Natural products as antifungal agents against clinically relevant pathogens

Fungi have emerged worldwide as increasingly frequent causes of healthcare-associated infections, but fungal infections have generally been considered curable, and thus the demand for new antifungal agents has been very low. Although superficial fungal infections of the skin and nails are common and are for the most part treated successfully with existing antifungal agents, serious fungal infections are becoming a growing danger for human health. This is particularly true for AIDS patients, but also for recipients of transplants, and users of antineoplastic agents, corticoids, and even antibiotics. A major problem is the increasing emergence of resistance to antimycotic agents, and since azoles--the most used class of antifungals--suffer a significant incidence of resistance, new efforts are now devoted to the discovery of new agents with different mechanisms of action. Not so long ago, combinatorial chemistry appeared to be the future for drug discovery, but in the late 1990s synthetic chemists realized that combinatorial libraries lacked the "complexity" usually associated with natural compounds. Research into biologically active natural products has thus had a reprise, in particular with the advent of the concept of diversity-oriented synthesis. This review reports what is so far known about natural products as antifungal agents, and provides an overview of natural compounds with both known and unknown mechanisms of action.