摘要/Abstract

合成了一系列葛根素衍生物，采用稳定表达钠-葡萄糖协同转运蛋白2（human sodium-dependent glucose cotransporter 2，hSGLT2）的中国仓鼠卵巢细胞（Chinese hamster ovary，CHO）和¹⁴C-甲基葡萄糖苷为底物评价衍生物体外抑制SGLT2的活性.葛根素衍生物具有显著的抑制SGLT2的活性，部分葛根素双取代衍生物的IC₅₀（hSGLT2）可达20~30 nmol·L^-1，是葛根素活性的40~60倍.单取代衍生物如正己基葛根素（1i）、正辛基葛根素（1j）、对甲基苄基葛根素（1l）和对甲氧基苄基葛根素（1m）也表现出很强的抑制SGLT2活性，且保留了7-OH结构，可能保留了母核葛根素抗氧化、调血脂的药理活性，这对糖尿病及其心血管并发症的治疗是有利的.
关键词: 葛根素, 衍生物, SGLT2抑制剂, 糖尿病, 体外生物活性
A new class of mild sodium-dependent glucose cotransporter 2 (SGLT2) inhibitors with glucosyl isoflavone structure were prepared from puerarin. The in vitro biological activity was performed on Chinese hamster ovary (CHO) cells stably expressing human SGLT2 while taking[¹⁴C]-methyl-D-glucopyranoside ([¹⁴C]-AMG) as the substrate. Some derivatives exhibited potent activity against SGLT2 with IC₅₀ among 20~30 nmol/L. The inhibitory activities of derivatives with more lipophilic substitutents were more potent. The compounds whose 4'-OH and 7-OH were both protected with alkyl or benzyl are more active than those with only the 4'-OH being protected. The inhibitory activity of some homologues has no great difference. 4'-O-n-Hexylpuerarin (1i), 4'-O-n-octylpuerarin (1j), 4'-O-(4-methylbenzyl)puerarin (1l), 4'-O-(4-methoxylbenzyl)-puerarin (1m) with moderate inhibitory activity against SGLT2 may have anti-oxidant and anti-atherosclerotic properties due to the presence of Ar-OH in the molecule structure, which will be very useful to treat diabetic disease and cardiovascular complications.
Key words: puerarin, derivative, SGLT2 inhibitor, diabetes, in vitro biological


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