Design, synthesis and antimycobacterial evaluation of 1-(4-(2-substitutedthiazol-4-yl)phenethyl)-4-(3-(4-substitutedpiperazin-1-yl)alkyl)piperazine hybrid analogues

• 26 new 2-substitutedthiazole analogues were screened for anti-tubercular activity.
• 7a, 7f, 7g, 7n and 7v exhibited good activity (MIC = 3.125 μg/mL).
• 7h was found to be most active against MTB H37RV strain (MIC = 1.56 μg/mL).
• Active compounds were subjected to cytotoxicity studies (RAW264.7 cell lines).
• Selectivity index value (>10) indicates new compounds are not cytotoxic.

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.

26 thiazole derivatives were screened against MTB H37Rv strain. Five compounds 7a, 7f, 7g, 7n and 7v (MIC = 3.125 μg/mL) exhibited good activity and compound 7h (MIC = 1.56 μg/mL) exhibited very good activity with selectivity index >30.Figure optionsDownload as PowerPoint slide