Antifungal drugs on the horizon.

Abstract

In the past 10 years there has been a major expansion in the development of antifungal drugs, but there are still weaknesses in the range and scope of current antifungal chemotherapy. New developments have included the modification of existing drug molecules to eliminate toxicity and improve activity, for instance, the development of the lipid formulations of the polyene antifungal agent amphotericin B. Three different amphotericin B derivatives, a unilamellar liposome (AmBisome), a colloidal dispersion (ABCD--Amphocil), and a lipid complex (ABLC) are undergoing evaluation. New triazoles with broad-spectrum antifungal activity, such as saperconazole, are also being assessed. The development of groups of drugs with novel modes of action such as cell wall biosynthesis inhibitors has been slower, although a number of molecules with activity against key enzymes, including chitin or glucan synthase, have been found. The morpholine antifungal amorolfine, a sterol biosynthesis inhibitor, has been developed for the topical treatment of fungal nail infections. The assessment of these drugs is a major challenge because it will be necessary to show that they have some advantage over existing compounds in efficacy, speed of action, or lack of toxicity.