Synthesis, cytotoxic and antimalarial activities of benzoyl thiosemicarbazone analogs of isoquinoline and related compounds

Abstract

Thiosemicarbazone analogs of papaveraldine and related compounds 1-6 were synthesized and evaluated for cytotoxic and antimalarial activities. The cytotoxic activity was tested against HuCCA-1, HepG2, A549 and MOLT-3 human cancer cell lines. Thiosemicarbazones 1-5 displayed cytotoxicity toward all the tested cell lines, while compounds 2-5 selectively showed potent activity against the MOLT-3 cell lines. Significantly, N(4)-phenyl-2-benzoylpyridine thiosemicarbazone 4 exhibited the most potent activity against HuCCA-1, HepG2, A549 and MOLT-3 cell lines with IC50 values of 0.03, 4.75, 0.04 and 0.004 μg/mL, respectively. In addition, 2-benzoylpyridine thiosemicarbazones 3 and 4 showed antimalarial activity against Plasmodium falciparum with IC 50 of 10-7 to < 10-6 M. The study demonstrates the quite promising activity of analog 4 as a lead molecule for further development. © 2010 by the authors.