Sterols fungicides

Kato, T. (1986). Sterol biosynthesis in fungi A target for broad spectrum fungicides. In Chemistry of Plant Protection No. 1 Sterol Biosynthesis Inhibitors and Anti-feeding Compounds. Berlin Springer-Verlag, 1-24. 

Imibenconazole is a triazole fungicide exhibiting direct cell membrane destruction as well as sterol biosynthesis inhibition for controlling major diseases of fruits, vegetables, cereals, ornamentals and turf. 

Although termed "SI" or "EBI" compounds, the latter referring to ergosterol biosythesis inhibitors, these compounds do not all inhibit ergosterol biosynthesis at the same metabolic site (Fig. 2). For instance, the fungicide tridemorph, unlike most EBI compounds, does not inhibit demethylation at C-14 but rather it apparently prevents the A A isomerization resulting in the accumulation of A containing sterols in treated cells (3). 

As an example of the techniques/ Figure 4 shows a comparison of the fungicidally active RR- diclobutrazol with the natural substrate lanosterol. The sterol C-32 alcohol is chelated to the iron porphyrin. The three central features of the model cytochrome P-450 can be elucidated. The hydrophobic binding site, the polar region between this hydrophobic region and the heme plane/ and a common complexation to the porphyrin iron. 

Morpholines such as tridemorph (9.112) attack sterol biosynthesis via A -reductase enzyme inhibition and are valuable agricultural fungicides. 

W. Koller, Antifungal Agents with Target Sites in Sterol Function and Biosynthesis , in Target Sites of Fungicide Action , ed. W. Koller, CRC Press, Boca Raton, FL, 1992, pp. 119-206. 

Well over 100 plant pathogens have become resistant to various fungicides under field conditions. Failure of the acyl alanines, benzimidazoles, thiophanates, carboxanilides, dicarboximides, hydroxypyrimidines, some organophosphates, and most of the antibiotics has occurred. In other cases, a moderate decrease in sensitivity without a rapid loss of disease control has been observed as in the case of sterol biosynthesis inhibitors (triazoles, pyrimidines, and imidazoles) and organophosphates. The most effective approach is to use fungicides having different modes of action in combination,... 

In research for new fungicides and antimycotics, one has to look for a concept for pathogen-specific inhibitors. This means that inhibition of sterol synthesis should not take place at any common step the aim is to only inhibit pathogen-specific steps in biosynthesis. The reason for this is to minimize the risk of human toxicity. If one compares the biosynthesis of mammalian cholesterol to that of ergosterol, the main sterol of pathogenic fungi, it becomes obvious that there are at least four pathogen-specific steps to be inhibited. 

In the next part of our research on EBI-fungicides, we restricted ourselves to Pyricularia oryzae since from our point of view the In vitro results with that organism are representative and the test procedure is rather simple. The test chemical is applied in a suitable concentration to the culture medium which is then inoculated from an untreated pre-culture. After a 24-hour fermentation, the cells are separated from the culture filtrate by centrifugation, resuspended in a chloroform/methanol-mixture and homogenized using an ultraturrax treatment. After this extraction procedure, the sterol-conjugates are split to free sterols by a potassium-hydroxide treatment. Adsorption of the sterols to a Sep-pak column and step-wise desorption leads to a sterol fraction which can be analyzed directly by gas chromatography on a SE-30 capillary column. 

Hickey, K.D., and Yoder, K.S. 1981. Field Performance of sterol-inhibiting fungicides against apple powdery mildew in the mid-Atlantic apple growing region. Plant Dis. 65 1002-1006. 

Jones, A.L. 1981. Fungicide resistance Past experience with benomyl and dodine and future concerns with sterol inhibitors. Plant Dis. 65 990-992. 

Schwabe, W.F.S., Jones, A.L., and Jonker, J.P. 1984. Greenhouse evaluation of the curative and protective action of sterol-inhibiting fungicides against apple scab. Phytopathology 74 249-252. 

Yoder, K.S., and Hickey, K.D. 1981. Sterol-inhibiting fungicides for control of certain diseases of apple in the Cumberland- Shenandoah region. Plant Dis. 65 998-1001. 

Siegel, M. R. 1981. Sterol-inhibiting fungicides Effects on sterol biosynthesis and sites of action. Plant Disease 65 986-989. 

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