Oxiconazole, a new imidazole derivative. Evaluation of antifungal activity in vitro and in vivo.
The new imidazole derivative Z-[2,4-dichloro-2-imidazol-1-yl)acetophenone]-O-(2,4-dichlorobenzyl)-oxime nitrate (oxiconazole, Ro 13-8996) is characterized by a broad fungistatic spectrum against the agents of human mycoses in vitro. In addition, fungicidal activity of various degree was found in selected species (Aspergillus fumigatus, Cryptococcus neoformans, Candida albicans and Trichophyton mentagrophytes). Synthesis of DNA was inhibited by subinhibitory concentrations of oxiconazole in parallel to cell multiplication, whereas synthesis of RNA, protein and carbohydrate was decreased to a lesser extent. The most relevant findings was high topical activity in both trichophytosis in the guinea-pig and vaginal candidiasis in the rat. In these 2 models, oxiconazole proved to be more potent than several reference compounds from the group of imidazole antimycotics. Systemic oral activity of oxiconazole was also found in three mouse models, namely in dermal infection with T. mentagrophytes var. quinckeanum, systemic histoplasmosis and, just to a low degree, systemic candidiasis, but the compound proved to be inactive in cryptococcosis and aspergillosis in the mouse. Based on our findings, a clinical evaluation of oxiconazole as a topical antimycotic in human superficial mycosis, seems to be justified.
D000818:Animals; D000935:Antifungal Agents; D002176:Candida albicans / Q000378:metabolism; D002181:Candidiasis, Vulvovaginal / Q000188:drug therapy; D003470:Culture Media; D005260:Female; D006168:Guinea Pigs; D007093:Imidazoles / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D051379:Mice; D009181:Mycoses / Q000188:drug therapy; D051381:Rats; D014005:Tinea / Q000188:drug therapy
D000935:Antifungal Agents; D003470:Culture Media; D007093:Imidazoles; C022155:oxiconazole