On the mode of action of the fungicide etridiazole

Etridiazole (5-ethoxy-3(trichloromethyl)-1,2,4-thiadiazole) is a fungicide primarily effective against fungi of the Oomycete group. After addition of the compound to the medium, growth of Mucor mucedo was impaired almost immediately. Oxygen uptake of the mycelia decreased only slightly at growth-inhibiting concentrations. Respiration of isolated mitochondria of Mucor was inhibited about 50% by high concentrations of the fungicide, while the respiratory control quotient remained constant. In contrast, rat liver mitochondria were not very sensitive to etridiazole. Etridiazole stimulates the hydrolysis of membrane-bound phospholipids to free fatty acids and lysophosphatides in isolated mitochondria of Mucor. Procaine, a well-known inhibitor of phospholipases, acts as an antidote for etridiazole in growth tests as well as in the hydrolysis of phosphatidylcholine by isolated mitochondria. Calcium ions in millimolar concentrations act like procaine. Therefore, it was assumed that the fungistatic effect of etridiazole was mainly caused by an activation of phospholipases in the mitochondrial membranes. Moreover, under the influence of etridiazole, a lipid peroxidation of membranes is observed. Tocopherol acts as an antidote. This could be the primary toxic effect in the mechanism of action of this fungicide. The enzymes involved are not yet identified.