Novel daidzein napsylates (DD4 and DD5) were synthesized by microwave irradiation, according to structural modification of daidzein (DAI) using the principle of pharmacokinetic transformation. The pharmacological properties of DD4 and DD5 were evaluated via high performance liquid chromatography (HPLC) and calculated based on the drug design software ChemAxon 16.1.18. The cell uptake changes of DD4 and DD5 were investigated to analyse the structure–property relationship. The metabolisms of DD4 and DD5 were analysed by HPLC-mass spectrometry in human aortic vascular smooth muscle cells (HAVSMCs) and their possible metabolic pathways were inferred in vivo. The results showed that the solubility of DD4 and DD5 was increased by 2.79 × 10⁵ and 2.16 × 10⁵ times compared to that of DAI, separately, in ethyl acetate. The maximum absorption rates of DD4 and DD5 were enhanced by 4.3–4.5 times relative to DAI. Preliminary studies on metabolites of DD4 and DD5 in HAVSMCs showed that DD4 and DD5 were hydrolysed into DAI under the action of intracellular hydrolase in two ways, ester hydrolysis or ether hydrolysis. Then, DAI was combined with glucuronic acid to form daidzein monoglucuronate under the action of uridine diphosphate (UDP)-glucuronidase. Meanwhile, it was also found that metabolite M5 of DD5 could undergo glucuronidation under the action of UDP-glucuronosyltransferase and competitive sulphation under the action of sulphotransferase to produce its sulfate conjugate M7. Analysis of structure–property relationships indicated that the absorption and utilization of drugs is closely relative to the physical properties and could be improved by adjusting the liposolubility. The pharmaceutical properties were optimized comprehensively after DAI was modified by naphthalene sulphonate esterification. This indicates that this kind of derivatives may have relatively good absorption and transport characteristics and biological activities in vivo. The research on biological activities of the new derivatives (DD4 and DD5) is ongoing in our laboratory.

根据黄豆苷元（DAI）的结构修饰，利用药代动力学转化原理，通过微波辐照合成了新的黄豆苷元萘酸酯（DD4和DD5）。DD4和DD5的药理特性通过高效液相色谱（HPLC）进行评估，并根据药物设计软件C hem A xon 16.1.18进行计算。研究了DD4和DD5的细胞摄取变化，以分析其结构与性质之间的关系。DD4和DD5的代谢物通过HPLC质谱在人主动脉血管平滑肌细胞（HAVSMCs）和它们可能的代谢途径分析被推测在体内。结果表明DD4和DD5的溶解度提高了2.79×10 ⁵和2.16×10 ⁵与DAI相比，在乙酸乙酯中的分离倍数。相对于DAI，DD4和DD5的最大吸收率提高了4.3-4.5倍。对HAVSMCs中DD4和DD5代谢产物的初步研究表明，在细胞内水解酶的作用下，DD4和DD5被酯水解或醚水解两种方式水解为DAI。然后，在尿苷二磷酸（UDP）-葡糖醛酸糖苷酶的作用下，将DAI与葡糖醛酸结合以形成大豆苷元单葡糖醛酸酸酯。同时，还发现DD5的代谢物M5在UDP-葡萄糖醛酸糖基转移酶的作用下可以进行葡糖醛酸化，而在磺基转移酶的作用下进行竞争性硫酸化以产生其硫酸盐结合物M7。结构-性质关系的分析表明，药物的吸收和利用与物理性质密切相关，可以通过调节脂溶性来改善。通过萘磺酸酯化改性DAI后，可全面优化药物性能。这表明这种衍生物可能具有相对较好的吸收和运输特性以及生物活性。体内。新衍生物（DD4和DD5）的生物活性研究正在我们的实验室中进行。