Synthesis of New Thiazolidine-2,-4-dione-azole Derivatives and Evaluation of Their α-Amylase and α-Glucosidase Inhibitory Activity

Abstract

In a search for α-amylase and α-glucosidase inhibitors to treat type 2 diabetes in this study, a new series of thiazolidine-2,4-dione derivatives with azole heterocyclic compounds were designed and synthesized via Knoevenagel condensation for the first time. These synthesized compounds are characterized by IR, 1H NMR, 13C NMR, DEPT-135, and HRMS. All the synthesized compounds were evaluated for α-amylase and α-glucosidase inhibitory activity using acarbose as standard. The lipophilicity (C log P) and molar refractivity (MR) for the compounds were also studied. Structure–activity relationship study (SAR) revealed that compounds 14a–c exhibited maximum inhibition due to the presence of fluorine in a hydrophobic site of aromatic phenyl amine at the seventh position of azaindole. To further verify the effect of C log P of substituents and MR on biological activity, calculation of C log P and MR (molecular refractivity) parameter of all compounds have done using ChemDraw software. Compounds 14a–c found to show higher inhibition due to higher value of C log P (14a = 6.49, 14b = 5.63, 14c = 6.45) and MR (14a = 125, 14b = 117, 14c = 123). These properties make compounds 14a–c to have more inhibitory activity. Among the tested compounds, 14a–c showed inhibition in the range of standard acarbose at the concentration of 250 µg/ml against α-amylase and α-glucosidase.