Cytochrome P450 of Fungi: Primary Target for Azole Antifungal Agents
- 1 January 1988
- book chapter
- Published by Springer Nature
- Vol. 2, 388-418
- https://doi.org/10.1007/978-1-4612-3730-3_11
Abstract
Numerous azole compounds have been developed as potent antifungal agents. These compounds inhibit the growth of fungi by disturbing membrane and membrane-bound enzyme systems. Such disturbance is caused by the depletion of ergosterol and the accumulation of 14-methylsterols such as lanosterol, 24-methylene-24,25-dihydrolanosterol, obtusifoliol, and 14-methylfecosterol in the membrane. Ergosterol is synthesized from lanosterol with the 14-methylsterols appearing as intermediates in the metabolic pathway. The azole antifungal agents inhibit the 14a-demethylation of methylsterols. The 14a-demethylation is a cytochrome P450-dependent reaction, and the cytochrome P450 that catalyzes removal of the 14a-methyl group of 14-methylsterols is believed to be the primary target for azole antifungal agents [for a review, see (101)].Keywords
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