1. Synthesis, biological evaluation and molecular modeling studies on novel quinonoid inhibitors of CDC25 phosphatases
- Author
-
Simone Berardozzi, Mattia Mori, Gilles Hanquet, Denyse Bagrel, Francesca Ghirga, Bruno Botta, Don Antoine Lanfranchi, Christophe Bour, Emilie Evain-Bana, Lucie Schiavo, Laboratoire de chimie moléculaire (LCM), Université de Strasbourg (UNISTRA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Substances naturelles/chimie moléculaire, Université Louis Pasteur - Strasbourg I-Ecole européenne de chimie, polymères et matériaux [Strasbourg]-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'innovation moléculaire et applications (LIMA), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), and Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)
- Subjects
0301 basic medicine ,Models, Molecular ,CDC25A ,Molecular model ,Cdc25 ,enzyme inhibitors ,Regulator ,Chemical biology ,molecular structure ,Biology ,Crystallography, X-Ray ,03 medical and health sciences ,chemistry.chemical_compound ,models ,0302 clinical medicine ,SYNCAT ,Drug Discovery ,drug discovery3003 pharmaceutical science ,molecular ,crystallography ,humans ,quinones ,CDC25 ,cdc25 phosphatases ,[CHIM.ORGA]Chemical Sciences/Organic chemistry ,molecular modeling ,lcsh:RM1-950 ,General Medicine ,Cell cycle ,organic synthesis ,quinonoid ,crystallography, X-Ray ,enzyme Inhibitors ,models, molecular ,pharmacology ,Small molecule ,3. Good health ,030104 developmental biology ,lcsh:Therapeutics. Pharmacology ,Biochemistry ,chemistry ,030220 oncology & carcinogenesis ,biology.protein ,X-Ray ,Organic synthesis ,Original Article - Abstract
The cell division cycle 25 phosphatases (CDC25A, B, and C; E.C. 3.1.3.48) are key regulator of the cell cycle in human cells. Their aberrant expression has been associated with the insurgence and development of various types of cancer, and with a poor clinical prognosis. Therefore, CDC25 phosphatases are a valuable target for the development of small molecule inhibitors of therapeutic relevance. Here, we used an integrated strategy mixing organic chemistry with biological investigation and molecular modeling to study novel quinonoid derivatives as CDC25 inhibitors. The most promising molecules proved to inhibit CDC25 isoforms at single digit micromolar concentration, becoming valuable tools in chemical biology investigations and profitable leads for further optimization. [Formula: see text].
- Published
- 2017
- Full Text
- View/download PDF