C14a-Demethylation

The azoles are used to control a wide range of diseases, especially in cereals Septoria spp., Puccinia spp. and Pseudocercosporella herpotri-coides), fruit (Venturia spp.) and vegetables. 

The principle action of the DMI fungicides is to inhibit the action of the cytochrome 450-dependent removal of the 14a-methyl group from 24-methylene dihydrolanosterol. The resulting accumulation of the substrate 24-methylene dihydrolanosterol, obtusifoliol and 14a-methyl-fecosterol, together with the consequent reduction in ergosterol synthesis, disrupts the normal functioning of cell membranes and was thought to be the basis of DMI activity. 

However, recent studies suggest that the toxic activity resulting from the inhibition of C14-demethylation is more complex and the precise consequences are still uncertain.3 The growth of some fungi does not correlate with the amount of 14-methyl sterols accumulated following 

24(28)-dien-3/ ,6a-diol, a sterol now considered to be the main agent in membrane disruption. 

There are significant differences in performance between DMIs. These may be due to differences in their binding affinities to the haem moiety of the cytochrome 450-dependent demethylase enzyme. 

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