Squalene epoxidase (SE) was considered an important antifungal target to block ergosterol synthesis. In this study, molecular models of CASE including the homology model and the SBP were constructed, respectively. Three representative SE inhibitors were selected and docked into the active site of CASE. Subsequently, the novel SE inhibitors were designed based on the analysis of the inhibitor binding mode and the distribution of pharmacophore features. These compounds were further synthesized and tested in vitro. They exhibited a certain degree of antifungal activity, especially compound 7a-2, which also has a significant inhibitory effect on resistant fungi. Further analysis found that compound 7a-2 could inhibit SE, which is similar to naftifine. The study proved the rationality of the molecular models; they can help us design and discover more potent antifungal SE inhibitors.

中文翻译：

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分子模型的构建和评估：新型SE抑制剂的指导和设计。

角鲨烯环氧酶（SE）被认为是阻止麦角固醇合成的重要抗真菌靶标。本研究建立了CASE分子模型，包括同源性模型和SBP。选择了三种代表性的SE抑制剂并将其停靠在CASE的活性位点。随后，基于对抑制剂结合模式和药效团特征分布的分析，设计了新型SE抑制剂。这些化合物进一步合成和体外测试。它们表现出一定程度的抗真菌活性，尤其是化合物7a-2，它对耐药真菌也具有明显的抑制作用。进一步分析发现化合物7a-2可以抑制SE，这类似于萘替芬。研究证明了分子模型的合理性。他们可以帮助我们设计和发现更有效的抗真菌SE抑制剂。