Antifungal natural products and their derivatives: A review of their activity and mechanism of actions

Secondary metabolites, also called specialized metabolites, are essential in defense and cell-to-cell communication that play a significant role in pharmacotherapy. Secondary plant or microbial metabolites played an important role in alleviating infectious diseases in traditional Chinese medicine (TCM) and folk uses. Natural products play considerable roles in TCM, as their biological activities are related to TCM efficacy and provide chemical and biological diversity for drug discovery. This paper summarizes the literature describing the anti-fungal natural products against fungal pathogens and semi-synthetic compounds with improved anti-fungal properties, which will also be included. The mechanisms and targets of anti-fungal drugs may differ among different natural compounds, the discovered anti-fungal natural products are divided into different groups, and their structures, sources, anti-fungal effects, and mechanisms are summarized in detail around a series of anabolic disorders, signaling pathway disorders, and intracellular substance transport abnormalities caused by fungal cells. More than eighty anti-fungal natural products and their derivatives were summarized, classified into eight main groups according to their antifungal mechanism of action, and the types of compounds were illustrated, with the mode of action of some additional compounds unreported or unknown. The summarized compounds showed activity against animal pathogenic fungi of different origins in addition to some compounds being active against plant pathogenic fungi. In this review, we wish to draw readers' attention to the rapidly evolving recognition that plants or microorganisms produce an increasing number of anti-fungal natural products, highlighting their underlying modes of anti-fungal actions, and discussing key opportunities in anti-fungal drug discovery.