tetano
Editor, Senior Moderator
Eur J Med Chem. 2017 Jun 8;138:128-139. doi: 10.1016/j.ejmech.2017.06.015. [Epub ahead of print]
[h=1]Exploring the cycloheptathiophene-3-carboxamide scaffold to disrupt the interactions of the influenza polymerase subunits and obtain potent anti-influenza activity.[/h] Desantis J[SUP]1[/SUP], Nannetti G[SUP]2[/SUP], Massari S[SUP]1[/SUP], Barreca ML[SUP]1[/SUP], Manfroni G[SUP]1[/SUP], Cecchetti V[SUP]1[/SUP], Pal? G[SUP]2[/SUP], Goracci L[SUP]3[/SUP], Loregian A[SUP]4[/SUP], Tabarrini O[SUP]5[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] With the aim to identify small molecules able to disrupt PA-PB1 subunits interaction of influenza virus (flu) RNA-dependent RNA polymerase, and based on previous structural and computational information, in this paper we have designed and synthesized a new series of cycloheptathiophene-3-carboxamide (cHTC) derivatives. Their biological evaluation led to highlight important structural insights along with new interesting compounds, such as the 2-hydroxybenzamido derivatives 29, 31, and 32, and the 4-aminophenyl derivative 54, which inhibited viral growth in the low micromolar range (EC[SUB]50[/SUB] = 0.18-1.2 μM) at no toxic concentrations (CC[SUB]50[/SUB] > 250 μM). This study permitted to obtain among the most potent anti-flu compounds within the PA-PB1 interaction inhibitors, confirming the cHTC scaffold as particularly suitable to achieve innovative anti-flu agents.
Copyright ? 2017 Elsevier Masson SAS. All rights reserved.
[h=4]KEYWORDS:[/h] Influenza virus inhibitors; Influenza virus polymerase; PA-PB1 interaction; Protein-protein interaction inhibitors
PMID: 28666191 DOI: 10.1016/j.ejmech.2017.06.015
[h=1]Exploring the cycloheptathiophene-3-carboxamide scaffold to disrupt the interactions of the influenza polymerase subunits and obtain potent anti-influenza activity.[/h] Desantis J[SUP]1[/SUP], Nannetti G[SUP]2[/SUP], Massari S[SUP]1[/SUP], Barreca ML[SUP]1[/SUP], Manfroni G[SUP]1[/SUP], Cecchetti V[SUP]1[/SUP], Pal? G[SUP]2[/SUP], Goracci L[SUP]3[/SUP], Loregian A[SUP]4[/SUP], Tabarrini O[SUP]5[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] With the aim to identify small molecules able to disrupt PA-PB1 subunits interaction of influenza virus (flu) RNA-dependent RNA polymerase, and based on previous structural and computational information, in this paper we have designed and synthesized a new series of cycloheptathiophene-3-carboxamide (cHTC) derivatives. Their biological evaluation led to highlight important structural insights along with new interesting compounds, such as the 2-hydroxybenzamido derivatives 29, 31, and 32, and the 4-aminophenyl derivative 54, which inhibited viral growth in the low micromolar range (EC[SUB]50[/SUB] = 0.18-1.2 μM) at no toxic concentrations (CC[SUB]50[/SUB] > 250 μM). This study permitted to obtain among the most potent anti-flu compounds within the PA-PB1 interaction inhibitors, confirming the cHTC scaffold as particularly suitable to achieve innovative anti-flu agents.
Copyright ? 2017 Elsevier Masson SAS. All rights reserved.
[h=4]KEYWORDS:[/h] Influenza virus inhibitors; Influenza virus polymerase; PA-PB1 interaction; Protein-protein interaction inhibitors
PMID: 28666191 DOI: 10.1016/j.ejmech.2017.06.015