Novel naphthoquinone and quinolinedione inhibitors of CDC25 phosphatase activity with antiproliferative properties.
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.
Braud
Emmanuelle
E
Université Paris Descartes, UFR biomédicale, Laboratoire de Pharmacochimie Moléculaire et Cellulaire, 45 rue des Saints-Pères, Paris F-75006, France.
Goddard
Mary-Lorène
ML
Kolb
Stéphanie
S
Brun
Marie-Priscille
MP
Mondésert
Odile
O
Quaranta
Muriel
M
Gresh
Nohad
N
Ducommun
Bernard
B
Garbay
Christiane
C
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*
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