Section Review: Anti-infectives: The potential of novel antifungal drugs for the treatment of disease in the immunocompromised host

Abstract

There is a growing need for new antifungal drugs to complement those already in clinical use. Analogues and new formulations of existing drugs continue to give improvements in chemotherapy, but this account concentrates on possible new areas of development. These have been inspired chiefly by results from screening for new natural products. The most promising are three groups of antibiotics targeting the fungal cell walls. The echinocandins and related lipopeptides and their semisynthetic derivatives, and the papulacandin glycolipids are potent specific inhibitors of β-(1–3)-glucan synthesis. Pradimicins and benanomicins bind to mannan in the cell wall, but then target the cell membrane, disrupting its function. A wide range of other novel antifungal natural products, some with very unusual structures, are currently under critical investigation. The possible selective antifungal activity of members of the families of immunosuppressive drugs, cyclosporins and rapamycins, is worthy of further study. In a different approach, much current research in the metabolism and molecular biology of pathogenic fungi is directed ultimately at rational design of specific antifungal agents, but at present this is a hope for the future.