Pancholia Sahaj, Dhameliya Tejas M, Shah Parth, Jadhavar Pradeep S, Sridevi Jonnalagadda Padma, Yogeshwari Perumal, Sriram Dharmarajan, Chakraborti Asit K
Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S. A. S. Nagar, 160 062, Punjab, India.
Department of Pharmacy, Birla Institute of Technology & Science - Pilani, Hyderabad Campus, Jawahar Nagar, Hyderabad, 500 078, India.
Eur J Med Chem. 2016 Jun 30;116:187-199. doi: 10.1016/j.ejmech.2016.03.060. Epub 2016 Mar 23.
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 (<50% inhibition at 50 μg/mL). The therapeutic index of these hits is 8-64. The quantitative structure activity relationship has been established adopting a statistically reliable CoMFA model showing high prediction (rpred(2)=0.718,rncv(2)=0.995).
苯并[d]噻唑-2-基（哌嗪-1-基）甲酮骨架已被鉴定为新型抗分枝杆菌化学类型。已制备了36种结构多样的苯并[d]噻唑-2-甲酰胺，并通过对结核分枝杆菌H37Rv菌株的体外测试以及对RAW 264.7细胞系的细胞毒性评估，来评估它们潜在的抗结核活性。17种化合物显示出抗分枝杆菌潜力，其最低抑菌浓度在低（1-10）μM范围内。5-三氟甲基苯并[d]噻唑-2-基（哌嗪-1-基）甲酮似乎是最有前景的，产生了6个阳性结果（2.35-7.94μM），并且显示出低细胞毒性（在50μg/mL时抑制率<50%）。这些阳性结果的治疗指数为8-64。采用统计可靠的比较分子场分析（CoMFA）模型建立了定量构效关系，该模型显示出高预测性（rpred(2)=0.718，rncv(2)=0.995）。
