Miconazole at minimal fungitoxic concentrations inhibits ergosterol biosynthesis in sporidia of Ustilago maydis by interference with sterol C14 demethylation. The action is analogous to that of the fungicides tiarimol and fenariniol. The fungicide 1-dodecylimidazole at low concentrations (0.1 to 0.25 yg/ml) inhibits sterol C14 demethylation; however, at higher concentrations (1.0 ug/ml or greater) it also inhibits 2,3-oxidosqualene cyclization and subsequent tranamethylation. It is postulated that this diversity of effects of 1-dodecylimidazole results from binding of the inhibitor to sterol carrier protein(s).Miconazole is a fungitoxic agent with a wide antifungal spectrum used medically to control mycotic infections (27). Various observations with Candida albicans after exposure times ranging from 3 to 24 h indicated that miconazole affects membrane permeability and transport as well as cell morphology (8-10, 26, 28).In studies with imazalil, a miconazole analog, Van Tuyl observed that cross-resistance invariably occured between the fonner compound and fenarimol in mutants of Aspergillus nidulans (30,31). Fenarimol, like triarimol, is an inhibitor of ergosterol biosynthesis (3, 19). These results suggested that the mode of action of miconazole was possibly analogous to that of the sterol C14 demethylation inhibitors triarimol (18,21), fenarimol, imazalil (16,24), triadimefon (2), triforine (23), and Denmert (14). Recent studies show, in fact, that miconazole is an inhibitor of ergosterol biosynthesis in Ustilago maydis (12) and C. albicans (29).N-dodecylimidazole, like miconazole, is a fungitoxic 1-alkylimidazole. This compound is reported to inhibit cholesterol biosynthesis in rat livers (K. H. Baggaley, R. M. Hindley, J. L. Tee, and G. S. Brooks, British Patent 1,364,312, January 1971). Atkin et al. concluded that it is a specific inhibitor of 2,3-oxidosqualene cyclase, the enzyme which converts 2,3-oxidosqualene to lanosterol (1). It was of interest to compare the effects of these two inhibitors on the sterol biosynthetic pathway in U. mnaydis, an organism in which the action of triarimol has been thoroughly investigated (12,18,20,21). This report presents the results of these investigations.MATERIALS AND METHODS Sporidia of U. maydis (DC) Cda. ATCC 14826 were cultured as previously described (5,20), in a defined nutrient medium at an initial concentration of 6.9 x 106 sporidia per ml (0.2 mg [dry Wvt] per ml). Inhibitors were added as methanolic solutions so that the methanol did not exceed 1% in the culture media. After centrifugation from culture media, sporidia were lyophilized, and crude lipids were extracted with chloroform-methanol (2:1, vol/vol) (11,18,20 Sterols of unsaponified lipid samples were analyzed by gas-liquid chromitography after separation by TLC, whereas saponified lipid smples were analyzed directly. Analyses were performed on a Glowall Chromalab 310 chromatograph by using a coluimn (1.8 m by 3.4 mm) packed with 3% SE-30 on Gas Chrom Q (100 to 120 mesh) at 255°C. Compounds were detecte...