2. Academic Validation
  3. Synthesis and antitubercular evaluation of 4-carbonyl piperazine substituted 1,3-benzothiazin-4-one derivatives

Synthesis and antitubercular evaluation of 4-carbonyl piperazine substituted 1,3-benzothiazin-4-one derivatives

  • Bioorg Med Chem Lett. 2015 Apr 1;25(7):1373-6. doi: 10.1016/j.bmcl.2015.02.061.
Cui-Ting Peng 1,  Chao Gao 2,  Ning-Yu Wang 2,  Xin-Yu You 3,  Li-Dan Zhang 3,  Yong-Xia Zhu 2,  Ying Xv 2,  Wei-Qiong Zuo 2,  Kai Ran 2,  Hong-Xia Deng 2,  Qian Lei 2,  Kun-Jie Xiao 2,  Luo-Ting Yu 4
Affiliations

Affiliations

  • 1 Department of Pharmaceutical and Bioengineering, School of Chemical Engineering, Sichuan University, Chengdu, Sichuan 610065, China.
  • 2 State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China.
  • 3 Department of Pharmaceutical and Bioengineering, School of Chemical Engineering, Sichuan University, Chengdu, Sichuan 610065, China; State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China.
  • 4 Department of Pharmaceutical and Bioengineering, School of Chemical Engineering, Sichuan University, Chengdu, Sichuan 610065, China; State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China. Electronic address: yuluot@scu.edu.cn.
PMID: 25754492 DOI: 10.1016/j.bmcl.2015.02.061
Abstract

Tuberculosis (TB) remains a major human health problem. New therapeutic antitubercular agents are urgent needed to control the global tuberculosis pandemic. We synthesized a new series of 4-carbonyl piperazine substituted 1,3-benzothiazin-4-one derivatives and evaluated their anti-mycobacterial activities against Mycobacterium tuberculosis H37Ra as well as their druggabilities. The results showed that most of these derivatives, especially the compounds with simple alkyl side chains, exhibited good antitubercular activities and favorable aqueous solubilities with no obvious cytotoxicity. It suggested that the 4-carbonyl piperazine substituents in benzothiazinone scaffold were well tolerated, in which the compound 8h, with an antitubercular activity of MIC 0.008 μM, exhibited an excellent aqueous solubility of 104 μg/mL, which was 100-fold better than the potent DprE1 inhibitor Comp.1 (BTZ038), also more soluble than PBTZ169.

Keywords

Aqueous solubility; Benzothiazinones; Structure–activity relationships (SAR); Tuberculosis.

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