Inspired by the application of natural products against pathogenic fungi, two series of dehydroabietyl oxime ester derivatives were synthesized using rosin as a raw material. Based on the evaluation and screening of in vitro antifungal activities against Botrytis cinerea (B. cinerea), Sclerotinia sclerotiorum, Valsa mali, Rhizoctonia solani, Fusarium oxysporum, and Alternaria alternata, compound 4f exhibited the best antifungal activity against B. cinerea, and its EC50 was 0.798 mg/L, which was lower than that of the positive control trifloxystrobin (1.112 mg/L). The in vivo antifungal activity results showed that 4f had satisfactory protective and curative effects on tomato. Physiological and biochemical studies showed that the action mechanism of compound 4f against B. cinerea is to change the morphology and the ultrastructure of the mycelium, increase the permeability of the cell membrane, and cause nucleus and mitochondrial dysfunction, thus leading to apoptosis. In addition, qualitative and quantitative structure–activity relationship studies showed that the inductive and conjugative interactions between compound 4f and the target receptor form an electron transfer process, thereby achieving an antifungal effect. These results indicated that compound 4f, which was derived from the natural product rosin, is a novel potential fungicidal candidate against B. cinerea.

BACKGROUND The use of fungicides to protect crops from diseases is an effective method, and novel environmentally friendly plant‐derived fungicides with enhanced performance and low toxicity are urgent requirements for sustainable agriculture. RESULTS Two kinds of rosin‐based acylhydrazone compounds were designed and prepared. Based on the antifungal activity assessment against Rhizoctonia solani, Fusarium oxysporum, Phytophthora capsici, Sclerotinia sclerotiorum, and Botrytis cinerea, acylhydrazone derivatives containing a thiophene ring were screened and showed an inhibitory effect on rice R. solani. Among them, Compound 4n, with an electron‐withdrawing group on the benzene ring structure attached to the thiophene ring, showed optimal activity, and the EC50 value was 0.981 mg L−1, which was lower than that of carbendazim. Furthermore, it was indicated that 4n could affect the mycelial morphology, cell membrane permeability and microstructure, cause the generation of reactive oxygen species in fungal cells, and damage the nucleus and mitochondrial physiological function, resulting in the cell death of R. solani. Meanwhile, Compound 4n exhibited a better therapeutic effect on in vivo rice plants. However, the induction activity of 4n on the defense enzyme in rice leaf sheaths showed that 4n stimulates the initial resistance of rice plants by removing active oxygen, thereby protecting the cell membrane or enhancing the strength of the cell wall. Through the quantitative structure–activity relationship study, the quantitative chemical and electrostatic descriptors significantly affect the binding of 4n with the receptor, which improves its antifungal activity. CONCLUSION This study provides a basis for exploiting potential rosin‐based fungicides in promoting sustainable crop protection. © 2022 Society of Chemical Industry.

Two series of dehydroabietyl-1,2,4-triazole-4-Schiff-based derivatives were synthesized from rosin to control plant fungal diseases. In vitro evaluation and screening of the antifungal activity were performed using Valsa mali, Colletotrichum orbiculare, Fusarium graminearum, Sclerotinia sclerotiorum, and Gaeumannomyces graminis. Compound 3f showed excellent fungicidal activity against V. mali (EC50 = 0.537 μg/mL), which was significantly more effective than the positive control fluconazole (EC50 = 4.707 μg/mL). Compound 3f also had a considerable protective effect against V. mali (61.57%–92.16%), which was slightly lower than that of fluconazole (85.17–100%) at 25–100 μg/mL. Through physiological and biochemical analyses, the preliminary mode of action of compound 3f against V. mali was explored. Ultrastructural observation of mycelia showed that compound 3f hindered the growth of the mycelium and destroyed the ultrastructure of V. mali seriously. Conductivity analysis and laser scanning confocal microscope staining showed that compound 3f changed cell-membrane permeability and caused accumulation of reactive oxygen species. The enzyme activity results showed that compound 3f significantly inhibited the activity of CYP51 (59.70%), SOD (76.9%), and CAT (67.86%). Molecular docking identified strong interaction energy between compound 3f and crystal structures of CYP51 (−11.18 kcal/mol), SOD (−9.25 kcal/mol), and CAT (−8.79 kcal/mol). These results provide guidance for the discovery of natural product-based antifungal pesticide candidates.