Determination of the inhibition profiles of pyrazolyl–thiazole derivatives against aldose reductase and α‐glycosidase and molecular docking studies

Abstract

Aldose reductase (AR) is the first and rate-limiting enzyme of the polyol pathway, which converts glucose to sorbitol in an NADPH-dependent reaction. α-Glycosidase breaks down starch and disaccharides to glucose. Hence, inhibition of these enzymes can be regarded a considerable approach in the treatment of diabetic complications. AR was purified from sheep liver using simple chromatographic methods. The inhibitory effects of pyrazolyl-thiazoles ((3aR,4S,7R,7aS)-2-(4-{1-[4-(4-bromophenyl) thiazol-2-yl]-5-(aryl)-4,5-dihydro-1H-pyrazol-3-yl}phenyl)-3a,4,7,7a-tetrahydro-1H-4,7-methanoisoindole-1,3(2H)-dione derivatives; 3a-i) on AR and α-glycosidase enzymes were investigated. All compounds showed a good inhibitory action against AR and α-glycosidase. Among these compounds, compound 3d exhibited the best inhibition profiles against AR, with a K i value of 7.09 ± 0.19 µM, whereas compound 3e showed the lowest inhibition effects, with a K i value of 21.89 ± 1.87 µM. Also, all compounds showed efficient inhibition profiles against α-glycosidase, with K i values in the range of 0.43 ± 0.06 to 2.30 ± 0.48 µM, whereas the K i value of acarbose was 12.60 ± 0.78 µM. Lastly, molecular modeling approaches were implemented to predict the binding affinities of compounds against AR and α-glycosidase. In addition, the ADME analysis of the molecules was performed.

Thiazole Ring—A Biologically Active Scaffold

“…The inhibitory effects of pyrazolyl-thiazoles derivatives (116a-i) (Figure 49) on AR and α-glycosidase enzymes were investigated by Demir et al [170]. All compounds showed good AR inhibitory activity, with compound 116d being the most potent, with a K i value of 7.09 ± 0.19 µM.…”

Transition‐Metal Complexes of Bidentate Schiff‐Base Ligands: In Vitro and In Silico Evaluation as Non‐Classical Carbonic Anhydrase and Potential Acetylcholinesterase Inhibitors

“…In this study, the procedures applied in synthesis, biological assay, and in silico analyses were provided in the Supporting Information [25–64] …”

Examination of anti-oxidant properties and molecular docking parameters of some compounds in human body

“…The parameters showing the numerical values of the interaction between the molecule and the enzyme are Glide hbond, Glide evdw, Glide ecoul. On the other hand, Glide emodel, Glide energy, Glide einternal, and Glide posenum parameters are the numerical values of the exposure formed between the molecule and protein [65][66][67][68][69].…”