tetano
Editor, Senior Moderator
J Med Chem. 2013 Nov 15. [Epub ahead of print]
3-Azatetracyclo[5.2.1.15,8.01,5]undecane Derivatives: From Wild-Type Inhibitors of the M2 Ion Channel of Influenza A Virus to Derivatives with Potent Activity against the V27A Mutant.
Rey-Carrizo M, Torres E, Ma C, Barniol-Xicota M, Wang J, Wu Y, Naesens L, Degrado WF, Lamb RA, Pinto LH, V?zquez S.
Source
Laboratori de Qu?mica Farmac?utica (Unitat Associada al CSIC), Facultat de Farm?cia, and Institute of Biomedicine (IBUB), Universitat de Barcelona , Av. Joan XXIII s/n, Barcelona E-08028, Spain.
Abstract
We have synthesized and characterized a series of compounds containing the 3-azatetracyclo[5.2.1.15,8.01,5]undecane scaffold designed as analogues of amantadine, an inhibitor of the M2 proton channel of influenza A virus. Inhibition of the wild-type (WT) M2 channel and the amantadine-resistant A/M2-S31N and A/M2-V27A mutant ion channels were measured in Xenopus oocytes using two-electrode voltage clamp (TEV) assays. Most of the novel compounds inhibited the WT ion channel in the low micromolar range. Of note, several compounds inhibited the A/M2 V27A mutant ion channel, one of them with submicromolar IC50. None of the compounds was found to inhibit the S31N mutant ion channel. The antiviral activity of three novel dual WT and A/M2-V27A channels inhibitors was confirmed by influenza virus yield assays.
PMID:
24237039
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24237039
3-Azatetracyclo[5.2.1.15,8.01,5]undecane Derivatives: From Wild-Type Inhibitors of the M2 Ion Channel of Influenza A Virus to Derivatives with Potent Activity against the V27A Mutant.
Rey-Carrizo M, Torres E, Ma C, Barniol-Xicota M, Wang J, Wu Y, Naesens L, Degrado WF, Lamb RA, Pinto LH, V?zquez S.
Source
Laboratori de Qu?mica Farmac?utica (Unitat Associada al CSIC), Facultat de Farm?cia, and Institute of Biomedicine (IBUB), Universitat de Barcelona , Av. Joan XXIII s/n, Barcelona E-08028, Spain.
Abstract
We have synthesized and characterized a series of compounds containing the 3-azatetracyclo[5.2.1.15,8.01,5]undecane scaffold designed as analogues of amantadine, an inhibitor of the M2 proton channel of influenza A virus. Inhibition of the wild-type (WT) M2 channel and the amantadine-resistant A/M2-S31N and A/M2-V27A mutant ion channels were measured in Xenopus oocytes using two-electrode voltage clamp (TEV) assays. Most of the novel compounds inhibited the WT ion channel in the low micromolar range. Of note, several compounds inhibited the A/M2 V27A mutant ion channel, one of them with submicromolar IC50. None of the compounds was found to inhibit the S31N mutant ion channel. The antiviral activity of three novel dual WT and A/M2-V27A channels inhibitors was confirmed by influenza virus yield assays.
PMID:
24237039
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24237039