synergistic effect of nucleating agents and plasticizers on the thermal and mechanical performance of PLA nanocomposites was investigated with the objective of increasing the crystallinity and balancing the stiffness and toughness of PLA mechanical properties. Calcium carbonate, halloysite nanotubes, talc and LAK [...] Read more.

The synergistic effect of nucleating agents and plasticizers on the thermal and mechanical performance of PLA nanocomposites was investigated with the objective of increasing the crystallinity and balancing the stiffness and toughness of PLA mechanical properties. Calcium carbonate, halloysite nanotubes, talc and LAK (sulfates) were compared with each other as heterogeneous nucleating agents. Both the DSC isothermal and non-isothermal studies indicated that talc and LAK were the more effective nucleating agents among the selected fillers. Poly(D-lactic acid) (PDLA) acted also as a nucleating agent due to the formation of the PLA stereocomplex. The half crystallization time was reduced by the addition of talc to about 2 min from 37.5 min of pure PLA by the isothermal crystallization study. The dynamic mechanical thermal study (DMTA) indicated that nanofillers acted as both reinforcement fillers and nucleating agents in relation to the higher storage modulus. The plasticized PLA studied by DMTA indicated a decreasing glass transition temperature with the increasing of the PEG content. The addition of nanofiller increased the Young’s modulus. PEG had the plasticization effect of increasing the break deformation, while sharply decreasing the stiffness and strength of PLA. The synergistic effect of nanofillers and plasticizer achieved the balance between stiffness and toughness with well-controlled crystallization. Full article

(This article belongs to the Section Organic Chemistry)

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Open AccessArticle

Cytotoxic Activity and Composition of Petroleum Ether Extract from Magydaris tomentosa (Desf.) W. D. J. Koch (Apiaceae)

by Giuseppina Autore, Stefania Marzocco, Carmen Formisano, Maurizio Bruno, Sergio Rosselli, Mariem Ben Jemia and Felice Senatore

Molecules 2015, 20(1), 1571-1578; https://doi.org/10.3390/molecules20011571 - 16 Jan 2015

Cited by 30 | Viewed by 9462

Abstract

The petroleum ether extract of Magydaris tomentosa flowers (Desf.) W. D. J. Koch has been analyzed by GC-MS. It is mainly constituted by furanocoumarins such as xanthotoxin, xanthotoxol, isopimpinellin, and bergaptene. Other coumarins such as 7-methoxy-8-(2-formyl-2-methylpropyl) coumarin and osthole also occurred. The antiproliferative [...] Read more.

The petroleum ether extract of Magydaris tomentosa flowers (Desf.) W. D. J. Koch has been analyzed by GC-MS. It is mainly constituted by furanocoumarins such as xanthotoxin, xanthotoxol, isopimpinellin, and bergaptene. Other coumarins such as 7-methoxy-8-(2-formyl-2-methylpropyl) coumarin and osthole also occurred. The antiproliferative activity of Magydaris tomentosa flower extract has been evaluated in vitro on murine monocye/macrophages (J774A.1), human melanoma (A375) and human breast cancer (MCF-7) tumor cell lines, showing a major activity against the latter. Full article

(This article belongs to the Collection Bioactive Compounds)

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Open AccessArticle

Comparative Pharmacokinetics of Hypaconitine after Oral Administration of Pure Hypaconitine, Aconitum carmichaelii Extract and Sini Decoction to Rats

by Wen Zhang, Hai Zhang, Sen Sun, Feng-Feng Sun, Jun Chen, Liang Zhao and Guo-Qing Zhang

Molecules 2015, 20(1), 1560-1570; https://doi.org/10.3390/molecules20011560 - 16 Jan 2015

Cited by 28 | Viewed by 7333

Abstract

Hypaconitine (HC) is one of the main aconitum alkaloids in Aconitum carmichaelii (AC), which is considered to be effective on cardiovascular disease, although it also has high toxicity. Sini Decoction (SND), composed of Aconitum carmichaelii, Glycyrrhiza uralensis and Zingiber officinale, is [...] Read more.

