以3D-QSAR模型为导向的优化,将Pyrazole β-Ketonitrile衍生物与二乙醇部分作为新型强效的酸盐脱酶抑制剂
Liangliang Cheng1, Cong Zhou1, Qinglong Yuan1
1Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai, China.
Pest management science
|June 28, 2024
概括
研究人员开发了新的pyrazole β-ketonitrile杀菌剂,以对抗耐药性问题. 化合物A23显示出酸脱酶 (SDH) 的强烈抑制和对大米病的有效性,为新的杀菌剂开发提供了有希望的头.
科学领域:
- 农业化学科学 农业化学科学
- 药品化学 药品化学 是一个
- 控制真菌病的控制 控制真菌病的控制
背景情况:
- 酸脱酶抑制剂 (SDHI) 杀菌剂对于控制植物真菌病至关重要.
- 对现有的SDHI的抗性和交叉抗性需要开发新的化学结构.
- 当前SDHI的频繁应用和结构相似性有助于抵抗挑战.
研究的目的:
- 设计和合成新的pyrazole β-ketonitrile衍生物作为潜在的SDHI杀菌剂.
- 为了确定强大的SDH抑制剂,改善结构多样性,以克服耐药性.
- 评估新合成的化合物对植物真菌病原体的疗效.
主要方法:
- 以3D-QSAR模型为指导的合理设计.
- 合成31个pyrazole β-ketonitrile衍生物的合成,其中包括一个二乙醇部分.
- 在体外酶抑制对猪和真菌糖酸脱酶 (SDH) 的测定.
- 在体内测试对由Rhizoctonia solani引起的米病的疗效.
- 分子对接研究以阐明SDH酶的乌比奎农位点内的结合相互作用.
主要成果:
- 最优的化合物A23在体外表现出强烈的Rhizoctonia solani抑制 (EC50 = 0.0398μg/mL),与fluxapyroxad.com可比.
- 化合物A23是猪酸脱酶 (IC50 = 0.0425μm) 的强抑制剂.
- A23在体内表现出适度的保护功效,对抗大米病.
- 对接研究显示,A23通过键和π-π相互作用与R. solani SDH的乌比奎农位点结合.
结论:
- 新型β-基尼特化合物A23,包含二乙醇部分,是一种强大的酸脱酶抑制剂.
- A23代表了一种有前途的化合物,用于研究和优化下一代SDHI杀菌剂.
- 这些发现支持了pyrazole β-ketonitriles作为开发新农业化学品以打击杀菌剂耐药性的支架的潜力.
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