New mononuclear complexes [Mn(NO)(sac)(HO)(bzimpy)]·2DMF (Mn), [Fe(sac)(HO)(bzimpy)]·2HO (Fe), [Co(bzimpy)](sac)·2HO (Co), [Ni(bzimpy)](sac)·HO·i-PrOH (Ni) and [Cu(sac)(bzimpy)]·3DMF (Cu) (sac = saccharinate and bzimpy = 2,6-bis(2-benzimidazolyl)pyridine) were synthesized and structurally characterized by elemental analysis, UV-Vis, IR, ESI-MS and X-ray diffraction. The anticancer activity of the metal complexes against A549 (lung), MCF-7 (breast), HT29 (colon) cancer cells and MCF10A (normal human breast epithelial) cells was tested and compared with those of cisplatin and bzimpy. The complexes displayed potent cytotoxic activity especially in MCF-7 and A549 cell lines, but they were practically inactive against the normal cells. Mechanistic studies with Mn and Cu complexes on A549 cells indicated that the complexes induced G0/G1 arrest. Both complexes increased intracellular ROS (reactive oxygen species) levels and successfully caused both mitochondrial dysfunction and double-strand DNA breaks. The up-regulated Bax and down-regulated Bcl-2 expression levels, caspase-3/7 activation and reduced Fas expression indicated that Mn and Cu induced ROS-dependent mitochondria-mediated intrinsic apoptosis in A549 cells.

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http://dx.doi.org/10.1016/j.ejmech.2020.112535DOI Listing

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