2. Academic Validation
  3. Dihydrochalcone Glucosides from the Subaerial Parts of Thonningia sanguinea and Their in Vitro PTP1B Inhibitory Activities

Dihydrochalcone Glucosides from the Subaerial Parts of Thonningia sanguinea and Their in Vitro PTP1B Inhibitory Activities

  • J Nat Prod. 2018 Sep 28;81(9):2091-2100. doi: 10.1021/acs.jnatprod.8b00450.
Luca Pompermaier 1,  Elke H Heiss 2,  Mostafa Alilou 1,  Fabian Mayr 1 3,  Mawunu Monizi 4,  Thea Lautenschlaeger 5,  Daniela Schuster 3 6,  Stefan Schwaiger 1,  Hermann Stuppner 1
Affiliations

Affiliations

  • 1 Institute of Pharmacy/Pharmacognosy, Center for Molecular Biosciences Innsbruck , University of Innsbruck , Innrain 80/82 , Innsbruck 6020 , Austria.
  • 2 Department of Pharmacognosy, Faculty of Life Sciences , University of Vienna , Althanstrasse 14 , Vienna 1090 , Austria.
  • 3 Institute of Pharmacy/Computer-aided Molecular Design Group, Center for Molecular Biosciences Innsbruck , University of Innsbruck , Innrain 80/82 , Innsbruck 6020 , Austria.
  • 4 Universidade Kimpa Vita , Province of Uíge, Rua Henrique Freitas No. 1, Bairro Popular , Uíge , Angola.
  • 5 Department of Biology, Institute of Botany, Faculty of Science , Technische Universität Dresden , Zellescher Weg 20 , 01217 Dresden , Germany.
  • 6 Department of Pharmaceutical and Medicinal Chemistry, Institute of Pharmacy , Paracelsus Medical University Salzburg , Strubergasse 21 , 5020 Salzburg , Austria.
PMID: 30207720 DOI: 10.1021/acs.jnatprod.8b00450
Abstract

Six new and four known dihydrochalcone glucoside derivatives (1-10), the phenylpropanoid coniferin (11), and the Lignans (+)-pinoresinol (12) and lariciresinol (13) were isolated from the subaerial plant parts of Thonningia sanguinea in the course of a screening campaign for new antidiabetic lead compounds. The structures of the new substances were elucidated by HRESIMS, NMR, GC-MS, and ECD data evaluation. 2'- O-(3-Galloyl-4,6- O- Sa-hexahydroxydiphenoyl-β-d-glucopyranosyl)-3-hydroxyphloretin (4), 2'- O-(4,6- O- Sa-hexahydroxydiphenoyl-β-d-glucopyranosyl)phloretin (5), 2'- O-(3- O-galloyl-4,6- O- Sa-hexahydroxydiphenoyl-β-d-glucopyranosyl)phloretin (6), and thonningianin B (9) showed moderate protein tyrosine phosphatase-1B inhibition in an enzyme assay (IC50 values ranging from 19 to 25 μM), whereas thonningianin A (10) was identified as a more potent inhibitor (IC50 = 4.4 μM). The observed activity differences could be explained by molecular docking experiments. The activity of 10 could further be confirmed in HEPG2 liver carcinoma cells, where the compound was able to increase the level of phosphorylated Insulin receptors in a concentration-dependent manner.

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