Zeng Rong, Zou Xiuxiu, Huang Cong, Si Hongyan, Song Jie, Zhang Ji, Luo Hai, Wang Zongde, Wang Peng, Fan Guorong, Rao Xiaoping, Liao Shengliang, Chen Shangxing
College of Forestry, Jiangxi Agricultural University; East China Woody Fragrance and Flavor Engineering Research Center of National Forestry and Grassland Administration; Camphor Engineering Research Center of National Forestry and Grassland Administration/Jiangxi Province, Nanchang 330045, People's Republic of China.
Department of Natural Sciences, University of Michigan-Flint, 303E Kearsley, Flint, Michigan 48502, United States.
J Agric Food Chem. 2023 Feb 9. doi: 10.1021/acs.jafc.2c07851.
Although much progress has been made in developing botanical fungicides to combat fungal diseases in crops, there remains a great need to improve the efficiency and long-term safety of these fungicides. This study proposes a novel strategy for designing citral-thiourea derivatives that feature such desirable properties. The motivation of the work herein was to enhance the antifungal activity of citral against by exploiting the synergistic effect that arises from combining citral and thiourea compounds, thereby producing citral-thiourea derivatives that exhibit good long-term safety. The results revealed that the generated compounds , , , , and showed remarkable antifungal activities against , with corresponding EC values reaching 0.16, 1.66, 1.37, 4.76, and 4.60 mg/L, respectively, showing that the compounds significantly outperformed both the positive control kresoxim-methyl and the commercially available fungicide carbendazim. Furthermore, compound showed stronger protective efficacy against than carbendazim on mango fruit at 25 mg/L. Investigating the preliminary structure-activity relationship (SAR) of the compounds also revealed that the citral-thiourea derivatives exhibited higher antifungal activities against compared to citral and thiourea compounds. This reinforcement of antifungal activity observed in the derivatives was found to be attributable to the two characteristics of low molecular size and the presence of a fluorine atom in the meta-position of the benzene ring. Beyond this, it was determined from QSAR that two molecular descriptors (the Kier-Hall index (order 3) and Tot dipole of the molecules) were negatively related to the antifungal activity of the citral-thiourea derivatives, while one other (the maximum resonance energy of a C-H bond) was positively related to their antifungal activity. More importantly, the citral-thiourea derivatives with high antifungal activities (, compounds , , , , , , and ) exhibited negligible cytotoxicity to LO2 and HEK293T cell lines. The antifungal mechanism of the generated citral-thiourea derivatives was investigated by scanning electron microscopy (SEM) and relative conductivity. The derivatives were found to affect mycelial morphology and increase fungal cell membrane permeability, thereby resulting in the destruction of fungal cell membranes. These promising results provide novel insights into the study and potential application value of citral-thiourea derivatives as high-efficiency antifungal agents against .
尽管在开发用于防治作物真菌病害的植物源杀菌剂方面已经取得了很大进展，但仍迫切需要提高这些杀菌剂的效率和长期安全性。本研究提出了一种设计具有此类理想特性的柠檬醛 - 硫脲衍生物的新策略。本文工作的动机是通过利用柠檬醛和硫脲化合物结合产生的协同效应来增强柠檬醛对[具体真菌名称未给出]的抗真菌活性，从而制备出具有良好长期安全性的柠檬醛 - 硫脲衍生物。结果表明，生成的化合物[具体化合物名称未给出]、[具体化合物名称未给出]、[具体化合物名称未给出]、[具体化合物名称未给出]和[具体化合物名称未给出]对[具体真菌名称未给出]表现出显著的抗真菌活性，相应的EC值分别达到0.16、1.66、1.37、4.76和4.60 mg/L，表明这些化合物明显优于阳性对照嘧菌酯和市售杀菌剂多菌灵。此外，在25 mg/L时，化合物[具体化合物名称未给出]对芒果果实上的[具体真菌名称未给出]的保护效果比多菌灵更强。对这些化合物的初步构效关系（SAR）研究还表明，与柠檬醛和硫脲化合物相比，柠檬醛 - 硫脲衍生物对[具体真菌名称未给出]表现出更高的抗真菌活性。在衍生物中观察到的这种抗真菌活性增强归因于低分子尺寸和苯环间位存在氟原子这两个特征。除此之外，通过定量构效关系（QSAR）确定，两个分子描述符（Kier - Hall指数（3级）和分子的总偶极矩）与柠檬醛 - 硫脲衍生物的抗真菌活性呈负相关，而另一个（C - H键的最大共振能）与它们的抗真菌活性呈正相关。更重要的是，具有高抗真菌活性的柠檬醛 - 硫脲衍生物（[具体化合物名称未给出]、化合物[具体化合物名称未给出]、[具体化合物名称未给出]、[具体化合物名称未给出]、[具体化合物名称未给出]、[具体化合物名称未给出]、[具体化合物名称未给出]和[具体化合物名称未给出]）对LO2和HEK293T细胞系的细胞毒性可忽略不计。通过扫描电子显微镜（SEM）和相对电导率研究了生成的柠檬醛 - 硫脲衍生物的抗真菌机制。发现这些衍生物会影响菌丝形态并增加真菌细胞膜通透性，从而导致真菌细胞膜被破坏。这些有前景的结果为柠檬醛 - 硫脲衍生物作为针对[具体真菌名称未给出]的高效抗真菌剂的研究和潜在应用价值提供了新的见解。
