Design and Synthesis of Resveratrol-Based Nitrovinylstilbenes as Antimitotic Agents

被引：94

作者：

Reddy, M. Amarnath ^{[2
]}

Jain, Nishant ^{[2
]}

Yada, Deepthi ^{[2
]}

Kishore, Chandan ^{[1
]}

Reddy, Vangala Janakiram ^{[1
]}

Reddy, P. Surendra ^{[2
]}

Addlagatta, Anthony ^{[1
]}

Kalivendi, Shasi V. ^{[1
]}

Sreedhar, Bojja ^{[2
]}

机构：

[1] CSIR, Indian Inst Chem Technol, Ctr Chem Biol, Hyderabad 500607, Andhra Pradesh, India

[2] CSIR, Indian Inst Chem Technol, Inorgan & Phys Chem Div, Hyderabad 500607, Andhra Pradesh, India

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2011年 / 54卷 / 19期

关键词：

ANTICANCER DRUGS; CANCER CELLS; APOPTOSIS; TUBULIN; ANALOG; PROLIFERATION; INHIBITION; ACTIVATION; EXPRESSION; PATHWAY;

D O I：

10.1021/jm200639r

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A new series of resveratrol analogues was designed, synthesized, and demonstrated to be tubulin polymerization inhibitors. Most of these compounds exhibited antiproliferative activity and inhibited in vitro tubulin polymerization effectively at concentrations of 4.4-68.1 and 17-62 mu M, respectively. Flow cytometry studies showed that compounds 7c, 7e, and 7g arrested cells in the G2/M phase of the cell cycle. Immunocytochemistry revealed loss of intact microtubule structure in cells treated with 7c and 7e. Docking of compounds 7c and 7e with tubulin suggested that the A-ring of the compounds occupies the colchicine binding site of tubulin, which coordinates with Cys241, Leu242, Ala250, Val318, Val328, and I378, and that the nitrovinyl side chain forms two hydrogen bonds with the main loop of the beta-chain at Asn249 and Ala250.

引用

页码：6751 / 6760

页数：10

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