Issue 38, 2018

Magnolol dimer-derived fragments as PPARγ-selective probes


Partial agonists of the transcription factor PPARγ (peroxisome proliferator-activated receptor γ) have shown potential for the treatment of metabolic and inflammatory conditions and novel activators serve as valuable tool and lead compounds. Based on the natural product magnolol (I) and recent structural information of the ligand–target interaction we have previously developed magnolol dimer (II) which has been shown to have enhanced affinity towards PPARγ and improved selectivity over RXRα (retinoid X receptor α), PPARγ's heterodimerization partner. In this contribution we report the synthesis and evaluation of three fragments of the dimeric lead compound by structural simplifications. Sesqui magnolol A and B (III and IV) were found to exhibit comparable activities to magnolol dimer (II) and selectivity over RXRα persisted. Computational studies suggest a common pharmacophore of the distinctive biphenyl motifs. Truncated magnolol dimer (V) on the other hand does not share this feature and was found to act as an antagonist.

Graphical abstract: Magnolol dimer-derived fragments as PPARγ-selective probes

Supplementary files

Article information

Article type
20 Jul 2018
29 Aug 2018
First published
20 Sep 2018
This article is Open Access
Creative Commons BY license

Org. Biomol. Chem., 2018,16, 7019-7028

Magnolol dimer-derived fragments as PPARγ-selective probes

D. Dreier, M. Resetar, V. Temml, L. Rycek, N. Kratena, M. Schnürch, D. Schuster, V. M. Dirsch and M. D. Mihovilovic, Org. Biomol. Chem., 2018, 16, 7019 DOI: 10.1039/C8OB01745J

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