tetano
Editor, Senior Moderator
Eur J Med Chem. 2019 Apr 5;173:305-313. doi: 10.1016/j.ejmech.2019.04.006. [Epub ahead of print]
[h=1]Discovery of novel acylhydrazone neuraminidase inhibitors.[/h] Zhao ZX[SUP]1[/SUP], Cheng LP[SUP]2[/SUP], Li M[SUP]1[/SUP], Pang W[SUP]3[/SUP], Wu FH[SUP]4[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Neuraminidase (NA) plays a crucial role in the replication and transmission of influenza virus. NA inhibitors have been developed as effective treatments for influenza A and B infections. In this paper, a new lead neuraminidase inhibitor 6a (IC[SUB]50[/SUB] = 7.10 ? 0.2 μM) was discovered by ligand-based virtual screening, receptor-based virtual screening, molecular dynamics simulation (MD), and bioassay validation. MD simulation indicates that the morpholinyl group of 6a could be embedded in 430-loop of NA. To exploit the 430-loop in the active site, a series of novel acylhydrazone NA inhibitors 6b-6g were designed and synthesized based on the lead compound 6a. Compound 6e exerts the most potency, with IC[SUB]50[/SUB] value of 2.37 ? 0.5 μM against NA, which is lower than that of oseltamivir carboxylate (OC) (IC[SUB]50[/SUB] = 3.84 μM). Overall, this work provided unique insights in the discovery of potent inhibitors against NA.
Copyright ? 2019 Elsevier Masson SAS. All rights reserved.
[h=4]KEYWORDS:[/h] 430-Loop; Acylhydrazone; Neuraminidase inhibitor; Virtual screening
PMID: 31022584 DOI: 10.1016/j.ejmech.2019.04.006
[h=1]Discovery of novel acylhydrazone neuraminidase inhibitors.[/h] Zhao ZX[SUP]1[/SUP], Cheng LP[SUP]2[/SUP], Li M[SUP]1[/SUP], Pang W[SUP]3[/SUP], Wu FH[SUP]4[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Neuraminidase (NA) plays a crucial role in the replication and transmission of influenza virus. NA inhibitors have been developed as effective treatments for influenza A and B infections. In this paper, a new lead neuraminidase inhibitor 6a (IC[SUB]50[/SUB] = 7.10 ? 0.2 μM) was discovered by ligand-based virtual screening, receptor-based virtual screening, molecular dynamics simulation (MD), and bioassay validation. MD simulation indicates that the morpholinyl group of 6a could be embedded in 430-loop of NA. To exploit the 430-loop in the active site, a series of novel acylhydrazone NA inhibitors 6b-6g were designed and synthesized based on the lead compound 6a. Compound 6e exerts the most potency, with IC[SUB]50[/SUB] value of 2.37 ? 0.5 μM against NA, which is lower than that of oseltamivir carboxylate (OC) (IC[SUB]50[/SUB] = 3.84 μM). Overall, this work provided unique insights in the discovery of potent inhibitors against NA.
Copyright ? 2019 Elsevier Masson SAS. All rights reserved.
[h=4]KEYWORDS:[/h] 430-Loop; Acylhydrazone; Neuraminidase inhibitor; Virtual screening
PMID: 31022584 DOI: 10.1016/j.ejmech.2019.04.006