Discovery and Optimization of Two Eis Inhibitor Families as Kanamycin Adjuvants against Drug-Resistant .

ACS Med Chem Lett

Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, Kentucky 40536, United States.

Published: December 2016

Drug-resistant tuberculosis (TB) is a global threat and innovative approaches such as using adjuvants of anti-TB therapeutics are required to combat it. High-throughput screening yielded two lead scaffolds of inhibitors of () acetyltransferase Eis, whose upregulation causes resistance to the anti-TB drug kanamycin (KAN). Chemical optimization on these scaffolds resulted in potent Eis inhibitors. One compound restored the activity of KAN in a KAN-resistant strain. Model structures of Eis-inhibitor complexes explain the structure-activity relationship.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5150678PMC
http://dx.doi.org/10.1021/acsmedchemlett.6b00261DOI Listing

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