Synthesis, α-Amylase Inhibitory Activity and Molecular Docking Studies of 2,4-Thiazolidinedione Derivatives

Abstract

2,4-Thiazolidinedione and its derivatives exhibit a variety of pharmacological activities including antidiabetic, antiviral, antifungal, anti-inflammatory, anti-cancer and aldose reductase inhibitory activities. Keeping in mind the pharmacological potential of 2,4-Thiazolidinedione derivatives as antidiabetic agents, seven arylidene derivatives of 2,4-thiazolidinedione1(a-g)and four corresponding acetic acid derivatives 2(a-d)have been synthesized by a three-step procedure.All the synthesized compounds were characterized by elemental analysis, FTIR,1HNMR, and13CNMR and further screened for their α-amylase inhibitory potential.All the compounds1(a-g)and2(a-d)showed varying degree of α-amylase inhibition, especially compound1c(IC50= 6.59μg/ml),1d(IC50=2.03μg/ml) and1g(IC50= 3.14μg/ml) displayed significantly potent α-amylase inhibition as compared to the standard acarbose (IC50= 8.26μg/ml). None of the acetic acid derivatives of 5-arylidene-2,4-thiazolidinedione showed prominent inhibitory activity. Docking results indicated that the best binding conformation was found inside the active site cleft of enzyme responsible for hydrolysis of carbohydrates.Therefore, it can be concluded that 2,4-thiazolidinedione derivatives can be used as effective lead molecules for the development of α-amylase inhibitors for the management of diabetes.