Open Chemistry Journal
2018, 5 : 134-144Published online 2018 November 30. DOI: 10.2174/1874842201805010134
Publisher ID: CHEM-5-134
RESEARCH ARTICLE
Synthesis, α-Amylase Inhibitory Activity and Molecular Docking Studies of 2,4-Thiazolidinedione Derivatives
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
* Address correspondence to this author at the Riphah Institute of Pharmaceutical Sciences, G-7/4, Islamabad, Pakistan; Tel: 03235010850; E-mail: humaira.nadeem@riphah.edu.pk
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, 1HNMR, and 13CNMR 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 (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.
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.