Bismuth(III) complexes with 2-acetylpyridine- and 2-benzoylpyridine-derived hydrazones: Antimicrobial and cytotoxic activities and effects on the clonogenic survival of human solid tumor cells

Complexes [Bi(2AcPh)Cl₂]·0.5H₂O (1), [Bi(2AcpClPh)Cl₂] (2), [Bi(2AcpNO₂Ph)Cl₂] (3), [Bi(2AcpOHPh)Cl₂]·2H₂O (4), [Bi(H2BzPh)Cl₃]·2H₂O (5), [Bi(H2BzpClPh)Cl₃] (6), [Bi(2BzpNO₂Ph)Cl₂]·2H₂O (7) and [Bi(H2BzpOHPh)Cl₃]·2H₂O (8) were obtained with 2-acetylpyridine phenylhydrazone (H2AcPh), its -para-chloro-phenyl- (H2AcpClPh), -para-nitro-phenyl (H2AcpNO₂Ph) and -para-hydroxy-phenyl (H2AcpOHPh) derivatives, as well as with the 2-benzoylpyridine phenylhydrazone analogues (H2BzPh, H2BzpClPh, H2BzpNO₂Ph, H2BzpOHPh).Upon coordination to bismuth(III) antibacterial activity against Gram-positive and Gram-negative bacterial strains significantly improved except for complex (4).The cytotoxic effects of the compounds under study were evaluated on HL-60, Jurkat and THP-1 leukemia, and on MCF-7 and HCT-116 solid tumor cells, as well as on non-malignant Vero cells. In general, 2-acetylpyridine-derived hydrazones proved to be more potent and more selective as cytotoxic agents than the corresponding 2-benzoylpyridine-derived counterparts.Exposure of HCT-116 cells to H2AcpClPh, H2AcpNO₂Ph and complex (3) led to 99% decrease of the clonogenic survival. The IC₅₀ values of these compounds were three-fold smaller when cells were cultured in soft-agar (3D) than when cells were cultured in monolayer (2D), suggesting that they constitute interesting scaffolds, which should be considered in further studies aiming to develop new drug candidates for the treatment of colon cancer.