tetano
Editor, Senior Moderator
Eur J Med Chem. 2016 Jul 28;123:397-406. doi: 10.1016/j.ejmech.2016.07.064. [Epub ahead of print]
[h=1]Design and synthesis of 1,2,3-triazole-containing N-acyl zanamivir analogs as potent neuraminidase inhibitors.[/h] Das A[SUP]1[/SUP], Adak AK[SUP]1[/SUP], Ponnapalli K[SUP]1[/SUP], Lin CH[SUP]1[/SUP], Hsu KC[SUP]2[/SUP], Yang JM[SUP]3[/SUP], Hsu TA[SUP]4[/SUP], Lin CC[SUP]5[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] The design of potent metabolically stable neuraminidase (NA) inhibitors represents an attractive approach for treating influenza virus infection. In this study, we describe the exploitation of the 150-cavity in the active site of group 1 NA for the design, synthesis, and in vitro evaluation of new triazole-containing N-acyl derivatives related to Zanamivir. Inhibition studies with influenza virus NAs of group 1 (H1N1) and group 2 (H3N2) revealed that several of them are good inhibitors, with IC[SUB]50[/SUB] values in the low nanomolar (2.3 nM-31 nM) range. Substituents that form stable van der Waals interaction with the 150-cavity residues play crucial roles in NA inhibition as demonstrated by the potency of 6a (H1N1 IC[SUB]50[/SUB] = 2.3 nM, and H3N2 IC[SUB]50[/SUB] = 2.9 nM). Docking studies indicated that the cyclohexane-substituted triazole ring extended toward the hydrophobic region in the active site of group 1 NA in open form. The high potency observed for inhibitor 6a may be attributable to the highly favorable hydrophobic interactions in this region.
Copyright ? 2016 Elsevier Masson SAS. All rights reserved.
[h=4]KEYWORDS:[/h] Influenza; Neuraminidase inhibitors; Triazole; Zanamivir
PMID: 27487569 DOI: 10.1016/j.ejmech.2016.07.064
[PubMed - as supplied by publisher]
[h=1]Design and synthesis of 1,2,3-triazole-containing N-acyl zanamivir analogs as potent neuraminidase inhibitors.[/h] Das A[SUP]1[/SUP], Adak AK[SUP]1[/SUP], Ponnapalli K[SUP]1[/SUP], Lin CH[SUP]1[/SUP], Hsu KC[SUP]2[/SUP], Yang JM[SUP]3[/SUP], Hsu TA[SUP]4[/SUP], Lin CC[SUP]5[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] The design of potent metabolically stable neuraminidase (NA) inhibitors represents an attractive approach for treating influenza virus infection. In this study, we describe the exploitation of the 150-cavity in the active site of group 1 NA for the design, synthesis, and in vitro evaluation of new triazole-containing N-acyl derivatives related to Zanamivir. Inhibition studies with influenza virus NAs of group 1 (H1N1) and group 2 (H3N2) revealed that several of them are good inhibitors, with IC[SUB]50[/SUB] values in the low nanomolar (2.3 nM-31 nM) range. Substituents that form stable van der Waals interaction with the 150-cavity residues play crucial roles in NA inhibition as demonstrated by the potency of 6a (H1N1 IC[SUB]50[/SUB] = 2.3 nM, and H3N2 IC[SUB]50[/SUB] = 2.9 nM). Docking studies indicated that the cyclohexane-substituted triazole ring extended toward the hydrophobic region in the active site of group 1 NA in open form. The high potency observed for inhibitor 6a may be attributable to the highly favorable hydrophobic interactions in this region.
Copyright ? 2016 Elsevier Masson SAS. All rights reserved.
[h=4]KEYWORDS:[/h] Influenza; Neuraminidase inhibitors; Triazole; Zanamivir
PMID: 27487569 DOI: 10.1016/j.ejmech.2016.07.064
[PubMed - as supplied by publisher]