Oomycetes, particularly those from the genus Phytophthora, 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 of Phytophthora and template models. Herein, we generated the OSBP model of the well-reported Phytophthora capsici using AlphaFold 2 and studied the binding mechanism of OXA. Based on it, a series of OXA analogues were designed. Then, compound 2l, the most potent candidate, was successfully designed and synthesized, showing a control efficiency comparable to that of OXA. Moreover, field trial experiments showed that 2l exhibited nearly the same activity (72.4%) as OXA against cucumber downy mildew at 25 g/ha. The present work indicated that 2l could be used as a leading compound for the discovery of new OSBP fungicides.

中文翻译：

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新型氧化硫哌脯林衍生物作为氧甾醇结合蛋白抑制剂的设计与合成及其在植物病原卵菌中的应用

卵菌，特别是疫霉菌属的卵菌，对全球粮食安全和自然生态系统构成重大威胁。Oxathiapiprolin (OXA) 是一种有效的卵菌杀菌剂，针对氧甾醇结合蛋白 (OSBP)，但 OXA 的结合机制仍不清楚，由于疫霉属和模板模型的序列同一性较低，这限制了农药的设计。在此，我们使用 AlphaFold 2 生成了报道较多的辣椒疫霉的 OSBP 模型，并研究了 OXA 的结合机制。在此基础上设计了一系列OXA类似物。然后，化合物2l最有效的候选物 已成功设计和合成，显示出与 OXA 相当的防治效率。此外，田间试验表明，2l在 25 g/ha 浓度下表现出与 OXA 几乎相同的抗黄瓜霜霉病活性（72.4%）。目前的工作表明2l可以作为发现新型OSBP杀菌剂的先导化合物。