Synthèse de composés hétérocycliques à visée anticancèreuse.

Abstract

Our work focuses on the development of new synthetic approaches to anticancer compounds. This work was carried out at the University of Constantine and Strasbourg, under Prof. Taoues Boumoud and Dr. Laurent Désaubry’s supervision. Triarylimidazoles and spirooxindoles are heterocycles found among several important anti-cancer agents. In order to facilitate the pharmacochemical exploration of these compounds, improving their synthesis was aimed. Novel catalytic ways were developped for the synthesis of triarylimidazoles and spiro[chroméne-oxindoles] with good yields via multicomponent reactions in the presence of citric acid and BF3.OEt2 as catalysts respectively. Two articles demonstarting the catalytic effects of the former catalysts in the synthesis of benzimidazoles and spirooxindole derivatives were published. Original work carried out in Strasbourg has demonstrated the cytotoxic properties of an iminobenzimidazole on cancerous lines. Analogues of this compound, were prepered, to determine the structural requirements for this cytotoxicity. An article describing these works was published inThe Open Medicinal Chemistry Journal. Another cytotoxic agent “fluorizoline” and analogues thereof were also prepared. Two first articles demonstrating the inhibition of KRAS oncogene by this compound and its activity in models of chronic lymphocytic leukemia were also published.