Improved Potency of Indole-Based NorA Efflux Pump Inhibitors: From Serendipity toward Rational Design and Development

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• 作者：Federica Buonerba ; Susan LepriLaura Goracci ; Bryan D. SchindlerSusan M. Seo ; Glenn W. Kaatz ; Gabriele Cruciani
• 刊名：Journal of Medicinal Chemistry
• 出版年：2017
• 出版时间：January 12, 2017
• 年：2017
• 卷：60
• 期：1
• 页码：517-523
• 全文大小：462K
• ISSN：1520-4804

文摘

The NorA efflux pump is a potential drug target for reversal of resistance to selected antibacterial agents, and recently we described indole-based inhibitor candidates. Herein we report a second class of inhibitors derived from them but with significant differences in shape and size. In particular, compounds 13 and 14 are very potent inhibitors in that they demonstrated the lowest IC₅₀ values (2 μM) ever observed among all indole-based compounds we have evaluated.