Synthesis, structural characterization and evaluation of anticancer activity of polymeric silver(I) complexes based on niflumic acid/naproxen and picoline derivatives

Abstract

Two polymeric mixed-ligand silver(I) complexes, [Ag(µ-nif)(4-pic)]n (1) and [Ag4(µ-nap)4(2-pic)2]n (2), where Hnif: niflumic acid, Hnap: naproxen, 4-pic: 4-picoline and 2-pic: 2-picoline, were synthesized and characterized by single-crystal X-ray diffraction, FT-IR and 1H NMR spectroscopies, elemental and thermal analysis techniques. In 1, nif ligand behaves as a µ3-N,O,O' bridge connecting three silver(I) ions and each silver(I) ion exhibits a seesaw geometry. In 2, nap ligands act as a µ-carboxylato-(O,O') bridge between two silver(I) ions and µ3-carboxylato-(O,O,O') bridge linking three silver(I) ions. Each silver(I) ion occurs in trigonal geometry. To uncover the anticancer properties of the complexes, first, their cytotoxic abilities were tested against three cancer cell lines, HT-29 (human colorectal adenocarcinoma), A-549 (human lung carcinoma), and MDA-MB-453 (human breast adenocarcinoma), and normal 3T3-L1 (mouse fibroblast) cell line by XTT tests. Afterwards, the anticancer mechanism of the complexes was tried to be elucidated through the flow cytometry analyzes. XTT assay results showed that the complexes exhibited the highest cytotoxic activity and selectivity on HT-29 cells among all the cell lines. Flow cytometry analyses revealed that both complexes induced the apoptosis through the mitochondrial membrane depolarization and activation of the caspase cascade in HT-29 cells.