In vitro antifungal evaluation and structure–activity relationships of a new series of chalcone derivatives and synthetic analogues, with inhibitory properties against polymers of the fungal cell wall

Here we report the synthesis, in vitro antifungal evaluation and SAR study of 41 chalcones and analogues. In addition, all active structures were tested for their capacity of inhibiting Saccharomyces cerevisiae β(1,3)-glucan synthase and chitin synthase, enzymes that catalyze the synthesis of the major polymers of the fungal cell wall.

Compounds of the general structure 1 were synthesized and examined or their antifungal properties with cellular and enzymatic assays. Many chalcone derivatives displayed potent activites against dermatophytes. A structure–activity relationship (SAR) study supported by theoretical calculations aided to identify the minimal structual requeriments for the antifungal action. Regarding the mode of action, all active structures inhibited β(1,3)-glucan synthase and mainly chitin synthase-1, enzymes that catalyze the synthesis of the two majors polymers of the fungal cell wall.Figure optionsDownload as PowerPoint slide