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.