State Key Laboratory of Elemento-Organic Chemistry, College of Chemistry, Nankai University, Tianjin 300071, China.
Frontiers Science Center for New Organic Matter, College of Chemistry, Nankai University, Tianjin 300071, China.
Molecules. 2023 Jul 4;28(13):5205. doi: 10.3390/molecules28135205.
The development of new fungicides is vital for safeguarding crops and ensuring sustainable agriculture. Building on our previous finding that 4-(3,4-dichloroisothiazole)-7-hydroxy coumarins can be used as fungicidal leads, 44 novel coumarin ester derivatives were designed and synthesized to evaluate whether esterification could enhance their fungicidal activity. In vitro fungicidal bioassays indicated that compound displayed good activity against , , , and , with an EC value ranging from 2.90 to 5.56 μg/mL, comparable to the lead compound , with its EC value ranging from 1.92 to 9.37 μg/mL. In vivo bioassays demonstrated that compounds , and showed comparable, excellent efficacy against at a dose of 25 µg/mL. Our research shows that the esterification of 4-(3,4-dichloroisothiazole) 7-hydroxycoumarins results in a fungicidal activity equivalent to that of its lead compounds. Furthermore, our density functional theory (DFT) calculations and 3D-QSAR modeling provide a rational explanation of the structure-activity relationship and offer valuable insights to guide further molecular design.
新型杀真菌剂的开发对于保护作物和确保可持续农业至关重要。基于我们之前发现的 4-(3,4-二氯异噻唑)-7-羟基香豆素可用作杀真菌先导化合物的发现，设计并合成了 44 种新型香豆素酯衍生物，以评估酯化是否可以提高它们的杀真菌活性。体外杀真菌生物测定表明，化合物 对 、 、 、 和 显示出良好的活性，EC 值范围为 2.90 至 5.56 μg/mL，与先导化合物 相当，其 EC 值范围为 1.92 至 9.37 μg/mL。体内生物测定表明，化合物 、 和 在 25 µg/mL 剂量下对 表现出相当优异的防治效果。我们的研究表明，4-(3,4-二氯异噻唑)-7-羟基香豆素的酯化导致其杀真菌活性与先导化合物相当。此外，我们的密度泛函理论（DFT）计算和 3D-QSAR 建模为构效关系提供了合理的解释，并为进一步的分子设计提供了有价值的见解。
