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基于药效团的已批准药物重新定位为新型金黄色葡萄球菌NorA外排泵抑制剂

Pharmacophore-Based Repositioning of Approved Drugs as Novel Staphylococcus aureus NorA Efflux Pump Inhibitors.

作者信息

Astolfi Andrea, Felicetti Tommaso, Iraci Nunzio, Manfroni Giuseppe, Massari Serena, Pietrella Donatella, Tabarrini Oriana, Kaatz Glenn W, Barreca Maria L, Sabatini Stefano, Cecchetti Violetta

机构信息

Department of Pharmaceutical Sciences, University of Perugia , Via del Liceo 1, 06123 Perugia, Italy.

John D. Dingell Department of Veterans Affairs Medical Center and the Department of Internal Medicine, Division of Infectious Diseases, School of Medicine, Wayne State University , Detroit, Michigan 48201, United States.

出版信息

J Med Chem. 2017 Feb 23;60(4):1598-1604. doi: 10.1021/acs.jmedchem.6b01439. Epub 2017 Feb 8.

Abstract

An intriguing opportunity to address antimicrobial resistance is represented by the inhibition of efflux pumps. Focusing on NorA, the most important efflux pump of Staphylococcus aureus, an efflux pump inhibitors (EPIs) library was used for ligand-based pharmacophore modeling studies. By exploitation of the obtained models, an in silico drug repositioning approach allowed for the identification of novel and potent NorA EPIs.

摘要

抑制外排泵为解决抗菌药物耐药性提供了一个有趣的机会。以金黄色葡萄球菌最重要的外排泵NorA为重点,利用一个外排泵抑制剂(EPI)文库进行基于配体的药效团建模研究。通过利用所获得的模型,一种计算机辅助药物重新定位方法得以识别新型强效NorA外排泵抑制剂。

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