Plant-derived isoquinoline alkaloids that target ergosterol biosynthesis discovered by using a novel antifungal screening tool

The ergosterol pathway is a prime antifungal target as it required for fungal survival, yet not involved in human homeostasis. Methods to study the pathway, however, are often time-consuming. minimum inhibitory concentration (MIC) assay simple research tool that determines lowest at which novel antimicrobial active vitro with limited scope determine mechanism of action drug. In this study, we show by adding hydrogen peroxide, an oxidative stressor, or glutathione (GSH), antioxidant, modify commonly performed MIC allowed us screen selectively new drugs biosynthesis fungi. A pathogen and dermatophyte, Microsporum gypseum, was used test organism. When exposed targeting drugs, peroxide treatment significantly decreased survival reducing cell wall, whereas GSH increased M. gypseum. Further, performing series experiments gypseum Trichophyton rubrum, determined stress from causes death different developmental stages based on species. These findings allow describe simple, high-throughput method simultaneously screening activity effects pathway. By using tool, two isoquinoline alkaloids were discovered be potent inhibitors amount without affecting expression 1,3-β-glucan. Both compounds also reduced severity acanthosis, hyperkeratosis, spongiosis dermal edema vivo.