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.

Details

Title
Synthesis, biological evaluation and molecular modeling studies on novel quinonoid inhibitors of CDC25 phosphatases
Author
Evain-Bana, Emilie 1 ; Schiavo, Lucie 2 ; Bour, Christophe 3 ; Lanfranchi, Don Antoine 2 ; Berardozzi, Simone 4 ; Ghirga, Francesca 5 ; Bagrel, Denyse 1 ; Botta, Bruno 6 ; Hanquet, Gilles 2 ; Mori, Mattia 5 

 Pôle Chimie Et Physique Moléculaire, UMR CNRS 7565, Laboratoire Structure et Réactivite des Systèmes Moléculaires Complexes, Université de Lorraine, Metz, France; 
 Ecole Européenne de Chimie, Polymères et Matériaux (ECPM), Laboratoire de Synthèse et Catalyze (UMR CNRS 7509), Université de Strasbourg, Strasbourg, France; 
 ICMMO, Université Orsay Cedex, France; 
 Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza University of Roma, Rome, Italy;; Istituto Italiano di Tecnologia, Center for Life Nano Science@Sapienza, Rome, Italy 
 Istituto Italiano di Tecnologia, Center for Life Nano Science@Sapienza, Rome, Italy 
 Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza University of Roma, Rome, Italy; 
End page
118
Publication year
2017
Publication date
Dec 2017
Publisher
Taylor & Francis Ltd.
ISSN
14756366
e-ISSN
14756374
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2195229222
Copyright
© 2017 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. This work is licensed under the Creative Commons Attribution License http://creativecommons.org/Licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.