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Incorporation of privileged structures into 3-O-β-chacotriosyl ursolic acid can enhance inhibiting the entry of the H5N1 virus

tetano

Editor, Senior Moderator
Bioorg Med Chem Lett. 2019 Jul 19. pii: S0960-894X(19)30484-6. doi: 10.1016/j.bmcl.2019.07.028. [Epub ahead of print]
[h=1]Incorporation of privileged structures into 3-O-β-chacotriosyl ursolic acid can enhance inhibiting the entry of the H5N1 virus.[/h] Li H[SUP]1[/SUP], Chen L[SUP]2[/SUP], Li S[SUP]3[/SUP], Liao Y[SUP]4[/SUP], Wang L[SUP]1[/SUP], Liu Z[SUP]1[/SUP], Liu S[SUP]5[/SUP], Song G[SUP]6[/SUP].
[h=3]Author information[/h]

[h=3]Abstract[/h] The glycoprotein hemagglutinin of influenza virus plays a key role in the initial stage of virus infection, making it a potential target for novel influenza viruses entry inhibitors. Two "privileged fragments", 2-(piperidin-1-yl)ethan-1-amine and 2-(1,3-oxazinan-3-yl)ethan-1-amine were integrated into 3-O-β-chacotriosyl ursolic acid producing new derivatives 5 and 6 with improved activity against IAVs in vitro. Mechanistically, compound 6 was effective in inhibiting infection of H1-, H3-, and H5-typed influenza A viruses by interfering with the viral hemagglutinin. Furthermore, the docking studies were in agreement with the antiviral data. These results showed that the title compound 6 as a new lead compound was meriting further optimization and development.
Copyright ? 2019 Elsevier Ltd. All rights reserved.


[h=4]KEYWORDS:[/h] 3-O-β-chacotriosyl ursolic acid; Entry inhibitors; Hemagglutinin; Influenza viruses

PMID: 31371135 DOI: 10.1016/j.bmcl.2019.07.028
 
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