Hypaconitine (HC) is one of the main aconitum alkaloids in Aconitum carmichaelii (AC), which is considered to be effective on cardiovascular disease, although it also has high toxicity. Sini Decoction (SND), composed of Aconitum carmichaelii, Glycyrrhiza uralensis and Zingiber officinale, is a traditional Chinese multi-herbal formula for recuperating the depleted yang. The aim of this study was to compare the pharmacokinetics of HC in rat plasma after oral administration of HC, AC extract and SND, and investigate the effect of other two herbal ingredients on absorption, metabolism and elimination of HC. A sensitive and specific LC-MS/MS method was developed to determine HC in rat plasma. Eighteen male Sprague-Dawley rats were randomly assigned to three groups: HC, AC and SND group. Plasma concentrations of HC were determined at designated points after oral administration, and main pharmacokinetic parameters were estimated. It was found that there was obvious difference (p < 0.05) on the pharmacokinetic parameters among three groups. Compared with AC group, T_max, C_max, k, AUC_(0-24) and AUC_(0-∞) decreased in SND group, while t_1/2 and MRT had been lengthened, which indicated that the ingredients in other two herbs could influence the pharmacokinetic behavior of HC. Full article

(This article belongs to the Section Medicinal Chemistry)

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Open AccessArticle

New Sesquiterpenoids and a Diterpenoid from Alpinia oxyphylla

by Lei Hou, Gang Ding, Baolin Guo, Wenhua Huang, Xiaojian Zhang, Zhiyong Sun and Xiangfen Shi

Molecules 2015, 20(1), 1551-1559; https://doi.org/10.3390/molecules20011551 - 16 Jan 2015

Cited by 20 | Viewed by 6229

Abstract

The new compounds 2-methyl-6-isopropyl-7-hydroxymethyl naphthalene (1), oxyphyllenone H (2), epi-oxyphyllenone (6), (E)-labda-12,14-dien-15(16)-olide-17-oic acid (3), and two new natural products 4 and 5 were isolated from the ethyl acetate part of 95% ethanol [...] Read more.

The new compounds 2-methyl-6-isopropyl-7-hydroxymethyl naphthalene (1), oxyphyllenone H (2), epi-oxyphyllenone (6), (E)-labda-12,14-dien-15(16)-olide-17-oic acid (3), and two new natural products 4 and 5 were isolated from the ethyl acetate part of 95% ethanol extract of Alpinia oxyphylla, together with six known compounds 7–12. The inhibitory effects of compounds 1–12 on α-glucosidase were evaluated, and compounds 1, 3 and 6 showed moderate bioactive effect, with inhibitory rates of 10.3%, 10.0% and 11.5%, respectively, compared to the positive control acarbose (41.9%) at 20 µg/mL. Full article

(This article belongs to the Section Natural Products Chemistry)

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Open AccessCommunication

Cross-Amplification of Vicia sativa subsp. sativa Microsatellites across 22 Other Vicia Species

by Sebastin Raveendar, Gi-An Lee, Young-Ah Jeon, Yun Jeong Lee, Jung-Ro Lee, Gyu-Taek Cho, Joon-Hyeong Cho, Jong-Hyun Park, Kyung-Ho Ma and Jong-Wook Chung

Molecules 2015, 20(1), 1543-1550; https://doi.org/10.3390/molecules20011543 - 16 Jan 2015

Cited by 28 | Viewed by 6094

Abstract

The temperate and herbaceous genus Vicia L. is a member of the legume tribe Fabeae of the subfamily Papilionoideae. The genus Vicia comprises 166 annual or perennial species distributed mainly in Europe, Asia, and North America, but also extending to the temperate regions [...] Read more.

The temperate and herbaceous genus Vicia L. is a member of the legume tribe Fabeae of the subfamily Papilionoideae. The genus Vicia comprises 166 annual or perennial species distributed mainly in Europe, Asia, and North America, but also extending to the temperate regions of South America and tropical Africa. The use of simple sequence repeat (SSR) markers for Vicia species has not been investigated as extensively as for other crop species. In this study, we assessed the potential for cross-species amplification of cDNA microsatellite markers developed from common vetch (Vicia sativa subsp. sativa). For cross-species amplification of the SSRs, amplification was carried out with genomic DNA isolated from two to eight accessions of 22 different Vicia species. For individual species or subspecies, the transferability rates ranged from 33% for V. ervilia to 82% for V. sativa subsp. nigra with an average rate of 52.0%. Because the rate of successful SSR marker amplification generally correlates with genetic distance, these SSR markers are potentially useful for analyzing genetic relationships between or within Vicia species. Full article

(This article belongs to the Section Molecular Diversity)

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Open AccessArticle

Energy and Molecules from Photochemical/Photocatalytic Reactions. An Overview

by Davide Ravelli, Stefano Protti and Angelo Albini

Molecules 2015, 20(1), 1527-1542; https://doi.org/10.3390/molecules20011527 - 16 Jan 2015

Cited by 14 | Viewed by 8885

Abstract

Photocatalytic reactions have been defined as those processes that require both a (not consumed) catalyst and light. A previous definition was whether such reactions brought a system towards or away from the (thermal) equilibrium. This consideration brings in the question whether a part [...] Read more.

