Ergosterol biosynthesis inhibitors examples

Ketoconazole. For treatment of systemic mycoses with amphotericin B or miconazole, the patient must be admitted to a hospital. This is not always possible, particularly in areas where systemic mycoses occur frequently, nor is it always desirable, because of the expense. For these reasons, it was desirable to find an antimycotic that combined safety and broad-spectmm activity with oral adraiinistration. Ketoconazole (10), which is orally active, met most of these requirements. This inhibitor of the ergosterol biosynthesis is an A/-substituted imidazole, that differs from its precursors by the presence of a dioxolane ring (6,7). Ketoconazole is rapidly absorbed in the digestive system after oral adrninistration. Sufficient gastric acid is required to dissolve the compound and for absorption. Therefore, medication that affects gastric acidity (for example, cimetidine and antacids) should not be combined with ketoconazole. 

Sterol biosynthesis inhibiting insecticides. The earliest examples of sterol biosynthesis inhibitors were triadimefon, imazalil, and triarimol. These compounds act by blocking the C14 alpha demethylation step in ergosterol biosynthesis [54], Further work in this area has resulted in numerous fungicides, a number of them containing aromatic fluorine, perfluoroalkyl ethers, and the trifluoromethylphenyl group (Fig. 11). In this section, we will discuss the trifluoromethylphenyl sterol biosynthesis inhibitors, such as triflumizole and fluotrimazole. 

For example, the total sterol content of mycelium of the peanut leafspot pathogen Cercospora arachidicola treated with 0.1 ppm of propiconazole is 1.5 ug/mg dry weight, 80% of which is C-14 methyl sterols, compared to 0.7 ug/mg in non-treated mycelium, (42). The ergosterol content is reduced 50% on a dry weight basis by treatment with the inhibitor. This increase in total sterol may be due to a reduction in feedback inhibition of sterol biosynthesis by ergosterol or one of its metabolites. However, the increase in total sterol does not occur in some fungi (e.g. cerevisiae). 

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