Design and Synthesis of Novel Oxathiapiprolin Derivatives as Oxysterol Binding Protein Inhibitors and Their Application in Phytopathogenic Oomycetes
Design and Synthesis of Novel Oxathiapiprolin Derivatives as Oxysterol Binding Protein Inhibitors and Their Application in Phytopathogenic Oomycetes
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DOI：
10.1021/acs.jafc.3c00990
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发表时间：
2023-06-07
影响因子：
6.1
通讯作者：
Yang，Guang-Fu
中科院分区：
文献类型：
--
作者：
Li，Jian-Long;Yang，Jing-Fang;Yang，Guang-Fu
卵菌，特别是疫霉属的卵菌，对全球粮食安全和自然生态系统构成重大威胁。草硫菌素(OXA)是一种有效的针对氧固醇结合蛋白(OSBP)的卵菌杀菌剂，但其结合机制尚不清楚，这限制了杀虫剂的设计，这是由于疫霉和模板模型序列同源性较低造成的。在这里，我们使用AlphaFold 2建立了报道较多的辣椒疫霉的OSBP模型，并研究了OXA的结合机理。在此基础上，设计了一系列OXA类似物。然后，成功地设计合成了最具潜力的候选化合物2l，其控制效率与OXA相当。田间试验表明，2L对黄瓜霜霉病的防治效果与OXA相当(72.4%)，用量为25g/ha。本工作表明，21可以作为发现新的OSBP杀菌剂的先导化合物。
Oomycetes, particularly those from the genusPhytophthora, are significant threats to global food security and natural ecosystems. Oxathiapiprolin (OXA) is an effective oomycete fungicide that targets an oxysterol binding protein (OSBP), while the binding mechanism of OXA is still unclear, which limits the pesticide design, induced by the low sequence identity ofPhytophthoraand template models. Herein, we generated the OSBP model of the well-reportedPhytophthora capsiciusing AlphaFold 2 and studied the binding mechanism of OXA. Based on it, a series of OXA analogues were designed. Then, compound2l, the most potent candidate, was successfully designed and synthesized, showing a control efficiency comparable to that of OXA. Moreover, field trial experiments showed that2lexhibited nearly the same activity (72.4%) as OXA against cucumber downy mildew at 25 g/ha. The present work indicated that2lcould be used as a leading compound for the discovery of new OSBP fungicides.