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

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. 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