title: Synthesis, biological evaluation and molecular modeling studies on novel quinonoid inhibitors of CDC25 phosphatases.
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].
authors: a Pôle Chimie Et Physique Moléculaire, UMR CNRS 7565, Laboratoire Structure et Réactivite des Systèmes Moléculaires Complexes , Université de Lorraine , Metz , France.
authors: Emilie
authors: E
authors: Evain-Bana
authors: b Ecole Européenne de Chimie, Polymères et Matériaux (ECPM), Laboratoire de Synthèse et Catalyze (UMR CNRS 7509) , Université de Strasbourg , Strasbourg , France.
authors: Lucie
authors: L
authors: Schiavo
authors: c ICMMO , Université Orsay Cedex , France.
authors: Christophe
authors: C
authors: Bour
authors: b Ecole Européenne de Chimie, Polymères et Matériaux (ECPM), Laboratoire de Synthèse et Catalyze (UMR CNRS 7509) , Université de Strasbourg , Strasbourg , France.
authors: Don Antoine
authors: DA
authors: Lanfranchi
authors: d Dipartimento di Chimica e Tecnologie del Farmaco , Sapienza University of Roma , Rome , Italy.|e Istituto Italiano di Tecnologia , Center for Life Nano Science@Sapienza , Rome , Italy.
authors: Simone
authors: S
authors: Berardozzi
authors: e Istituto Italiano di Tecnologia , Center for Life Nano Science@Sapienza , Rome , Italy.
authors: Francesca
authors: F
authors: Ghirga
authors: a Pôle Chimie Et Physique Moléculaire, UMR CNRS 7565, Laboratoire Structure et Réactivite des Systèmes Moléculaires Complexes , Université de Lorraine , Metz , France.
authors: Denyse
authors: D
authors: Bagrel
authors: d Dipartimento di Chimica e Tecnologie del Farmaco , Sapienza University of Roma , Rome , Italy.
authors: Bruno
authors: B
authors: Botta
authors: b Ecole Européenne de Chimie, Polymères et Matériaux (ECPM), Laboratoire de Synthèse et Catalyze (UMR CNRS 7509) , Université de Strasbourg , Strasbourg , France.
authors: Gilles
authors: G
authors: Hanquet
authors: e Istituto Italiano di Tecnologia , Center for Life Nano Science@Sapienza , Rome , Italy.
authors: Mattia
authors: M
authors: Mori
mesh_terms: D018360:Crystallography, X-Ray; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D011809:Quinones / Q000494:pharmacology*; D020687:cdc25 Phosphatases / Q000037:antagonists & inhibitors*
chemical_list: D004791:Enzyme Inhibitors; D011809:Quinones; C517004:CDC25A protein, human; D020687:cdc25 Phosphatases
keywords: CDC25; enzyme inhibitors; molecular modeling; organic synthesis; quinonoid