4′-甲基-7-(2-萘磺酰基)大豆素的细胞吸收及代谢研究  

Cell Uptake and Metabolism of 4′-Methyl-7-(2-naphthalene sulfonyl) Daidzein

作　　者：李斌[1] 连重福 刘学强 焦艳晓 彭游[1] Li Bin;Lian Chongfu;Liu Xueqiang;Jiao Yanxiao;Peng You(College of Chemical and Chemical Engineering,Jiangxi Province Engineering Research Center of Ecological Chemical Industry,Jiujiang University,Jiujiang,332005)

机构地区：[1]九江学院化学化工学院江西省生态化工工程技术研究中心,九江332005

出　　处：《化学通报》2021年第7期732-737,共6页Chemistry

基　　金：国家自然科学基金项目(81660541);江西省自然科学基金项目(20202BABL203017);江西省教育厅科技项目(GJJ201839)资助。

摘　　要：对新型大豆素萘磺酸酯衍生物DD的细胞吸收和代谢变化进行研究,并根据实验结果预测其可能存在的体外代谢途径。利用高效液相色谱法对DD在人主动脉血管平滑肌细胞(HAVSMCs)内的吸收和利用率进行研究,并利用液相色谱-质谱联用技术考察其细胞代谢变化。HAVSMCs对DD的吸收率达到了74.3%,远远高于大豆素的细胞吸收率。细胞代谢研究表明,DD中4′-和7-位上的取代基影响其代谢途径和代谢产物。与4′-位的甲基相比,DD的7-位的萘磺酰基更容易水解。对药物分子进行适当的结构修饰和改造,可以增强药物分子的脂溶性,进而提高药物分子在细胞中的吸收利用率,说明药物的吸收利用率与其理化性质密切相关。The cellular absorption and metabolism of a novel derivative of daidzein naphthalene sulfonate DD were studied, and the possible metabolic pathway in vitro was predicted according to the experimental results. The absorption and utilization of DD in human aortic smooth muscle cells(HAVSMCs) were evaluated by high performance liquid chromatography(HPLC), and the metabolism of DD was investigated by liquid chromatography-mass spectrometry(LC-MS). The absorption rate of DD in HAVSMCs was 74.3%, which was much higher than that of daidzein. The study of metabolism showed that the substituents at 4′-and 7-positions in DD affected its metabolic pathway and metabolites. The naphthalene sulfonyl group at 7-position of DD was easier to hydrolyze, compared with the methyl group at 4′-position. The liposolubilities of drug molecules were enhanced by appropriate modification and transformation in their structures, and then improved their absorption and utilization in cells. It showed that the absorption and utilization rate of drugs is closely related to their physical and chemical properties.

关 键 词：大豆素萘磺酸酯 主动脉血管平滑肌细胞 细胞吸收 体外代谢途径 

分 类 号：R285[医药卫生—中药学]