New polycyclic dual inhibitors of the wild type and the V27A mutant M2 channel of the influenza A virus with unexpected binding mode
Articolo
Data di Pubblicazione:
2015
Citazione:
New polycyclic dual inhibitors of the wild type and the V27A mutant M2 channel of the influenza A virus with unexpected binding mode / M. Rey Carrizo, S. Gazzarrini, S. Llabrés, M. Frigolé Vivas, J. Juárez Jiménez, M. Font Bardia, L. Naesens, A. Moroni, F.J. Luque, S. Vázquez. - In: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0223-5234. - 96(2015 May 26), pp. 318-329. [10.1016/j.ejmech.2015.04.030]
Abstract:
Two new polycyclic scaffolds were synthesized and evaluated as anti-influenza A compounds. The 5-azapentacyclo[6.4.0.0(2,10).0(3,7).0(9,11)]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(2,5).0(3,11).0(4,9).0(6,17).0(12,16)]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.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
Amantadine; Influenza A; M2 channel; Molecular dynamics; Polycyclic amines; V27A mutant; Amantadine; Influenza A; M2 channel; Molecular dynamics; Polycyclic amines; V27A mutant; Amantadine; Influenza A; M2 channel; Molecular dynamics; Polycyclic amines; V27A mutant
Elenco autori:
M. Rey Carrizo, S. Gazzarrini, S. Llabrés, M. Frigolé Vivas, J. Juárez Jiménez, M. Font Bardia, L. Naesens, A. Moroni, F.J. Luque, S. Vázquez
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