Cytotoxic and apoptotic effects of ternary silver() complexes bearing 2-formylpyridine thiosemicarbazones and 1,10-phenanthroline

New silver( i ) compounds containing 2-formylpyridine- N (4)- R -thiosemicarbazones and 1,10-phenanthroline (phen) were synthesized and characterized by spectroscopic techniques (IR and NMR), elemental analysis, ESI-MS and molar conductance measurements. In these complexes, both phen and thiosemicarbazone ligands are coordinated in a chelating bidentate fashion. Compounds 1-3 not only showed good in vitro antiproliferative activity against human lung (A549) and breast tumor cells (MDA-MB-231 and MCF-7), with IC 50 values ranging from 1.49 to 20.90 μM, but were also demonstrated to be less toxic towards human breast non-tumor cells (MCF-10A). Cellular uptake studies indicated that compounds 1-3 were taken up by the MDA-MB-231 cells in 6 hours. Cell death assays in the MDA-MB-231 cells were conducted with compound 1 aiming to evaluate its effects on cell morphology, induction of apoptosis, the cell cycle, reactive oxygen species (ROS) formation and mitochondrial membrane potential (Δ ψ m ). Compound 1 caused morphological changes, such as cell shrinkage and rounding, increased the sub-G1 phase population, and induced apoptotic cell death, ROS formation and loss of mitochondrial membrane potential (Δ ψ m ). DNA binding results revealed that 1 interacted with the ct-DNA minor groove. Complexes 1-3 also exhibited good in vitro activity against M. tuberculosis H37Rv, with MIC values ranging from 3.37 to 4.65 μM. Ag( i ) complexes induced apoptosis in triple negative breast cancer cells and were appreciably less cytotoxic against non-tumor cells.