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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Novel tetrahydropyrido[1,2-a]isoindolone derivatives (valmerins): Potent cyclin-dependent kinase/glycogen synthase kinase 3 inhibitors with antiproliferative activities and antitumor effects in human tumor xenografts
Journal of Medicinal Chemistry, Volume 55, No. 22, Year 2012
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Description
The development of CDK and GSK3 inhibitors has been regarded as a potential therapeutic approach, and a substantial number of diverse structures have been reported to inhibit CDKs and GSK-3β in recent years. Only a few molecules have gone through or are currently undergoing clinical trials as CDK and GSK inhibitors. In this paper, we prepared valmerins, a new family containing the tetrahydropyrido[1,2-a]isoindone core. The fused heterocycle was prepared with a straightforward synthesis that was functionalized by a (het)arylurea. Twelve valmerins inhibited the CDK5 and GSK3 with an IC50 < 100 nM. A semiquantitative kinase scoring was realized, and a cellular screening was done. At the end of our study, we investigated the in vivo potency of one valmerin. Mice exhibited good tolerance to our lead, which proved its efficacy and clearly blocked tumor growth. Valmerins appear also as good candidates for further development as anticancer agents. © 2012 American Chemical Society.
Authors & Co-Authors
Boulahjar, R.
France, Orleans
Université D'orléans
Morocco, Casablanca
Hassan Ii University of Casablanca
Ouach, Aziz
France, Orleans
Université D'orléans
Matteo, Chiurato
France, Orleans
Université D'orléans
Bourg, Stephane
France, Orleans
Université D'orléans
Ravache, Myriam
France, Rennes
Biosit : Biologie, Santé, Innovation Technologique
Guével, Rémy Le
France, Rennes
Biosit : Biologie, Santé, Innovation Technologique
Marionneau, Séverine
France, Nantes
In Vivo Platform
Oullier, Thibauld
France, Nantes
In Vivo Platform
Lozach, Olivier
France, Roscoff
Station Biologique de Roscoff
Meijer, Laurent
France, Roscoff
Station Biologique de Roscoff
France, Roscoff
Centre de Perharidy
Guguen-Guillouzo, Christiane
France, Rennes
Biosit : Biologie, Santé, Innovation Technologique
Lazar, Saïd
Morocco, Casablanca
Hassan Ii University of Casablanca
Akssira, Mohamed
Morocco, Casablanca
Hassan Ii University of Casablanca
Troin, Yves
France, Clermont-ferrand
Université Clermont Auvergne
Guillaumet, Gérald E.
France, Orleans
Université D'orléans
Routier, Sylvain
France, Orleans
Université D'orléans
Statistics
Citations: 43
Authors: 16
Affiliations: 7
Identifiers
Doi:
10.1021/jm3008536
ISSN:
00222623
e-ISSN:
15204804
Research Areas
Cancer