Synthesis of antifungal 5-anilino-1,2,4-oxadiazoles and 5-anilino-1,2,4-thiadiazoles, and their inhibitory effects on fungal sterol biosynthesis

In the screening process we found that two 1,2,4-oxadiazole compounds showe d antifungal activity against Trychophyton mentagrophytes. Microscopic obse rvation revealed that these compounds inhibited mycelial growth with morpho logical changes without inhibition of germination. When treated with the ox adiazoles, ergosterol of Candida albicans decreased strikingly and much squ alene was accumulated. These results firmly suggested that the compounds we re new squalene epoxidase inhibitors. We synthesized the related oxadiazole s and thiadioazoles having various substituents to investigate the structur e-activity relationships. Among the synthesized compounds, 3-(2,6-dichlorop henyl)-5-(4-chforoanilino)-1,2,4-thiadiazole (51) showed the highest fungic idal activity against Botrytis cinerea, and accumulated squalene remarkably . This compound is of interest as a new lead of squalene epoxidase inhibito rs.