Hu Chunmei, Shen Dan, Qiu Yujiao, Tian Fang, Hu Qingxue, Pan Xiaoyan, Yang Ying, Peng Wanqiu, Ruan Xianghui, Xue Wei
State Key Laboratory of Green Pesticide, Center for R&D of Fine Chemicals of Guizhou University, Guiyang, 550025, China.
Mol Divers. 2025 Aug 15. doi: 10.1007/s11030-025-11318-z.
A series of flavonol derivatives containing pyrazole oxime ether moieties were designed and synthesized. In vivo antiviral assays revealed that some compounds exhibited remarkable inhibitory effects against tobacco mosaic virus (TMV). Among them, Both the curative activity (EC = 88.9 μg/mL) and protective activity (EC = 107.5 μg/mL) of H13 were shown to be significantly superior to those of the reference agent ningnanmycin (NNM) (208.4 μg/mL and 190.1 μg/mL, respectively). Mechanistic studies indicated that both microscale thermophoresis (MST) experiments and molecular docking results demonstrate that H13 exhibits stronger binding capacity and affinity for the tobacco mosaic virus coat protein (TMV-CP) than NNM. Density functional theory (DFT) calculations further revealed higher chemical reactivity of H13. Additionally, H13 treatment significantly enhanced chlorophyll content in tobacco leaves, improving photosynthetic efficiency, while reduced malondialdehyde (MDA) levels indicated strengthened disease resistance. ADME property prediction suggested no significant ocular toxicity or hERG inhibition risk for H13. Plant experiments confirmed that H13 caused no adverse effects on tobacco seed germination or leaf growth.
设计并合成了一系列含有吡唑肟醚部分的黄酮醇衍生物。体内抗病毒试验表明，一些化合物对烟草花叶病毒（TMV）表现出显著的抑制作用。其中，H13的治疗活性（EC = 88.9 μg/mL）和保护活性（EC = 107.5 μg/mL）均显著优于对照药剂宁南霉素（NNM）（分别为208.4 μg/mL和190.1 μg/mL）。机理研究表明，微量热泳动（MST）实验和分子对接结果均表明，H13对烟草花叶病毒外壳蛋白（TMV-CP）的结合能力和亲和力均强于NNM。密度泛函理论（DFT）计算进一步揭示了H13具有更高的化学反应活性。此外，H13处理显著提高了烟草叶片中的叶绿素含量，提高了光合效率，同时丙二醛（MDA）水平降低表明抗病性增强。ADME性质预测表明，H13没有明显的眼毒性或hERG抑制风险。植物实验证实，H13对烟草种子萌发或叶片生长没有不良影响。
