title: New 8-hydroxyquinoline galactosides. The role of the sugar in the antiproliferative activity of copper(II) ionophores.
abstract: 8-Hydroxyquinoline derivatives and their metal complexes have recently awakened interest as promising therapeutic agents in cancer therapy. We have previously synthesized and evaluated glucoconjugated 8-hydroxyquinolines as copper ionophores activated by β-glucosidases. In order to further evaluate the crucial role of the sugar, we designed and synthesized a series of new galactoconjugates of 8-hydroxyquinolines and investigated their biological properties in comparison with the 8-hydroxyquinoline analogs. The effect of copper(II) ions on their biological activities was evaluated. In particular, two compounds possess a pharmacologically relevant antiproliferative activity against specific tumor cells in the presence of copper(II) ions. Furthermore, the antiproliferative activity of the selected galactosides was successfully investigated in the presence of β-galactosidase as a preliminary model of antibody directed enzyme prodrug therapy.
authors.affiliation: University of Catania, Dipartimento di Scienze Chimiche, Viale A. Doria, 6, 95125 Catania, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Oliveri
authors.affiliation: IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, U.O.C. Bioterapie, L.go R. Benzi, 10, 16132 Genova, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Viale
authors.affiliation: IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, U.O.C. Bioterapie, L.go R. Benzi, 10, 16132 Genova, Italy.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Aiello
authors.affiliation: University of Catania, Dipartimento di Scienze Chimiche, Viale A. Doria, 6, 95125 Catania, Italy. Electronic address: gr.vecchio@unict.it.
authors.forename: Graziella
authors.initials: G
authors.lastname: Vecchio
mesh_terms: D000072283:A549 Cells; D049109:Cell Proliferation / Q000187:drug effects*; D003300:Copper; D004354:Drug Screening Assays, Antitumor; D056945:Hep G2 Cells; D006801:Humans; D007476:Ionophores / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D015125:Oxyquinoline / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: D007476:Ionophores; C033991:8-hydroxyquinoline glucoside; D015125:Oxyquinoline; D003300:Copper
keywords: ADEPT; Clioquinol; Copper; Galactoside; Ionophore