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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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5150678 | PMC |
http://dx.doi.org/10.1021/acsmedchemlett.6b00261 | DOI Listing |
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