title: Selected cytotoxic gold compounds cause significant inhibition of 20S proteasome catalytic activities.
abstract: Six structurally diverse cytotoxic gold compounds are reported to cause profound and differential inhibition of the three main catalytic activities of purified 20S proteasome whilst auranofin, an established gold(I) drug in clinical use, is nearly ineffective. In particular, the gold(I) complex [(pbiH)Au(PPh3)]PF6, turns out to be the most potent inhibitor of all three enzyme activities with sub-micromolar IC50 values. The present results further support the view that proteasome inhibition may play a major--yet not exclusive--role in the cytotoxic actions of gold based anticancer agents.
authors.affiliation: Department of Drug Sciences and Health Products, University of Messina, Viale Annunziata, 98168 Messina, Italy. Electronic address: nmicale@unime.it.
authors.forename: Nicola
authors.initials: N
authors.lastname: Micale
authors.affiliation: Institute of Pharmacy and Biochemistry, University of Mainz, Staudinger Weg 5, D-55099 Mainz, Germany.
authors.forename: Tanja
authors.initials: T
authors.lastname: Schirmeister
authors.affiliation: Department of Pharmaceutical Sciences, University of Milan, Via Mangiagalli 25, 20122 Milan, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Ettari
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 Chemical and Geological Sciences, University of Cagliari, S.S. 554, 09042 Monserrato, CA, Italy.
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.
authors.forename: Maria
authors.initials: M
authors.lastname: Serratrice
authors.affiliation: Department of Chemistry and Industrial Chemistry, via Risorgimento 35, 56126 Pisa, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Gabbiani
authors.affiliation: Laboratory of "Metals in Medicine" (METMED), Department of Chemistry "Ugo Schiff", University of Florence, Via della Lastruccia 3, Sesto Fiorentino, 50019 Firenze, Italy.
authors.forename: Lara
authors.initials: L
authors.lastname: Massai
authors.affiliation: Laboratory of "Metals in Medicine" (METMED), Department of Chemistry "Ugo Schiff", University of Florence, Via della Lastruccia 3, Sesto Fiorentino, 50019 Firenze, Italy. Electronic address: luigi.messori@unifi.it.
authors.forename: Luigi
authors.initials: L
authors.lastname: Messori
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry*; D001310:Auranofin / Q000737:chemistry; D055162:Biocatalysis; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry*; D003603:Cytotoxins / Q000138:chemical synthesis / Q000737:chemistry*; D006801:Humans; D020128:Inhibitory Concentration 50; D050607:Organogold Compounds / Q000138:chemical synthesis / Q000737:chemistry*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D061988:Proteasome Inhibitors / Q000138:chemical synthesis / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D003603:Cytotoxins; D050607:Organogold Compounds; D061988:Proteasome Inhibitors; D001310:Auranofin; D046988:Proteasome Endopeptidase Complex
keywords: Anticancer drugs; Enzyme inhibition; Gold compounds; Proteasome