Investigation of the antifungal activity and mechanism of action of 2-aryloxazolines derivatives on Candida albicans

Abstract

Systemic infections caused by fungi that a serious health risk and these have been increasing in recent decades, they are raising mortality and morbidity of the patients. Among these yeast, the Candida albicans accounts for 50%-70% of infections. Studies demonstrate, the appearance of resistant strains to the main antifungal agents in the treatment of candidiasis. New antifungal molecules are currently being researched, attending to new targets of action; the enzyme dihydrofolate reductase (DHFR) has being an interesting candidate. Inhibition of this enzyme leads to an interruption in folate biosynthesis, leading to deficiency in the tetrahydrofolate (THF) cofactor and it can induce the cell death. Antifolates are analogous compounds that interact with the DHFR enzyme site, which they modify and disrupt the folate pathway. Recently, our research group observed the antifungal effect of synthetic 2-aryloxazoline molecules (26 molecules) on the growth of Candida spp and inclusing the strains that are resistant to fluconazole. In addition, we hypothesized a possible interaction with the enzyme DHFR according to the molecular docking analysis. Thus, the present study aims to evaluate the antifungal efficiency and mechanism of action of 2-aryloxazolines derivatives on C. albicans. (AU)