Citation: Shi Yongheng, Bai Liming, Ma Li, Chen Yuyang, Liu Jiping, Zhang Enhu. Design, Synthesis and In vitro Biological Activity of SGLT2 Inhibitors Based on the Molecule Structure of Puerarin[J]. Chinese Journal of Organic Chemistry, ;2018, 38(8): 1963-1971. doi: 10.6023/cjoc201804032 shu

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

Shi Yongheng ^a,, ,
Bai Liming ^a,b ,
Ma Li ^a ,
Chen Yuyang ^a ,
Liu Jiping ^b ,
Zhang Enhu ^b,,

a.
College of Pharmacy, Shaanxi University of Chinese Medicine, Xianyang 712046
b.
Affiliated Hospital of Shaanxi University of Chinese Medicine, Xianyang 712000

Corresponding author: Shi Yongheng, shiyongheng1986@aliyun.com Zhang Enhu, zeh2006@163.com
Received Date: 16 April 2018
Revised Date: 22 May 2018
Available Online: 29 August 2018
Fund Project: the National Students' Training Program for Innovation and Entrepreneurship 201710716008the Young Talent Fund of University Association for Science and Technology in Shaanxi Province 20160227Project 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)

Figures(3)

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.
- puerarin,
- derivative,
- SGLT2 inhibitor,
- diabetes,
- in vitro biological
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