Evaluation of Antifungal Activity and Mode of Action of New Coumarin Derivative, 7-Hydroxy-6-nitro-2H-1-benzopyran-2-one, against Aspergillus spp.

Abstract

Aspergillus spp. produce a wide variety of diseases. For the treatment of such infections, the azoles and Amphotericin B are used in various formulations. The treatment of fungal diseases is often ineffective, because of increases in azole resistance and their several associated adverse effects. To overcome these problems, natural products and their derivatives are interesting alternatives. The aim of this study was to examine the effects of coumarin derivative, 7-hydroxy-6-nitro-2H-1-benzopyran-2-one (Cou-NO, both alone and with antifungal drugs. Its mode of action against Aspergillus spp. Cou-NOwas tested to evaluate its effects on mycelia growth and germination of fungal conidia of Aspergillus spp. We also investigated possible Cou-NOaction on cell walls (0.8 M sorbitol) and on Cou-NOto ergosterol binding in the cell membrane. The study shows that Cou-NOis capable of inhibiting both the mycelia growth and germination of conidia for the species tested, and that its action affects the structure of the fungal cell wall. At subinhibitory concentration, Cou-NOenhanced the in vitro effects of azoles. Moreover, in combination with azoles (voriconazole and itraconazole) Cou-NOdisplays an additive effect. Thus, our study supports the use of coumarin derivative 7-hydroxy-6-nitro-2H-1-benzopyran-2-one as an antifungal agent against Aspergillus species.