Cytotoxic and apoptotic effects of ternary silver(I) 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 condutance measurements. In these complexes, both phen and thiosemicarbazone ligands are coordinated in a chelating bidentate fashion. The compounds 1-3 showed not only good in vitro antiproliferative activity against human lung (A549) and breast tumor cells (MDA-MB-231 and MCF-7), with IC50 values ranging from 1.49 to 20.90 μM, but also demonstrated to be less toxic towards human breast non-tumor cells (MCF-10A). Uptake cellular studies indicated that compounds 1-3 were taken up by MDA-MB-231 cells in 6 hours. Cell death assays in MDA-MB-231 cells were conducted with compound 1 aiming at to evaluate its effects in cell morphology, induction of apoptosis, cell cycle, reactive oxygen species (ROS) and mitochondrial membrane potential (ΔΨm). Compound 1 caused morphological changes, such as cell shrinkage and rounding, increased the sub-G1 phase population, induced apoptotic cell death, ROS formation and loss of mitochondrial membrane potential (ΔΨm). DNA binding results revealed that 1 interacted with ct-DNA minor groove. Complexes 1-3 also exhibited good in vitro activity against M. tuberculosis H37Rv, with MIC values varying from 3.37-4.65 μM.