Turning potential natural products into value-added fungicides is a bioactivity-guided mixed synthesis method. Thirty-two derivatives were designed and synthesized to improve the potential use of the osthole, a natural coumarin pharmacophore. Compound Os14 with 3-ClPh showed a high in vitro and in vivo antifungal activity than other derivatives. The preliminary structure-activity relationships (SARs) demonstrated that compounds with a short aliphatic chain or electron-withdrawing groups on phenyl ring would have more desirable potency. Meanwhile, the quantitative structure-activity relationship (QSAR) model (R2 = 0.928, F = 83.54, S2 = 0.0042) were performed using Gaussian and CODESSA software with optimal conformers and heuristic regression analysis, which revealed a correlation of antifungal activity and molecular structures. Thus, these results laid the foundation for further design of improved crop-protection agents based on osthole scaffold.

中文翻译：

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基于天然蛇床子素的酯衍生物作为潜在的杀菌剂：设计、合成和定量构效关系 (QSAR)

将潜在的天然产物转化为增值杀菌剂是一种生物活性引导的混合合成方法。设计并合成了 32 种衍生物，以提高蛇床子素（一种天然香豆素药效团）的潜在用途。具有 3-ClPh 的化合物Os14显示出比其他衍生物高的体外和体内抗真菌活性。初步的构效关系 (SAR) 表明，在苯环上具有短脂肪链或吸电子基团的化合物将具有更理想的效力。同时，定量构效关系（QSAR）模型（R 2 = 0.928, F = 83.54, S 2= 0.0042) 是使用 Gaussian 和 CODESSA 软件进行的，具有最佳构象异构体和启发式回归分析，揭示了抗真菌活性和分子结构的相关性。因此，这些结果为进一步设计基于蛇床子支架的改良作物保护剂奠定了基础。