2-(Thienothiazolylimino)-1,3-thiazolidin-4-ones inhibit cell division cycle 25 A phosphatase.
Fiche publication
Date publication
juillet 2016
Journal
Bioorganic & medicinal chemistry
Auteurs
Membres identifiés du Cancéropôle Est :
Pr SCHOHN Hervé
Tous les auteurs :
Huber-Villaume S, Revelant G, Sibille E, Philippot S, Morabito A, Dunand S, Chaimbault P, Bagrel D, Kirsch G, Hesse S, Schohn H
Lien Pubmed
Résumé
Cell division cycle dual phosphatases (CDC25) are essential enzymes that regulate cell progression in cell cycle. Three isoforms exist as CDC25A, B and C. Over-expression of each CDC25 enzyme is found in cancers of diverse origins. Thiazolidinone derivatives have been reported to display anti-proliferative activities, bactericidal activities and to reduce inflammation process. New 2-(thienothiazolylimino)-1,3-thiazolidin-4-ones were synthesized and evaluated as inhibitors of CDC25 phosphatase. Among the molecules tested, compound 6 inhibited CDC25A with an IC50 estimated at 6.2±1.0μM. The binding of thiazolidinone derivative 6 onto CDC25A protein was reversible. In cellulo, compound 6 treatment led to MCF7 and MDA-MB-231 cell growth arrest. To our knowledge, it is the first time that such 4-thiazolidinone derivatives are characterized as CDC25 potential inhibitor.
Mots clés
Antiproliferative activities, Breast cancer, CDC25 phosphatases inhibition, Cell cycle arrest, Thiazolyliminothiazolidin-4-ones
Référence
Bioorg. Med. Chem.. 2016 07 1;24(13):2920-2928