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Chem Biol Drug Des. 2013 Dec;82(6):756-60. doi: 10.1111/cbdd.12204. Epub 2013 Oct 25.

Improving the thrombin inhibitory activity of glycyrrhizin, a triterpenic saponin, through a molecular simplification of the carbohydrate moiety.

Chemical biology & drug design

Fernando T de Paula, Petrina Q Frauches, Conrado Pedebos, Markus Berger, Simone C B Gnoatto, Grace Gossmann, Hugo Verli, Jorge A Guimarães, Cedric S Graebin

Affiliations

  1. Laboratório de Diversidade Molecular e Química Medicinal (LaDMol-QM), Departamento de Química, Instituto de Ciências Exatas, Universidade Federal Rural do Rio de Janeiro, Rodovia BR-465, Km. 7, Seropédica, RJ, 23897-000, Brazil.

PMID: 23964664 DOI: 10.1111/cbdd.12204

Abstract

Glycyrrhizin, a saponin, and its aglycone glycyrrhetinic acid are natural products found in the Liquorice (Glycyrrhiza glabra L.) root extract. This saponin is known for its in vitro and in vivo thrombin inhibitory activity. The design and synthesis of five glycyrrhizin derivatives were carried out to improve the natural product activity. Compound 3b, a phthalic ester derivative of glycyrrhizin, presented a more pronounced thrombin inhibition (IC50  = 114.4 ± 1.3 μm) than the saponin (IC50  = 235.7 ± 1.4 μm). Molecular docking simulations performed to investigate the molecular interaction between compound 3b and the enzyme indicate that this product is, as previously determined for glycyrrhizin, an allosteric thrombin inhibitor.

© 2013 John Wiley & Sons A/S.

Keywords: glucuronic acid; glycyrrhetinic acid; glycyrrhizin; saponin; thrombin

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