title: Improving the thrombin inhibitory activity of glycyrrhizin, a triterpenic saponin, through a molecular simplification of the carbohydrate moiety.
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.
authors: 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.
authors: Fernando T
authors: FT
authors: de Paula
authors: Petrina Q
authors: PQ
authors: Frauches
authors: Conrado
authors: C
authors: Pedebos
authors: Markus
authors: M
authors: Berger
authors: Simone C B
authors: SC
authors: Gnoatto
authors: Grace
authors: G
authors: Gossmann
authors: Hugo
authors: H
authors: Verli
authors: Jorge A
authors: JA
authors: Guimarães
authors: Cedric S
authors: CS
authors: Graebin
mesh_terms: D001665:Binding Sites; D002241:Carbohydrates / Q000737:chemistry*; D020134:Catalytic Domain; D004789:Enzyme Activation / Q000187:drug effects; D006035:Glycyrrhiza / Q000737:chemistry / Q000378:metabolism; D019695:Glycyrrhizic Acid / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D062105:Molecular Docking Simulation; D018517:Plant Roots / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D012503:Saponins / Q000737:chemistry; D015842:Serine Proteinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D013917:Thrombin / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D002241:Carbohydrates; D012503:Saponins; D015842:Serine Proteinase Inhibitors; D019695:Glycyrrhizic Acid; D013917:Thrombin
keywords: glucuronic acid; glycyrrhetinic acid; glycyrrhizin; saponin; thrombin