Photocatalytic reactions have been defined as those processes that require both a (not consumed) catalyst and light. A previous definition was whether such reactions brought a system towards or away from the (thermal) equilibrium. This consideration brings in the question whether a part of the photon energy is incorporated into the photochemical reaction products. Data are provided for representative organic reactions involving or not molecular catalysts and show that energy storage occurs only when a heavily strained structure is generated, and in that case only a minor part of photon energy is actually stored (ΔG up to 25 kcal·mol⁻¹). The green role of photochemistry/photocatalysis is rather that of forming highly reactive intermediates under mild conditions. Full article

(This article belongs to the Special Issue Photocatalysis)

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Open AccessCommunication

Synthesis of Novel bis-1,5-Disubstituted-1H-Tetrazoles by an Efficient Catalyst-Free Ugi-Azide Repetitive Process

by Luís E. Cárdenas-Galindo, Alejandro Islas-Jácome, Karla M. Colmenero-Martínez, Antonio Martínez-Richa and Rocío Gámez-Montaño

Molecules 2015, 20(1), 1519-1526; https://doi.org/10.3390/molecules20011519 - 16 Jan 2015

Cited by 19 | Viewed by 5909

Abstract

A series of five novel bis-1,5-disubstituted-1H-tetrazoles (bis-1,5-DS-1H-T) were quickly prepared by a catalyst-free Ugi-azide repetitive process from easily accessible starting materials in excellent yields, either at room temperature (88%–95%) or using mild MW-heating conditions (80%–91%). These [...] Read more.

A series of five novel bis-1,5-disubstituted-1H-tetrazoles (bis-1,5-DS-1H-T) were quickly prepared by a catalyst-free Ugi-azide repetitive process from easily accessible starting materials in excellent yields, either at room temperature (88%–95%) or using mild MW-heating conditions (80%–91%). These molecules may have a wide range of applications, such as chelating agents, organocatalysts and luminescent materials, and mainly as bioactive compounds. Full article

(This article belongs to the Section Organic Chemistry)

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Open AccessReview

Relative Stability of cis- and trans-Hydrindanones

by Motoo Tori

Molecules 2015, 20(1), 1509-1518; https://doi.org/10.3390/molecules20011509 - 15 Jan 2015

Cited by 6 | Viewed by 7981

Abstract

The relative stabilities of several cis- and trans-hydrindanones were compared using both isomerization experiments and MM2 calculations. The generally believed rule that cis-hydrindanones are more stable than trans-isomers is applicable, but is not always true. This review introduces examples, [...] Read more.

The relative stabilities of several cis- and trans-hydrindanones were compared using both isomerization experiments and MM2 calculations. The generally believed rule that cis-hydrindanones are more stable than trans-isomers is applicable, but is not always true. This review introduces examples, mainly from studies in our laboratory, to explain these facts. Full article

(This article belongs to the Section Organic Chemistry)

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Open AccessReview

Chemically-Modified Cellulose Paper as a Microstructured Catalytic Reactor

by Hirotaka Koga, Takuya Kitaoka and Akira Isogai

Molecules 2015, 20(1), 1495-1508; https://doi.org/10.3390/molecules20011495 - 15 Jan 2015

Cited by 28 | Viewed by 9936

Abstract

We discuss the successful use of chemically-modified cellulose paper as a microstructured catalytic reactor for the production of useful chemicals. The chemical modification of cellulose paper was achieved using a silane-coupling technique. Amine-modified paper was directly used as a base catalyst for the [...] Read more.

