- Heck arylation of styrenes with arenediazonium salts: short, efficient, and stereoselective synthesis of resveratrol, DMU-212, and analogues
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Short, efficient, and stereoselective synthesis of the trans-stilbenes resveratrol, DMU-212, and analogues of both compounds are described. The synthesis of these important anti-cancer agents feature the palladium catalyzed Heck-Matsuda arylation of styre
- Moro, Angélica Venturini,Cardoso, Flávio Sega P.,Correia, Carlos Roque D.
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- Discovery of efficient stimulators for adult hippocampal neurogenesis based on scaffolds in dragon's blood
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Reduction of hippocampal neurogenesis caused by aging and neurological disorders would impair neural circuits and result in memory loss. A new lead compound (N-trans-3′,4'-methylenedioxystilben-4-yl acetamide 27) has been discovered to efficiently stimulate adult rats' neurogenesis. In-depth structure-activity relationship studies proved the necessity of a stilbene scaffold that is absent in highly cytotoxic analogs such as chalcones and heteroaryl rings and inactive analogs such as diphenyl acetylene and diphenyl ethane, and validated the importance of an NH in the carboxamide and a methylenedioxy substituent on the benzene ring. Immunohistochemical staining and biochemical analysis indicate, in contrast to previously reported neuroprotective chemicals, N-stilbenyl carboxamides have extra capacity for neuroproliferation-type neurogenesis, thereby providing a foundation for improving the plasticity of the adult mammalian brain.
- Liang, Jian-Hua,Yang, Liang,Wu, Si,Liu, Si-Si,Cushman, Mark,Tian, Jing,Li, Nuo-Min,Yang, Qing-Hu,Zhang, He-Ao,Qiu, Yun-Jie,Xiang, Lin,Ma, Cong-Xuan,Li, Xue-Meng,Qing, Hong
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p. 382 - 392
(2017/05/19)
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- Extraordinary radical scavengers: 4-mercaptostilbenes
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In the past decade, there was a great deal of interest and excitement in developing more active antioxidants and cancer chemoprevention agents than resveratrol, a naturally occurring stilbene. In this work, eight resveratrol-directed 4-mercaptostilbenes were constructed based on the inspiration that thiophenol should be a stronger radical scavenger than phenol, and their reaction rates with galvinoxyl (GO.) and 2,2-diphenyl-1-picrylhydrazyl (DPPH.) radicals in methanol and ethyl acetate were measured by using stopped-flow UV/Vis spectroscopy at 25 °C. Kinetic analysis demonstrates that 4-mercaptostilbenes are extraordinary radical scavengers, and the substitution of the 4-SH group for the 4-OH group in the stilbene scaffold is an important strategy to improve the radical-scavenging activity of resveratrol. Surprisingly, in methanol, some of the 4-mercaptostilbenes are 104-times more active than resveratrol, dozens of times to hundreds of times more effective than known antioxidants (α-tocopherol, ascorbic acid, quercetin, and trolox). The detailed radical-scavenging mechanisms were discussed based on acidified-kinetic analysis. Addition of acetic acid remarkably reduced the GO. and DPPH. radical-scavenging rates of the 4-mercaptostilbenes in methanol, a solvent that supports ionization, suggesting that the reactions proceed mainly through a sequential proton loss electron transfer mechanism. In contrast, an interesting acid-promoted kinetics was observed for the reactions of the 4-mercaptostilbenes with DPPH. in ethyl acetate, a solvent that weakly supports ionization. The increased ratio in rates is closely correlated with the electron-rich environment in the molecules, suggesting that the acceleration could benefit from the contribution of the electron transfer from the 4-mercaptostilbenes and DPPH.. However, the addition of acetic acid had no influence on the GO.-scavenging rates of the 4-mercaptostilbenes in ethyl acetate, due to the occurrence of the direct hydrogen atom transfer. Our results show that the radical-scavenging activity and mechanisms of 4-mercaptostilbenes depends significantly on the molecular structure and acidity, the nature of the attacking radical, and the ionizing capacity of the solvent. Copyright
- Cao, Xiao-Yan,Yang, Jie,Dai, Fang,Ding, De-Jun,Kang, Yan-Fei,Wang, Fu,Li, Xiu-Zhuang,Liu, Guo-Yun,Yu, Sha-Sha,Jin, Xiao-Ling,Zhou, Bo
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p. 5898 - 5905
(2012/06/30)
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- Hydroxyl substitutional effect on selective synthesis of CIS, trans stilbenes and 3-arylcoumarins through perkin condensation
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The substitutional effect in the selective synthesis of cis, trans stilbenes and 3-arylcoumarins has been described. The regio- and geometrical selectivity for synthesis of stilbene derivatives under the Perkin strategy strongly depends on the presence or absence of hydroxyl group as well as their positions in the phenyl ring. As a result, practical synthetic strategies were established for preparing various natural stilbenes including combretastatin A-4, pterostilbene, and resveratrol with satisfactory yields (49.2-63.7%). Copyright Taylor & Francis Group, LLC.
