tetano
Editor, Senior Moderator
Eur J Med Chem. 2017 Feb 21;130:185-194. doi: 10.1016/j.ejmech.2017.02.040. [Epub ahead of print]
[h=1]Oligothiophene compounds inhibit the membrane fusion between H5N1 avian influenza virus and the endosome of host cell.[/h] Zhu Z[SUP]1[/SUP], Yao Z[SUP]2[/SUP], Shen X[SUP]3[/SUP], Chen Z[SUP]3[/SUP], Liu X[SUP]4[/SUP], Parquette JR[SUP]5[/SUP], Liu S[SUP]6[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Hemagglutinin (HA) which is essential for influenza viral infection and replication has become a target for the design of anti-influenza drugs. A novel series of oligothiophene compounds focused on the target were synthesized as specific inhibitors against the H5 subtype of influenza A viruses because oligothiophene has stronger π-π interactions with residues F110[SUB]2[/SUB] and M24[SUB]1[/SUB] of HA2 side chains. Oligothiophene compounds were designed and synthesized by a series of alkylation, azidation, amination and amidation reactions. The entry inhibitory activities of those compounds were tested at a cellular level against H5N1 influenza pseudovirus. Compound 3sf was revealed as the most active inhibitor in this series with an IC[SUB]50[/SUB] of 0.029 μM. The activity of 3sf is almost 1000 times that of the positive reference compound (CL-385319). A structure-activity analysis of these compounds demonstrated that the size of the oligothiophene compounds was very important for the inhibitory activity. Four compounds (3sk, 3sf, 3sc and 4sc) of strong inhibitiory activity against H5N1 influenza pseudovirus were assessed against H1N1 influenza virus MDCK. They also showed strong inhibitiory activity with IC[SUB]50s[/SUB] of 3.292 μM, 1.240 μM, 1.119 μM and 0.768 μM, respectively.
Copyright ? 2017 Elsevier Masson SAS. All rights reserved.
[h=4]KEYWORDS:[/h] Fusion inhibitor; H5N1 influenza virus; Hemagglutinin(HA); Oligothiophene compounds
PMID: 28246043 DOI: 10.1016/j.ejmech.2017.02.040
[PubMed - as supplied by publisher]
[h=1]Oligothiophene compounds inhibit the membrane fusion between H5N1 avian influenza virus and the endosome of host cell.[/h] Zhu Z[SUP]1[/SUP], Yao Z[SUP]2[/SUP], Shen X[SUP]3[/SUP], Chen Z[SUP]3[/SUP], Liu X[SUP]4[/SUP], Parquette JR[SUP]5[/SUP], Liu S[SUP]6[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Hemagglutinin (HA) which is essential for influenza viral infection and replication has become a target for the design of anti-influenza drugs. A novel series of oligothiophene compounds focused on the target were synthesized as specific inhibitors against the H5 subtype of influenza A viruses because oligothiophene has stronger π-π interactions with residues F110[SUB]2[/SUB] and M24[SUB]1[/SUB] of HA2 side chains. Oligothiophene compounds were designed and synthesized by a series of alkylation, azidation, amination and amidation reactions. The entry inhibitory activities of those compounds were tested at a cellular level against H5N1 influenza pseudovirus. Compound 3sf was revealed as the most active inhibitor in this series with an IC[SUB]50[/SUB] of 0.029 μM. The activity of 3sf is almost 1000 times that of the positive reference compound (CL-385319). A structure-activity analysis of these compounds demonstrated that the size of the oligothiophene compounds was very important for the inhibitory activity. Four compounds (3sk, 3sf, 3sc and 4sc) of strong inhibitiory activity against H5N1 influenza pseudovirus were assessed against H1N1 influenza virus MDCK. They also showed strong inhibitiory activity with IC[SUB]50s[/SUB] of 3.292 μM, 1.240 μM, 1.119 μM and 0.768 μM, respectively.
Copyright ? 2017 Elsevier Masson SAS. All rights reserved.
[h=4]KEYWORDS:[/h] Fusion inhibitor; H5N1 influenza virus; Hemagglutinin(HA); Oligothiophene compounds
PMID: 28246043 DOI: 10.1016/j.ejmech.2017.02.040
[PubMed - as supplied by publisher]