title: Antifungal relative inhibition factors: BAY l-9139, bifonazole, butoconazole, isoconazole, itraconazole (R 51211), oxiconazole, Ro 14-4767/002, sulconazole, terconazole and vibunazole (BAY n-7133) compared in vitro with nine established antifungal agents.
abstract: Nine new antifungal agents were tested for their activity in vitro in terms of relative inhibition factors (RIFs) against 26 isolates of Candida species, eight isolates of Aspergillus species and six isolates of dermatophyte fungi. Eight of the new compounds were azole antifungals, the ninth was a phenylmorpholine derivative. Against Candida species, all the novel compounds gave RIFs that were of a similar order to RIFs for established imidazole compounds. Two topical antifungals, butoconazole and terconazole, and two systemic antifungals, itraconazole and vibunazole, gave mean RIFs less than 60% in tests with Candida species, and therefore matched clotrimazole, ketoconazole and tioconazole in terms of RIF. However, none of the new compounds gave RIFs as low as amphotericin B against the Candida isolates. Against Aspergillus isolates, itraconazole, with a mean RIF of 25%, was even more active in vitro than amphotericin B. Vibunazole was as active as ketoconazole against Aspergillus isolates. All the new antifungals except Bay l-9139 gave very low RIFs against dermatophyte isolates, and thus matched established imidazole antifungals for inhibitory effects in vitro. In terms of RIF data, all the nine new compounds tested appear to offer reasonable potential for antifungal chemotherapy in vivo. A similar conclusion would not have been drawn from minimal inhibitory concentration data, which tended to show most of the new antifungals in a very poor light. Tests with amphotericin B, 5-fluorocytosine and ketoconazole showed that RIF can vary substantially with the pH of the test medium. For amphotericin B and ketoconazole the best activity was seen at neutral pH values; for 5-fluorocytosine the greatest inhibitory activity was found at lower pH values.
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology*; D001230:Aspergillus / Q000187:drug effects; D002175:Candida / Q000187:drug effects; D003022:Clotrimazole / Q000494:pharmacology; D004464:Econazole / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D017964:Itraconazole; D007654:Ketoconazole / Q000031:analogs & derivatives / Q000494:pharmacology; D008825:Miconazole / Q000031:analogs & derivatives / Q000494:pharmacology; D009025:Morpholines / Q000494:pharmacology; D014230:Triazoles / Q000494:pharmacology
chemical_list: D000935:Antifungal Agents; D007093:Imidazoles; D009025:Morpholines; D014230:Triazoles; C037815:terconazole; C017125:butoconazole; D017964:Itraconazole; C038973:BAY-i 9139; C033308:sulconazole; D004464:Econazole; D008825:Miconazole; C037494:vibunazole; C038974:amorolfine; C022155:oxiconazole; D003022:Clotrimazole; C020382:isoconazole; C036596:bifonazole; D007654:Ketoconazole