Chin. J. Org. Chem. ›› 2018, Vol. 38 ›› Issue (8): 1963-1971.DOI: 10.6023/cjoc201804032 Previous Articles     Next Articles



史永恒a, 白黎明a,b, 马丽a, 陈宇阳a, 刘继平b, 张恩户b   

  1. a 陕西中医药大学药学院 咸阳 712046;
    b 陕西中医药大学附属医院 咸阳 712000
  • 收稿日期:2018-04-16 修回日期:2018-05-22 发布日期:2018-06-29
  • 通讯作者: 史永恒, 张恩户;
  • 基金资助:


Design, Synthesis and In vitro Biological Activity of SGLT2 Inhibitors Based on the Molecule Structure of Puerarin

Shi Yonghenga, Bai Liminga,b, Ma Lia, Chen Yuyanga, Liu Jipingb, Zhang Enhub   

  1. a College of Pharmacy, Shaanxi University of Chinese Medicine, Xianyang 712046;
    b Affiliated Hospital of Shaanxi University of Chinese Medicine, Xianyang 712000
  • Received:2018-04-16 Revised:2018-05-22 Published:2018-06-29
  • Contact: 10.6023/cjoc201804032;
  • Supported by:

    Project supported by the Young Talent Fund of University Association for Science and Technology in Shaanxi Province (No. 20160227) ane the National Students' Training Program for Innovation and Entrepreneurship (No. 201710716008).

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