Chapter 16. Recent Advances in Antifungal Agents

Abstract

This chapter summarizes the recent advancement in antifungal agents and discusses their theraputic use. Polyenes, including amphotericin B (AmB), fungizoneare, dimyristoylglycero, and hamycin, are the main therapeutics against systemic mycoses. In vitro and in vivo testing of these formulations, using different models, has given variable results. In the continued evaluation of toxicity of AmB and other antifungals, more sophisticated studies on the effects of antifungal agents on human neutrophils have been conducted. A series of vinylimidazoles has showed good anti-dermatophyte and anti-yeast activity in vitro. Saperconazole is another azole compound under development with broad spectrum fungicidal activity especially against disseminated candidosis and cryptococcosis. Polyoxins and nikkomycins competitively inhibit the chitin synthase of fungi with Candida albicans as the primary target organism. Nitroxoline, a synthetic quinoline useful as a urinary tract antiseptic, has been shown to have some antifungal activity in vitro. Isolation of marine natural products has produced a variety of macrocycles such as the myacolides A-C the patellazoles A-C and the ulithiacyclamides. All of these compounds are general cytotoxins and antifungal agents. Two antifungal agents from ectomycorrhizal fungi are pisolithin A and pisolithin B. Another macrocyclic family of antifungal antibiotics, aureobasidin A–R, has been isolated from the fermentation broth of a strain of black yeast. Inhibitors of glucosamine-6-phosphate synthase delivered through peptide transport systems have been reported to have anti-candidal activity. The most potent of these antifungal dipeptides is L-norvalyl-FMDP. Antifungal peptides produced as a natural defense mechanism are being isolated from various sources.