NO供体型丹皮酚氧异丁酸硝酸酯类衍生物的合成及降血脂活性研究

Synthesis and Hypolipidemic Activity of NO-donating Paeonoloxyisobutyrate Nitrate Derivatives

以丹皮酚为先导化合物,与α-溴代异丁酸通过Willamson合成法得到丹皮酚氧异丁酸,与不同碳数的二溴烷烃生成丹皮酚氧异丁酸溴代烷基酯中间体,再与硝酸银反应得到5个目标化合物。目标化合物结构经核磁共振氢谱、红外光谱和质谱确证。采用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对所得化合物进行活性研究。实验结果表明目标化合物降血脂活性高于丹皮酚,其中丹皮酚氧异丁酸硝氧乙基酯活性最好,其升高HDL-C能力高于非诺贝特。当目标化合物浓度为5 mg/mL时,脂肪酶抑制率可达40%左右,对甘氨胆酸钠(SG)、牛黄胆酸钠(ST)的结合率可达80%左右。

Paeonol oxyisobutyric acid was synthesized from paeonol andα-bromoisobutyric acid by Willamson method,and then reacted with dibromoalkanes with different carbon numbers to form paeonol oxyisobutyric acid alkyl ester intermediate.The intermediate was then reacted with silver nitrate to obtain five target compounds.The structure of the target compound was confirmed by 1HMNR,IR and MS.The target compounds were subjected to activity studies by using HepG2 hyperlipidemia assay,lipase activity inhibition and cholate binding capacity assay.The HepG2 experimental results showed that the lipid-lowering activities of target compounds were higher than that of paeonol,among which 2-(nitrooxy)ethyl 2-(2-acetyl-5-methoxyphenoxy)-2-methylpropanoate had the best activity.Moreover,the ability to increase HDL-C of target compound was higher than that of fenofibrate,and the inhibition rate of lipase was about 40%,the binding rate to sodium glycocholate(SG)and sodium taurocholate(ST)can reach about 80%,when the concentration of target compound was 5 mg/mL.