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Design of Benzothiazolone‐Based Carboxylic Acid Aldose Reductase Inhibitors
Author(s) -
Lei Yanqi,
Zhang Xin,
Zhang Xiaonan,
Xu Long,
Liu Wenchao,
Chen Huan,
Zhu Changjin,
Ma Bing
Publication year - 2021
Publication title -
chemistryselect
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.437
H-Index - 34
ISSN - 2365-6549
DOI - 10.1002/slct.202101443
Subject(s) - aldose reductase , aldose reductase inhibitor , acetic acid , aldehyde reductase , chemistry , dpph , antioxidant , lipid peroxidation , reductase , carboxylic acid , biochemistry , enzyme , stereochemistry
Aldose Reductase (AR, ALR2) is a member of the aldo‐keto reductase superfamily that plays a critical role in diabetic complications. In this work, benzothiazolone was employed as the scaffold, and the C6 position was modified with aryl and heterocyclic groups to design potent inhibitor against ALR2. 2‐(6‐(4‐hydroxystyryl)‐2‐oxobenzothiazol‐3(2H)‐yl)acetic acid ( 6 c ) was identified the most active with IC 50 value of 18.8 nM. 2‐(6‐(3,4‐dihydroxyphenyl)‐2‐oxobenzothiazol‐3(2H)‐yl)acetic acid ( 4 c ) and 2‐(6‐(4‐hydroxy‐3‐methoxystyryl)‐2‐oxobenzothiazol‐3(2H)‐yl)acetic acid ( 6 b ) were also strong in the ALR2 inhibition, and even exhibited good antioxidant activity by tests of DPPH radical scavenging and lipid peroxidation suppression. 6 b having C6‐hydroxymethoxystyryl sidechain is suggested as a promising candidate for further structure optimizations.