Synthesis, α-Amylase Inhibitory Activity and Molecular Docking Studies of 2,4-Thiazolidinedione Derivatives
Fawad Naeem1, Humaira Nadeem2, *, Aun Muhammad3, Muhammad Ammar Zahid1, Adil Saeed2
1 Department of Pharmaceutical Chemistry, Shifa Tameer-e-Millat University, Islamabad, Pakistan
2 Department of Pharmaceutical Chemistry, Riphah Institute of Pharmaceutical Sciences, G-7/4, Islamabad, Pakistan
3 Department of Biotechnology, Institute of Molecular Biology and Biotechnology, Bahauddin Zikariya University, Multan, Pakistan
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.
All the synthesized compounds were characterized by elemental analysis, FTIR, 1HNMR, and 13CNMR and further screened for their α-amylase inhibitory potential.
All the compounds 1(a-g) and 2(a-d) showed varying degree of α-amylase inhibition, especially compound 1c (IC50 = 6.59μg/ml), 1d (IC50=2.03μg/ml) and 1g (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.
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* Address correspondence to this author at the Riphah Institute of Pharmaceutical Sciences, G-7/4, Islamabad, Pakistan; Tel: 03235010850; E-mail: email@example.com