Molecular genetic studies on the mode of action of azole antifungal agents.

Cytochrome P-450 catalysing the 14ademethylation of sterol is inhibited in fungi by azole antifungal compounds resulting in a fungistatic or a fungicidal effect [ 11. The azoles themselves represent a useful tool for investigating P-450 structure through the differential affinities with different P450 forms. [Z]. Of practical importance is the identification of the molecular features which result in the strong inhibition of a cytochrome P-450 and which may lead to the development of better antifungals, as well as other therapeutic agents and agrochemicals. The extensive use of azoles is also resulting in increasing reports of resistance in agriculture and in the clinic and we have been interested in the relationship of the resistance mechanisms to the target enzyme and the mode of action of azole antifungals