alpha-Glucosidase inhibitory effect of Potentilla astracanica and some isoflavones: Inhibition kinetics and mechanistic insights through in vitro and in silico studies

ŞÖHRETOĞLU D., SARI S., ÖZEL A., Barut B.

INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES, cilt.105, ss.1062-1070, 2017 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 105
  • Basım Tarihi: 2017
  • Doi Numarası: 10.1016/j.ijbiomac.2017.07.132
  • Dergi Adı: INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.1062-1070
  • Anahtar Kelimeler: alpha-Glucosidase, Potentilla, Molecular dynamics, TYPE-2 DIABETES-MELLITUS, MOLECULAR-DYNAMICS, ACCURATE DOCKING, PRUNUS-CERASUS, FORCE-FIELDS, PROTEIN, GENISTEIN, GLIDE, IDENTIFICATION, BACKBONE
  • Karadeniz Teknik Üniversitesi Adresli: Evet

Özet

alpha-Glucosidase enzyme inhibitors are clinically used for the treatment of Type 2 diabetes mellitus. We tested alpha-glucosidase inhibitory effects of Potentilla astracanica Jacq. extracts (1, 2), two compounds isolated from these extracts, prunetin 5-O-beta-glucopyranoside (3) and genistein 5-O-beta-glucopyranoside (4), and their aglycon forms (5 and 6). All the tested materials possessed remarkable alpha-glucosidase inhibitor activity compared to the positive control, acarbose. Genistein (6) showed the highest activity with an IC50 value of 1.47 (+/- 0.11) mu g/ml. An enzyme kinetics analysis revealed that 3 and 6 were uncompetitive, 5 was noncompetitive, and 4 was competitive inhibitors. Using molecular modeling techniques we tried to provide insight into molecular mechanisms of their activity and how allosteric binding of 6 affected binding interactions between the agonist (maltose) and the enzyme. (C) 2017 Elsevier B.V. All rights reserved.