The dual action of binuclear silver(i) terpyridine complexes: anticancer and wound healing properties

Reaction between 4'-(2-pyridyl)-2,2':6',2″-terpyridine (1) and silver(i) trifluoromethane sulfonate in methanol afforded the [Ag₂(CF₃SO₃)₂(1)₂] (2). The dimeric structure of 2 was modified by the incorporation of a secondary ligand, including diphenyl pyridyl phosphine, 4,4'-bipyridine, and the antifungal agent clotrimazole, resulting in the formation of ternary complexes 4, 6, and 8, respectively. The silver(i) complexes were fully characterized using various analytical and spectroscopic techniques prior to the evaluation of their cytotoxicity against the malignant A375 and normal HDFn cell lines. Complexes 4 and 8 exhibited promising cytotoxicity against the A375 cell line with IC₅₀ values of 3.06 ± 0.1 and 4.7 ± 0.5 µg mL^-1, respectively. However, compared with the cancerous A375 cell line, the normal cell line HDFn was more responsive to the tested compounds we evaluated. Cell cycle analysis revealed distinct cell line dependent responses, with cell cycle arrest during S-phase in the HDFn cells and the G0-G1 phase in the A375 cells. The complexes markedly accelerated wound healing at relatively low doses, with complexes 4, 6, and 8 showing the fastest rates of cell migration. Molecularly, the compounds increased the levels of TGF-β1 and PDGF proteins. In parallel, complex 4 showed antibacterial activity intermediate between those of complexes 2/6 and 8 against all tested microorganisms.