Discovery of potent alpha-glucosidase inhibitor flavonols: Insights into mechanism of action through inhibition kinetics and docking simulations

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

BIOORGANIC CHEMISTRY, cilt.79, ss.257-264, 2018 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 79
  • Basım Tarihi: 2018
  • Doi Numarası: 10.1016/j.bioorg.2018.05.010
  • Dergi Adı: BIOORGANIC CHEMISTRY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.257-264
  • Hacettepe Üniversitesi Adresli: Evet

Özet

Beside other pharmaceutical benefits, flavonoids are known for their potent a-glucosidase inhibition. In the present study, we investigated alpha-glucosidase inhibitory effects of structurally related 11 flavonols, among which quercetin-3-O-(3 ''-O-galloyl)-beta-galactopyranoside (8) and quercetin 3-O-(6 ''-O-galloyl)-beta-glucopyranoside (9) showed significant inhibition compared to the positive control, acarbose, with IC50 values of 0.97 +/- 0.02 and 1.35 +/- 0.06 mu M, respectively. It was found that while sugar substitution to C3-OH of C ring reduced the alpha-glucosidase inhibitory effect, galloyl substitution to these sugar units increased it. An enzyme kinetics analysis revealed that 7 was competitive, whereas 1, 2, 8, and 9 were uncompetitive inhibitors. In the light of these findings, we performed molecular docking studies to predict their inhibition mechanisms at atomic level.