Synthesis, structural characterization, anti-proliferative and antimicrobial activity of binuclear and mononuclear Pt(II) complexes with perfluoroalkyl-heterocyclic ligands

Abstract

In this paper we report the synthesis of four Pt(II) complexes with 5-perfluoroalkyl-1,2,4-oxadiazolyl-pyridine and 3-perfluoroalkyl-1-methyl-1,2,4-triazolyl-pyridine ligands. Two binuclear complexes [PtCl(pfibap)2](µ-Cl)2 (1), [Pt2(µ-Cl)2(pfioap)4]Cl2 (2), and two mononuclear [PtCl2(pfptp)] (3), [PtCl2(pfhtp)2] (4), were synthesized with the ligands: 2-(5-perfluoropropyl)-1,2,4-oxadiazole-3yl)-pyridine (pfpop), 2-(5-perfluoroheptyl-1,2,4-oxadiazole-3yl)-pyridine (pfhop), 2-(3-perfluoropropyl-1-methyl-1,2,4-triazole-5yl)-pyridine (pfptp), 2-(3-perfluoroheptyl-1-methyl-1,2,4-triazole-5yl)-pyridine (pfhtp), and were structurally characterized. All complexes were tested in vitro on three tumor cell lines MCF-7 (human breast cancer), Hela (epithelioid cervix carcinoma), HCT-116 (human colorectal carcinoma). Compounds 1 and 2 showed a dose-dependent anti-proliferative effect against the three tumor cell lines whereas they did not affect viability of intestinal normal-like differentiated Caco-2 cells. Results showed that both the compounds act as pro-apoptotic agents inducing a clear shift of viable cells towards early apoptosis, while they do not exert any necrotic effect. They also caused cell cycle perturbation with significant decrease in the percentage of cells in the G0/G1 phase, accompanied by a concomitant percentage increase of cells in the G2/M phase, and appearance of a subG1-cell population. Moreover, all complexes showed antimicrobial activity against Escherichia coli, Kocuria rhizophila and two Staphylococcus aureus strains and a different behavior in binding activity to DNA.