Diarylmethanon, bromophenol and diarylmethane compounds: Discovery of potent aldose reductase, α-amylase and α-glycosidase inhibitors as new therapeutic approach in diabetes and functional hyperglycemia


Taslimi P., Aslan H. E., Demir Y., Oztaskin N., MARAŞ A., GÜLÇİN İ., ...More

International Journal of Biological Macromolecules, vol.119, pp.857-863, 2018 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 119
  • Publication Date: 2018
  • Doi Number: 10.1016/j.ijbiomac.2018.08.004
  • Journal Name: International Journal of Biological Macromolecules
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.857-863
  • Keywords: Aldose reductase, Bromophenols, Diarylmethanons, α-Amylase, α-Glycosidase
  • Bilecik Şeyh Edebali University Affiliated: Yes

Abstract

Diabetes mellitus (DM) is a chronic metabolic disease in which there are high blood sugar levels over a prolonged period. Aldose reductase (AR) belongs to aldo-keto reductase superfamily and plays a key role in the polyol pathway. α-Glycosidase and α-amylase are important enzymes in glucose metabolism. In this study, AR was purified from purified from cow liver. The enzyme was obtained with 139.17 purification fold and with a specific activity of 1.67 EU/mg protein. Then, it is observed the inhibition effect of diarylmethanons (1a–d), bromophenols (2a–d and 4a–d) and diarylmethanes (3a–d) on aldose reductase, α-glycosidase and α-amylase enzymes. In these series, compound 2a showed lowest inhibitory activity against AR with a Ki value of 1.09 ± 0.29 μM while compound 2d showed highest inhibitory activity against AR with a Ki value of 0.092 ± 0.015 μM. Additionally, α-glycosidase and α-amylase enzymes were easily inhibited by these compounds. All compounds were tested for their inhibition effects against of α-glycosidase enzyme and demonstrated efficient inhibition profiles with Ki values in the range of 14.44 ± 0.88–43.53 ± 9.06 nM, and IC50 values in the range of 11.72–46.11 nM. Also, inhibition of the α-amylase enzyme, which determined an effective inhibition profile with IC50 values, is in the range of 3.84–29.61 nM.