Design, synthesis and structure-activity relationships of novel taxane-based multidrug resistance reversal agents

被引：39

作者：

Ojima, I ^{[1
]}

Borella, CP

Wu, XY

Bounaud, PY

Oderda, CF

Sturm, M

Miller, ML

Chakravarty, S

Chen, J

Huang, Q

Pera, P

Brooks, TA

Baer, MR

Bernacki, RJ

机构：

[1] SUNY Stony Brook, Dept Chem, Stony Brook, NY 11794 USA

[2] Roswell Pk Canc Inst, Dept Expt Therapeut, Grace Canc Ctr, Buffalo, NY 14263 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2005年 / 48卷 / 06期

关键词：

D O I：

10.1021/jm049483y

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of novel taxane-based multidrug resistance (MDR) reversal agents (TRAs) has been designed and synthesized. Structure-activity relationship (SAR) study clearly indicates that modification of the C-7 position with hydrophobic arenecarbonyleinnamoyl groups brings about high potency against drug efflux mediated by P-glycoprotein (P-gp). Six TRAs exhibit ability to modulate a wide range of ATP-binding cassette (ABC) transporters, such as P-gp, multidrug resistance-associated protein 1 (MRP1), and breast cancer resistance protein (BCRP), which may serve as novel broad-spectrum modulators of ABC transporters.

引用

页码：2218 / 2228

页数：11

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