title: Glycosylated copper(II) ionophores as prodrugs for β-glucosidase activation in targeted cancer therapy.
abstract: 8-Hydroxyquinoline derivatives are metal-binding compounds that have recently attracted interest as therapeutic agents for cancer therapy. In this scenario, we designed and synthesized three new glucoconjugates, 5,7-dichloro-8-quinolinyl-β-D-glucopyranoside, 5-chloro-8-quinolinyl-β-D-glucopyranoside and 2-methyl-8-quinolinyl-β-D-glucopyranoside and investigated their biological properties in comparison to the parent 8-hydroxyquinoline derivatives in the presence of Cu(2+). In vitro data show that 2 out of 3 glycosylated compounds possess a pharmacologically-relevant antiproliferative activity against tumor cells, similar to that of their parent compounds; this activity is associated with a relevant triggering of apoptosis. The pharmacological profile of the glucoconjugates depends on the cellular enzymatic β-glucosidase activity, as demonstrated by the inhibition of antiproliferative activity in the presence of the 2,5-dideoxy-2,5-imino-D-mannitol.
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.forename: Maurizio
authors.initials: M
authors.lastname: Viale
authors.forename: Giulia
authors.initials: G
authors.lastname: Caron
authors.forename: Cinzia
authors.initials: C
authors.lastname: Aiello
authors.forename: Rosaria
authors.initials: R
authors.lastname: Gangemi
authors.forename: Graziella
authors.initials: G
authors.lastname: Vecchio
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000627:therapeutic use / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects; D001665:Binding Sites; D018938:Caco-2 Cells; D020134:Catalytic Domain; D045744:Cell Line, Tumor; D056831:Coordination Complexes / Q000737:chemistry / Q000627:therapeutic use / Q000633:toxicity; D003300:Copper / Q000737:chemistry*; D004789:Enzyme Activation; D006031:Glycosylation; D006801:Humans; D006912:Hydroxyquinolines / Q000737:chemistry; D007476:Ionophores / Q000737:chemistry*; D062105:Molecular Docking Simulation; D009369:Neoplasms / Q000188:drug therapy; D011355:Prodrugs / Q000737:chemistry* / Q000627:therapeutic use / Q000633:toxicity; D055550:Protein Stability; D001617:beta-Glucosidase / Q000737:chemistry / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D006912:Hydroxyquinolines; D007476:Ionophores; D011355:Prodrugs; D003300:Copper; D001617:beta-Glucosidase