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Synergistic Activity of Nitroimidazole-Oxazolidinone Conjugates against Anaerobic Bacteria

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TenNor Therapeutics Limited, 218 Xinghu Street, Building B2, Suite 711, Suzhou Industrial Park, Suzhou 215123, China
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Department of Pharmacology, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing Chest Hospital, Capital Medical University, 97 Ma Chang Street, Beijing 101149, China
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WuXi AppTec. Co. Ltd., 288 Fute Zhong Road, Waigaoqiao Free Trade Zone, Shanghai 200131, China
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Janssen Research & Development LLC., 1400 McKean Road, Spring House, PA 18940, USA
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Global Alliance for TB Drug Development, 40 Wall Street, New York, NY 10005, USA
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Auckland Cancer Society Research Centre, School of Medical Sciences, University of Auckland, Private Bag 92019, Auckland 1142, New Zealand
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Author to whom correspondence should be addressed.
Academic Editors: Larry Wakelin and Sandra Gemma
Molecules 2020, 25(10), 2431; https://doi.org/10.3390/molecules25102431
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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MDPI and ACS Style

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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