Marine-Derived Compounds Against WHO Critical Priority Fungal Pathogens Candida albicans and Candidozyma auris: Recent Advances in Antifungal Research (2021–2026)

Abstract

The increasing incidence of fungal infections caused by Candida albicans and the multidrug-resistant emerging pathogen Candidozyma auris (formerly Candida auris) represents a major global healthcare challenge. Current antifungal therapies are limited by toxicity, drug–drug interactions, rapid resistance emergence, and poor efficacy against fungal biofilms, highlighting the urgent need for novel antifungal agents with new mechanisms of action. In this context, marine ecosystems have emerged as an exceptional source of structurally diverse natural products with promising pharmacological properties. This review summarizes recent advances in marine-derived compounds exhibiting antifungal activity against C. albicans and C. auris. The available evidence is organized according to major chemical classes, including polyketides, alkaloids, terpenoids and meroterpenoids, and miscellaneous marine metabolites. Particular emphasis is placed on antifungal potency, mechanisms of action, anti-biofilm and anti-virulence activities, synergistic interactions with conventional antifungal drugs, and reported structure–activity relationships. Several compounds demonstrated potent direct antifungal activity, while others showed mainly antibiofilm, anti-virulence, synergistic, or resistance-modifying effects despite having limited direct growth-inhibitory activity. Although many promising candidates remain at the preclinical stage, current evidence suggests that marine natural products have significant potential as scaffolds for discovering and developing next-generation antifungal therapeutics. Continued interdisciplinary research integrating natural product chemistry, medicinal chemistry, pharmacology, and translational studies will be essential for transforming these compounds into clinically useful antifungal drugs.