Discovery of Antifungal Agents from Natural Sources: Virulence Factor Targets
ABSTRACT Important strategic decisions in the drug discovery process are highlighted, with special emphasis on the rationale and technical challenges of natural products-based programs. Discovery of useful new antifungal compounds is specifically treated, with an overview of the existing and emerging therapies, and a rationale for selecting fungal virulence factors as antifungal drug targets. Selected examples are described for three different classes of fungal virulence factors — the secreted aspartic proteinases of Candida species, the phenoloxidase system of Cryptococcus neoformans, and siderophores produced by these and other pathogenic fungi, including Histoplasma and Aspergillus. The rationale and biological evaluation methods are presented, along with a general overview of progess in screening and bioassay-directed fractionation to date.