title: Synthesis and biological evaluation of the suberoylanilide hydroxamic acid (SAHA) beta-glucuronide and beta-galactoside for application in selective prodrug chemotherapy.
abstract: The beta-O-glucuronide and beta-O-galactoside of SAHA have been prepared and evaluated as prodrugs for selective cancer chemotherapy (ADEPT, PMT). These new compounds are stable under physiological conditions and do not exhibit any antiproliferative activity compared to the parent drug after a 48-h treatment of H661 cells. The glucuronide derivative did not lead to the release of the drug in the presence of either Escherichia coli or bovine liver beta-glucuronidase. On the other hand, under enzymatic cleavage of galactoside prodrug by the corresponding enzyme, a rapid release of SAHA was observed demonstrating that the beta-O-galactoside of SAHA is a promising candidate for in vivo investigations.
authors.affiliation: UMR-CNRS 6514, Synthèse et Réactivité des Substances Naturelles, Université de Poitiers, 40, Av. du Recteur Pineau, 86022 Poitiers, France.
authors.forename: Mickaël
authors.initials: M
authors.lastname: Thomas
authors.forename: Freddy
authors.initials: F
authors.lastname: Rivault
authors.forename: Isabelle
authors.initials: I
authors.lastname: Tranoy-Opalinski
authors.forename: Joëlle
authors.initials: J
authors.lastname: Roche
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Gesson
authors.forename: Sébastien
authors.initials: S
authors.lastname: Papot
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy; D002417:Cattle; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D002986:Clinical Trials as Topic; D005697:Galactosides / Q000138:chemical synthesis / Q000494:pharmacology; D020719:Glucuronides / Q000138:chemical synthesis / Q000494:pharmacology; D006801:Humans; D006868:Hydrolysis; D006877:Hydroxamic Acids / Q000138:chemical synthesis* / Q000494:pharmacology*; D011355:Prodrugs / Q000138:chemical synthesis* / Q000494:pharmacology*; D000077337:Vorinostat
chemical_list: D000970:Antineoplastic Agents; D005697:Galactosides; D020719:Glucuronides; D006877:Hydroxamic Acids; D011355:Prodrugs; D000077337:Vorinostat