Determination of the inhibition profiles of pyrazolyl-thiazole derivatives against aldose reductase and alpha-glycosidase and molecular docking studies

Demir Y., Taslimi P., KOÇYİĞİT Ü. M. , Akkus M., Ozaslan M. S. , Duran H. E. , ...More

ARCHIV DER PHARMAZIE, vol.353, no.12, 2020 (Journal Indexed in SCI) identifier identifier

  • Publication Type: Article / Article
  • Volume: 353 Issue: 12
  • Publication Date: 2020
  • Doi Number: 10.1002/ardp.202000118
  • Title of Journal : ARCHIV DER PHARMAZIE


Aldose reductase (AR) is the first and rate-limiting enzyme of the polyol pathway, which converts glucose to sorbitol in an NADPH-dependent reaction. alpha-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 ((3aR,4S,7R,7aS)-2-(4-{1-[4-(4-bromophenyl)thiazol-2-yl]-5-(aryl)-4,5-dihydro-1H-pyrazol-3-yl}phenyl)-3a,4,7,7a-tetrahydro-1H-4,7-methanoisoindole-1,3(2H)-dione derivatives;3a-i) on AR and alpha-glycosidase enzymes were investigated. All compounds showed a good inhibitory action against AR and alpha-glycosidase. Among these compounds, compound3dexhibited the best inhibition profiles against AR, with aK(i)value of 7.09 +/- 0.19 mu M, whereas compound3eshowed the lowest inhibition effects, with aK(i)value of 21.89 +/- 1.87 mu M. Also, all compounds showed efficient inhibition profiles against alpha-glycosidase, withK(i)values in the range of 0.43 +/- 0.06 to 2.30 +/- 0.48 mu M, whereas theK(i)value of acarbose was 12.60 +/- 0.78 mu M. Lastly, molecular modeling approaches were implemented to predict the binding affinities of compounds against AR and alpha-glycosidase. In addition, the ADME analysis of the molecules was performed.