Tyrosinase and alpha-glucosidase inhibitory potential of compounds isolated from Quercus coccifera bark: In vitro and in silico perspectives

SARI S., Barut B., ÖZEL A., Kuruuzum-Uz A., ŞÖHRETOĞLU D.

BIOORGANIC CHEMISTRY, vol.86, pp.296-304, 2019 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 86
  • Publication Date: 2019
  • Doi Number: 10.1016/j.bioorg.2019.02.015
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.296-304
  • Keywords: alpha-Glucosidase, Tyrosinase, Quercus, Polydatin, Molecular modelling, MECHANISTIC INSIGHTS, ACCURATE DOCKING, MEDICINAL-PLANTS, KINETICS, GLIDE, ANTIOXIDANT, FLAVONOIDS
  • Karadeniz Technical University Affiliated: Yes


Bark of Quercus coccifera is widely used in folk medicine. We tested tyrosinase and alpha-glucosidase inhibitory effects of Q. coccifera bark extract and isolated compounds from it. The extract inhibited tyrosinase with an IC50 value of 75.13 +/- 0.44 mu g/mL. Among the isolated compounds, polydatin (6) showed potent tyrosinase inhibition compared to the positive control, kojic acid, with an IC50 value of 4.05 +/- 0.30 mu g/mL. The Q. coccifera extract also inhibited alpha-glucosidase significantly with an IC50 value of 3.26 +/- 0.08 mu g/mL. (-)-8-Chlorocatechin (5) was the most potent isolate, also more potent than the positive control, acarbose, with an IC50 value of 43.60 +/- 0.67 mu g/mL. According to the kinetic analysis, 6 was a noncompetitive and 5 was a competitive inhibitor of tyrosinase, and 5 was a noncompetitive a-glucosidase inhibitor. In the light of these findings, we performed in silico molecular docking studies for 5 and 6 with QM/MM optimizations to predict their tyrosinase inhibition mechanisms at molecular level and search for correlations with the in vitro results. We found that the ionized form of 5 (5i) showed higher affinity and more stable binding to tyrosinase catalytic site than its neutral form, while 6 bound to the predicted allosteric sites of the enzyme better than the catalytic site.