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

Abstract

Introduction: 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-thiazolidinedione 1(a-g) and four corresponding acetic acid derivatives 2(a-d) have been synthesized by a three-step procedure. Methods: All the synthesized compounds were characterized by elemental analysis, FTIR, 1 HNMR, and 13 CNMR and further screened for their α-amylase inhibitory potential. Results: All the compounds 1(a-g) and 2(a-d) showed varying degree of α-amylase inhibition, especially compound 1c (IC 50 = 6.59μg/ml), 1d (IC 50 =2.03μg/ml) and 1g (IC 50 = 3.14μg/ml) displayed significantly potent α-amylase inhibition as compared to the standard acarbose (IC 50 = 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. Conclusion: 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.