Synthèse et évaluation pharmacologique de composés azahétérocycliques à visée antitumorale

Malgré la découverte de nouvelles molécules antitumorales et l'application de nouveaux traitements, le cancer reste une des principales causes de décès dans les pays développés. Des travaux antérieurs ont montré que des composés à structure pyrido[2,3-b ]pyrazine possédaient un niveau d'activité prometteur sur la cascade des MAP kinases impliquée dans la prolifération de nombreux cancers. Nous avons décidé, en collaboration avec les laboratoires AEterna Zentaris, de développer des molécules originales, à structure 1,5- naphtyridine, dérivées des composés précédemment cités. Dans un premier temps, une synthèse efficace a donc été mise au point, puis dans un deuxième temps, une pharmacomodulation couplée à des évaluations pharmacologiques nous ont permis d'obtenir de nouveaux inhibiteurs de kinasesDespite the discovery of novel antitumor agents and the application of new therapies, cancer disease is one of the most important cause of death in developed countries. Previous works demonstrated that pyrido[2,3-b [pyrazine derivatives exhibited a promising activity on MAP kinases cascade which is involved in tumor proliferation. Thus, we decided, in collaboration with AEterna Zentaris laboratories, to develop new 1,5-naphthyridine compounds derived from the previous ones. First, we perfected an efficient synthesis, then we made pharmacomodulation and pharmacological evaluations to obtain new kinases inhibitors.NANTES-BU Médecine pharmacie (441092101) / SudocSudocFranceF

Discovery of (7-aryl-1,5-naphthyridin-2-yl)ureas as dual inhibitors of ERK2 and Aurora B kinases with antiproliferative activity against cancer cells

International audienc

Huprines as a new family of dual acting trypanocidal–antiplasmodial agents

A series of 19 huprines has been evaluated for their activity against cultured bloodstream forms of Trypanosoma brucei and Plasmodium falciparum. Moreover, cytotoxicity against rat myoblast L6 cells was assessed for selected huprines. All the tested huprines are moderately potent and selective trypanocidal agents, exhibiting IC50 values against T. brucei in the submicromolar to low micromolar range and selectivity indices for T. brucei over L6 cells of approximately 15, thus constituting interesting trypanocidal lead compounds. Two of these huprines were also found to be active against a chloroquine-resistant strain of P. falciparum, thus emerging as interesting trypanocidal–antiplasmodial dual acting compounds, but they exhibited little selectivity for P. falciparum over L6 cells