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Issue 38, 2018
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Magnolol dimer-derived fragments as PPARγ-selective probes

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Abstract

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

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Publication details

The article was received on 20 Jul 2018, accepted on 29 Aug 2018 and first published on 20 Sep 2018


Article type: Paper
DOI: 10.1039/C8OB01745J
Citation: Org. Biomol. Chem., 2018,16, 7019-7028
  • Open access: Creative Commons BY license
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    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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