Inhibition of N-Type Calcium Channels by Fluorophenoxyanilide Derivatives

Ellen C. Gleeson; Janease E. Graham; Sandro Spiller; Irina Vetter; Richard J. Lewis; Peter J. Duggan; Kellie L. Tuck

doi:10.3390/md13042030

Marine Drugs (Apr 2015)

Inhibition of N-Type Calcium Channels by Fluorophenoxyanilide Derivatives

Ellen C. Gleeson,
Janease E. Graham,
Sandro Spiller,
Irina Vetter,
Richard J. Lewis,
Peter J. Duggan,
Kellie L. Tuck

Affiliations

Ellen C. Gleeson: School of Chemistry, Monash University, Clayton VIC 3800, Australia
Janease E. Graham: School of Chemistry, Monash University, Clayton VIC 3800, Australia
Sandro Spiller: School of Chemistry, Monash University, Clayton VIC 3800, Australia
Irina Vetter: Institute for Molecular Bioscience, The University of Queensland, St Lucia QLD 4072, Australia
Richard J. Lewis: Institute for Molecular Bioscience, The University of Queensland, St Lucia QLD 4072, Australia
Peter J. Duggan: CSIRO Manufacturing Flagship, Clayton South, VIC 3169, Australia
Kellie L. Tuck: School of Chemistry, Monash University, Clayton VIC 3800, Australia

DOI: https://doi.org/10.3390/md13042030
Journal volume & issue: Vol. 13, no. 4
pp. 2030 – 2045

Abstract

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A set of fluorophenoxyanilides, designed to be simplified analogues of previously reported ω-conotoxin GVIA mimetics, were prepared and tested for N-type calcium channel inhibition in a SH-SY5Y neuroblastoma FLIPR assay. N-type or Cav2.2 channel is a validated target for the treatment of refractory chronic pain. Despite being significantly less complex than the originally designed mimetics, up to a seven-fold improvement in activity was observed.

Published in Marine Drugs

ISSN: 1660-3397 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Science: Biology (General)
Website: http://www.mdpi.com/journal/marinedrugs

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