RESUMEN
Based on metabolic mechanism of scutellarin in vivo that scutellarin could be hydrolyzed into scutellarein by ß-glucuronide enzyme, some glucose-containing scutellarein derivatives were designed and synthesized through the introduction of glucose moiety at C-7 position of scutellarein via a glucosidic bond. Biological activity evaluation showed that these glucose-containing scutellarein derivatives exhibited potent DPPH radical scavenging activities. Furthermore, the improvement of physicochemical properties such as anticoagulant and neuroprotective activities alongside with the water solubility was achieved by introducing glucose. These findings suggest that the introduction of the glucose moiety to scutellarein wattants further development of this kind of compounds as neuroprotective agents.
Asunto(s)
Apigenina/química , Apigenina/metabolismo , Diseño de Fármacos , Glucosa/química , Glucuronatos/metabolismo , Fármacos Neuroprotectores/síntesis química , Animales , Anticoagulantes/síntesis química , Anticoagulantes/química , Anticoagulantes/metabolismo , Apigenina/síntesis química , Apigenina/farmacología , Sitios de Unión , Supervivencia Celular/efectos de los fármacos , Depuradores de Radicales Libres/síntesis química , Depuradores de Radicales Libres/química , Depuradores de Radicales Libres/farmacología , Peróxido de Hidrógeno/toxicidad , Simulación del Acoplamiento Molecular , Fármacos Neuroprotectores/química , Fármacos Neuroprotectores/farmacología , Células PC12 , Unión Proteica , Estructura Terciaria de Proteína , Ratas , Solubilidad , Trombina/antagonistas & inhibidores , Trombina/metabolismoRESUMEN
Two series of 8-aminomethylated derivatives were prepared by Mannich reaction of scutellarein (2) with appropriate aliphatic amines, alicyclic amines and formaldehyde. All the compounds were tested for their thrombin inhibition activity through the analyzation of prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT) and fibrinogen (FIB). The antioxidant activities of these target products were assessed by 1,1-diphenyl-2-picrylhydrazyl radical 2,2-diphenyl-1-(2,4,6-trinitrophenyl) hydrazyl (DPPH) assay using 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) assay method and the solubility were assessed by ultraviolet (UV). The results showed that morpholinyl aminomethylene substituent derivative (3d) demonstrated stronger anticoagulant activity, better water solubility and good antioxidant activity compared with scutellarein (2), which warrants further development as a agent for ischemic cerebrovascular disease treatment.
