Benzo[d]thiazol-2-yl(piperazin-1-yl)methanones as new anti-mycobacterial chemotypes: Design, synthesis, biological evaluation and 3D-QSAR studies

• Published in: European journal of medicinal chemistry 2016-06, Vol.116, p.187-199
• Main Authors: Pancholia, Sahaj, Dhameliya, Tejas M., Shah, Parth, Jadhavar, Pradeep S., Sridevi, Jonnalagadda Padma, Yogeshwari, Perumal, Sriram, Dharmarajan, Chakraborti, Asit K.
• Format: Article
• Language: English
• Subjects: and 3D-QSAR; Animals; Anti-mycobacterial activity; Antitubercular Agents - chemical synthesis; Antitubercular Agents - chemistry; Antitubercular Agents - pharmacology; Antitubercular Agents - toxicity; Benzo[d]thiazole-2-carboxamides; Chemistry Techniques, Synthetic; COMFA; Drug Design; Mice; Microbial Sensitivity Tests; Models, Molecular; Molecular Conformation; Mycobacterium tuberculosis - drug effects; New antibacterial chemotypes; Piperazines - chemical synthesis; Piperazines - chemistry; Piperazines - pharmacology; Piperazines - toxicity; Quantitative Structure-Activity Relationship; RAW 264.7 Cells; Tuberculosis
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2016.03.060

The benzo[d]thiazol-2-yl(piperazin-1-yl)methanones scaffold has been identified as new anti-mycobacterial chemotypes. Thirty-six structurally diverse benzo[d]thiazole-2-carboxamides have been prepared and subjected to assessment of their potential anti-tubercular activity through in vitro testing against Mycobacterium tuberculosis H37Rv strain and evaluation of cytotoxicity against RAW 264.7 cell lines. Seventeen compounds showed anti-mycobacterial potential having MICs in the low (1–10) μM range. The 5-trifluoromethyl benzo[d]thiazol-2-yl(piperazin-1-yl)methanones emerged to be the most promising resulting in six positive hits (2.35–7.94 μM) and showed low-cytotoxicity (60.•The 3D-QSAR for anti-TB compounds has been established with significant CoMFA model.