Abstract
Freshwater fungi have attracted considerable attention as a potential source of lead compounds with diverse and novel chemical structures and biological activities in drug discovery. This review summarizes 307 natural products of freshwater fungi from 1988 to the end of October 2025. These compounds are categorized into fourteen structural types, including fatty acids and their lactones (compounds 1-18), furans and furanones (compounds 19-31), pyrans and pyranones (compounds 32-109), benzoquinones, phenols and phenolic acids (compounds 110-141), naphthalenes and naphthalenones (compounds 142-192), authraquinones and xanthones (compounds 193-211, depsidones (compounds 212-217), macrolides (compounds 218-234), polyesters (compounds 235-237), alkaloids (compounds 238-251), peptides (compounds 252-280), terpenoids (compounds 281-300), steroids (compounds 301 and 302), and other compounds (compounds 303-307). Some of them displayed promising biological activity, mainly comprising antibacterial, cytotoxic, and nematicidal activities. The preliminary analysis of the Structure--Activity Relationship (SAR) of important compounds is also discussed. In the last section, current challenges and prospective research perspectives are briefly proposed based on opinions from previous reviews. This review would contribute to the understanding of the utilization and development of natural products derived from freshwater fungi as potent medical resources in the future.