Discovery of Novel Oxathiapiprolin Derivatives as Potent Fungicide Candidates,Journal of Agricultural and Food Chemistry

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Discovery of Novel Oxathiapiprolin Derivatives as Potent Fungicide Candidates
Journal of Agricultural and Food Chemistry ( IF 5.7 ) Pub Date : 2024-07-24 , DOI: 10.1021/acs.jafc.4c03971
Li-Ming Zhou ₁ , Jing-Fang Yang ₁ , Hong-Hao Li ₁ , Wei Chen ₁ , Yi-Wen Li ₁ , Xiao-Lei Zhu ₁ , Guang-Fu Yang _{1,

2}

Affiliation

Oxathiapiprolin (OXA), which targets the oxysterol-binding protein (OSBP), is an outstanding piperidinyl thiazole isoxazoline (PTI) fungicide that can be used to control oomycetes diseases. In this study, starting from the structure of OXA, a series of novel OSBP inhibitors were designed and synthesized by introducing an indole moiety to replace the pyrazole in OXA. Finally, compound b24 was found to exhibit the highest control effect (82%) against cucumber downy mildew (CDM) in the greenhouse at a very low dosage of 0.069 mg/L, which was comparable to that of OXA (88%). Furthermore, it showed better activity against potato late blight (PLB) than other derivatives of indole. The computational results showed that the R-conformation of b24 should be the dominant conformation binding to PcOSBP. The results of the present work indicate that the 3-fluorine-indole ring is a favorable fragment to increasing the electronic energy when binding with PcOSBP. Furthermore, compound b24 could be used as a lead compound for the discovery of new OSBP inhibitors.

中文翻译：

发现新型 Oxathiapiprolin 衍生物作为有效候选杀菌剂

Oxathiapiprolin (OXA) 以氧甾醇结合蛋白 (OSBP) 为靶点，是一种出色的哌啶基噻唑异恶唑啉 (PTI) 杀菌剂，可用于控制卵菌疾病。本研究从OXA的结构出发，通过引入吲哚部分取代OXA中的吡唑，设计合成了一系列新型OSBP抑制剂。最后，发现化合物b24在0.069 mg/L的极低剂量下对温室中的黄瓜霜霉病（CDM）表现出最高的防效（82%），与OXA的防效（88%）相当。此外，它比其他吲哚衍生物表现出更好的抗马铃薯晚疫病（PLB）活性。计算结果表明b24的R构象应该是与PcOSBP结合的主要构象。目前的工作结果表明，3-氟吲哚环是与PcOSBP结合时增加电子能量的有利片段。此外，化合物b24可用作发现新 OSBP 抑制剂的先导化合物。

更新日期：2024-07-24

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