title: Novel naphthoquinone and quinolinedione inhibitors of CDC25 phosphatase activity with antiproliferative properties.
abstract: CDC25 phosphatases are considered as attractive targets for anti-cancer therapy. To date, quinone derivatives are among the most potent inhibitors of CDC25 phosphatase activity. We present in this paper the synthesis and the biological evaluation of new quinolinedione and naphthoquinone derivatives, containing carboxylic or malonic acids groups introduced to mimic the role of the phosphate moieties of Cyclin-Dependent Kinase complexes. The most efficient compounds show inhibitory activity against CDC25B with IC(50) values in the 10 microM range, and are cytotoxic against HeLa cells.
authors.affiliation: Université Paris Descartes, UFR biomédicale, Laboratoire de Pharmacochimie Moléculaire et Cellulaire, 45 rue des Saints-Pères, Paris F-75006, France.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Braud
authors.forename: Mary-Lorène
authors.initials: ML
authors.lastname: Goddard
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Kolb
authors.forename: Marie-Priscille
authors.initials: MP
authors.lastname: Brun
authors.forename: Odile
authors.initials: O
authors.lastname: Mondésert
authors.forename: Muriel
authors.initials: M
authors.lastname: Quaranta
authors.forename: Nohad
authors.initials: N
authors.lastname: Gresh
authors.forename: Bernard
authors.initials: B
authors.lastname: Ducommun
authors.forename: Christiane
authors.initials: C
authors.lastname: Garbay
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D002264:Carboxylic Acids / Q000737:chemistry; D018844:Cyclin-Dependent Kinases / Q000737:chemistry / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D008314:Malonates; D018716:Molecular Mimicry; D009285:Naphthoquinones / Q000138:chemical synthesis / Q000494:pharmacology*; D010710:Phosphates / Q000737:chemistry; D015363:Quinolones / Q000138:chemical synthesis / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D020687:cdc25 Phosphatases / Q000037:antagonists & inhibitors*
chemical_list: D000970:Antineoplastic Agents; D002264:Carboxylic Acids; D004791:Enzyme Inhibitors; D008314:Malonates; D009285:Naphthoquinones; D010710:Phosphates; D015363:Quinolones; C030290:malonic acid; D018844:Cyclin-Dependent Kinases; D020687:cdc25 Phosphatases