Publications in Scientific Journals:
L. Rycek, R. Puthenkalam, M. Schnürch, M. Ernst, M.D. Mihovilovic:
"Metal-Assisted Synthesis of Unsymmetrical Magnolol Analogs and their Biological Assessment as GABAA Receptor Ligands";
Bioorganic & Medicinal Chemistry Letters,
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 a1b2c2 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 3 lM, 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 a1b2c2 and the a1b1c2 subtypes compared to honokiol, and thus improved subtype selectivity.
magnolol, honokiol, cross-coupling
"Official" electronic version of the publication (accessed through its Digital Object Identifier - DOI)
Created from the Publication Database of the Vienna University of Technology.