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Synthesis and biological evaluation of NH2-acyl oseltamivir analogues as potent neuraminidase inhibitors

tetano

Editor, Senior Moderator
Eur J Med Chem. 2017 Oct 5. pii: S0223-5234(17)30796-1. doi: 10.1016/j.ejmech.2017.10.004. [Epub ahead of print]
[h=1]Synthesis and biological evaluation of NH2-acyl oseltamivir analogues as potent neuraminidase inhibitors.[/h] Wang K[SUP]1[/SUP], Yang F[SUP]1[/SUP], Wang L[SUP]2[/SUP], Liu K[SUP]1[/SUP], Sun L[SUP]3[/SUP], Lin B[SUP]1[/SUP], Hu Y[SUP]1[/SUP], Wang B[SUP]1[/SUP], Cheng M[SUP]4[/SUP], Tian Y[SUP]5[/SUP].
[h=3]Author information[/h]

[h=3]Abstract[/h] Neuraminidase inhibitors can deter nascent viruses from infecting intact cells by preventing their release from host cells. Herein, a neuraminidase inhibitor 11b absent of basic moieties was discovered in the process of searching for inhibitors targeting 150 cavity. It exhibited potent inhibitions against wild-type neuraminidases from group 1 (H5N1 and H1N1) and group 2 (H7N9) subtypes with IC[SUB]50[/SUB] values similar to those of oseltamivir carboxylate. Moreover, 11b showed moderate inhibitions against mutant neuraminidases from H5N1-H274Y and H1N1-H274Y with IC[SUB]50[/SUB] values of 2075 nM and 1382 nM, which were inferior to those of oseltamivir carboxylate (6095 nM and 4071 nM). The results were not consistent with the recognized SARs that a basic moiety was an indispensable part of a potent inhibitor.
Copyright ? 2017. Published by Elsevier Masson SAS.


[h=4]KEYWORDS:[/h] 150 cavity; Influenza virus; Neuraminidase inhibitors; Oseltamivir analogues

PMID: 29107426 DOI: 10.1016/j.ejmech.2017.10.004
 
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