Synthesis and Structure-Activity Relationships of 1-Benzyl-4,5,6-trimethoxyindoles as a Novel Class of Potent Antimitotic Agents

被引：12

作者：

Lai, Mei-Jung ^{[1
]}

Kuo, Ching-Chuan ^{[2
]}

Yeh, Teng-Kuang ^{[3
]}

Hsieh, Hsing-Pang ^{[3
]}

Chen, Li-Tzong ^{[2
]}

Pan, Wen-Yu ^{[2
]}

Hsu, Kuang-Yang ^{[1
]}

Chang, Jang-Yang ^{[2
,4
]}

Liou, Jing-Ping ^{[1
]}

机构：

[1] Taipei Med Univ, Coll Pharm, Taipei 110, Taiwan

[2] Natl Hlth Res Inst, Natl Inst Canc Res, Tainan 704, Taiwan

[3] Natl Hlth Res Inst, Div Biotechnol & Pharmaceut Res, Zhunan Town 350, Miaoli County, Taiwan

[4] Natl Cheng Kung Univ Hosp, Div Hematol Oncol, Dept Internal Med, Tainan 704, Taiwan

来源：

CHEMMEDCHEM | 2009年 / 4卷 / 04期

关键词：

antitumor agents; drug design; inhibitors; structure-activity relationships; tubulin polymerization; VASCULAR DISRUPTING AGENTS; INHIBIT TUBULIN POLYMERIZATION; HUMAN CANCER-CELLS; ANTITUBULIN AGENTS; BIOLOGICAL EVALUATION; ANTINEOPLASTIC AGENTS; MEDICINAL CHEMISTRY; IN-VIVO; MICROTUBULE; ANALOGS;

D O I：

10.1002/cmdc.200800405

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of 1-benzyl-4,5,6-trimethoxyindoles was designed and prepared as a novel class of potent antimitotic agents acting through the colchicine binding site of tubulin. Compounds 10 and 11 showed excellent antiproliferative activity with mean IC50 values of 26 and 27 nM, respectively, in a diverse set of human cancer lines from different organs, including a MDR+ line. They also displayed substantial antitubulin efficacy with IC50 values of 3.5 and 2.6 mu M, respectively, representing an improvement over colchicine (IC50=4.3 mu M).

引用

页码：588 / 593

页数：6

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