title: Organogold(III) compounds as experimental anticancer agents: chemical and biological profiles.
abstract: In the last few years gold(III) complexes have attracted growing attention in the medicinal chemistry community as candidate anticancer agents. In particular some organogold(III) compounds manifested quite attractive pharmacological behaviors in preclinical studies. Here we compare the chemical and biological properties of the novel organogold(III) complex [Au(bipy(dmb)-H)(NH(CO)CH3)][PF6] (Aubipy(aa)) with those of its parent compounds [Au(bipy(dmb)-H)(OH)][PF6] (Aubipy(c)) and [Au2(bipy(dmb)-H)2)(μ-O)][PF6]2 (Au2bipy(c)), previously synthesized and characterized. The three study compounds were comparatively assessed for their antiproliferative actions against HCT-116 cancer cells, revealing moderate cytotoxic effects. Proapoptotic and cell cycle effects were also monitored. Afterward, to gain additional mechanistic insight, the three gold compounds were challenged against the model proteins HEWL, RNase A and cytochrome c and reactions investigated through UV-Vis and ESI-MS analysis. A peculiar and roughly invariant protein metalation profile emerges in the three cases consisting of protein binding of {Au(bipy(dmb)-H)} moieties. The implications of these results are discussed in the frame of current knowledge on anticancer gold compounds.
authors.affiliation: Department of Chemistry, University of Florence, Via Della Lastruccia 3, Sesto Fiorentino, 50019, Florence, Italy. lara.massai@unifi.it.
authors.forename: Lara
authors.initials: L
authors.lastname: Massai
authors.affiliation: Department of Chemistry, University of Florence, Via Della Lastruccia 3, Sesto Fiorentino, 50019, Florence, Italy.
authors.forename: Damiano
authors.initials: D
authors.lastname: Cirri
authors.affiliation: Mass Spectrometry Center (CISM), University of Florence, Via U. Schiff 6, Sesto Fiorentino, 50019, Florence, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Michelucci
authors.affiliation: Department of Experimental and Clinical Medicine, University of Florence, Viale GB Morgagni 50, 50134, Florence, Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Bartoli
authors.affiliation: Department of Chemistry, University of Florence, Via Della Lastruccia 3, Sesto Fiorentino, 50019, Florence, Italy.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Guerri
authors.affiliation: Department of Chemistry and Pharmacy, University of Sassari, Via Vienna 2, 07100, Sassari, Italy.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Cinellu
authors.affiliation: Department of Chemistry and Pharmacy, University of Sassari, Via Vienna 2, 07100, Sassari, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Cocco
authors.affiliation: Department of Chemistry and Industrial Chemistry, University of Pisa, Via Moruzzi 13, 56124, Pisa, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Gabbiani
authors.affiliation: Department of Chemistry, University of Florence, Via Della Lastruccia 3, Sesto Fiorentino, 50019, Florence, Italy. luigi.messori@unifi.it.
authors.forename: Luigi
authors.initials: L
authors.lastname: Messori
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D018360:Crystallography, X-Ray; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D045325:HCT116 Cells; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D050607:Organogold Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D050607:Organogold Compounds
keywords: Anticancer drugs; ESI–MS; Gold compounds; Protein metalation