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

doi:10.6023/cjoc201804032

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

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基于葛根素结构的SGLT2抑制剂的设计、合成与体外生物活性研究

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

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 E-mail:shiyongheng1986@aliyun.com;zeh2006@163.com
基金资助:
陕西省高校科协青年人才托举计划（No.20160227）和国家级大学生创新创业训练计划（No.201710716008）资助项目.

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

Received:2018-04-16 Revised:2018-05-22 Published:2018-06-29
Contact: 10.6023/cjoc201804032 E-mail:shiyongheng1986@aliyun.com;zeh2006@163.com
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).

1. Design, Synthesis and In vitro Biological Activity of SGLT2 Inhibitors Based on the Molecule Structure of Puerarin.PDF(2355KB)

Abstract

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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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]. Chin. J. Org. Chem., 2018, 38(8): 1963-1971.

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基于葛根素结构的SGLT2抑制剂的设计、合成与体外生物活性研究

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

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