4.4 Article

Design, Synthesis and Anti-influenza A Virus Evaluation of Oleanolic Acid C3-Glycoconjugates

期刊

CHINESE JOURNAL OF ORGANIC CHEMISTRY
卷 41, 期 6, 页码 2454-2466

出版社

SCIENCE PRESS
DOI: 10.6023/cjoc202010029

关键词

oleanolic acid; glycoconjugates; influenza virus; CuAAC reaction; inhibitors

资金

  1. Science and Technology Plan Project of Yunnan Provincial Department of Science and Technology [2019FB125]
  2. Open-Fund Program of the State Key Laboratory of Natural and Biomimetic Drugs [K202003]

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Inhibitors targeting the entry stage of influenza viruses are a key focus in anti-influenza drug development. A series of oleanolic acid C3 glycoconjugates were designed and synthesized, with compound 12a demonstrating the strongest anti-influenza activity. The compound may target viral envelope hemagglutinin (HA) to inhibit virus attachment to host cells, without showing cytotoxic effects on MDCK cells.
Inhibitors targeting the entry stage of influenza viruses are a hot spot in the development of anti-influenza drugs. Our previous studies showed that oleanolic acid (OA) C28 glycoconjugates displayed strong anti-influenza virus activity. In this paper, a series of oleanolic acid C3 glycoconjugates 7a similar to 14c were designed and synthesized via copper(I)-catalyzed alkyne-azide cycloaddition (CuAAC) reaction. The anti-influenza activities of all these compounds were evaluated in vitro. Among them, oleanane-12-enyl-28-benzyloxycarbonyl-3-O-(4-methylene-1,2,3-triazole-1-(2,3,4,6-tetra-O-acetyl-beta-D-galacto-side)) (12a) showed the strongest activity with an IC50 of 12.45 mu mol.L-1, and no obvious cytotoxic effect on MDCK cells was observed at 100 mu mol.L-1. Hemagglutination inhibition and molecular docking experiments indicated that compound 12a might target viral envelope hemagglutinin (HA), thus inhibiting the attachment of viruses to host cells. This study improved the structure-activity relationships of oleanolic acid and its derivatives against influenza virus, and provided a basis for further research on anti-virus by these natural products.

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