title: 2-(Thienothiazolylimino)-1,3-thiazolidin-4-ones inhibit cell division cycle 25 A phosphatase.
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, 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.
authors.affiliation: Université de Lorraine, UMR CNRS 7565, Structure et Réactivité des Systèmes Moléculaires Complexes, Equipe 5 (MIC), Campus Bridoux, rue du Général Delestraint, 57070 Metz Cedex, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Huber-Villaume
authors.affiliation: Université de Lorraine, UMR CNRS 7565, Structure et Réactivité des Systèmes Moléculaires Complexes, Equipe 3 (HECRIN), 1 Boulevard Arago, 57078 Metz Technopôle, France.
authors.forename: Germain
authors.initials: G
authors.lastname: Revelant
authors.affiliation: Université de Lorraine, EA 4632-Laboratoire de Chimie et Physique Approche Multi-échelle des Milieux Complexes, 1 boulevard Arago, 57078 Metz Cedex 3, France.
authors.forename: Estelle
authors.initials: E
authors.lastname: Sibille
authors.affiliation: Université de Lorraine, UMR CNRS 7565, Structure et Réactivité des Systèmes Moléculaires Complexes, Equipe 5 (MIC), Campus Bridoux, rue du Général Delestraint, 57070 Metz Cedex, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Philippot
authors.affiliation: Université de Lorraine, UMR CNRS 7565, Structure et Réactivité des Systèmes Moléculaires Complexes, Equipe 5 (MIC), Campus Bridoux, rue du Général Delestraint, 57070 Metz Cedex, France.
authors.forename: Angelica
authors.initials: A
authors.lastname: Morabito
authors.affiliation: Université de Lorraine, UMR CNRS 7565, Structure et Réactivité des Systèmes Moléculaires Complexes, Equipe 3 (HECRIN), 1 Boulevard Arago, 57078 Metz Technopôle, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Dunand
authors.affiliation: Université de Lorraine, EA 4632-Laboratoire de Chimie et Physique Approche Multi-échelle des Milieux Complexes, 1 boulevard Arago, 57078 Metz Cedex 3, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Chaimbault
authors.affiliation: Université de Lorraine, UMR CNRS 7565, Structure et Réactivité des Systèmes Moléculaires Complexes, Equipe 5 (MIC), Campus Bridoux, rue du Général Delestraint, 57070 Metz Cedex, France.
authors.forename: Denyse
authors.initials: D
authors.lastname: Bagrel
authors.affiliation: Université de Lorraine, UMR CNRS 7565, Structure et Réactivité des Systèmes Moléculaires Complexes, Equipe 3 (HECRIN), 1 Boulevard Arago, 57078 Metz Technopôle, France.
authors.forename: Gilbert
authors.initials: G
authors.lastname: Kirsch
authors.affiliation: Université de Lorraine, UMR CNRS 7565, Structure et Réactivité des Systèmes Moléculaires Complexes, Equipe 3 (HECRIN), 1 Boulevard Arago, 57078 Metz Technopôle, France. Electronic address: stephanie.hesse@univ-lorraine.fr.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Hesse
authors.affiliation: Université de Lorraine, UMR CNRS 7565, Structure et Réactivité des Systèmes Moléculaires Complexes, Equipe 5 (MIC), Campus Bridoux, rue du Général Delestraint, 57070 Metz Cedex, France. Electronic address: herve.schohn@univ-lorraine.fr.
authors.forename: Hervé
authors.initials: H
authors.lastname: Schohn
mesh_terms: D001943:Breast Neoplasms / Q000188:drug therapy; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D006801:Humans; D020128:Inhibitory Concentration 50; D061986:MCF-7 Cells; D015394:Molecular Structure; D053778:Thiazolidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D020687:cdc25 Phosphatases / Q000037:antagonists & inhibitors*
chemical_list: D053778:Thiazolidines; C517004:CDC25A protein, human; D020687:cdc25 Phosphatases
keywords: Antiproliferative activities; Breast cancer; CDC25 phosphatases inhibition; Cell cycle arrest; Thiazolyliminothiazolidin-4-ones