Shanxi Key Laboratory of Integrated Pest Management in Agriculture, College of Plant Protection, Shanxi Agricultural University, Taigu 030801, Shanxi Province, P. R. China.
Shanxi Key Laboratory for Modernization of TCVM, College of Veterinary Medicine, Shanxi Agricultural University, Taigu 030801, Shanxi Province, P. R. China.
J Agric Food Chem. 2023 Jul 26;71(29):11239-11251. doi: 10.1021/acs.jafc.3c02435. Epub 2023 Jul 14.
As part of our ongoing efforts to discover novel agricultural fungicidal candidates from natural sesquiterpene lactones, in the present work, sixty-three xanthatin-based derivatives containing a arylpyrazole, arylimine, thio-acylamino, oxime, oxime ether, or oxime ester moiety were synthesized. Their structures were well characterized by H and C nuclear magnetic resonance and high-resolution mass spectrometry, while the absolute configurations of compounds and were further determined by single-crystal X-ray diffraction. Meanwhile, the antifungal activities of the prepared compounds against several phytopathogenic fungi were investigated using the spore germination method and the mycelium growth rate method . The bioassay results illustrated that compounds , , and exhibited excellent inhibitory activity against the tested fungal spores and displayed remarkable inhibitory effects on fungal mycelia. Compounds and exhibited more potent inhibitory activity (IC = 1.1 and 24.8 μg/mL, respectively) against the spore of than their precursor xanthatin (IC = 37.6 μg/mL), wherein the antifungal activity of compound was 34-fold higher than that of xanthatin and 71-fold higher than that of the positive control, difenoconazole (IC = 78.5 μg/mL). Notably, compound also demonstrated broad-spectrum inhibitory activity against the four tested fungal spores. Meanwhile, compounds , , , and showed prominent inhibitory activity against the mycelia of with the EC values of 2.3, 11.7, 11.1, and 3.0 μg/mL, respectively, whereas the EC value of xanthatin was 14.8 μg/mL. Additionally, compounds and exhibited good therapeutic and protective effects against with values of 55.4 and 62.8%, respectively. The preliminary structure-activity relationship analysis revealed that the introduction of oxime, oxime ether, or oxime ester structural fragment at the C-4 position of xanthatin or the introduction of a chlorine atom at the C-3 position of xanthatin might be significantly beneficial to antifungal activity. In conclusion, the comprehensive investigation indicated that partial xanthatin-based derivatives from this study could be considered for further exploration as potential lead structures toward developing novel fungicidal candidates for crop protection.
作为从天然倍半萜内酯中发现新型农用杀真菌剂候选物的持续努力的一部分，本工作合成了 63 种含有芳基吡唑、芳基亚胺、硫代酰氨基、肟、肟醚或肟酯部分的 xanthatin 类衍生物。它们的结构通过氢核和碳核磁共振以及高分辨率质谱得到了很好的表征，而化合物和的绝对构型通过单晶 X 射线衍射进一步确定。同时，采用孢子萌发法和菌丝生长速率法研究了所制备化合物对几种植物病原菌的抑菌活性。生物测定结果表明，化合物、和表现出对测试真菌孢子的优异抑制活性，并对真菌菌丝显示出显著的抑制作用。化合物和表现出更强的抑制活性（IC = 1.1 和 24.8 μg/mL，分别）对测试真菌孢子的抑制作用比其前体 xanthatin（IC = 37.6 μg/mL）更强，其中化合物的抑菌活性比 xanthatin 高 34 倍，比阳性对照 difenoconazole（IC = 78.5 μg/mL）高 71 倍。值得注意的是，化合物也表现出对四种测试真菌孢子的广谱抑制活性。同时，化合物、、、和对的菌丝表现出显著的抑制活性，EC 值分别为 2.3、11.7、11.1 和 3.0 μg/mL，而 xanthatin 的 EC 值为 14.8 μg/mL。此外，化合物和对表现出良好的治疗和保护效果，抑制率分别为 55.4%和 62.8%。初步的构效关系分析表明，在 xanthatin 的 C-4 位引入肟、肟醚或肟酯结构片段或在 xanthatin 的 C-3 位引入氯原子可能对抑菌活性有显著的益处。总之，全面的调查表明，本研究中的部分 xanthatin 类衍生物可作为进一步探索的潜在候选物，以开发用于作物保护的新型杀真菌剂。
