human-pathogenic fungi. For example, the azole
fungicides(imidazoles and triazoles) were first devel-
oped to control plant diseases, but in modified forms
they are now widely used to control human mycoses.
Similarly, the naturally occurring antifungal antibiotic
griseofulvinwas first discovered as a “curling factor”
that caused the germ-tubes of a plant-pathogenic
fungus, Botrytis allii, to grow in a distorted spiral fash-
ion, but it was developed commercially as an orally
administered antibiotic to control infections caused
by the dematophytic fungi. It acts by disrupting fungal
microtubules, and this explains its morphogenetic
effect because microtubules are involved in the deliv-
ery of cellular components to the growing hyphal tip
(Chapter 4).
Principal cellular targets of antifungal
agents
The main cellular targetscurrently used to control
plant or human diseasesare shown in Fig. 17.2. At
first sight it might seem that there are a large number
of cellular targets that could be exploited for disease
control. But in practice the range is limited. Many
of the compounds shown in Fig. 17.2 have a very
restricted usage (shown as “R”) and are used mainly in
Japanese agriculture. If we exclude these compounds
then we are left with just five main types of antifungal
target:1 the cell membrane, because fungi are unique in
having ergosterolas their characteristic membrane
sterol;
2 the microtubules and microtubule-associated
proteins, which are disrupted by the antibiotic gri-
seofulvin, and by benzimidazole fungicides (which
have now been withdrawn);
3 mitochondrial respiration, which is targeted by
some plant fungicides;
4 fungal cell wall components, especially β1-3 glucans,
for which a new group of drugs, the echinocandins,
has recently come into use (2002);
5 various aspects of general metabolism.342 CHAPTER 17
Fig. 17.2The main cellular targets for
chemical control of fungi that cause
plant and human diseases. Compounds
shown as “(R)” have limited usage.