title: Synthesis and structure-activity relationship studies of phenolic hydroxyl derivatives based on quinoxalinone as aldose reductase inhibitors with antioxidant activity.
abstract: To enhance aldose reductase (ALR2) inhibition and add antioxidant ability, phenolic hydroxyl was introduced both to the quinoxalinone core and C3 side chain, resulting in a series of derivatives as ALR2 inhibitors. Biological activity tests suggested that most of the derivatives were potent and selective inhibitors with IC50values ranging from 0.059 to 6.825μM, and 2-(3-(4-hydroxystyryl)-7-methoxy-2-oxoquinoxalin-1(2H)-yl)acetic acid (6b) was the most active. Particularly, it was encouraging to find that some derivatives endowed with obvious antioxidant activity, and among them the phenolic 3,4-dihydroxyl compound 6f with 7-hydroxyl in the quinoxalinone core showed the most potent activity, even comparable with the well-known antioxidant Trolox. Structure-activity relationship and docking studies highlighted the importance of phenolic hydroxyl both in C3 side chain and the core structure for constructing potent ALR2 inhibitors with antioxidant activity.
authors.affiliation: School of Chemistry and Chemical Engineering, Beijing Institute of Technology, No. 5, Zhongguancun South Street, 100081 Beijing, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Hao
authors.affiliation: School of Chemistry and Chemical Engineering, Beijing Institute of Technology, No. 5, Zhongguancun South Street, 100081 Beijing, China.
authors.forename: Zhongfei
authors.initials: Z
authors.lastname: Han
authors.affiliation: School of Chemistry and Chemical Engineering, Beijing Institute of Technology, No. 5, Zhongguancun South Street, 100081 Beijing, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.affiliation: School of Chemistry and Chemical Engineering, Beijing Institute of Technology, No. 5, Zhongguancun South Street, 100081 Beijing, China.
authors.forename: Chenying
authors.initials: C
authors.lastname: Li
authors.affiliation: School of Chemistry and Chemical Engineering, Beijing Institute of Technology, No. 5, Zhongguancun South Street, 100081 Beijing, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Wang
authors.affiliation: School of Chemistry and Chemical Engineering, Beijing Institute of Technology, No. 5, Zhongguancun South Street, 100081 Beijing, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: School of Chemistry and Chemical Engineering, Beijing Institute of Technology, No. 5, Zhongguancun South Street, 100081 Beijing, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Yang
authors.affiliation: School of Chemistry and Chemical Engineering, Beijing Institute of Technology, No. 5, Zhongguancun South Street, 100081 Beijing, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Ma
authors.affiliation: School of Chemistry and Chemical Engineering, Beijing Institute of Technology, No. 5, Zhongguancun South Street, 100081 Beijing, China. Electronic address: zcj@bit.edu.cn.
authors.forename: Changjin
authors.initials: C
authors.lastname: Zhu
mesh_terms: D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000975:Antioxidants / Q000737:chemistry; D001665:Binding Sites; D020134:Catalytic Domain; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D020128:Inhibitory Concentration 50; D062105:Molecular Docking Simulation; D010636:Phenols / Q000737:chemistry*; D011485:Protein Binding; D011810:Quinoxalines / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D000975:Antioxidants; D004791:Enzyme Inhibitors; D010636:Phenols; D011810:Quinoxalines; D000449:Aldehyde Reductase
keywords: Aldose reductase inhibitors; Antioxidant activity; Phenolic hydroxyl; Quinoxalinones