We discuss the successful use of chemically-modified cellulose paper as a microstructured catalytic reactor for the production of useful chemicals. The chemical modification of cellulose paper was achieved using a silane-coupling technique. Amine-modified paper was directly used as a base catalyst for the Knoevenagel condensation reaction. Methacrylate-modified paper was used for the immobilization of lipase and then in nonaqueous transesterification processes. These catalytic paper materials offer high reaction efficiencies and have excellent practical properties. We suggest that the paper-specific interconnected microstructure with pulp fiber networks provides fast mixing of the reactants and efficient transport of the reactants to the catalytically-active sites. This concept is expected to be a promising route to green and sustainable chemistry. Full article

(This article belongs to the Special Issue New Trends in Cellulose and Chitin Chemistry)

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Open AccessArticle

Seven-Membered Rings through Metal-Free Rearrangement Mediated by Hypervalent Iodine

by Siguara Bastos Lemos Silva, Adriana Della Torre, João Ernesto De Carvalho, Ana Lúcia Tasca Gois Ruiz and Luiz F. Silva, Jr.

Molecules 2015, 20(1), 1475-1494; https://doi.org/10.3390/molecules20011475 - 15 Jan 2015

Cited by 23 | Viewed by 10689

Abstract

A versatile and metal-free approach for the synthesis of carbocycles and of heterocycles bearing seven- and eight-membered rings is described. The strategy is based on ring expansion of 1-vinylcycloalkanols (or the corresponding silyl or methyl ether) mediated by the hypervalent iodine reagent HTIB [...] Read more.

A versatile and metal-free approach for the synthesis of carbocycles and of heterocycles bearing seven- and eight-membered rings is described. The strategy is based on ring expansion of 1-vinylcycloalkanols (or the corresponding silyl or methyl ether) mediated by the hypervalent iodine reagent HTIB (PhI(OH)OTs). Reaction conditions can be easily adjusted to give ring expansion products bearing different functional groups. A route to medium-ring lactones was also developed. Full article

(This article belongs to the Section Organic Chemistry)

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2129 KiB

Open AccessReview

Glutathionylspermidine in the Modification of Protein SH Groups: The Enzymology and Its Application to Study Protein Glutathionylation

by Jason Ching-Yao Lin, Bing-Yu Chiang, Chi-Chi Chou, Tzu-Chieh Chen, Yi-Ju Chen, Yu-Ju Chen and Chun-Hung Lin

Molecules 2015, 20(1), 1452-1474; https://doi.org/10.3390/molecules20011452 - 15 Jan 2015

Cited by 11 | Viewed by 10327

Abstract

Cysteine is very susceptible to reactive oxygen species. In response; posttranslational thiol modifications such as reversible disulfide bond formation have arisen as protective mechanisms against undesired in vivo cysteine oxidation. In Gram-negative bacteria a major defense mechanism against cysteine overoxidation is the formation [...] Read more.

Cysteine is very susceptible to reactive oxygen species. In response; posttranslational thiol modifications such as reversible disulfide bond formation have arisen as protective mechanisms against undesired in vivo cysteine oxidation. In Gram-negative bacteria a major defense mechanism against cysteine overoxidation is the formation of mixed protein disulfides with low molecular weight thiols such as glutathione and glutathionylspermidine. In this review we discuss some of the mechanistic aspects of glutathionylspermidine in prokaryotes and extend its potential use to eukaryotes in proteomics and biochemical applications through an example with tissue transglutaminase and its S-glutathionylation. Full article

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

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717 KiB

Open AccessReview

Molecular Progress in Research on Fruit Astringency

by Min He, Henglu Tian, Xiaowen Luo, Xiaohua Qi and Xuehao Chen

Molecules 2015, 20(1), 1434-1451; https://doi.org/10.3390/molecules20011434 - 15 Jan 2015

Cited by 52 | Viewed by 8845

Abstract

Astringency is one of the most important components of fruit oral sensory quality. Astringency mainly comes from tannins and other polyphenolic compounds and causes the drying, roughening and puckering of the mouth epithelia attributed to the interaction between tannins and salivary proteins. There [...] Read more.

