丹皮酚异丁酸酯类衍生物的合成及体外降血脂活性研究

Study on Synthesis and Hypolipidemic Activities in vitro of Paeonol Isobutyrate Derivatives

目的研究丹皮酚异丁酸酯类衍生物的合成,寻找比先导化合物丹皮酚降血脂活性更佳的目标化合物。方法以丹皮酚为原料,碱性条件下与α-溴代异丁酸发生取代反应,再与不同的醇成酯;以HepG2高血脂细胞实验、脂肪酶活性抑制和胆酸盐结合能力实验研究丹皮酚异丁酸酯类衍生物的体外降血脂活性。结果合成得到6个丹皮酚异丁酸酯类衍生物,化合物结构经核磁共振氢谱、红外光谱和质谱确证;体外降血脂细胞实验发现与丹皮酚组相比,目标化合物2c、2f能明显降低总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)水平(P<0.05),提升高密度脂蛋白胆固醇(HDL-C)水平(P<0.05);2c、2f脂肪酶活性抑制和结合胆酸盐能力实验结果显示,在浓度为5 mg/mL时,脂肪酶的抑制率均可达到60%左右,2c、2f对甘氨胆酸钠(SG)、牛黄胆酸钠(ST)的结合率分别达到了80%和90%左右。结论目标化合物2c、2f具有良好的体外降血脂活性。

Objective To study and synthesis paeonol isobutyrate derivatives,and search for the compounds that have better lipid lowing activity.Methods Paeonol is substituted withα-bromoisobutyric acid in alkaline condition,and then esters with different alcohols,the hypolipidemic activity of paeonol isobutyrate derivatives in vitro is studied by HepG2 hyperlipidemia cell test,lipase activity inhibition and bile salt binding test.Results Six paeonol isobutyrate derivatives are synthesized and their structures are characterized by 1 H-NMR,IR and MS,compared with paeonol group,the target compounds 2 c and 2 f could significantly reduce the level of TC,TG,LDL-C(P<0.05)and increase the level of HDL-C(P<0.05),the experimental results of lipase activity inhibition and bile salt binding ability of 2 c and 2 f show that when the concentration is 5 mg/mL,the inhibition rate of lipase is about 60%,and the binding rate of 2 c and 2 f to SG and ST is about 80%and 90%,respectively.Conclusion Compounds 2 c and 2 f have good hypolipidemic activity in vitro.