Antimycobacterial activity of novel N-(substituted)-2-isonicotinoylhydrazinocarbothioamide endowed with high activity towards isoniazid resistant tuberculosis

Various isonicotinoylhydrazinocarbothioamides were prepared by reacting isonicotinoyl hydrazide (INH) with appropriate potassium salt of substituted phenyl thiocarbamate and were tested for their antimycobacterial activity in vitro against Mycobacterium tuberculosis H(37)R(v) and INH resistant M. tuberculosis using the agar dilution method. Among the synthesized compounds, 2-isonicotinoyl-N-[2-(trifluoromethyl)phenyl]hydrazinecarbothioamide (4i) was found to be the most potent compound with minimum inhibitory concentration of 0.58 mu M against M. tuberculosis H(37)R(v) and INH resistant M. tuberculosis. When compared to INH, 4i was found to be 1.24 and 157 times more active against M. tuberculosis H(37)R(v) and INH resistant M. tuberculosis respectively, with a selectivity index of >218. (C) 2008 Published by Elsevier Masson SAS.