Polyene macrolide antibiotics and their applications in human therapy

Fungal infections represent a serious problem for patients with immune systems compromized either by HIV infection, or administration of immumosuppressive drugs during cancer therapy and organ transplantation. High dissemination and proliferation rates of many pathogenic fungi along with their insusceptibility to common antimicrobial drugs urge implementation of efficient and reliable antifungal therapy. Up to date, polyene macrolide antibiotics proved to be the most effective antifungal agents due to their potent fungicidal activity, broad spectrum, and relatively low frequency of resistance among the fungal pathogens. However, polyene macrolides are rather toxic, causing such serious side effects as renal failure,, hypokalemia and thrombophlebitis, especially upon intravenous administration. Current views on the biosynthesis of polyene macrolides, their mode of action and structure-function relationship, as well as strategies used to overcome the toxicity problem are discussed in this review. In addition, some of the new potential applications for polyene macrolides in therapy of prion diseases, HIV infection and cancer are highlighted.