Synergistic Activity of Nitroimidazole-Oxazolidinone Conjugates against Anaerobic Bacteria.

Molecules (Basel, Switzerland), Volume: 25, Issue: 10
May 22, 2020
Zhijun Zhuang Z, Dawei Wan D, Jun Ding J, Shijie He S, Qian Zhang Q, Xiaomei Wang X, Ying Yuan Y, Yu Lu Y, Charles Z Ding CZ, Anthony Simon Lynch AS, Anna M Upton AM, Christopher B Cooper CB, William A Denny WA, Zhenkun Ma Z

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.