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

作者：Shi, Yongheng^*; Bai, Liming; Ma, Li; Chen, Yuyang; Liu, Jiping; Zhang, Enhu^*

来源：Chinese Journal of Organic Chemistry, 2018, 38(8): 1963-1971.

DOI：10.6023/cjoc201804032

• puerarin
• derivative
• SGLT2 inhibitor
• diabetes
• in vitro biological

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[C-14]-methyl-D-glucopyranoside ([C-14]-AMG) as the substrate. Some derivatives exhibited potent activity against SGLT2 with IC50 among 20 similar to 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.

• 出版日期2018-8-25
• 单位陕西中医药大学