Ligand Promiscuity between the Efflux Pumps Human P-Glycoprotein and S. aureus NorA

被引：20

作者：

Brincat, Jean Pierre ^{[1
]}

Broccatelli, Fabio ^{[1
]}

Sabatini, Stefano ^{[2
]}

Frosini, Maria ^{[3
]}

Neri, Annalisa ^{[3
]}

Kaatz, Glenn W. ^{[4
,5
]}

Cruciani, Gabriele ^{[1
]}

Carosati, Emanuele ^{[1
]}

机构：

[1] Univ Perugia, Dipartimento Chim, I-06123 Perugia, Italy

[2] Univ Perugia, Dipartimento Chim & Tecnol Farmaco, I-06123 Perugia, Italy

[3] Univ Siena, Dept Neurosci, Pharmacol Unit, I-53100 Siena, Italy

[4] Wayne State Univ, Sch Med, Div Infect Dis, Dept Internal Med, Detroit, MI 48201 USA

[5] John D Dingell Dept Vet Affairs Med Ctr, Detroit, MI 48201 USA

来源：

ACS MEDICINAL CHEMISTRY LETTERS | 2012年 / 3卷 / 03期

关键词：

Multiple drug resistance; NorA; P-glycoprotein; promiscuous activity; efflux pump inhibitor; S; aureus; GENETICALLY RELATED STRAINS; MULTIDRUG-RESISTANCE; IN-VITRO; INHIBITORS; TRANSPORTER; CIPROFLOXACIN; DERIVATIVES; ASSAYS; CNS;

D O I：

10.1021/ml200293c

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Thirty-two diverse compounds were evaluated for their ability to inhibit both Pgp-mediated efflux in mouse T-lymphoma L5178 MDR1 and NorA-mediated efflux in S. aureus SA-1199B. Only four compounds were strong inhibitors of both efflux pumps. Three compounds were found to inhibit Pgp exclusively and strongly, while seven compounds inhibited only NorA. These results demonstrate that Pgp and NorA inhibitors do not necessarily overlap, opening the way to safer therapeutic use of effective NorA inhibitors.

引用

页码：248 / 251

页数：4

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