Abstract

Hyperglycemia has been shown to be the major risk factor responsible for the systemic complications that are the cause of morbidity and mortality in patients with diabetes. The elevated glucose concentration in blood, activates several pathways such as polyol pathway, PKC pathway, hexosamine pathway and plays an important role not only in cataract but also in the pathogenesis of diabetic complications such as neuropathy, nephropathy and retinopathy. The activation of polyol pathway through aldose reductase enzyme leads to accumulate sorbitol in tissues during diabetic stage. Accumulation of sorbitol causes diabetic complications such as cataract, kidney disease. Inhibition of aldose reductase enzyme activity would be an effective treatment of diabetic complications. In the present study, 21 thiazolyl-2,4- thiazolidinediones (TZDs) (compounds 1-21) were tested for their probable inhibitory ability on kidney aldose reductase enzyme. The enzyme activity was determined spectrophotometrically by monitoring NADPH oxidation which accompanies the reduction of D -L-glyceraldehyde which is used as substrate. The inhibition study was performed merely by using 10^-4 M concentration of each drug and IC₅₀ values of compounds 1-6, 16-21 were studied. 10^-4, 10^-5 and 10^-6M concentrations were performed for calculating IC₅₀ values. Compound 1 (5-((2, 4-dichlorothiazol-5-yl) methylene) thiazolidine-2, 4-dione) is showed the greatest inhibition capacity with the rate 91.11%. TZD-derivatives which have the compound numbers 2, 5, 16 and 20 are followed the compound 1 with the inhibition capacities of 77.50%, 81.31%, 77.36% and 78.97%, respectively. All the remaining TZD-derivatives are showed inhibitory activity between the rates 4.00 - 76.58 %.

Keywords: Thiazolyl-2, 4-thiazolidinediones, Aldose reductase, Enzyme, Inhibition, Diabetes, Polyol pathway