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

Apeng Wang; Shijie Xu; Yun Chai; Guimin Xia; Bin Wang; Kai Lv; Dan Wang; Xiaoyu Qin; Bin Jiang; Wenhao Wu; Mingliang Liu; Yu Lu

doi:10.1016/j.bmc.2021.116529

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. Epub 2021 Nov 25.

Authors

Apeng Wang¹, Shijie Xu¹, Yun Chai², Guimin Xia³, Bin Wang⁴, Kai Lv¹, Dan Wang¹, Xiaoyu Qin¹, Bin Jiang⁵, Wenhao Wu⁵, Mingliang Liu⁶, Yu Lu⁷

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: xiaguimin@126.com.
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: lmllyx@126.com.
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: luyu4876@hotmail.com.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antitubercular Agents / chemical synthesis
Antitubercular Agents / chemistry
Antitubercular Agents / pharmacology*
Dose-Response Relationship, Drug
Drug Design*
Humans
Microbial Sensitivity Tests
Molecular Structure
Mycobacterium tuberculosis / drug effects*
Nitrofurans / chemistry
Nitrofurans / pharmacology*
Oxadiazoles / chemistry
Oxadiazoles / pharmacology*
Structure-Activity Relationship

Substances

Antitubercular Agents
Nitrofurans
Oxadiazoles
1,3,4-oxadiazole