Investigation on the pharmacological profile of 2,6-diacetylpyridine bis(benzoylhydrazone) derivatives and their antimony(III) and bismuth(III) complexes

Complexes [Sb(HAcPh)Cl2] (1), [Sb(HAcpClPh)Cl2] (2), [Sb(HAcpNO2Ph)Cl2] (3) and [Bi(HAcPh)Cl2] (4), [Bi(HAcpClPh)Cl2] (5), [Bi(HAcpNO2Ph)Cl2] (6) were obtained with 2,6-diacetylpyridine bis(benzoylhydrazone) (H2AcPh), 2,6-diacetylpyridine bis(para-chlorobenzoylhydrazone) (H2AcpClPh), and 2,6-diacetylpyridine bis(para-nitrobenzoylhydrazone) (H2AcpNO2Ph). The bis(benzoylhydrazones) were inactive as antimicrobial agents against gram-positive and gram-negative bacteria and against Candida albicans but upon coordination to antimony(III) and bismuth(III) antimicrobial activity was demonstrated. The studied compounds were tested for their cytotoxic activities against Jurkat and HL60 (leukemia), MCF-7 (breast tumor), HCT-116 (colorectal carcinoma) and peripheral blood mononuclear (PBMC) cells. All bis(benzoylhydrazones) proved to be poorly cytotoxic. Upon coordination of the bis(benzoylhydrazones) to antimony(III) and bismuth(III) cytotoxicity significantly improved. Complex (5) presented high therapeutic indexes (TI = 11-508) against all cell lineages.

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► Sb(III) and Bi(III) complexes of bis(benzoylhydrazones) were obtained.
► Hydrazones were inactive as antimicrobial and poorly active as cytotoxic agents.
► The Sb(III) and Bi(III) complexes presented antimicrobial activity.
► The complexes exhibited high cytotoxic activity against human tumor cell lines.
► The Bi(III) complexes could be good antitumor drug candidates.