title: Bifonazole and clotrimazole. Their mode of action and the possible reason for the fungicidal behaviour of bifonazole.
abstract: Bifonazole (Bay h 4502, Mycospor) and clotrimazole (Bay b 5097, Canesten) are potent inhibitors of ergosterol synthesis in yeasts and dermatophytes. Inhibition of demethylation of 4,4',14-trimethylsterols is accepted as primary mode of action responsible for their fungistatic efficacy. In Candida albicans, Microsporum canis, Trichophyton mentagrophytes as well as in Epidermophyton floccosum the ergosterol precursor 24-methylendihydrolanosterol accumulates, whereas in Torulopsis glabrata lanosterol accumulation occurs, due to the fact that in this organism side chain alkylation proceeds after demethylation reactions. Bifonazole additionally leads to a generally decreased rate of sterol biosynthesis as compared to clotrimazole, due to a direct inhibition of microsomal HMG-CoA-reductase. The additional fungicidal effects of bifonazole are considered to originate from a sequential action by inhibition of HMG-CoA-reductase and of cytochrome P450.
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology*; D002175:Candida / Q000187:drug effects; D002176:Candida albicans / Q000187:drug effects; D003022:Clotrimazole / Q000494:pharmacology*; D004821:Epidermophyton / Q000187:drug effects; D005285:Fermentation; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007093:Imidazoles / Q000494:pharmacology*; D008861:Microsomes / Q000378:metabolism; D008864:Microsporum / Q000187:drug effects; D013261:Sterols / Q000096:biosynthesis; D014249:Trichophyton / Q000187:drug effects
chemical_list: D000935:Antifungal Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007093:Imidazoles; D013261:Sterols; D003022:Clotrimazole; C036596:bifonazole