Synthesis and antifungal action of new tricyclazole analogues

Melanins are very important pigments for the survival and longevity of fungi, so their biosynthesis inhibition is a new biochemical target aiming at the discovery of selective fungicides. In this work is described the synthesis of new pyrazolo-thiazolo-triazole compounds, analogues of tricyclazole (a commercial antifungal product that acts by inhibiting melanin synthesis), and their biological activity was studied on some dermatophytes and phytopathogens. The compounds poorly inhibited the growth and pigmentation of fungi tested and were less efficient than tricyclazole. Electron microscopy on Botrytis cinerea showed that treatment with the most active compound caused abnormally thickened and stratified walls in fungi, whose ultrastructure was, in contrast, generally normal. The fungus treated with tricyclazole, on the other hand, appeared to be drastically altered, so as to become completely disorganized. These results suggest that the new azole compounds employ an action mechanism similar to that of other azoles, but dissimilar to that of tricyclazole.