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Synergistic Activity of Nitroimidazole-Oxazolidinone Conjugates against Anaerobic Bacteria

TenNor Therapeutics Limited, 218 Xinghu Street, Building B2, Suite 711, Suzhou Industrial Park, Suzhou 215123, China
Department of Pharmacology, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing Chest Hospital, Capital Medical University, 97 Ma Chang Street, Beijing 101149, China
WuXi AppTec. Co. Ltd., 288 Fute Zhong Road, Waigaoqiao Free Trade Zone, Shanghai 200131, China
Janssen Research & Development LLC., 1400 McKean Road, Spring House, PA 18940, USA
Global Alliance for TB Drug Development, 40 Wall Street, New York, NY 10005, USA
Auckland Cancer Society Research Centre, School of Medical Sciences, University of Auckland, Private Bag 92019, Auckland 1142, New Zealand
Author to whom correspondence should be addressed.
Academic Editors: Larry Wakelin and Sandra Gemma
Molecules 2020, 25(10), 2431;
Received: 8 May 2020 / Revised: 19 May 2020 / Accepted: 19 May 2020 / Published: 22 May 2020
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. View Full-Text
Keywords: drug conjugates; anaerobic bacterium; synergy; nitroimidazole and oxazolidinone drug conjugates; anaerobic bacterium; synergy; nitroimidazole and oxazolidinone
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Zhuang, Z.; Wan, D.; Ding, J.; He, S.; Zhang, Q.; Wang, X.; Yuan, Y.; Lu, Y.; Z. Ding, C.; Lynch, A.S.; M. Upton, A.; B. Cooper, C.; A. Denny, W.; Ma, Z. Synergistic Activity of Nitroimidazole-Oxazolidinone Conjugates against Anaerobic Bacteria. Molecules 2020, 25, 2431.

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