Discovery and Optimization of Two Eis Inhibitor Families as Kanamycin Adjuvants against Drug-Resistant M. tuberculosis
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- 作者：Atefeh Garzan ; Melisa J. Willby ; Keith D. Green ; Oleg V. Tsodikov ; James E. Posey ; Sylvie Garneau-Tsodikova
- 刊名：ACS Medicinal Chemistry Letters
- 出版年：2016
- 出版时间：December 8, 2016
- 年：2016
- 卷：7
- 期：12
- 页码：1219-1221
- 全文大小：196K
- ISSN：1948-5875
文摘
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 Mycobacterium tuberculosis (Mtb) 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 Mtb strain. Model structures of Eis-inhibitor complexes explain the structure–activity relationship.