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

Demir Y., Taslimi P., Koçyiğit Ü., Akkuş M., Özaslan M., Duran H., ...Daha Fazla

Archiv der Pharmazie, cilt.353, sa.12, 2020 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 353 Sayı: 12
  • Basım Tarihi: 2020
  • Doi Numarası: 10.1002/ardp.202000118
  • Dergi Adı: Archiv der Pharmazie
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, CAB Abstracts, Chimica, EMBASE, International Pharmaceutical Abstracts, MEDLINE, Veterinary Science Database
  • Anahtar Kelimeler: aldose reductase, enzyme inhibition, molecular docking, pyrazolyl-thiazole, alpha-glycosidase, CARBONIC-ANHYDRASE, CRYSTAL-STRUCTURE, BORON COMPLEXES, ANTIMICROBIAL ACTIVITY, IN-VITRO, ANTICANCER, PROTEIN, BUTYRYLCHOLINESTERASE, ACETYLCHOLINESTERASE
  • Atatürk Üniversitesi Adresli: Evet

Özet

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.