Interaction of microsomal cytochrome P-450 isolated fromAspergillus fumigatuswith fluconazole and itraconazole
- 1 January 1990
- journal article
- Published by Oxford University Press (OUP) in Medical Mycology
- Vol. 28 (4), 327-334
- https://doi.org/10.1080/02681219080000411
Abstract
A simple procedure has been developed for isolating a microsomal fraction from Aspergillus fumigatus which contains cytochrome P-450. Maximum absorbance of the carbon monoxide/ferrous cytochrome P-450 difference spectrum was at a wavelength of 451 nm. The triazole antifungal agents, fluconazole and itraconazole, produced type II binding difference spectra with ferric cytochrome P-450 in A. fumigatus microsomes and an azole concentration of 0.5 μm was sufficient to saturate the spectroscopic response when the cytochrome P-450 concentration was 0.07μm. This extremely high affinity binding precluded the determination of apparent dissociation constants for the cytochrome P-450-azole complexes. Itraconazole was found to have a marginally greater affinity for cytochrome P-450 than fluconazole, as determined from a comparison of their potential to reduce the rate of binding of carbon monoxide to the ferrous haemoprotein. The high affinity binding of both compounds to the cytochrome P-450 from A. fumigatus is consistent with their proposed antifungal mode of action through inhibition of the sterol 14α-demethylase cytochrome P-450 required for ergosterol biosynthesis.Keywords
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