tetano
Editor, Senior Moderator
Eur J Med Chem. 2015 Dec 15;108:605-615. doi: 10.1016/j.ejmech.2015.12.013. [Epub ahead of print]
[h=1]Imidazole-based pinanamine derivatives: Discovery of dual inhibitors of the wild-type and drug-resistant mutant of the influenza A virus.[/h] Dong J[SUP]1[/SUP], Chen S[SUP]1[/SUP], Li R[SUP]2[/SUP], Cui W[SUP]1[/SUP], Jiang H[SUP]2[/SUP], Ling Y[SUP]1[/SUP], Yang Z[SUP]2[/SUP], Hu W[SUP]3[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] We previously reported potent hit compound 4 inhibiting the wild-type influenza A virus A/HK/68 (H3N2) and A/M2-S31N mutant viruses A/WS/33 (H1N1), with its latter activity quite weak. To further increase its potency, a structure-activity relationship study of a series of imidazole-linked pinanamine derivatives was conducted by modifying the imidazole ring of this compound. Several compounds of this series inhibited the amantadine-sensitive virus at low micromolar concentrations. Among them, 33 was the most potent compound, which was identified as being active on an amantadine-sensitive virus through blocking of the viral M2 ion channel. Furthermore, 33 markedly inhibited the amantadine-resistant virus (IC[SUB]50[/SUB] = 3.4 μM) and its activity increased by almost 24-fold compared to initial compound, with its action mechanism being not M2 channel mediated.
Copyright ? 2015 Elsevier Masson SAS. All rights reserved.
[h=4]KEYWORDS:[/h] Dual inhibitory activity; Influenza A virus; M2 ion channel; Pinanamine derivatives
PMID: 26722757 [PubMed - as supplied by publisher]
[h=1]Imidazole-based pinanamine derivatives: Discovery of dual inhibitors of the wild-type and drug-resistant mutant of the influenza A virus.[/h] Dong J[SUP]1[/SUP], Chen S[SUP]1[/SUP], Li R[SUP]2[/SUP], Cui W[SUP]1[/SUP], Jiang H[SUP]2[/SUP], Ling Y[SUP]1[/SUP], Yang Z[SUP]2[/SUP], Hu W[SUP]3[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] We previously reported potent hit compound 4 inhibiting the wild-type influenza A virus A/HK/68 (H3N2) and A/M2-S31N mutant viruses A/WS/33 (H1N1), with its latter activity quite weak. To further increase its potency, a structure-activity relationship study of a series of imidazole-linked pinanamine derivatives was conducted by modifying the imidazole ring of this compound. Several compounds of this series inhibited the amantadine-sensitive virus at low micromolar concentrations. Among them, 33 was the most potent compound, which was identified as being active on an amantadine-sensitive virus through blocking of the viral M2 ion channel. Furthermore, 33 markedly inhibited the amantadine-resistant virus (IC[SUB]50[/SUB] = 3.4 μM) and its activity increased by almost 24-fold compared to initial compound, with its action mechanism being not M2 channel mediated.
Copyright ? 2015 Elsevier Masson SAS. All rights reserved.
[h=4]KEYWORDS:[/h] Dual inhibitory activity; Influenza A virus; M2 ion channel; Pinanamine derivatives
PMID: 26722757 [PubMed - as supplied by publisher]