Structure-activity requirements for flavone cytotoxicity and binding to tubulin

被引：118

作者：

Beutler, JA

Hamel, E

Vlietinck, AJ

Haemers, A

Rajan, P

Roitman, JN

Cardellina, JH

Boyd, MR ^{[1
]}

机构：

[1] NCI, Lab Drug Discovery Res & Dev, Dev Therapeut Program, Div Canc Treatment & Diag, Frederick, MD 21702 USA

[2] Univ Antwerp, B-2610 Antwerp, Belgium

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1998年 / 41卷 / 13期

关键词：

D O I：

10.1021/jm970842h

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of 79 flavones related to centaureidin (3,6,4'-trimethoxy-5,7,3'-trihydroxyflavone 1) was screened for cytotoxicity in the NCI in vitro 60-cell line human tumor screen. The resulting cytotoxicity profiles of these flavones were compared for degree of similarity to the profile of 1. Selected compounds were further evaluated with in vitro assays of tubulin polymerization and [H-3]colchicine binding to tubulin. Maximum potencies for tubulin interaction and production of differential cytotoxicity profiles characteristic of 1 were observed only with compounds containing hydroxyl substituents at C-3' and C-5 and methoxyl groups at C-3 and C-4'.

引用

页码：2333 / 2338

页数：6

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