1. Synergistic Activity of Nitroimidazole-Oxazolidinone Conjugates against Anaerobic Bacteria
- Author
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Yu Lu, Zhuang Zhijun, Charles Z. Ding, Anthony Simon Lynch, Christopher B. Cooper, Wang Xiaomei, Ding Jun, William A. Denny, Zhenkun Ma, Ying Yuan, Wan Dawei, Qian Zhang, Anna M. Upton, and Shijie He
- Subjects
Antitubercular Agents ,Pharmaceutical Science ,synergy ,Drug resistance ,Article ,Analytical Chemistry ,Microbiology ,lcsh:QD241-441 ,Mycobacterium tuberculosis ,03 medical and health sciences ,chemistry.chemical_compound ,Bacteria, Anaerobic ,0302 clinical medicine ,lcsh:Organic chemistry ,Drug Resistance, Multiple, Bacterial ,Drug Discovery ,Tuberculosis, Multidrug-Resistant ,Humans ,nitroimidazole and oxazolidinone ,Physical and Theoretical Chemistry ,Oxazolidinones ,030304 developmental biology ,0303 health sciences ,Nitroimidazole ,biology ,Bicyclic molecule ,Organic Chemistry ,Linezolid ,Drug Synergism ,Antimicrobial ,biology.organism_classification ,chemistry ,Chemistry (miscellaneous) ,Nitroimidazoles ,030220 oncology & carcinogenesis ,Pretomanid ,drug conjugates ,Molecular Medicine ,anaerobic bacterium ,Anaerobic bacteria - Abstract
The introductions of the bicyclic 4-nitroimidazole and the oxazolidinone classes of antimicrobial agents represented the most significant advancements in the infectious disease area during the past two decades. Pretomanid, a bicyclic 4-nitroimidazole, and linezolid, an oxazolidinone, are also part of a combination regimen approved recently by the US Food and Drug Administration for the treatment of pulmonary, extensively drug resistant (XDR), treatment-intolerant or nonresponsive multidrug-resistant (MDR) Mycobacterium tuberculosis (TB). To identify new antimicrobial agents with reduced propensity for the development of resistance, a series of dual-acting nitroimidazole-oxazolidinone conjugates were designed, synthesized and evaluated for their antimicrobial activity. Compounds in this conjugate series have shown synergistic activity against a panel of anaerobic bacteria, including those responsible for serious bacterial infections.
- Published
- 2020