Discovery of Novel Inhibitors of the NorA Multidrug Transporter of Staphylococcus aureus

被引：65

作者：

Brincat, Jean Pierre ^{[1
]}

Carosati, Emanuele ^{[1
]}

Sabatini, Stefano ^{[2
]}

Manfroni, Giuseppe ^{[2
]}

Fravolini, Arnaldo ^{[2
]}

Raygada, Jose L. ^{[3
,4
]}

Pate, Diixa

Kaatz, Glenn W. ^{[3
,4
]}

Cruciani, Gabriele ^{[1
]}

机构：

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

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

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

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

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2011年 / 54卷 / 01期

关键词：

MOLECULAR INTERACTION FIELDS; EFFLUX PUMP INHIBITORS; CALCIUM-CHANNEL BLOCKERS; UNITED-STATES; ANTIMICROBIAL RESISTANCE; DERIVATIVES; CIPROFLOXACIN; INFECTIONS; ANTIBIOTICS; MECHANISMS;

D O I：

10.1021/jm1011963

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Four novel inhibitors of the NorA efflux pump of Staphylococcus aureus, discovered through a virtual screening process, are reported The four compounds belong to different chemical classes and were tested for their in vitro ability to block the efflux of a well-known NorA substrate, as well as for their ability to potentiate the effect of ciprofloxacin (CPX) on several strains of S aureus, including a NorA overexpressing strain Additionally, the MIC values of each of the compounds individually are reported A structure-activity relationship study was also performed on these novel chemotypes, revealing three new compounds that are also potent NorA inhibitors The virtual screening procedure employed FLAP, a new methodology based on GRID force field descriptors

引用

页码：354 / 365

页数：12

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