Synthesis and biological evaluation of novel coumarin-based inhibitors of Cdc25 phosphatases.
The cell division cycle 25 (Cdc25) family of proteins are dual specificity phosphatases that activate cyclin-dependent kinase (CDK) complexes, which in turn regulate progression through the cell division cycle. Overexpression of Cdc25 proteins has been reported in a wide variety of cancers; their inhibition may thus represent a novel approach for the development of anticancer therapeutics. Herein we report new coumarin-based scaffolds endowed with a selective inhibition against Cdc25A and Cdc25C, being 6a and 6d the most efficient inhibitors and worthy of further investigation as anticancer agents.
Valente
Sergio
S
Laboratoire d'Ingénierie Moléculaire et Biochimie Pharmacologique, Institut Jean Barriol, Université Paul Verlaine, FR CNRS 2843, 1 Boulevard Arago, 57070 Metz, France.
Bana
Emilie
E
Viry
Elodie
E
Bagrel
Denyse
D
Kirsch
Gilbert
G
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D003374:Coumarins / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy; D020687:cdc25 Phosphatases / Q000037:antagonists & inhibitors* / Q000378:metabolism
D000970:Antineoplastic Agents; D003374:Coumarins; D004791:Enzyme Inhibitors; C030123:coumarin; D020687:cdc25 Phosphatases