A Prodrug Approach to the Use of Coumarins as Potential Therapeutics for Superficial Mycoses

摘要: Superficial mycoses are fungal infections of the outer layers skin, hair and nails that affect 20–25% world's population, with increasing incidence. Treatment superficial mycoses, predominantly caused by dermatophytes, is topical and/or oral regimens. New therapeutic options improved efficacy safety profiles desirable. There renewed interest in natural product-based antimicrobials as alternatives to conventional treatments, including treatment mycoses. We investigated potential coumarins dermatophyte-specific antifungal agents describe for first time their utility antifungals using a prodrug approach. Here we demonstrate an inactive coumarin glycone, esculin, hydrolysed aglycone, esculetin dermatophytes. Esculin β-glucosidases. β-glucosidases produced dermatophytes well members dermal microbiota, this activity sufficient hydrolyse esculin concomitant activity. A β-glucosidase inhibitor (conduritol B epoxide), inhibited preventing hydrolysis. demonstrates good aqueous solubility (<6 g/l) could be readily formulated delivered topically water-based gel or cream. This work proof-of-principle application glycosylated prodrugs converted active situ. It anticipated approach will applicable other glycones.