Astringency is one of the most important components of fruit oral sensory quality. Astringency mainly comes from tannins and other polyphenolic compounds and causes the drying, roughening and puckering of the mouth epithelia attributed to the interaction between tannins and salivary proteins. There is growing interest in the study of fruit astringency because of the healthy properties of astringent substances found in fruit, including antibacterial, antiviral, anti-inflammatory, antioxidant, anticarcinogenic, antiallergenic, hepatoprotective, vasodilating and antithrombotic activities. This review will focus mainly on the relationship between tannin structure and the astringency sensation as well as the biosynthetic pathways of astringent substances in fruit and their regulatory mechanisms. Full article

(This article belongs to the Section Natural Products Chemistry)

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705 KiB

Open AccessArticle

An Alkaloid and a Steroid from the Endophytic Fungus Aspergillus fumigatus

by Zizhen Liang, Tiantian Zhang, Xiaoqian Zhang, Jia Zhang and Changqi Zhao

Molecules 2015, 20(1), 1424-1433; https://doi.org/10.3390/molecules20011424 - 14 Jan 2015

Cited by 31 | Viewed by 6378

Abstract

Two new compounds, fumitremorgin 12-methoxy-13-[5'-hydroxy-2'-(1''-hydroxy-3''-methoxy-5''-methylbenzoyl)-3'-methoxy]benzoic acid methyl ester (fumitremorgin D, 1) and 4,8,10,14-tetramethyl-6-acetoxy-14-[16-acetoxy-19-(20,21-dimethyl)-18-ene]-phenanthrene-1-ene-3,7-dione (2) were isolated from the cultured endophytic isolated fungus Aspergillus fumigatus, together with fourteen known compounds. Their structures were elucidated by 1-D and 2-D NMR analyses. [...] Read more.

Two new compounds, fumitremorgin 12-methoxy-13-[5'-hydroxy-2'-(1''-hydroxy-3''-methoxy-5''-methylbenzoyl)-3'-methoxy]benzoic acid methyl ester (fumitremorgin D, 1) and 4,8,10,14-tetramethyl-6-acetoxy-14-[16-acetoxy-19-(20,21-dimethyl)-18-ene]-phenanthrene-1-ene-3,7-dione (2) were isolated from the cultured endophytic isolated fungus Aspergillus fumigatus, together with fourteen known compounds. Their structures were elucidated by 1-D and 2-D NMR analyses. The cytotoxicity profile of the compound against the human hepatocellular carcinoma cell line HepG2 was evaluated by MTT antiproliferative assays. Full article

(This article belongs to the Section Natural Products Chemistry)

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Open AccessReview

Possible Roles of Plant Sulfurtransferases in Detoxification of Cyanide, Reactive Oxygen Species, Selected Heavy Metals and Arsenate

by Parvin Most and Jutta Papenbrock

Molecules 2015, 20(1), 1410-1423; https://doi.org/10.3390/molecules20011410 - 14 Jan 2015

Cited by 47 | Viewed by 10672

Abstract

Plants and animals have evolved various potential mechanisms to surmount the adverse effects of heavy metal toxicity. Plants possess low molecular weight compounds containing sulfhydryl groups (-SH) that actively react with toxic metals. For instance, glutathione (γ-Glu-Cys-Gly) is a sulfur-containing tripeptide thiol and [...] Read more.

Plants and animals have evolved various potential mechanisms to surmount the adverse effects of heavy metal toxicity. Plants possess low molecular weight compounds containing sulfhydryl groups (-SH) that actively react with toxic metals. For instance, glutathione (γ-Glu-Cys-Gly) is a sulfur-containing tripeptide thiol and a substrate of cysteine-rich phytochelatins (γ-Glu-Cys)_2–11-Gly (PCs). Phytochelatins react with heavy metal ions by glutathione S-transferase in the cytosol and afterwards they are sequestered into the vacuole for degradation. Furthermore, heavy metals induce reactive oxygen species (ROS), which directly or indirectly influence metabolic processes. Reduced glutathione (GSH) attributes as an antioxidant and participates to control ROS during stress. Maintenance of the GSH/GSSG ratio is important for cellular redox balance, which is crucial for the survival of the plants. In this context, sulfurtransferases (Str), also called rhodaneses, comprise a group of enzymes widely distributed in all phyla, paving the way for the transfer of a sulfur atom from suitable sulfur donors to nucleophilic sulfur acceptors, at least in vitro. The best characterized in vitro reaction is the transfer of a sulfane sulfur atom from thiosulfate to cyanide, leading to the formation of sulfite and thiocyanate. Plants as well as other organisms have multi-protein families (MPF) of Str. Despite the presence of Str activities in many living organisms, their physiological role has not been clarified unambiguously. In mammals, these proteins are involved in the elimination of cyanide released from cyanogenic compounds. However, their ubiquity suggests additional physiological functions. Furthermore, it is speculated that a member of the Str family acts as arsenate reductase (AR) and is involved in arsenate detoxification. In summary, the role of Str in detoxification processes is still not well understood but seems to be a major function in the organism. Full article

