2-(Thienothiazolylimino)-1, 3-thiazolidin-4-ones inhibit cell division cycle 25 A phosphatase. Issue 13 (1st July 2016)

• Record Type: Journal Article
• Authors: Huber-Villaume, Sophie; Revelant, Germain; Sibille, Estelle; Philippot, Stéphanie; Morabito, Angelica; Dunand, Sandrine; Chaimbault, Patrick; Bagrel, Denyse; Kirsch, Gilbert; Hesse, Stéphanie; Schohn, Hervé
• Is Part Of: Bioorganic & medicinal chemistry. Volume 24:Issue 13(2016)
• Page Start: 2920
• Page End: 2928
• Publication Date: 2016-07-01
• Subjects: Thiazolyliminothiazolidin-4-ones -- Antiproliferative activities -- CDC25 phosphatases inhibition -- Cell cycle arrest -- Breast cancer; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2016.04.063
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: Abstract: 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, compound6 inhibited CDC25A with an IC50 estimated at 6.2 ± 1.0 μM. The binding of thiazolidinone derivative6 onto CDC25A protein was reversible. In cellulo, compound6 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.