Borneol-Containing Cinnamic Acid Derivatives from Pinus yunnanensis as CYP51 Inhibitors: Design, Synthesis, and
Danling Huang1, Zhenling Yuan1, Xi Han1
1Institute for Inheritance-Based Innovation of Chinese Medicine, Guangdong Provincial Key Laboratory of Chinese Medicine Ingredients and Gut Microbiomics, School of Pharmacy, Shenzhen University Medical School, Shenzhen 518060, P. R. China.
Journal of Agricultural and Food Chemistry
|November 5, 2025
Summary
New fungicidal agents were developed from Pinus yunnanensis. Derivative SX-6-6 showed potent activity against key plant pathogens and was safe for rodents, offering a novel precursor for crop protection.
Area of Science:
- Agricultural Science
- Organic Chemistry
- Mycology
Background:
- Pinus yunnanensis exudates contain bioactive compounds.
- Cinnamic acid derivatives are explored for fungicidal properties.
- SX-6, a borneol-bearing cinnamic acid derivative, serves as a lead compound.
Purpose of the Study:
- To design and synthesize novel fungicidal agents based on SX-6.
- To evaluate the fungicidal efficacy of SX-6 derivatives against plant pathogenic fungi.
- To investigate the mechanism of action and safety profile of promising derivatives.
Main Methods:
- Synthesis of 35 SX-6 derivatives.
- In vitro fungicidal activity testing (EC50 values) against Botrytis cinerea, Sclerotinia sclerotiorum, and Curvularia mebaldsii.
- Photoreaction to synthesize Z-isomer SX-6-6i.
- In vivo protective effect assays.
- Mechanism of action studies (CYP51 inhibition, ergosterol synthesis).
- Acute toxicity tests in rodents.
Main Results:
- SX-6-6 exhibited potent fungicidal activity (EC50: 3.29-8.22 mg/L) against tested fungi, comparable or superior to hymenoxazol.
- SX-6-6i showed enhanced activity against S. sclerotiorum (EC50: 2.97 mg/L).
- Both SX-6-6 and SX-6-6i demonstrated excellent in vivo protective effects.
- SX-6-6 acts by inhibiting 14α-demethylase (CYP51), disrupting ergosterol synthesis and fungal cell membranes.
- SX-6-6 showed no acute toxicity in rodents at 1 g/kg.
Conclusions:
- Novel fungicidal derivatives were successfully synthesized from SX-6.
- SX-6-6 and SX-6-6i represent promising candidates for new fungicidal agents.
- The study provides the first report on active derivatives from P. yunnanensis for plant protection.
- These findings offer a novel structural precursor for designing effective and safe fungicidal agents.
