Biochemical changes associated with the antifungal action of the triazole ICI 153,066 on Candida albicans and Trichophyton quinckeanum.
The triazole antifungal agent, ICI 153,066, acts on Candida albicans and Trichophyton quinckeanum by inhibiting demethylation of the sterol ring. In C. albicans this is at the level of lanosterol whereas in T. quinckeanum it is at the level of 24-methylene lanosterol. Inhibition of the demethylation system was shown to be non-competitive, the Vmax of the enzyme was reduced rather than affinity for the substrate lanosterol. The changes in the sterols of C. albicans lead to inhibition of the transport of amino acids into the yeasts which probably resulted from alterations in the membrane bound permeation systems. The reduction in uptake of amino acids was shown to reflect a change in the velocity of transport rather than the affinity of the amino acids for the transport systems.
Barrett-Bee
K
K
Bioscience 1 Department, ICI Pharmaceuticals, Mereside, Macclesfield, Cheshire, U.K.
Newboult
L
L
Pinder
P
P
D000085:Acetates / Q000378:metabolism; D019342:Acetic Acid; D000596:Amino Acids / Q000378:metabolism; D000935:Antifungal Agents / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects* / Q000378:metabolism; D004875:Ergosterol / Q000032:analysis; D008401:Gas Chromatography-Mass Spectrometry; D007810:Lanosterol / Q000378:metabolism; D008798:Mevalonic Acid / Q000378:metabolism; D013261:Sterols / Q000096:biosynthesis; D014230:Triazoles / Q000494:pharmacology*; D014249:Trichophyton / Q000187:drug effects* / Q000378:metabolism
D000085:Acetates; D000596:Amino Acids; D000935:Antifungal Agents; D013261:Sterols; D014230:Triazoles; D007810:Lanosterol; C040032:ICI 153066; D019342:Acetic Acid; D008798:Mevalonic Acid; D004875:Ergosterol