Novel structure-activity relationships and selectivity profiling of cage dimeric 1,4-dihydropyridines as multidrug resistance (MDR) modulators

被引：31

作者：

Coburger, Claudius ^{[1
]}

Wollmann, Joerg ^{[1
]}

Krug, Martin ^{[1
]}

Baumert, Christiane ^{[1
]}

Seifert, Marianne ^{[1
]}

Molnar, Josef ^{[2
]}

Lage, Hermann ^{[3
]}

Hilgeroth, Andreas ^{[1
]}

机构：

[1] Univ Halle Wittenberg, Inst Pharm, D-06120 Halle, Germany

[2] Univ Szeged, Dept Med Microbiol, Szeged, Hungary

[3] Charite Hosp, Inst Pathol, Berlin, Germany

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2010年 / 18卷 / 14期

关键词：

Structure-activity relationships (SAR); Multidrug resistance (MDR); P-Glycoprotein (P-gp); Multidrug resistance associated protein (MRP); Breast cancer resistant protein (BCRP); Selectivity; P-GLYCOPROTEIN; CHANNEL BLOCKERS; CANCER; TRANSPORTERS; INHIBITION; EXPRESSION;

D O I：

10.1016/j.bmc.2010.06.004

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：

Synthesized series of cage dimeric 1,4-dihydropyridines have been systematically evaluated as MDR modulators in in vitro assays to investigate structure-dependent selectivity properties of inhibiting most cancer-relevant efflux pump proteins. Structure-activity relationships of each P-glycoprotein (P-gp) and multidrug resistance associated protein (MRP) 1 and MRP2 inhibition are discussed and prove to be mainly determined by certain aromatic substitution patterns. The characterization of breast cancer resistance protein (BCRP) inhibition results in the discovery of benzyloxy substituted derivatives as selective P-gp inhibitors. (C) 2010 Elsevier Ltd. All rights reserved.

引用

页码：4983 / 4990

页数：8

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