Search

Your search keyword '"Puthenkalam R"' showing total 2 results
Start Over Author "Puthenkalam R" Journal bioorganic medicinal chemistry letters
2 results on '"Puthenkalam R"'

2. Metal-assisted synthesis of unsymmetrical magnolol and honokiol analogs and their biological assessment as GABAA receptor ligands.

Author

Rycek L, Puthenkalam R, Schnürch M, Ernst M, and Mihovilovic MD

Subjects
Animals, Anti-Inflammatory Agents, Non-Steroidal chemistry, Anti-Inflammatory Agents, Non-Steroidal pharmacology, Biphenyl Compounds pharmacology, Lignans pharmacology, Molecular Structure, Oocytes cytology, Oocytes metabolism, Patch-Clamp Techniques, Protein Subunits, Rats, Recombinant Proteins metabolism, Structure-Activity Relationship, Xenopus growth & development, Xenopus metabolism, Biphenyl Compounds chemistry, GABA Modulators chemistry, GABA Modulators metabolism, Lignans chemistry, Metals pharmacology, Oocytes drug effects, Receptors, GABA-A metabolism
Abstract

We present the synthesis of new derivatives of natural products magnolol (1) and honokiol (2) and their evaluation as allosteric ligands for modulation of GABAA receptor activity. New derivatives were prepared via metal assisted cross-coupling reactions in two consecutive steps. Compounds were tested by means of two-electrode voltage clamp electrophysiology at the α1β2γ2 receptor subtype at low GABA concentrations. We have identified several compounds enhancing GABA induced current (IGABA) in the range similar or even higher than the lead structures. At 3μM, compound 8g enhanced IGABA by factor of 443, compared to 162 and 338 of honokiol and magnolol, respectively. Furthermore, 8g at EC10-20 features a much bigger window of separation between the α1β2γ2 and the α1β1γ2 subtypes compared to honokiol, and thus improved subtype selectivity., (Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Published
2015
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results