Synthesis and biological evaluation of dialkylsubstituted maleic anhydrides as novel inhibitors of Cdc25 dual specificity phosphatases.
An efficient synthesis of dialkylsubstituted maleic anhydrides 1a-j is described. The inhibitory potential of these original anhydride derivatives was tested toward the three human isoforms A, B and C of dual specific phosphatases Cdc25. A micromolar range inhibition of Cdc25s was observed with the maleic anhydrides bearing simple alkyl side chains longer than C(9), to reach the optimal activity with a C(17) chain length.
Brault
Laurent
L
LIMBP, Université Paul Verlaine-Metz, Metz Technopôle, 57078 Metz, France.
Denancé
Mickaël
M
Banaszak
Estelle
E
El Maadidi
Souhayla
S
Battaglia
Eric
E
Bagrel
Denyse
D
Samadi
Mohammad
M
D000469:Alkaline Phosphatase / Q000037:antagonists & inhibitors / Q000737:chemistry; D000818:Animals; D006736:Horses; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000737:chemistry; D008099:Liver / Q000201:enzymology; D008299:Maleic Anhydrides / Q000138:chemical synthesis* / Q000737:chemistry; D009596:Nitrophenols / Q000737:chemistry; D009943:Organophosphorus Compounds / Q000737:chemistry; D013329:Structure-Activity Relationship; D020687:cdc25 Phosphatases / Q000037:antagonists & inhibitors* / Q000737:chemistry
D007527:Isoenzymes; D008299:Maleic Anhydrides; D009596:Nitrophenols; D009943:Organophosphorus Compounds; C008644:nitrophenylphosphate; D000469:Alkaline Phosphatase; D020687:cdc25 Phosphatases