tetano
Editor, Senior Moderator
Eur J Med Chem. 2015 Apr 14;96:318-329. doi: 10.1016/j.ejmech.2015.04.030. [Epub ahead of print]
[h=1]New polycyclic dual inhibitors of the wild type and the V27A mutant M2 channel of the influenza A virus with unexpected binding mode.[/h] Rey-Carrizo M[SUP]1[/SUP], Gazzarrini S[SUP]2[/SUP], Llabr?s S[SUP]3[/SUP], Frigol?-Vivas M[SUP]1[/SUP], Ju?rez-Jim?nez J[SUP]3[/SUP], Font-Bardia M[SUP]4[/SUP], Naesens L[SUP]5[/SUP], Moroni A[SUP]2[/SUP], Luque FJ[SUP]3[/SUP], V?zquez S[SUP]6[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Two new polycyclic scaffolds were synthesized and evaluated as anti-influenza A compounds. The 5-azapentacyclo[6.4.0.0[SUP]2,10[/SUP].0[SUP]3,7[/SUP].0[SUP]9,11[/SUP]]dodecane derivatives were only active against the wild-type M2 channel in the low-micromolar range. However, some of the 14-azaheptacyclo[8.6.1.0[SUP]2,5[/SUP].0[SUP]3,11[/SUP].0[SUP]4,9[/SUP].0[SUP]6,17[/SUP].0[SUP]12,16[/SUP]]heptadecane derivatives were dual inhibitors of the wild-type and the V27A mutant M2 channels. The antiviral activity of these molecules was confirmed by cell culture assays. Their binding mode was analysed through molecular dynamics simulations, which showed the existence of distinct binding modes in the wild type M2 channel and its V27A variant.
Copyright ? 2015 Elsevier Masson SAS. All rights reserved.
[h=4]KEYWORDS:[/h] Amantadine; Influenza A; M2 channel; Molecular dynamics; Polycyclic amines; V27A mutant
PMID: 25899336 [PubMed - as supplied by publisher]
[h=1]New polycyclic dual inhibitors of the wild type and the V27A mutant M2 channel of the influenza A virus with unexpected binding mode.[/h] Rey-Carrizo M[SUP]1[/SUP], Gazzarrini S[SUP]2[/SUP], Llabr?s S[SUP]3[/SUP], Frigol?-Vivas M[SUP]1[/SUP], Ju?rez-Jim?nez J[SUP]3[/SUP], Font-Bardia M[SUP]4[/SUP], Naesens L[SUP]5[/SUP], Moroni A[SUP]2[/SUP], Luque FJ[SUP]3[/SUP], V?zquez S[SUP]6[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Two new polycyclic scaffolds were synthesized and evaluated as anti-influenza A compounds. The 5-azapentacyclo[6.4.0.0[SUP]2,10[/SUP].0[SUP]3,7[/SUP].0[SUP]9,11[/SUP]]dodecane derivatives were only active against the wild-type M2 channel in the low-micromolar range. However, some of the 14-azaheptacyclo[8.6.1.0[SUP]2,5[/SUP].0[SUP]3,11[/SUP].0[SUP]4,9[/SUP].0[SUP]6,17[/SUP].0[SUP]12,16[/SUP]]heptadecane derivatives were dual inhibitors of the wild-type and the V27A mutant M2 channels. The antiviral activity of these molecules was confirmed by cell culture assays. Their binding mode was analysed through molecular dynamics simulations, which showed the existence of distinct binding modes in the wild type M2 channel and its V27A variant.
Copyright ? 2015 Elsevier Masson SAS. All rights reserved.
[h=4]KEYWORDS:[/h] Amantadine; Influenza A; M2 channel; Molecular dynamics; Polycyclic amines; V27A mutant
PMID: 25899336 [PubMed - as supplied by publisher]