School of Pharmacy, Hunan University of Chinese Medicine, Changsha, Hunan, People's Republic of China.
TCM and Ethnomedicine Innovation and Development International Laboratory, Hunan University of Chinese Medicine, Changsha, Hunan, People's Republic of China.
J Enzyme Inhib Med Chem. 2024 Dec;39(1):2390909. doi: 10.1080/14756366.2024.2390909. Epub 2024 Aug 29.
An oxidising and substituting one-pot reaction strategy has been developed to synthesise dihydromyricetin derivatives with the aim of enhancing the inhibitory activity of dihydromyricetin against SARS-CoV-2. Different -methoxy--oxeylkyl was introduced in C-OH site and yielded eight analogs, all of them showed good inhibitory activity against SARS-CoV-2 3CL with IC values ranging from 0.72 to 2.36 μM. In the Vero E6-cell, compound has a good activity of anti-SARS-CoV-2 virus (Omicron virus BA.5) in the prevention model, with an EC of 15.84 μM, and so do compound in the therapeutic model, with an EC of 11.52 μM. The results suggest that the introduction of long chain -oxeylkyl at C-OH facilitate the inhibition of viral replication in the therapeutic model, which is consistent with the binding energies predicted from molecular docking conclusions. It implies that dihydromyricetin derivatives have the potential to become effective inhibitors of SARS-CoV-2 Omicron and other viruses.
已开发出一种氧化取代一锅反应策略，用于合成二氢杨梅素衍生物，目的是增强二氢杨梅素对 SARS-CoV-2 的抑制活性。在 C-OH 位点引入不同的 -甲氧基--氧杂己基，得到了 8 个类似物，它们对 SARS-CoV-2 3CL 的抑制活性均较好，IC 值范围为 0.72-2.36 μM。在 Vero E6 细胞中，化合物 在预防模型中对 SARS-CoV-2（奥密克戎病毒 BA.5）具有良好的抗病毒活性，EC 值为 15.84 μM；化合物 在治疗模型中也具有良好的抗病毒活性，EC 值为 11.52 μM。结果表明，在 C-OH 处引入长链 -氧杂己基有利于治疗模型中病毒复制的抑制，这与分子对接结论预测的结合能一致。这表明二氢杨梅素衍生物有可能成为 SARS-CoV-2 奥密克戎和其他病毒的有效抑制剂。
