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

J Med Chem. 2017 Jan 12;60(1):517-523. doi: 10.1021/acs.jmedchem.6b01281. Epub 2016 Dec 15.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Drug Design
  • Drug Resistance, Bacterial / drug effects*
  • Indoles / chemistry
  • Indoles / pharmacology*
  • Microbial Sensitivity Tests
  • Staphylococcus aureus / drug effects

Substances

  • Anti-Bacterial Agents
  • Indoles