RESUMEN

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.

Asunto(s)

Carbohidratos/química , Ácido Glicirrínico/química , Ácido Glicirrínico/farmacología , Inhibidores de Serina Proteinasa/química , Trombina/antagonistas & inhibidores , Sitios de Unión , Dominio Catalítico , Activación Enzimática/efectos de los fármacos , Glycyrrhiza/química , Glycyrrhiza/metabolismo , Ácido Glicirrínico/síntesis química , Ácido Glicirrínico/metabolismo , Humanos , Simulación del Acoplamiento Molecular , Raíces de Plantas/química , Raíces de Plantas/metabolismo , Unión Proteica , Saponinas/química , Inhibidores de Serina Proteinasa/síntesis química , Inhibidores de Serina Proteinasa/metabolismo , Inhibidores de Serina Proteinasa/farmacología , Trombina/metabolismo