Cytotoxic and apoptotic effects of ternary silver(i) complexes bearing 2-formylpyridine thiosemicarbazones and 1,10-phenanthroline
- 23 March 2020
- journal article
- research article
- Published by Royal Society of Chemistry (RSC) in Dalton Transactions
- Vol. 49 (16), 5264-5275
- https://doi.org/10.1039/d0dt00253d
Abstract
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 IC50 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 (Δψm). 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 (Δψm). 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.Funding Information
- Fundação de Amparo à Pesquisa do Estado de São Paulo (2016/177115, 2015/12098)
- Conselho Nacional de Desenvolvimento Científico e Tecnológico (422105/2016-3, 407676/2016-3)
- Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
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