Design, synthesis, and quantitative structure-activity relationship of cytotoxic γ-carboline derivatives

被引：22

作者：

Chen, Jing ^{[1
]}

Dong, Xiaowu ^{[1
]}

Liu, Tao ^{[1
]}

Lou, Jianshu ^{[2
]}

Jiang, Chaoyi ^{[1
]}

Huang, Wenhai ^{[1
]}

He, Qiaojun ^{[2
]}

Yang, Bo ^{[2
]}

Hua, Yongzhou ^{[1
]}

机构：

[1] Zhejiang Univ, ZJU ENS Joint Lab Med Chem, Coll Pharmaceut Sci, Hangzhou 310058, Zhejiang, Peoples R China

[2] Zhejiang Univ, Inst Pharmacol & Toxicol, Coll Pharmaceut Sci, Hangzhou 310058, Zhejiang, Peoples R China

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2009年 / 17卷 / 09期

关键词：

gamma-Carboline derivatives; Cytotoxicity; CoMFA; 3D-QSAR; COMBRETASTATIN A-4; ANTINEOPLASTIC AGENTS; ANTITUMOR AGENT; TUBULIN; ANALOGS; POTENT; INHIBITION; SULFONAMIDE; BINDING; GROWTH;

D O I：

10.1016/j.bmc.2009.03.037

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Three series of gamma-carboline derivatives were designed and synthesized. All the compounds were tested for their cytotoxic activities in vitro against five human tumor cell lines (A549, SGC, HCT116, MCF-7, K562) and one multi-drug resistant subline (K562R). Most compounds showed moderate to potent cytotoxic activities against the tested cell lines. Sulfonate 11f exhibited more potent cytotoxic activities against almost all of the tested cells in comparison with the positive control, taxol, with IC50 values ranging from 0.15 to 4.5 mu M. The structure-activity relationships were discussed and a statistically reliable QSAR model (r(2) = 0.936, q(2) = 0.581) was established by the CoMFA analysis performed using the cytotoxic data against K562 cell line as a template. (C) 2009 Elsevier Ltd. All rights reserved.

引用

页码：3324 / 3331

页数：8

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