Glucosinolate derivatives as antifungals: A review

Area of Science:

• Mycology
• Natural Product Chemistry
• Pharmacology

Background:

• Fungal infections pose a growing global health risk, exacerbated by antibiotic overuse and increased immunocompromised populations.
• Emerging antifungal drug resistance necessitates the development of novel therapeutic strategies.
• Plant secondary metabolites, particularly glucosinolate (GSL) derivatives, offer a promising source for new antifungal drug discovery due to their diverse structures and potent activity.

Purpose of the Study:

• To review the antifungal mechanisms of isothiocyanates (ITCs) derived from glucosinolates.
• To summarize the antifungal activities of related GSL derivatives, including nitriles, epithionitriles, oxazolidin-2-thion, and thiocyanates.
• To consolidate current understanding of ITC interactions with fungal systems, including aflatoxin inhibition, transcriptomic effects, cell membrane targeting, efflux modulation, and synergistic potential.

Main Methods:

• Literature review focusing on GSL derivatives and their antifungal properties.
• Analysis of mechanisms of action for isothiocyanates (ITCs) against fungi.
• Compilation of data on the antifungal activity of nitriles, epithionitriles, oxazolidin-2-thion, and thiocyanates.
• Inclusion of cytotoxicity and clinical trial data where available.

Main Results:

• Isothiocyanates exhibit diverse antifungal mechanisms, including inhibition of aflatoxin biosynthesis and disruption of fungal cell membranes.
• ITCs influence fungal transcriptomes and modulate efflux pump activity.
• Other GSL derivatives like nitriles, epithionitriles, oxazolidin-2-thion, and thiocyanates also demonstrate antifungal activity.
• Synergistic effects of ITCs with other agents were observed.

Conclusions:

• Glucosinolate derivatives, especially isothiocyanates, represent a valuable resource for developing new antifungal agents.
• Further research, including extensive safety and clinical efficacy studies, is required to fully assess their therapeutic potential.
• These natural compounds offer a potential strategy to combat the increasing threat of fungal infections and drug resistance.