Design, synthesis, and biological activity evaluation of dihydromyricetin derivatives against SARS-CoV-2-Omicron virus

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 ω-methoxy-ω-oxeylkyl was introduced in C7-OH site and yielded eight analogs, all o...

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Main Authors: Cong Wu, Qi Jiang, Hui Zhong, Xudong Zhou, Leping Liu, Tong Pan, Chao Liu, Wei Wang, Wenbing Sheng
Format: Article
Language:English
Published: Taylor & Francis Group 2024-12-01
Series:Journal of Enzyme Inhibition and Medicinal Chemistry
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Online Access:https://www.tandfonline.com/doi/10.1080/14756366.2024.2390909
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author Cong Wu
Qi Jiang
Hui Zhong
Xudong Zhou
Leping Liu
Tong Pan
Chao Liu
Wei Wang
Wenbing Sheng
author_facet Cong Wu
Qi Jiang
Hui Zhong
Xudong Zhou
Leping Liu
Tong Pan
Chao Liu
Wei Wang
Wenbing Sheng
author_sort Cong Wu
collection DOAJ
description 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 ω-methoxy-ω-oxeylkyl was introduced in C7-OH site and yielded eight analogs, all of them showed good inhibitory activity against SARS-CoV-2 3CLpro with IC50 values ranging from 0.72 to 2.36 μM. In the Vero E6-cell, compound 3 has a good activity of anti-SARS-CoV-2 virus (Omicron virus BA.5) in the prevention model, with an EC50 of 15.84 μM, and so do compound 10 in the therapeutic model, with an EC50 of 11.52 μM. The results suggest that the introduction of long chain ω-oxeylkyl at C7-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.
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institution Kabale University
issn 1475-6366
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language English
publishDate 2024-12-01
publisher Taylor & Francis Group
record_format Article
series Journal of Enzyme Inhibition and Medicinal Chemistry
spelling doaj-art-b8c4afc4f0714be49ec04784f514c3292024-12-26T09:30:44ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742024-12-0139110.1080/14756366.2024.2390909Design, synthesis, and biological activity evaluation of dihydromyricetin derivatives against SARS-CoV-2-Omicron virusCong Wu0Qi Jiang1Hui Zhong2Xudong Zhou3Leping Liu4Tong Pan5Chao Liu6Wei Wang7Wenbing Sheng8School of Pharmacy, Hunan University of Chinese Medicine, Changsha, Hunan, People’s Republic of ChinaSchool of Pharmacy, Hunan University of Chinese Medicine, Changsha, Hunan, People’s Republic of ChinaSchool of Pharmacy, Hunan University of Chinese Medicine, Changsha, Hunan, People’s Republic of ChinaSchool of Pharmacy, Hunan University of Chinese Medicine, Changsha, Hunan, People’s Republic of ChinaTCM and Ethnomedicine Innovation and Development International Laboratory, Hunan University of Chinese Medicine, Changsha, Hunan, People’s Republic of ChinaSchool of Pharmacy, Hunan University of Chinese Medicine, Changsha, Hunan, People’s Republic of ChinaZhangjiajie Meicha Technology Research Center Hunan Qiankun Biotechnology Co., Ltd, Zhangjiajie, People’s Republic of ChinaSchool of Pharmacy, Hunan University of Chinese Medicine, Changsha, Hunan, People’s Republic of ChinaSchool of Pharmacy, Hunan University of Chinese Medicine, Changsha, Hunan, People’s Republic of ChinaAn 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 ω-methoxy-ω-oxeylkyl was introduced in C7-OH site and yielded eight analogs, all of them showed good inhibitory activity against SARS-CoV-2 3CLpro with IC50 values ranging from 0.72 to 2.36 μM. In the Vero E6-cell, compound 3 has a good activity of anti-SARS-CoV-2 virus (Omicron virus BA.5) in the prevention model, with an EC50 of 15.84 μM, and so do compound 10 in the therapeutic model, with an EC50 of 11.52 μM. The results suggest that the introduction of long chain ω-oxeylkyl at C7-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.https://www.tandfonline.com/doi/10.1080/14756366.2024.2390909DihydromyricetinflavonesynthesisSARS-CoV-2 3CLproOmicron virus BA.5
spellingShingle Cong Wu
Qi Jiang
Hui Zhong
Xudong Zhou
Leping Liu
Tong Pan
Chao Liu
Wei Wang
Wenbing Sheng
Design, synthesis, and biological activity evaluation of dihydromyricetin derivatives against SARS-CoV-2-Omicron virus
Journal of Enzyme Inhibition and Medicinal Chemistry
Dihydromyricetin
flavone
synthesis
SARS-CoV-2 3CLpro
Omicron virus BA.5
title Design, synthesis, and biological activity evaluation of dihydromyricetin derivatives against SARS-CoV-2-Omicron virus
title_full Design, synthesis, and biological activity evaluation of dihydromyricetin derivatives against SARS-CoV-2-Omicron virus
title_fullStr Design, synthesis, and biological activity evaluation of dihydromyricetin derivatives against SARS-CoV-2-Omicron virus
title_full_unstemmed Design, synthesis, and biological activity evaluation of dihydromyricetin derivatives against SARS-CoV-2-Omicron virus
title_short Design, synthesis, and biological activity evaluation of dihydromyricetin derivatives against SARS-CoV-2-Omicron virus
title_sort design synthesis and biological activity evaluation of dihydromyricetin derivatives against sars cov 2 omicron virus
topic Dihydromyricetin
flavone
synthesis
SARS-CoV-2 3CLpro
Omicron virus BA.5
url https://www.tandfonline.com/doi/10.1080/14756366.2024.2390909
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