A series of flavonol derivatives containing benzothiazole were designed and synthesized. The structures of all the compounds were characterized by NMR and HRMS. The results of the activity assay showed that some of the target compounds possessed outstanding in vivo antiviral activity against the tobacco mosaic virus (TMV). Among them, the median effective concentration (EC₅₀) of L20 was 90.5 and 202.2 μg/mL for curative and protective activity against TMV, respectively, which was better than that of ningnanmycin (NNM: 252.0 and 204.2 μg/mL). The results of microcalorimetric thermophoresis (MST) and molecular docking experiments indicate that L20 binds TMV-CP more strongly than NNM; density functional theory (DFT) calculation the indicating that L20 is more chemical reactivity than NNM. In addition, malondialdehyde (MDA) and superoxide dismutase assay (SOD) activity measurements also fully confirmed that L20 stimulated the plant immune system and strengthened the plant's resistance to diseases by lowering the MDA content and increasing the SOD activity. Furthermore, the chlorophyll content test experiment found that L20 could reduce the destructive effect of viruses on chloroplasts, increase the content of chlorophyll, and promote photosynthesis. In conclusion, above experimental results suggested that flavonol derivatives containing benzothiazole could be further investigated as new plant virus antiviral drugs.

Graphical abstract

中文翻译：

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基于类黄酮-苯并噻唑的高效抗病毒药物的发现 TMV

设计合成了一系列含有苯并噻唑的黄酮醇衍生物。通过 NMR 和 HRMS 对所有化合物的结构进行表征。活性测定结果表明，一些靶化合物对烟草花叶病毒 （TMV） 具有突出的体内抗病毒活性。其中，L20 对 TMV 的疗效和保护活性的中位有效浓度 （EC₅₀） 分别为 90.5 和 202.2 μg/mL，优于宁南霉素 （NNM： 252.0 和 204.2 μg/mL）。微量热泳 （MST） 和分子对接实验的结果表明，L20 与 TMV-CP 的结合比 NNM 更强;密度泛函理论 （DFT） 计算表明 L20 的化学反应性高于 NNM。此外，丙二醛 （MDA） 和超氧化物歧化酶测定 （SOD） 活性测定也充分证实 L20 通过降低 MDA 含量和增加 SOD 活性来刺激植物免疫系统并增强植物对病害的抵抗力。此外，叶绿素含量测试实验发现，L20 可以减少病毒对叶绿体的破坏作用，增加叶绿素含量，促进光合作用。综上所述，上述实验结果表明，含有苯并噻唑的黄酮醇衍生物可以作为新的植物病毒抗病毒药物进行进一步研究。

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