ITEM METADATA RECORD
Title: Easily accessible polycyclic amines that inhibit the wild-type and amantadine-resistant mutants of the M2 channel of influenza A virus
Authors: Rey-Carrizo, Matias ×
Barniol-Xicota, Marta
Ma, Chunlong
Frigolé-Vivas, Marta
Torres, Eva
Naesens, Lieve
Llabrés, Salomé
Juárez-Jiménez, Jordi
Luque, Francisco J
DeGrado, William F
Lamb, Robert A
Pinto, Lawrence H
Vázquez, Santiago #
Issue Date: Jul-2014
Publisher: ACS Publications
Series Title: Journal of Medicinal Chemistry vol:57 issue:13 pages:5738-5747
Article number: 10.1021/jm5005804
Abstract: Amantadine inhibits the M2 proton channel of influenza A virus, yet most of the currently circulating strains of the virus carry mutations in the M2 protein that render the virus amantadine-resistant. While most of the research on novel amantadine analogues has revolved around the synthesis of novel adamantane derivatives, we have recently found that other polycyclic scaffolds effectively block the M2 proton channel, including amantadine-resistant mutant channels. In this work, we have synthesized and characterized a series of pyrrolidine derivatives designed as analogues of amantadine. Inhibition of the wild-type M2 channel and the A/M2-S31N, A/M2-V27A, and A/M2-L26F mutant forms of the channel were measured in Xenopus oocytes using two-electrode voltage clamp assays. Most of the novel compounds inhibited the wild-type ion channel in the low micromolar range. Of note, two of the compounds inhibited the amantadine-resistant A/M2-V27A and A/M2-L26F mutant ion channels with submicromolar and low micromolar IC50, respectively. None of the compounds was found to inhibit the S31N mutant ion channel.
URI: 
ISSN: 0022-2623
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Virology and Chemotherapy (Rega Institute)
× corresponding author
# (joint) last author

Files in This Item:
File Description Status SizeFormat
2014130.pdf Published 2026KbAdobe PDFView/Open Request a copy

These files are only available to some KU Leuven Association staff members

 




All items in Lirias are protected by copyright, with all rights reserved.

© Web of science