Design, synthesis and biological evaluation of nitrofuran-1,3,4-oxadiazole hybrids as new antitubercular agents

  • Bioorg Med Chem. 2022 Jan 1;53:116529. doi: 10.1016/j.bmc.2021.116529.
Apeng Wang  1 ,  Shijie Xu  1 ,  Yun Chai  2 ,  Guimin Xia  3 ,  Bin Wang  4 ,  Kai Lv  1 ,  Dan Wang  1 ,  Xiaoyu Qin  1 ,  Bin Jiang  5 ,  Wenhao Wu  5 ,  Mingliang Liu  6 ,  Yu Lu  7
Affiliations
  • 1. Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
  • 2. Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China; Institute of Medical Research, Northwestern Polytechnical University, 127 West Youyi Road, Xi'an 710072, China.
  • 3. Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China. Electronic address: [email protected].
  • 4. Beijing Key Laboratory of Drug Resistance Tuberculosis Research, Department of Pharmacology, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing Chest Hospital, Capital College of Pharmacy, Medical University, Beijing 100149, China.
  • 5. Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China; Hebei Medical University, Shijiazhuang 050017, China.
  • 6. Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China. Electronic address: [email protected].
  • 7. Beijing Key Laboratory of Drug Resistance Tuberculosis Research, Department of Pharmacology, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing Chest Hospital, Capital College of Pharmacy, Medical University, Beijing 100149, China. Electronic address: [email protected].
PMID: 34861474 DOI: 10.1016/j.bmc.2021.116529
Abstract

Three series of novel nitrofuran-1,3,4-oxadiazole hybrids were designed and synthesized as new anti-TB agents. The structure activity relationship study indicated that the linkers and the substituents on the oxadiazole moiety greatly influence the activity, and the substituted benzenes are more favoured than the cycloalkyl or heterocyclic groups. Besides, the optimal compound in series 2 was active against both MTB H37Rv strain and MDR-MTB 16883 clinical isolate and also displayed low cytotoxicity, low inhibition of hERG and good oral PK, indicating its promising potential to be a lead for further structural modifications.

Keywords
Antitubercular activity; Nitrofuran-1,3,4-oxadiazole hybrids; Synthesis.
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