Diarylmethanon, bromophenol and diarylmethane compounds: Discovery of potent aldose reductase, alpha-amylase and alpha-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 identifier


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. alpha-Glycosidase and alpha-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, a-glycosidase and alpha-amylase enzymes. In these series, compound 2a showed lowest inhibitory activity against AR with a K-i value of 1.09 +/- 0.29 mu M while compound 2d showed highest inhibitory activity against AR with a K-i value of 0.092 +/- 0.015 mu M. Additionally, alpha-glycosidase and alpha-amylase enzymes were easily inhibited by these compounds. All compounds were tested for their inhibition effects against of alpha-glycosidase enzyme and demonstrated efficient inhibition profiles with K-i 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 alpha-amylase enzyme, which determined an effective inhibition profile with IC50 values, is in the range of 3.84-29.61 nM. (C) 2018 Elsevier B.V. All rights reserved.