Wang Jiulong, Duan Xinying, Li Jing, Yuan Wenjing, Si Hongyan, Zhang Ji, Song Jie, Chen Shangxing, Wang Zongde, Liao Shengliang
East China Woody Fragrance and Flavor Engineering Research Center of National Forestry and Grassland Administration, Jiangxi Provincial Key Laboratory of Improved Variety Breeding and Efficient Utilization of Native Tree Species, College of Forestry, Jiangxi Agricultural University, Nanchang 330045, People's Republic of China.
Yichun Forestry Bureau, Yichun 336099, People's Republic of China.
J Agric Food Chem. 2024 Oct 2. doi: 10.1021/acs.jafc.4c04448.
In order to explore novel antifungal lead compounds from plant essential oil, thirty-two pinonic acid derivatives containing thiourea groups were designed and synthesized using α-pinene as a raw material. One of these pinonic acid derivatives compound exhibited noteworthy antifungal activity against (EC = 9.22 mg/L), which was comparable to that of the positive control kresoxim-methyl (EC = 9.69 mg/L). Structure-activity relationship (SAR) studies demonstrated that the introduction of thiourea groups, F atoms, and Cl atoms into the structure of pinonic acid derivatives significantly improved their antifungal activity. The antifungal test revealed that compound could effectively control pear anthracnose. It also proved that compound showed low acute oral toxicity to honeybees (LD > 100 μg/bee) and low or no cytotoxicity to LO2 and HEK293 cell lines. The preliminary mechanism of action studies revealed that compound caused mycelium deformity, increased cell membrane permeability, blocked the normal process of phospholipase C on the cell membrane, and reduced mycelium protein content. The results of molecular docking studies demonstrated the stable binding of compound to phospholipase C and chitin synthetase. This study suggested that compound could be used as a promising lead compound for the development of novel antifungal agents targeting the cellular barrier of .
为了从植物精油中探索新型抗真菌先导化合物，以α-蒎烯为原料设计并合成了32种含硫脲基团的蒎酸衍生物。其中一种蒎酸衍生物化合物对（EC = 9.22 mg/L）表现出显著的抗真菌活性，与阳性对照醚菌酯（EC = 9.69 mg/L）相当。构效关系（SAR）研究表明，在蒎酸衍生物结构中引入硫脲基团、F原子和Cl原子可显著提高其抗真菌活性。抗真菌试验表明，化合物可有效防治梨炭疽病。还证明化合物对蜜蜂的急性经口毒性较低（LD > 100 μg/蜂），对LO2和HEK293细胞系的细胞毒性较低或无细胞毒性。初步作用机制研究表明，化合物导致菌丝体畸形，增加细胞膜通透性，阻断细胞膜上磷脂酶C的正常过程，并降低菌丝体蛋白质含量。分子对接研究结果表明化合物与磷脂酶C和几丁质合成酶稳定结合。该研究表明，化合物可作为一种有前景的先导化合物，用于开发针对细胞屏障的新型抗真菌剂。
