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Comparison of the Anti‐inflammatory Activities of Imidazole Antimycotics in Relation to Molecular Structure
Author(s) -
Steel Helen C.,
Tintinger Gregory R.,
Anderson Ronald
Publication year - 2008
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/j.1747-0285.2008.00694.x
Subject(s) - ketoconazole , itraconazole , pharmacology , chemistry , triazole , imidazole , voriconazole , azole , fluconazole , biochemistry , biology , antifungal , microbiology and biotechnology , organic chemistry
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 μ m ) in relation to their molecular structures. Anti‐inflammatory activity was determined according to the magnitude of inhibition of production of leukotriene B 4 and influx of Ca 2+ following activation of the cells with the chemo‐attractant platelet‐activating factor (200 n m ), 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 B 4 and attenuation of Ca 2+ 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.