Discovery of pinonic acid derivatives containing triazole Schiff base fragment as fungicidal candidates against Gaeumannomyces graminis var. tritici.

Background: Wheat Take-all disease seriously threatens global wheat production, while current fungicides are limited by high cost, toxicity, and emerging resistance. To reduce its threat to agricultural production and overcome the limitations of existing prevention and control methods, this study chose turpentine, a natural product with a unique structure and biological activity, to provide a promising alternative fungicide.

Results: A series of pinonic acid triazole Schiff base compounds with good antifungal activity from natural product turpentine were successfully synthesized and evaluated. Compound 4a, containing a 4-chlorophenyl substitution, exhibited strong antifungal activity against Gaeumannomyces graminis var. tritici (EC = 2.062 μg/mL). It significantly inhibited ergosterol biosynthesis by targeting CYP51 and damaging fungal cell membranes, while molecular docking confirmed strong binding with the key active site of CYP51. Two representative compounds 4a and 4a were selected for theoretical calculations to further explore the structure of activity relationships.

Conclusions: These results demonstrate that introducing a pinonic acid scaffold into triazole-thione structures yields potent, green fungicides, providing a scientific basis for the development of novel green pesticides to manage wheat Take-all disease and reduce reliance on conventional fungicides, advancing the development of more effective and environmentally friendly fungicidal candidates. © 2025 Society of Chemical Industry.