Novel silver(I) complexes bearing mefenamic acid and pyridine derivatives: Synthesis, chemical characterization and in vitro anticancer evaluation

Two Ag(I) complexes [Ag2(μ-mef)2(2-pymet)2] 1, [Ag2(μ-mef)2(2-pyet)2] 2 containing mefenamic acid, 2-pyridinemethanol and 2-pyridineethanol were synthesized and characterized by using SCXRD, FT-IR, elemental and thermal analysis techniques. The complex 1 was synthesized as a single crystal whereas the complex 2 was obtained as a microcrystalline powder. The complex 1 consists of binuclear structure. The argentophilic interaction occurs among silver(I) ions due to the short Ag⋯Ag distance (2.8710(10) Å). Two Ag(I) centers are connected by carboxylato oxygen-bridge to form the binuclear metal core. The FT-IR spectra and thermal analysis studies confirmed that both complexes exhibited similar structures. In vitro antiproliferative activity of both complexes were evaluated against MCF-7, HT-29 and HepG2 cancer cell lines. The apoptotic effects and intracellular ROS generation from both complexes were investigated in MCF-7 cell line by flow cytometry analysis. The XTT and LDH assays revealed that both complexes showed strong antiproliferative activity with higher selectivity towards cancer cells compared to the normal cells. In addition, Annexin V/propidium iodide assay exhibited that apoptotic cell number was increased in MCF-7 cells with increasing concentrations of Ag(I) complexes. Furthermore, both complexes induced the ROS generation considerably in MCF-7 cells suggesting the possible pro-oxidant activity of the novel synthesized Ag(I) complexes. Taken together, these findings provide a notable support for potential utility of Ag(I) complexes as novel anticancer agents against numerous kind of carcinogenesis. © 2019