Reversal of P-glycoprotein-mediated MDR by 5,7,3′,4′,5′-pentamethoxyflavone and SAR

被引：42

作者：

Choi, CH ^{[1
]}

Kim, JH

Kim, SH

机构：

[1] Chosun Univ, Res Ctr Resistant Cells, Kwangju 501759, South Korea

[2] Chosun Univ, Coll Med, Dept Pharmacol, Kwangju 501759, South Korea

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2004年 / 320卷 / 03期

关键词：

multidrug resistance; 5,7,3 ',4 ',5 '-pentamethoxyflavone; flavonoids; chemosensitizer; P-glycoprotein; structure-activity relationship;

D O I：

10.1016/j.bbrc.2004.06.020

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：

During screening for the flavonoid chemosensitizers, it was found that 5,7,3',4',5'-pentamethoxyflavone (PMF) was equipotent to verapamil in vitro with respect to the chemosensitizing effect. PMF appears to have a chemosensitizing effect not only by increasing the intracellular accumulation of the drugs without competition in a binding site of azidopine but also by interfering with the substrate-stimulated ATPase activity. Structure-activity relationship suggests that methoxylated substitution and its numbers or sites of the rings are more important than its hydroxylated counterparts in chemosensitization. Overall, PMF is anticipated to be a novel and highly potent second-generation flavonoid chemosensitizer because PMF has significant advantages of having a high therapeutic index, of being a non-transportable inhibitor, and of having a low possibility of drug interactions at the azidopine-binding site of Pgp. (C) 2004 Elsevier Inc. All rights reserved.

引用

页码：672 / 679

页数：8

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