Synthesis of platinum complexes with 2-(5-perfluoroalkyl-1,2,4-oxadiazol-3yl)-pyridine and 2-(3-perfluoroalkyl-1-methyl-1,2,4-triazole-5yl)-pyridine ligands and their in vitro antitumor activity

• Published in: Journal of inorganic biochemistry Vol. 155; pp. 92 - 100
• Main Authors: Rubino, Simona, Pibiri, Ivana, Costantino, Cristina, Buscemi, Silvestre, Girasolo, Maria Assunta, Attanzio, Alessandro, Tesoriere, Luisa
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-02-2016
• Subjects: Acridine Orange - chemistry; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Antitumor activity; Apoptosis - drug effects; Cell Line, Tumor; Ethidium - chemistry; Fluorescent Dyes - chemistry; Humans; Ligands; Mononuclear platinum complexes; Perfluoroalkyl heterocyclic ligands; Platinum Compounds - chemical synthesis; Platinum Compounds - chemistry; Platinum Compounds - pharmacology; Proton Magnetic Resonance Spectroscopy; Pyridines - chemistry; Spectrophotometry, Infrared; PBS; PS; DMSO; Mononuclear platinum complexes; Perfluoroalkyl heterocyclic ligands; TLC; FACS; MTT; AO; HRMS; FITC; FBS; Antitumor activity; PI; TMS; DMF; RPMI; EB; GC/MS
• ISSN: 0162-0134; 1873-3344
• DOI: 10.1016/j.jinorgbio.2015.11.020

Five new mononuclear Pt(II) complexes with 5-perfluoroalkyl-1,2,4-oxadiazolyl-pyridine and 3-perfluoroalkyl-1,2,4-triazolyl-pyridine ligands are reported. The ligands 2-(5-perfluoroheptyl-1,2,4-oxadiazole-3yl)-pyridine (pfhop), 2-(5-perfluoropropyl)-1,2,4-oxadiazole-3yl)-pyridine (pfpop), 2-(3-perfluoroheptyl-1-methyl-1,2,4-triazole-5yl)-pyridine (pfhtp), 2-(3-perfluoropropyl-1-methyl-1,2,4-triazole-5yl)-pyridine (pfptp) and their complexes [PtCl2(pfhop)2]·1.5 DMSO (2a), [PtCl2(pfpop)2]·1.5 DMSO (3a), [PtCl2(pfhtp)2]·1.5 DMSO (4a), PtCl2(pfhtp) (4b), [PtCl2(pfptp)2]·1.5 DMSO (5a) have been synthesized and structurally characterized. The complexes 2a, 3a, 4a and 5a have the same chemical environment of Pt(II) where PtCl2 moieties coordinate two molecules of ligand via N1 atom of pyridine in the case of pfhop and pfpop, and N2 atom of 1,2,4-triazole in the case of pfhtp and pfptp. For 4b, pfhtp behaves as bidentate ligand, coordinating Pt(II) ion via N4 atom of triazole and N1 atom of pyridine. All complexes have been tested in vitro by 3-(4,5-dimethyl-2-thiazolyl)bromide-2,5-diphenyl-2H-tetrazolium (MTT) test on four tumor cell lines MCF-7 (human breast cancer), HepG2 (human hepatocellular carcinoma), HCT116 (human colorectal carcinoma). Compounds 2a and 4b showed a dose-dependent anti-proliferative effect against the three tumor cell lines whereas did not affect viability of intestinal normal-like differentiated Caco-2 cells. The cell death of HepG2, MCF-7 and HCT116 induced by the compounds, was considered to be apoptotic by measuring the exposure of phosphatidylserine to the outer membrane and observing the typical apoptotic morphological change by acridine orange (AO)/ethidium bromide (EB) staining.
Five mononuclear Pt(II) complexes with ligands, 5-perfluoroalkyl-1,2,4-oxadiazolyl-pyridine and 3-perfluoroalkyl-1,2,4-triazolyl-pyridine, were synthesized, structural characterized and their biological activity were studied. Two of these compounds 2a and 4b showed dose-dependent anti-proliferative effect and apoptosis on three tumor cell lines MCF-7 (human breast cancer), HepG2 (human hepatocellular carcinoma) and HCT116 (human colorectal carcinoma). [Display omitted]
•Five Pt(II) complexes were synthesized with fluorinated heterocyclic ligands.•Complexes 2a and 4b showed anti-proliferative effect on three cancer cell lines.•Active compounds were effective inducer of apoptotic death.