Department of Chemistry, Birla Institute of Technology & Science-Pilani, Hyderabad Campus, R.R. District, 500078, Telangana, India.
Department of Pharmacy, Birla Institute of Technology & Science-Pilani, Hyderabad Campus, R.R. District, 500078, Telangana, India.
Eur J Med Chem. 2014 Sep 12;84:605-13. doi: 10.1016/j.ejmech.2014.07.067. Epub 2014 Jul 21.
A series of twenty six new 1-(4-(2-substitutedthiazol-4-yl)phenethyl)-4-(3-(4-substitutedpiperazin-1-yl)alkyl)piperazine analogues were synthesized by seven steps and evaluated for their anti-tubercular activity against Mycobacterium tuberculosis H37Rv strain. Among the tested compounds, 7j, 7p, and 7r exhibited moderate activity (MIC = 6.25 μg/mL) and compounds 7a, 7f, 7g, 7n and 7v exhibited good activity (MIC = 3.125 μg/mL), while 7h displayed excellent activity (MIC = 1.56 μg/mL) by inhibiting 99% growth of M. tuberculosis H37Rv strain. In addition, all the active compounds were subjected to cytotoxic studies against mouse macrophage (RAW264.7) cell lines and the selectivity index values for most of the compounds is >10 indicating suitability of compounds in an endeavour to attain lead molecule for further drug development.
合成了一系列 26 种新型 1-(4-(2-取代噻唑-4-基)苯乙基)-4-(3-(4-取代哌嗪-1-基)烷基)哌嗪类似物，经过七步反应进行合成，并对其抗结核分枝杆菌 H37Rv 菌株的活性进行了评估。在测试的化合物中，7j、7p 和 7r 表现出中等活性（MIC=6.25μg/mL），化合物 7a、7f、7g、7n 和 7v 表现出良好的活性（MIC=3.125μg/mL），而 7h 通过抑制 99%的结核分枝杆菌 H37Rv 菌株生长表现出优异的活性（MIC=1.56μg/mL）。此外，所有活性化合物均进行了抗鼠巨噬细胞（RAW264.7）细胞系的细胞毒性研究，大多数化合物的选择性指数值>10，表明化合物适合进一步开发药物以获得先导分子。
