Design and structure-activity relationships anticandidosic of diazaheteroaryl functionalized by Michaël acceptors

Abstract

Benzimidazole and imidazopyridine heterocycles associated with Michaël acceptors have shown strong anticandidosic potential in our previous work. After a decade of research, we have designed, synthesized and evaluated the anticandidosic activities of several new compounds with the structure benzimidazolyl-arylpropenone or benzimidazolylarylacrylonitriles or benzimidazolyl-arylcyanopropenone and imidazopyridinyl-arylpropenone. The evaluation of their antifungal activities by the bioautography method showed that these molecules possessed anticandidosic properties with MIQs ranging from 10 to 0.16 µg. These results also highlighted that the anticandidosic performance of our compounds was related to the nature of the Michaël acceptor and structural variations undertaken on the benzene homocycle. In this paper, we discuss the pharmacochemical design, the chemical synthesis and especially the structure-activity relationship studies of diazaheteroaryls functionalized by a Michaël acceptor of the arylpropenone or arylacrylonitrile or arylcyanopropenone type.