title: 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.
abstract: 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.
authors.affiliation: Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche (STEBICEF), Università di Palermo, Viale delle Scienze Ed. 17, Parco d'Orleans, 90128 Palermo, Italy. Electronic address: simona.rubino@unipa.it.
authors.forename: Simona
authors.initials: S
authors.lastname: Rubino
authors.affiliation: Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche (STEBICEF), Università di Palermo, Viale delle Scienze Ed. 17, Parco d'Orleans, 90128 Palermo, Italy. Electronic address: ivana.pibiri@unipa.it.
authors.forename: Ivana
authors.initials: I
authors.lastname: Pibiri
authors.affiliation: Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche (STEBICEF), Università di Palermo, Viale delle Scienze Ed. 17, Parco d'Orleans, 90128 Palermo, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Costantino
authors.affiliation: Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche (STEBICEF), Università di Palermo, Viale delle Scienze Ed. 17, Parco d'Orleans, 90128 Palermo, Italy.
authors.forename: Silvestre
authors.initials: S
authors.lastname: Buscemi
authors.affiliation: Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche (STEBICEF), Università di Palermo, Viale delle Scienze Ed. 17, Parco d'Orleans, 90128 Palermo, Italy.
authors.forename: Maria Assunta
authors.initials: MA
authors.lastname: Girasolo
authors.affiliation: Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche (STEBICEF), Università di Palermo, Viale delle Scienze Ed. 17, Parco d'Orleans, 90128 Palermo, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Attanzio
authors.affiliation: Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche (STEBICEF), Università di Palermo, Viale delle Scienze Ed. 17, Parco d'Orleans, 90128 Palermo, Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Tesoriere
mesh_terms: D000165:Acridine Orange / Q000737:chemistry; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D004996:Ethidium / Q000737:chemistry; D005456:Fluorescent Dyes / Q000737:chemistry; D006801:Humans; D008024:Ligands; D017671:Platinum Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D066244:Proton Magnetic Resonance Spectroscopy; D011725:Pyridines / Q000737:chemistry*; D013055:Spectrophotometry, Infrared
chemical_list: D000970:Antineoplastic Agents; D005456:Fluorescent Dyes; D008024:Ligands; D017671:Platinum Compounds; D011725:Pyridines; D004996:Ethidium; D000165:Acridine Orange; C023666:pyridine
keywords: Antitumor activity; Mononuclear platinum complexes; Perfluoroalkyl heterocyclic ligands