Mashooq Ahmed Bhat
King Saud University, Kingdom of Saudi Arabia
Mashooq Ahmed Bhat is a associate professor in King Saud University, Kingdom of Saudi Arabia
Isoniazid analogues were designed based on lead compound A.Eighteen compounds were synthesized, characterized andevaluated against ten clinical isolates of Candida spp. and compared with itraconazole.Introduction of p-Chloro, p-Iodo, m-Chloro ando-Nitro substitution at phenyl ring of thiosemicarbazide enhanced the anti-Candida activity.Compoundbearing p-cholorophenyl ringwas found to be the most effectiveagainst Candida albicans ATCC 66027, Candida spp. 12810 (blood) and Candida spp. 178 (HVS) with MIC value of 0.09-0.78 µg/ml whereas itraconazole exhibits the inhibitory activity with MIC value of 0.04-1.56 µg/ml against all tested strains. There is a correlation between anti-Candidal activity and p-chloro substitution at phenyl ring of thiosemicarbazide. The compounds were also investigated for their cytotoxic effects using MTT assay against three cell lines HT1080 (skin), HepG2 (liver) and A549 (lung). The compounds showed lowest cytotoxic activity against all three cell lines.Moreover, displaying better activity compared to reference drug (itraconazole), they represent good leads for the development of newer, potent and broad spectrum anti-Candidal agents.