ABSTRACT
Only three cellular processes, sterol biosynthesis and function, cell wall biosynthesis, and nucleic acid metabolism, have been successfully exploited commercially as targets for chemotherapeutic intervention (reviewed in [I)). The azole family of drugs, which inhibit sterol biosynthesis, and polyenes, which disrupt membrane integrity, are the most widely used classes of antifungals. Fluorocytosine, due to its toxic side effects, is typically used in combination therapies. More recently, antifungal drugs which inhibit enzymes required for cell wall biosynthesis, ceramide synthase, and translation have been evaluated for clinical efficacy [2], though it remains to be seen if these new drugs will have a clinical impact. Despite such advances, there remain a limited number of targets described and developed. With the advent of highthroughput screens, antimicrobial drug discovery and development relies more and more on mechanism-based bioassays to identify lead candidates from very large numbers of compounds. There are three basic strategies for identification of potential targets (Fig. I): the use of known antifungal compounds; the use of knowledge of cellular physiology and metabolism; and the use of molecular genetics and bioinformatics.