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

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Open AccessReview

Beyond the Excluded Volume Effects: Mechanistic Complexity of the Crowded Milieu

by Irina M. Kuznetsova, Boris Y. Zaslavsky, Leonid Breydo, Konstantin K. Turoverov and Vladimir N. Uversky

Molecules 2015, 20(1), 1377-1409; https://doi.org/10.3390/molecules20011377 - 14 Jan 2015

Cited by 157 | Viewed by 11809

Abstract

Macromolecular crowding is known to affect protein folding, binding of small molecules, interaction with nucleic acids, enzymatic activity, protein-protein interactions, and protein aggregation. Although for a long time it was believed that the major mechanism of the action of crowded environments on structure, [...] Read more.

Macromolecular crowding is known to affect protein folding, binding of small molecules, interaction with nucleic acids, enzymatic activity, protein-protein interactions, and protein aggregation. Although for a long time it was believed that the major mechanism of the action of crowded environments on structure, folding, thermodynamics, and function of a protein can be described in terms of the excluded volume effects, it is getting clear now that other factors originating from the presence of high concentrations of “inert” macromolecules in crowded solution should definitely be taken into account to draw a more complete picture of a protein in a crowded milieu. This review shows that in addition to the excluded volume effects important players of the crowded environments are viscosity, perturbed diffusion, direct physical interactions between the crowding agents and proteins, soft interactions, and, most importantly, the effects of crowders on solvent properties. Full article

(This article belongs to the Section Metabolites)

959 KiB

Open AccessArticle

Synthesis and Cytotoxicity Evaluation of Some Novel Thiazoles, Thiadiazoles, and Pyrido[2,3-d][1,2,4]triazolo[4,3-a]pyrimidin-5(1H)-ones Incorporating Triazole Moiety

by Sobhi M. Gomha, Sayed A. Ahmed and Abdou O. Abdelhamid

Molecules 2015, 20(1), 1357-1376; https://doi.org/10.3390/molecules20011357 - 14 Jan 2015

Cited by 77 | Viewed by 9003

Abstract

Reactions of hydrazonoyl halides and each of methyl 2-(1-(5-methyl-1-phenyl-1H-1,2,3-triazol-4-yl)ethylidene)hydrazine-1-carbodithioate and 2-(1-(5-methyl-1-phenyl-1H-1,2,3-triazol-4-yl)ethylidene)hydrazine-1-carbothioamide afforded 2-(1-(5-methyl-1-phenyl-1H-1,2,3-triazol-4-yl)ethylidene)hydrazono)-3-phenyl-5-substituted-2,3-dihydro-1,3,4-thiadiazoles and 5-(4-substituted)diazenyl)-2-(2-(1-(5-methyl-1-phenyl-1H-1,2,3-triazol-4-yl)ethylidene)hydrazinyl)-4-arylthiazoles, respectively. Analogously, the reactions of hydrazonoyl halides with 7-(5-methyl-1-phenyl-1H-1,2,3-triazol-4-yl)-5-phenyl-2-thioxo-2,3-dihydropyrido[2,3-d]pyrimidin-4(1H)-one gave 3-(4-substituted)-8-(5-methyl-1-phenyl-1H-1,2,3-triazol-4-yl)-6-phenyl-1-arylpyrido[2,3-d [...] Read more.