- Xiao, Chun-Fen,Zou, Yong,Du, Jian-Li,Sun, Hong-Yi,Liu, Xian-Ke
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experimental part
p. 1243 - 1258
(2012/04/04)
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- Anticancer effects of the metabolic products of the resveratrol analogue, DMU-212: Structural requirements for potency
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The methoxylated trans-stilbene resveratrol analogue, (E)-3,4,5,4′- tetramethoxystilbene (1), has shown promising antiproliferative activity in in vitro cell line and in vivo models. In vivo 1 gives rise to several metabolic products through demethylation or hydroxylation reactions at the stilbene moiety. In the present study we examined the anticancer activity of 1 and the metabolites (E)-3′-hydroxy-3,4,5,4′-tetramethoxystilbene (2), (E)-4′-hydroxy-3,4,5-trimethoxystilbene (3), (E)-4-hydroxy-3,5,4′- trimethoxystilbene (4) and (E)-3-hydroxy-4,5,4′-trimethoxystilbene (5) by means of cell viability testing, cell cycle analysis, immunostaining and Western blotting. Compounds 1 and 2 exhibited submicromolar toxicity in MCF-7 breast adenocarcinoma and HepG2 hepatoma cells, whereas 3, 4 and 5 were inactive in terms of inhibition of cellular proliferation. Incubation with 1 or 2 at 10 μM for 24 h induced apoptosis and G2/M cell cycle arrest in MCF-7 and HepG2 cells. Immunostaining of MCF-7 cells for β-tubulin in the presence of either 1 or 2 revealed shorter localization of the protein around the nucleus, as compared to control cells. Western blot analyses further demonstrated that treatment with either 1 or 2 at concentrations between 30 and 50 μM for 24 h caused a downregulation in the levels of β-tubulin and cyclin D1 expression and an upregulation in the levels of p53 expression in MCF-7 and HepG2 cells. 2 further increased the ratio of mRNA levels of the apoptosis-related genes Bax/Bcl-xL in both MCF-7 and HepG2 cells in a dose-dependent manner. We conclude that 2 inhibits HepG2 and MCF-7 cellular proliferation by inducing apoptosis and G2/M arrest through p53 and Bax/Bcl-xL upregulation. Our findings further demonstrate that trimethoxy substitutions along with the presence of a methoxy group at position 4′ are necessary for retaining the activity of 1.
- Androutsopoulos, Vasilis P.,Ruparelia, Ketan C.,Papakyriakou, Athanasios,Filippakis, Harilaos,Tsatsakis, Aristeidis M.,Spandidos, Demetrios A.
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experimental part
p. 2586 - 2595
(2011/06/21)
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- Stilbene derivatives as anticancer agents
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The present invention relates to stilbene derivatives which possess utility as anti-cancer agents. The compounds can be used to treat cancers which are susceptible to treatment therewith, and can be utilized in a method of treating such cancers. Pharmaceu
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- Synthesis and Evaluation of Stilbene and Dihydrostilbene Derivatives as Potential Anticancer Agents That Inhibit Tubulin Polymerization
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An array of cis-, trans-, and dihydrostilbenes and some N-arylbenzylamines were synthesized and evaluated for their cytotoxicity in the five cancer cell cultures A-549 lung carcinoma, MCF-7 breast carcinoma, HT-29 colon adenocarcinoma, SKMEL-5 melanoma, a
- Cushman, Mark,Nagarathnam, Dhanapalan,Gopal, D.,Chakraborti, Asit K.,Lin, Chii M.,Hamel, Ernest
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p. 2579 - 2588
(2007/10/02)
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