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, 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.

The medicinal perspective of 2,4‐thiazolidinediones based ligands as antimicrobial, antitumor and antidiabetic agents: A review

“…Docking studies revealed that all the compounds showed good binding affinities ranging from 7.2 to −6.3 kJ/mol due to hydrogen bond formation capacity at multiple sites especially the carbonyl groups present in the ring are involved in hydrogen bonding in the active site. [ 134 ]…”

“…Docking studies revealed that all the compounds showed good binding affinities ranging from 7.2 to −6.3 kJ/mol due to hydrogen bond formation capacity at multiple sites especially the carbonyl groups present in the ring are involved in hydrogen bonding in the active site. [134] Srivastava et al reported the synthesis, biological evaluation, and molecular docking studies of novel 3,5-disubstituted 2,4-TZDs derivatives (87, Figure 49). All the synthesized compounds were structurally characterized and evaluated for antidiabetic, anti-inflammatory, and antioxidant activity.…”

Antifungal Thiazolidines: Synthesis and Biological Evaluation of Mycosidine Congeners

“…Condensation of commercially available 1 , 14 , and 15 with aromatic aldehydes was carried out according to a previously developed method in boiling acetic acid with a 33% methylamine as a catalyst (method A) [ 56 ]. Some of the 5-arylidene derivatives 4 , 10 , and 12 were obtained and described before: 4a [ 53 , 67 , 68 , 69 , 70 , 71 , 72 ] ; 4c [ 69 , 70 ] ; 4d [ 70 ] ; 10a [ 57 ] ; 12b, 17b [ 12 ] ). The alkylation reaction for the compounds 4a – e and 15b with chloroacetic or bromoacetic acid esters was carried out in a DMF solution in the presence of K 2 CO 3 .…”

“…(Z) - 5-(4-Chlorobenzylidene)thiazolidine-2,4-dione (4a) [ 53 , 67 , 68 , 69 , 70 , 71 , 72 ]. A solution of 4-chlorobenzaldehyde (147.5 g. 1.05 mol), 2,4-thiazolidinedione ( 1 ) (117.2 g, 1.0 mol), 33% aqueous solution of methylamine (0.2 mL, 1.6 mmol) in acetic acid (500 mL) was refluxed for 6 h. The reaction mixture was cooled to room temperature and evaporated in vacuo.…”

Design, Synthesis and Antidiabetic Activity of Biphenylcarbonitrile‐Thiazolidinedione Conjugates as Potential α‐Amylase Inhibitors

“…[15] Consequently, glycoside derivatives Voglibose (5 a) and Acarbose (5 b) have been developed as αamylase inhibitors ( Figure 2) for the clinical use. [16] Further, nonglycosidic inhibitors are also being explored which includes arylidine-pyrazolones (6), [17] chalcone-thiazolidinone conjugates (7), [18] pyrazole-thiazolidinone hybrids (8) etc. [19] as potential antidiabetic agents.…”