Reactions of hydrazonoyl halides and each of methyl 2-(1-(5-methyl-1-phenyl-1H-1,2,3-triazol-4-yl)ethylidene)hydrazine-1-carbodithioate and 2-(1-(5-methyl-1-phenyl-1H-1,2,3-triazol-4-yl)ethylidene)hydrazine-1-carbothioamide afforded 2-(1-(5-methyl-1-phenyl-1H-1,2,3-triazol-4-yl)ethylidene)hydrazono)-3-phenyl-5-substituted-2,3-dihydro-1,3,4-thiadiazoles and 5-(4-substituted)diazenyl)-2-(2-(1-(5-methyl-1-phenyl-1H-1,2,3-triazol-4-yl)ethylidene)hydrazinyl)-4-arylthiazoles, respectively. Analogously, the reactions of hydrazonoyl halides with 7-(5-methyl-1-phenyl-1H-1,2,3-triazol-4-yl)-5-phenyl-2-thioxo-2,3-dihydropyrido[2,3-d]pyrimidin-4(1H)-one gave 3-(4-substituted)-8-(5-methyl-1-phenyl-1H-1,2,3-triazol-4-yl)-6-phenyl-1-arylpyrido[2,3-d]-[1,2,4]-triazolo-[4,3-a]pyrimidin- 5(1H)-ones in a good yield. The structures of the newly synthesized were elucidated via elemental analysis, spectral data and alternative synthesis routes whenever possible. Twelve of the newly synthesized compounds have been evaluated for their antitumor activity against human breast carcinoma (MCF-7) and human hepatocellular carcinoma (HepG2) cell lines. Their structure activity relationships (SAR) were also studied. The 1,3,4-thiadiazole derivative 9b (IC₅₀ = 2.94 µM) has promising antitumor activity against the human hepatocellular carcinoma cell line and the thiazole derivative 12a has promising inhibitory activity against both the human hepatocellular carcinoma cell line and the breast carcinoma cell line (IC₅₀ = 1.19, and 3.4 µM, respectively). Full article

(This article belongs to the Section Organic Chemistry)

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Open AccessReview

The Viability of Photocatalysis for Air Purification

by Stephen O. Hay, Timothy Obee, Zhu Luo, Ting Jiang, Yongtao Meng, Junkai He, Steven C. Murphy and Steven Suib

Molecules 2015, 20(1), 1319-1356; https://doi.org/10.3390/molecules20011319 - 14 Jan 2015

Cited by 75 | Viewed by 14628

Abstract

Photocatalytic oxidation (PCO) air purification technology is reviewed based on the decades of research conducted by the United Technologies Research Center (UTRC) and their external colleagues. UTRC conducted basic research on the reaction rates of various volatile organic compounds (VOCs). The knowledge gained [...] Read more.

Photocatalytic oxidation (PCO) air purification technology is reviewed based on the decades of research conducted by the United Technologies Research Center (UTRC) and their external colleagues. UTRC conducted basic research on the reaction rates of various volatile organic compounds (VOCs). The knowledge gained allowed validation of 1D and 3D prototype reactor models that guided further purifier development. Colleagues worldwide validated purifier prototypes in simulated realistic indoor environments. Prototype products were deployed in office environments both in the United States and France. As a result of these validation studies, it was discovered that both catalyst lifetime and byproduct formation are barriers to implementing this technology. Research is ongoing at the University of Connecticut that is applicable to extending catalyst lifetime, increasing catalyst efficiency and extending activation wavelength from the ultraviolet to the visible wavelengths. It is critical that catalyst lifetime is extended to realize cost effective implementation of PCO air purification. Full article

(This article belongs to the Special Issue Photocatalysis)

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Open AccessArticle

Synthesis and Evaluation of Paeonol Derivatives as Potential Multifunctional Agents for the Treatment of Alzheimer’s Disease

by An Zhou, Hongfei Wu, Jian Pan, Xuncui Wang, Jiaming Li, Zeyu Wu and Ailing Hui

Molecules 2015, 20(1), 1304-1318; https://doi.org/10.3390/molecules20011304 - 14 Jan 2015

Cited by 37 | Viewed by 8277

Abstract

Alzheimer’s disease (AD) is a progressive neurodegenerative brain disorder characterized by memory loss, language impairment, personality changes and intellectual decline. Taking into account the key pathological features of AD, such as low levels of acetylcholine, beta-amyloid (Aβ) aggregation, oxidative stress and dyshomeostasis of [...] Read more.

Alzheimer’s disease (AD) is a progressive neurodegenerative brain disorder characterized by memory loss, language impairment, personality changes and intellectual decline. Taking into account the key pathological features of AD, such as low levels of acetylcholine, beta-amyloid (Aβ) aggregation, oxidative stress and dyshomeostasis of biometals, a new series of paeonol derivatives 5a–5d merging three different functions, i.e., antioxidant, anti-acetylcholinesterase (AChE) activity, metal chelating agents for AD treatment have been synthesized and characterized. Biological assays revealed that compared with paeonol (309.7 μM), 5a–5d had a lower DPPH IC₅₀ value (142.8–191.6 μM). 5a–5d could significantly inhibit hydrogen peroxide-induced neuronal PC12 cell death assessed by MTT assay in the concentration range of 5–40 μM. AChE activity was effectively inhibited by 5a–5d, with IC₅₀ values in the range of 0.61–7.04 μM. 5a–5d also exhibited good metal-chelating ability. All the above results suggested that paeonol derivatives may be promising multifunctional agents for AD treatment. Full article

