2-(Thienothiazolylimino)-1,3-thiazolidin-4-ones inhibit cell division cycle 25 A phosphatase

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• 作者：Sophie Huber-Villaume^a ; Germain Revelant^b ; Estelle Sibille^c ; Sté ; phanie Philippot^a ; Angelica Morabito^a ; Sandrine Dunand^b ; Patrick Chaimbault^c ; Denyse Bagrel^a ; Gilbert Kirsch^b ; Sté ; phanie Hesse^b ; ^{stephanie.hesse@univ-lorraine.fr" class="auth_mail" title="E-mail the corresponding author} ; Hervé ; Schohn^a ; ^{herve.schohn@univ-lorraine.fr" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Thiazolyliminothiazolidin-4-ones ; Antiproliferative activities ; CDC25 phosphatases inhibition ; Cell cycle arrest ; Breast cancer
• 刊名：Bioorganic & Medicinal Chemistry
• 出版年：2016
• 出版时间：1 July 2016
• 年：2016
• 卷：24
• 期：13
• 页码：2920-2928
• 全文大小：1010 K

文摘

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 ± 1.0 μM. 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.