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

• Autor(a) principal: Silva, Débora E. S. [UNESP]
• Data de Publicação: 2020
• Outros Autores: Becceneri, Amanda B., Solcia, Mariana C. [UNESP], Santiago, João V. B. [UNESP], Moreira, Mariete B. [UNESP], Gomes Neto, José A. [UNESP], Pavan, Fernando R. [UNESP], Cominetti, Márcia R., Pereira, José C. M. [UNESP], Netto, Adelino V. G. [UNESP]
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UNESP
• Texto Completo: http://dx.doi.org/10.1039/d0dt00253d; http://hdl.handle.net/11449/200364

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.