Design, synthesis, and biological evaluation of benzoselenazole-stilbene hybrids as multi-target-directed anti-cancer agents

被引：63

作者：

Yan, Jun ^{[1
]}

Guo, Yueyan ^{[1
]}

Wang, Yali ^{[1
]}

Mao, Fei ^{[1
]}

Huang, Ling ^{[1
]}

Li, Xingshu ^{[1
]}

机构：

[1] Sun Yat Sen Univ, Sch Pharmaceut Sci, Inst Drug Synth & Pharmaceut Proc, Guangzhou 510006, Guangdong, Peoples R China

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2015年 / 95卷

关键词：

Benzoselenazole-stilbene hybrids; Antiproliferative activity; Apoptosis; G2/M cell cycle arrest; TrxR; ROS; THIOREDOXIN REDUCTASE; MAMMALIAN THIOREDOXIN; CELL-CYCLE; GROWTH-INHIBITION; CANCER; RESVERATROL; APOPTOSIS; SELENIUM; MECHANISM; SUBSTRATE;

D O I：

10.1016/j.ejmech.2015.03.030

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

To identify novel multi-target-directed drug candidates for the treatment of cancer, a series of benzoselenazole-stilbene hybrids were synthesised by combining the pharmacophores of resveratrol and ebselen. The biological assay indicated that all of the hybrids exhibited antiproliferative activities against four human cancer cell lines and demonstrated good TrxR inhibitory activities. The mechanism of cell apoptosis was investigated in G2/M cell cycle arrest induced by compound 6e and the apoptosis of the human liver carcinoma Bel-7402 cell line. The significant increase in intracellular ROS confirmed that compound 6e was capable of causing oxidative stress-induced apoptosis in cancer cells. Our results support the potential of compound 6e as a candidate for further studies examining the development of novel drugs for cancer treatment. (C) 2015 Elsevier Masson SAS. All rights reserved.

引用

页码：220 / 229

页数：10

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