Phenolic 4-hydroxy and 3,5-dihydroxy derivatives of 3-phenoxyquinoxalin-2(1H)-one as potent aldose reductase inhibitors with antioxidant activity

A group of novel quinoxalinone derivatives (4a-h) were prepared and investigated for their inhibitory activity against ALR2 and antioxidant activity. Most of them were found to be potent aldose reductase inhibitors with IC50 values ranging from 0.019 to 0.982 mu M. The most active compound 2-(3-(4-hydroxyphenoxy)-6-fluoro-2-oxoquinoxalin-1(2H)-yl) acetic acid (4c) also had an excellent selectivity. In addition, a number of compounds showed strong antioxidant activity and the phenolic 3,5-dihydroxyl compound 4f with 7-chloro in the quinoxalinone core was most active in scavenging the DPPH radical and suppressing lipid peroxidation. (C) 2015 Elsevier Ltd. All rights reserved.