计算导向的分子设计,合成和酸脱酶抑制剂的杀菌活性
Kun Li1,2, Shuang Hong1,2, Zhenwu Yu1,2
1State Key Laboratory of Elemento-Organic Chemistry, College of Chemistry, Nankai University, Tianjin 300071, P. R. China.
Journal of agricultural and food chemistry
|December 4, 2023
概括
酸脱酶抑制剂 (SDHI) 是重要的杀菌剂. 这项研究使用了计算方法和合成来发现新的SDHI,识别了针对真菌病原体的强效化合物F9和F4.
科学领域:
- 农业化学 农业化学
- 计算化学计算化学
- 菌类学 菌类学是指菌类学.
背景情况:
- 酸脱酶抑制剂 (SDHI) 是一种重要的杀菌剂,向致病性真菌中的线粒体酸脱酶 (SDH).
- 开发新的SDHI对于可持续农业和管理杀菌剂耐药性至关重要.
研究的目的:
- 通过计算建模和实验验证,指导新的酸脱酶抑制剂 (SDHI) 的创新.
- 识别具有强大作用于关键植物病原菌的新型SDHI化合物,例如*Rhizoctonia cerealis*和*Botrytis cinerea*.
主要方法:
- 利用分子对接来研究SDH抑制剂结合模式.
- 对33种化合物进行了三维定量结构-活性关系 (3D-QSAR) 研究,对抗R. cerealis.
- 采用分子动力学 (MD) 模拟和结合性自由能计算 (MM/GBSA) 来评估复杂的稳定性和相互作用.
主要成果:
- 分子对接和MD模拟揭示了SDH抑制剂复合物的稳定性,其中范德瓦尔斯和脂性相互作用是关键.
- 3D-QSAR模型确定了结构-活性关系,指导了新化合物的设计.
- 合成了12种新型化合物;F9对*R. cerealis* (EC50 = 9.43μg/mL) 具有高活性,F4,F5和F9对*Botrytis cinerea* (EC50 = 5.80,3.17和1.63μg/mL) 具有显著活性.
结论:
- 计算方法,包括分子对接,3D-QSAR和MD模拟,有效地引导了新型SDHI的发现.
- 已识别的化合物,特别是F9,F4和F5,表现出与现有商业产品相比的有前途的杀菌活性.
- 这项研究为下一代SDHI杀菌剂的合理设计提供了宝贵的见解和策略.
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