tetano
Editor, Senior Moderator
Eur J Med Chem. 2018 Aug 13;157:743-758. doi: 10.1016/j.ejmech.2018.08.032. [Epub ahead of print]
[h=1]Synthesis and biological evaluation of a library of hybrid derivatives as inhibitors of influenza virus PA-PB1 interaction.[/h] D'Agostino I[SUP]1[/SUP], Giacchello I[SUP]2[/SUP], Nannetti G[SUP]3[/SUP], Fallacara AL[SUP]1[/SUP], Deodato D[SUP]1[/SUP], Musumeci F[SUP]2[/SUP], Grossi G[SUP]2[/SUP], Pal? G[SUP]3[/SUP], Cau Y[SUP]1[/SUP], Trist IM[SUP]1[/SUP], Loregian A[SUP]4[/SUP], Schenone S[SUP]5[/SUP], Botta M[SUP]6[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] The limited treatment options against influenza virus along with the growing public health concerns regarding the continuous emergence of drug-resistant viruses make essential the development of new anti-flu agents with novel mechanisms of action. One of the most attractive targets is the interaction between two subunits of the RNA-dependent RNA polymerase, PA and PB1. Herein we report the rational design of hybrid compounds starting from a 3-cyano-4,6-diphenylpyridine scaffold recently identified as disruptor of PA-PB1 interactions. Guided by the previously reported SAR data, a library of amino acid derivatives was synthesized. The biological evaluation led to the identification of new PA-PB1 inhibitors, that do not show appreciable toxicity. Molecular modeling shed further lights on the inhibition mechanism of these compounds.
[h=4]KEYWORDS:[/h] Amino acid coupling; Anti-Influenza; Diphenyl-pyridine; PA-PB1; RdRp; SPPS
PMID: 30142611 DOI: 10.1016/j.ejmech.2018.08.032
[h=1]Synthesis and biological evaluation of a library of hybrid derivatives as inhibitors of influenza virus PA-PB1 interaction.[/h] D'Agostino I[SUP]1[/SUP], Giacchello I[SUP]2[/SUP], Nannetti G[SUP]3[/SUP], Fallacara AL[SUP]1[/SUP], Deodato D[SUP]1[/SUP], Musumeci F[SUP]2[/SUP], Grossi G[SUP]2[/SUP], Pal? G[SUP]3[/SUP], Cau Y[SUP]1[/SUP], Trist IM[SUP]1[/SUP], Loregian A[SUP]4[/SUP], Schenone S[SUP]5[/SUP], Botta M[SUP]6[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] The limited treatment options against influenza virus along with the growing public health concerns regarding the continuous emergence of drug-resistant viruses make essential the development of new anti-flu agents with novel mechanisms of action. One of the most attractive targets is the interaction between two subunits of the RNA-dependent RNA polymerase, PA and PB1. Herein we report the rational design of hybrid compounds starting from a 3-cyano-4,6-diphenylpyridine scaffold recently identified as disruptor of PA-PB1 interactions. Guided by the previously reported SAR data, a library of amino acid derivatives was synthesized. The biological evaluation led to the identification of new PA-PB1 inhibitors, that do not show appreciable toxicity. Molecular modeling shed further lights on the inhibition mechanism of these compounds.
[h=4]KEYWORDS:[/h] Amino acid coupling; Anti-Influenza; Diphenyl-pyridine; PA-PB1; RdRp; SPPS
PMID: 30142611 DOI: 10.1016/j.ejmech.2018.08.032