(This article belongs to the Section Organic Chemistry)

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Open AccessArticle

Ginsenoside Rc Promotes Anti-Adipogenic Activity on 3T3-L1 Adipocytes by Down-Regulating C/EBPα and PPARγ

by Ji-Won Yang and Sung Soo Kim

Molecules 2015, 20(1), 1293-1303; https://doi.org/10.3390/molecules20011293 - 14 Jan 2015

Cited by 53 | Viewed by 7171

Abstract

Panax ginseng and its major components, the ginsenosides, are widely used in oriental medicine for the prevention of various disorders. In the present study, the inhibitory activity of ginsenoside Rc on adipogenesis was investigated using the 3T3-L1 cell line. The results obtained showed [...] Read more.

Panax ginseng and its major components, the ginsenosides, are widely used in oriental medicine for the prevention of various disorders. In the present study, the inhibitory activity of ginsenoside Rc on adipogenesis was investigated using the 3T3-L1 cell line. The results obtained showed that Rc reduced the proliferation and viability of 3T3-L1 preadipocytes in a dose-dependent manner. Treatment with Rc decreased the number of adipocytes and reduced lipid accumulation in maturing 3T3-L1 preadipocytes, demonstrating an inhibitory effect on lipogenesis. Moreover, it was found that Rc directly induced lipolysis in adipocytes and down-regulated the expression of major transcription factors of the adipogenesis pathway, such as PPARγ and C/EBPα. These findings indicate that Rc is capable of suppressing adipogenesis and therefore they seem to be natural bioactive factors effective in adipose tissue mass modulation. Full article

(This article belongs to the Section Medicinal Chemistry)

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Open AccessArticle

Bisdemethoxycurcumin Induces Apoptosis in Activated Hepatic Stellate Cells via Cannabinoid Receptor 2

by Phil Jun Lee, Seung Je Woo, Jun-Goo Jee, Sang Hyun Sung and Hong Pyo Kim

Molecules 2015, 20(1), 1277-1292; https://doi.org/10.3390/molecules20011277 - 14 Jan 2015

Cited by 30 | Viewed by 9224

Abstract

Activated Hepatic Stellate Cells (HSCs), major fibrogenic cells in the liver, undergo apoptosis when liver injuries cease, which may contribute to the resolution of fibrosis. Bisdemethoxycurcumin (BDMC) is a natural derivative of curcumin with anti-inflammatory and anti-cancer activities. The therapeutic potential of BDMC [...] Read more.

Activated Hepatic Stellate Cells (HSCs), major fibrogenic cells in the liver, undergo apoptosis when liver injuries cease, which may contribute to the resolution of fibrosis. Bisdemethoxycurcumin (BDMC) is a natural derivative of curcumin with anti-inflammatory and anti-cancer activities. The therapeutic potential of BDMC in hepatic fibrosis has not been studied thus far in the context of the apoptosis in activated HSCs. In the current study, we compared the activities of BDMC and curcumin in the HSC-T6 cell line and demonstrated that BDMC relatively induced a potent apoptosis. BDMC-induced apoptosis was mediated by a combinatory inhibition of cytoprotective proteins, such as Bcl₂ and heme oxygenase-1 and increased generation of reactive oxygen species. Intriguingly, BDMC-induced apoptosis was reversed with co-treatment of sr144528, a cannabinoid receptor (CBR) 2 antagonist, which was confirmed with genetic downregulation of the receptor using siCBR2. Additionally, incubation with BDMC increased the formation of death-induced signaling complex in HSC-T6 cells. Treatment with BDMC significantly diminished total intracellular ATP levels and upregulated ATP inhibitory factor-1. Collectively, the results demonstrate that BDMC induces apoptosis in activated HSCs, but not in hepatocytes, by impairing cellular energetics and causing a downregulation of cytoprotective proteins, likely through a mechanism that involves CBR2. Full article

(This article belongs to the Special Issue Curcumin, Inflammation, and Chronic Diseases: How are They Linked?)

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Molecules, Volume 20, Issue 1 (January 2015) – 107 articles , Pages 1-1754

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