title: Cytotoxic properties of a new organometallic platinum(II) complex and its gold(I) heterobimetallic derivatives.
abstract: A novel platinum(ii) organometallic complex, [Pt(pbi)(Me)(DMSO)], bearing the 2-(2'-pyridyl)-benzimidazole (pbiH) ligand, was synthesized and fully characterized. Interestingly, the reaction of this organometallic platinum(ii) complex with two distinct gold(i) phosphane compounds afforded the corresponding heterobimetallic derivatives with the pbi ligand bridging the two metal centers. The antiproliferative properties in vitro of [Pt(pbi)(Me)(DMSO)] and its gold(i) derivatives as well as those of the known coordination platinum(ii) and palladium(ii) complexes with the same ligand, of the general formula [MCl2(pbiH)], were comparatively evaluated against A2780 cancer cells, either sensitive or resistant to cisplatin. A superior biological activity of the organometallic compound clearly emerged compared to the corresponding platinum(ii) complex; the antiproliferative effects are further enhanced upon attaching the gold(i) triphenylphosphine moiety to the organometallic Pt compound. Remarkably, these novel metal species are able to overcome nearly complete resistance to cisplatin. Significant mechanistic insight into the study compounds was gained after investigating their reactions with a few representative biomolecules by electrospray mass spectrometry and X-ray crystallography. The obtained results are comprehensively discussed.
authors.affiliation: Department of Chemistry and Pharmacy, University of Sassari, via Vienna 2, 07100 Sassari, Italy. cinellu@uniss.it.
authors.forename: Maria
authors.initials: M
authors.lastname: Serratrice
authors.affiliation: Department of Chemistry and Pharmacy, University of Sassari, via Vienna 2, 07100 Sassari, Italy. cinellu@uniss.it.
authors.forename: Laura
authors.initials: L
authors.lastname: Maiore
authors.affiliation: Department of Chemistry and Pharmacy, University of Sassari, via Vienna 2, 07100 Sassari, Italy. cinellu@uniss.it and CIRCC, Consorzio Interuniversitario Reattività Chimica e Catalisi, Università di Bari, Via Celso Ulpiani 27, 70126 Bari, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Zucca
authors.affiliation: Department of Chemistry and Pharmacy, University of Sassari, via Vienna 2, 07100 Sassari, Italy. cinellu@uniss.it and CIRCC, Consorzio Interuniversitario Reattività Chimica e Catalisi, Università di Bari, Via Celso Ulpiani 27, 70126 Bari, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Stoccoro
authors.affiliation: Department of Health Sciences, Section of Clinical Pharmacology and Oncology, University of Florence, viale Pieraccini 6, 50139 Firenze, Italy.
authors.forename: Ida
authors.initials: I
authors.lastname: Landini
authors.affiliation: Department of Health Sciences, Section of Clinical Pharmacology and Oncology, University of Florence, viale Pieraccini 6, 50139 Firenze, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Mini
authors.affiliation: Laboratory of Metals in Medicine, Department of Chemistry, University of Florence, via della Lastruccia 3, 50019 Sesto Fiorentino, Florence, Italy. luigi.messori@unifi.it.
authors.forename: Lara
authors.initials: L
authors.lastname: Massai
authors.affiliation: Department of Chemical Sciences, University of Naples Federico II, via Cintia, 80126, Napoli, Italy.
authors.forename: Giarita
authors.initials: G
authors.lastname: Ferraro
authors.affiliation: Department of Chemical Sciences, University of Naples Federico II, via Cintia, 80126, Napoli, Italy and CNR Institute of Biostructures and Bioimges, Via Mezzocannone 16, 80100, Napoli, Italy.
authors.forename: Antonello
authors.initials: A
authors.lastname: Merlino
authors.affiliation: Laboratory of Metals in Medicine, Department of Chemistry, University of Florence, via della Lastruccia 3, 50019 Sesto Fiorentino, Florence, Italy. luigi.messori@unifi.it.
authors.forename: Luigi
authors.initials: L
authors.lastname: Messori
authors.affiliation: Department of Chemistry and Pharmacy, University of Sassari, via Vienna 2, 07100 Sassari, Italy. cinellu@uniss.it and CIRCC, Consorzio Interuniversitario Reattività Chimica e Catalisi, Università di Bari, Via Celso Ulpiani 27, 70126 Bari, Italy.
authors.forename: Maria Agostina
authors.initials: MA
authors.lastname: Cinellu
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001665:Binding Sites; D020134:Catalytic Domain; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D018360:Crystallography, X-Ray; D047150:Eosinophil Cationic Protein / Q000737:chemistry / Q000378:metabolism; D006046:Gold / Q000737:chemistry*; D006801:Humans; D020128:Inhibitory Concentration 50; D056004:Molecular Dynamics Simulation; D010984:Platinum / Q000737:chemistry*; D021241:Spectrometry, Mass, Electrospray Ionization; D013056:Spectrophotometry, Ultraviolet
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D010984:Platinum; D006046:Gold; D047150:Eosinophil Cationic Protein