Design and synthesis of potent and multifunctional aldose reductase inhibitors based on quinoxalinones

Xiangyu Qin, Xin Hao, Hui Han, Shaojuan Zhu, Yanchun Yang, Bobin Wu, Saghir Hussain, Shagufta Parveen, Chaojun Jing, Bing Ma, Changjin Zhu*

*此作品的通讯作者

科研成果: 期刊稿件文章同行评审

203 引用 (Scopus)

摘要

Quinoxalin-2(1H)-one based design and synthesis produced several series of aldose reductase (ALR2) inhibitor candidates. In particular, phenolic structure was installed in the compounds for the combination of antioxidant activity and strengthening the ability to fight against diabetic complications. Most of the series 6 showed potent and selective effects on ALR2 inhibition with IC50 values in the range of 0.032-0.468 μM, and 2-(3-(2,4-dihydroxyphenyl)-7-fluoro-2-oxoquinoxalin-1(2H)-yl)acetic acid (6e) was the most active. More significantly, most of the series 8 revealed not only good activity in the ALR2 inhibition but also potent antioxidant activity, and 2-(3-(3-methoxy-4-hydroxystyryl)-2-oxoquinoxalin-1(2H)-yl)acetic acid (8d) was even as strong as the well-known antioxidant Trolox at a concentration of 100 μM, verifying the C3 p-hydroxystyryl side chain as the key structure for alleviating oxidative stress. These results therefore suggest an achievement of multifunctional ALR2 inhibitors having both potency for ALR2 inhibition and as antioxidants.

源语言英语
页(从-至)1254-1267
页数14
期刊Journal of Medicinal Chemistry
58
3
DOI
出版状态已出版 - 12 2月 2015

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