2. Academic Validation
  3. Design, synthesis and biological activity of N-(amino)piperazine-containing benzothiazinones against Mycobacterium tuberculosis

Design, synthesis and biological activity of N-(amino)piperazine-containing benzothiazinones against Mycobacterium tuberculosis

  • Eur J Med Chem. 2021 Jun 5:218:113398. doi: 10.1016/j.ejmech.2021.113398.
Apeng Wang 1,  Shijie Xu 1,  Yun Chai 2,  Guimin Xia 3,  Bin Wang 4,  Kai Lv 1,  Chao Ma 1,  Dan Wang 1,  Aoyu Wang 5,  Xiaoyu Qin 1,  Mingliang Liu 6,  Yu Lu 7
Affiliations

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: 33823392 DOI: 10.1016/j.ejmech.2021.113398
Abstract

A series of novel benzothiazinone derivatives containing a N-(amino)piperazine moiety, based on the structure of WAP-1902 discovered in our lab, were designed and synthesized as new anti-TB agents. Many of the compounds exhibited excellent in vitro activity against both drug-sensitive MTB strain H37Rv and multidrug-resistant clinical isolates (MIC: < 0.016 μg/mL), and good safety index (CC50: >64 μg/mL). Especially compound 1o displayed low hERG cardiac toxicity and acceptable oral pharmacokinetic profiles, indicating its promising potential to be a lead compound for future antitubercular drug discovery.

Keywords

Antitubercular activity; Benzothiazinones; N-(amino)piperazine; Synthesis.

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