Antifungal Sterol Biosynthesis Inhibitors

Abstract
Herbal medicines and related drugs used to treat infective organisms were available in ancient cultures and detailed in the first pharmacopoeia reported in 1146 ad, titled “Antidotarium Niclai” (Grun, 1991). During the following millennium, there has been continued interest in drug discovery and application. However, only in the last fifty years have effective therapeutic agents for fungal disease been developed that exploit a fundamental difference between the biochemistry or physiology of the pathogens and their hosts. Sterol biosynthesis is one of the few areas of difference in primary metabolism between fungi and animals. Unlike animals that synthesize 24-desalkyl sterols, such as cholesterol (cholest-5-en-3β-ol), many pathogenic fungi synthesize 24-alkylsterols, such as ergosterol (24β-methyl cholesta-5,7,22-trien-3β-ol). The major difference in the two sterols stems structurally from the presence and nature of the 24-alkyl group.

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