大豆苷元苯磺酸酯衍生物的细胞代谢研究

Study on Cell Metabolism of Daidzein Benzene Sulfonate Derivatives

该文研究了大豆苷元苯磺酸酯衍生物D1~D3在人主动脉血管平滑肌细胞中的代谢途径。利用高效液相色谱-质谱(HPLC-MS)检测了大豆苷元苯磺酸酯衍生物的细胞代谢产物,初步推断出苯磺酸酯衍生物的体外代谢途径。研究发现,大豆苷元苯磺酸酯衍生物D1~D3水解代谢产物的进一步葡萄糖醛酸苷化和硫酸化是其主要代谢途径,二者存在竞争关系,衍生物均可以代谢成先导物大豆苷元(DD)。其中化合物D2是先发生苯磺酸酯基的水解,然后甲基醚水解生成DD的代谢途径,表明在细胞内水解酶的作用下苯磺酸酯键比甲基醚键更易发生水解。而化合物D1、D3则存在两种可能的代谢途径,表明在细胞内水解酶的作用下,乙酰基、乙基和苯磺酸酯基可以同时发生水解。该体外代谢途径的研究可为化合物D1~D3的整体实验提供可靠的理论依据。

The metabolic pathways of daidzein benzene sulfonate derivatives D1-D3 in human aortic vascular smooth muscle cells were studied in this paper.The cellular metabolites of daidzein benzene sulfonate derivatives were detected by HPLC-MS to infer the metabolic pathways in vitro of benzene sulfonate derivatives preliminarily.It was found that further glucuronidation and sulfation of the hydrolytic metabolites of daidzein benzene sulfonate derivatives D1-D3 were the main metabolic pathways,and there is a competition between these two reactions.The derivatives all could be metabolized to lead compound——daidzein(DD).The benzene sulfonate group of D2 underwent hydrolysis,followed by hydrolysis of methyl ether to form DD in the metabolic pathway.It indicated that the hydrolysis of phenylsulfonate bond was easier than that of methyl ether bond under the action of intracellular hydrolase.However,there were two possible metabolic pathways for compounds D1 and D3,which showed that acetyl,ethyl and benzenesulfonate groups could be hydrolyzed simultaneously under the action of intracellular hydrolase.This study on metabolism in vitro provided a reliable theoretical basis for the overall experiment of compounds D1-D3.