Synergistic Activity of Nitroimidazole-Oxazolidinone Conjugates against Anaerobic Bacteria

• Published in: Molecules (Basel, Switzerland) Vol. 25; no. 10; p. 2431
• Main Authors: Zhuang, Zhijun, Wan, Dawei, Ding, Jun, He, Shijie, Zhang, Qian, Wang, Xiaomei, Yuan, Ying, Lu, Yu, Ding, Charles Z, Lynch, Anthony Simon, Upton, Anna M, Cooper, Christopher B, Denny, William A, Ma, Zhenkun
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI 22.05.2020; MDPI AG
• Subjects: anaerobic bacterium; Antitubercular Agents - chemistry; Antitubercular Agents - pharmacology; Bacteria, Anaerobic - drug effects; drug conjugates; Drug Resistance, Multiple, Bacterial - drug effects; Drug Synergism; Humans; Linezolid - chemistry; Mycobacterium tuberculosis - drug effects; Mycobacterium tuberculosis - pathogenicity; nitroimidazole and oxazolidinone; Nitroimidazoles - chemistry; Nitroimidazoles - pharmacology; Oxazolidinones - chemistry; Oxazolidinones - pharmacology; synergy; Tuberculosis, Multidrug-Resistant - drug therapy; Tuberculosis, Multidrug-Resistant - microbiology; nitroimidazole and oxazolidinone; anaerobic bacterium; synergy; drug conjugates
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules25102431

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) (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.