Brief Primer on the Discovery of New Antifungal Drugs from Plant Sources.

Rationale: The antifungal armamentarium is shrinking while resistance to licensed agents rises. Historically, actinomycetes and fungi delivered nystatin, amphotericin B, griseofulvin and the echinocandin scaffold, yet plant-derived compounds-despite potent in-vitro activity-have rarely reached the clinic.

Objective: To frame the recent in-vivo success of papaya-seed essential oil against fluconazole-sensitive and -resistant Candida albicans within the broader context of plant-based antifungal discovery, and to propose rigorous criteria that can accelerate translation, especially considering varying resource settings.

Key points: Commentary on Ma et al. (Mycopathologia 190(5):1-14, 2025) showing that benzyl-isothiocyanate-rich papaya-seed oil outperforms fluconazole in a murine systemic candidiasis model without acute toxicity; Historical perspective on how soil microbes provided the first broad-spectrum antifungals; An eight-point checklist for future plant-extract studies, with essential and suggested elements to promote high-quality research across different laboratory settings.

Conclusion: Adherence to core methodological standards, along with suggested advanced analyses where feasible, will help identify promising plant-derived antifungal leads and support a more inclusive and effective discovery pipeline.