Synergistic Activity of Nitroimidazole-Oxazolidinone Conjugates against Anaerobic Bacteria

Molecules

WilliamA. Denny¹  Yu Lu²  AnnaM. Upton³  ChristopherB. Cooper³  AnthonySimon Lynch⁴  Zhijun Zhuang⁵  Jun Ding⁵  Dawei Wan⁵  Shijie He⁵  Zhenkun Ma⁵  Xiaomei Wang⁵  Ying Yuan⁵  Qian Zhang⁵  CharlesZ. Ding⁶ 

[1] Auckland Cancer Society Research Centre, School of Medical Sciences, University of Auckland, Private Bag 92019, Auckland 1142, New Zealand;Department of Pharmacology, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing Chest Hospital, Capital Medical University, 97 Ma Chang Street, Beijing 101149, China;Global Alliance for TB Drug Development, 40 Wall Street, New York, NY 10005, USA;Janssen Research & Development LLC., 1400 McKean Road, Spring House, PA 18940, USA;TenNor Therapeutics Limited, 218 Xinghu Street, Building B2, Suite 711, Suzhou Industrial Park, Suzhou 215123, China;WuXi AppTec. Co. Ltd., 288 Fute Zhong Road, Waigaoqiao Free Trade Zone, Shanghai 200131, China;

关键词: drug conjugates;    anaerobic bacterium;    synergy;    nitroimidazole and oxazolidinone;   

DOI  :  10.3390/molecules25102431

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown