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Comparison of the anti-inflammatory activities of imidazole antimycotics in relation to molecular structure
Helen C Steel1, Gregory R Tintinger, Ronald Anderson
1Medical Research Council Unit for Inflammation and Immunity, Department of Immunology, Faculty of Health Sciences, University of Pretoria and Tshwane Academic Division of the National Health Laboratory Service, Pretoria, South Africa.
Abstract:
The objective of this study was to compare the anti-inflammatory potencies of the imidazole antimycotics, fluconazole, itraconazole, ketoconazole and voriconazole (0.5 and 5 microM) in relation to their molecular structures. Anti-inflammatory activity was determined according to the magnitude of inhibition of production of leukotriene B4 and influx of Ca2+ following activation of the cells with the chemo-attractant platelet-activating factor (200 nM), using enzyme-linked immunosorbent assay and spectrofluorometric procedures, respectively. Treatment of platelet-activating factor-activated neutrophils with the imidazole antimycotics resulted in inhibition of production of leukotriene B4 and attenuation of Ca2+ influx, the order of potency being itraconazole > ketoconazole > fluconazole = voriconazole. These observations demonstrate the requirement for both the diazole/triazole moiety (all four agents), and the substituted phenylpiperazinyl ether side chain (itraconazole and ketoconazole only) for maximal anti-inflammatory activity of this class of pharmacological agents.
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