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Determination of the inhibition profiles of pyrazolyl–thiazole derivatives against aldose reductase and α‐glycosidase and molecular docking studies
Author(s) -
Demir Yeliz,
Taslimi Parham,
Koçyiğit Ümit M.,
Akkuş Musa,
Özaslan Muhammet Serhat,
Duran Hatice Esra,
Budak Yakup,
Tüzün Burak,
Gürdere Meliha B.,
Ceylan Mustafa,
Taysi Seyithan,
Gülçin İlhami,
Beydemir Şükrü
Publication year - 2020
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.202000118
Subject(s) - chemistry , aldose reductase , glycoside hydrolase , polyol pathway , acarbose , stereochemistry , enzyme , thiazole , iminosugar , aldehyde reductase , aldose , biochemistry , glycoside
Aldose reductase (AR) is the first and rate‐limiting enzyme of the polyol pathway, which converts glucose to sorbitol in an NADPH‐dependent reaction. α‐Glycosidase breaks down starch and disaccharides to glucose. Hence, inhibition of these enzymes can be regarded a considerable approach in the treatment of diabetic complications. AR was purified from sheep liver using simple chromatographic methods. The inhibitory effects of pyrazolyl–thiazoles ((3a R ,4 S ,7 R ,7a S )‐2‐(4‐{1‐[4‐(4‐bromophenyl)thiazol‐2‐yl]‐5‐(aryl)‐4,5‐dihydro‐1 H ‐pyrazol‐3‐yl}phenyl)‐3a,4,7,7a‐tetrahydro‐1 H ‐4,7‐methanoisoindole‐1,3(2 H )‐dione derivatives; 3a – i ) on AR and α‐glycosidase enzymes were investigated. All compounds showed a good inhibitory action against AR and α‐glycosidase. Among these compounds, compound 3d exhibited the best inhibition profiles against AR, with a K i value of 7.09 ± 0.19 µM, whereas compound 3e showed the lowest inhibition effects, with a K i value of 21.89 ± 1.87 µM. Also, all compounds showed efficient inhibition profiles against α‐glycosidase, with K i values in the range of 0.43 ± 0.06 to 2.30 ± 0.48 µM, whereas the K i value of acarbose was 12.60 ± 0.78 µM. Lastly, molecular modeling approaches were implemented to predict the binding affinities of compounds against AR and α‐glycosidase. In addition, the ADME analysis of the molecules was performed.