In vitro and in silico studies of fluorinated 2,3‐disubstituted thiazolidinone‐pyrazoles as potential α‐amylase inhibitors and antioxidant agents

Abstract

As part of our effort to identify potent α-amylase inhibitors, in the present study, a novel series of fluorinated thiazolidinone-pyrazole hybrid molecules were prepared by the condensation of 3-(aryl/benzyloxyaryl)-pyrazole-4-carbaldehydes with fluorinated 2,3disubstituted thiazolidin-4-ones. The structures of the newly synthesized compounds were confirmed by infrared, 1 H nuclear magnetic resonance (NMR), 13 C NMR, and liquid chromatography-mass spectrometry data. All the compounds were screened for their αamylase inhibitory and free radical scavenging activities by DPPH (1,1-diphenyl-2picrylhydrazyl) and ABTS methods. Among the tested compounds, compound 8g emerged as a promising α-amylase inhibitor with IC 50 = 0.76 ± 1.23 µM, and it was found to be more potent than the standard drug acarbose (IC 50 = 0.86 ± 0.81 μM). Compounds 8b and 8g showed strong free radical scavenging activity compared to the standard butylated hydroxyl anisole. The kinetic study of compound 8g revealed the reversible, classical competitive inhibition mode on the α-amylase enzyme. Molecular docking and dynamic simulations studies were performed for the most potent compound 8g, which displayed remarkable hydrogen bonding with the α-amylase protein (PDB ID: 1DHK).

Discovery of Novel Coumarin Derivatives as Potential Dual Inhibitors against α-Glucosidase and α-Amylase for the Management of Post-Prandial Hyperglycemia via Molecular Modelling Approaches

“…However, while investigating the intermolecular interactions, acarbose formed more hydrogen bonds (seven) in comparison with CD-59 (six) during the simulation. The MD simulation run for α-amylase complexed with CD-59 was in accordance with the previous results obtained in [37][38][39]. The stability of CD-59 inside the inhibitor binding site of the protein was hence proven in comparison with the published literature.…”

“…(5-(7-methoxy-2H-chromen-2-one)-1,3,4-oxadiazol-2-yl)methoxy)-3,5-dimethylphenyl)(2-nitrophenyl)methanone With basic skeleton, coumarin contains methoxy group at 7th position, 2-methyl groups present at ortho position of phenyl ring of benzophenone and nitro group is present at ortho position of benzoyl ring of benzophenone (5-(7-methoxy-2H-chromen-2-one)-1,3,4-oxadiazol-2-yl)methoxy)-3,5-dimethylphenyl)(4-chlorophenyl)methanone (CD-37) With basic skeleton, coumarin contains methoxy group at 7th position, 2-methyl groups present at ortho position of phenyl ring of benzophenone and chloro group is present at para position of benzoyl ring of benzophenone O (5-(7-methoxy-2H-chromen-2-one)-1,3,4-oxadiazol-2-yl)methoxy)-3,5-dimethylphenyl)(4-t-butylphenyl)methanone With basic skeleton, coumarin contains methoxy group at 7th position, 2-methyl groups present at ortho position of phenyl ring of benzophenone and t-butyl group is present at para position of benzoyl ring of benzophenone (5-(7-methoxy-2H-chromen-2-one)-1,3,4-oxadiazol-2-yl)methoxy)-3,5-dimethylphenyl)(4-methylphenyl)methanone (CD-39) With basic skeleton, coumarin contains methoxy group at 7th position, 2-methyl groups present at ortho position of phenyl ring of benzophenone and methyl group is present at para position of benzoyl ring of benzophenone O (5-(7-methoxy-2H-chromen-2-one)-1,3,4-oxadiazol-2-yl)methoxy)-3,5-dimethylphenyl)(4-iodophenyl)methanone (CD-40)With basic skeleton, coumarin contains methoxy group at 7th position, 2-methyl groups present at ortho position of phenyl ring of benzophenone and iodo group is present at para position of benzoyl ring of benzophenone4-((5-(7-methoxy-2H-chromen-2-one)-1,3,4-oxadiazol-2yl)methoxy)-3,5-dimethylphenyl)(4chlorophenyl)methanone (CD-37)With basic skeleton, coumarin contains methoxy group at 7th position, 2-methyl groups present at ortho position of phenyl ring of benzophenone and chloro group is present at para position of benzoyl ring of (5-(7-methoxy-2H-chromen-2-one)-1,3,4-oxadiazol-2-yl)methoxy)-3,5-dimethylphenyl)(2-nitrophenyl)methanone (CD-36)With basic skeleton, coumarin contains methoxy group at 7th position, 2-methyl groups present at ortho position of phenyl ring of benzophenone and nitro group is present at ortho position of benzoyl ring of benzophenone (5-(7-methoxy-2H-chromen-2-one)-1,3,4-oxadiazol-2-yl)methoxy)-3,5-dimethylphenyl)(4-chlorophenyl)methanone (CD-37) With basic skeleton, coumarin contains methoxy group at 7th position, 2-methyl groups present at ortho position of phenyl ring of benzophenone and chloro group is present at para position of benzoyl ring of benzophenoneO (5-(7-methoxy-2H-chromen-2-one)-1,3,4-oxadiazol-2-yl)methoxy)-3,5-dimethylphenyl)(4-t-butylphenyl)methanone (CD-38)With basic skeleton, coumarin contains methoxy group at 7th position, 2-methyl groups present at ortho position of phenyl ring of benzophenone and t-butyl group is present at para position of benzoyl ring of benzophenone (5-(7-methoxy-2H-chromen-2-one)-1,3,4-oxadiazol-2-yl)methoxy)-3,5-dimethylphenyl)(4-methylphenyl)methanone (CD-39) With basic skeleton, coumarin contains methoxy group at 7th position, 2-methyl groups present at ortho position of phenyl ring of benzophenone and methyl group is present at para position of benzoyl ring of benzophenoneO (5-(7-methoxy-2H-chromen-2-one)-1,3,4-oxadiazol-2-yl)methoxy)-3,5-dimethylphenyl)(4-iodophenyl)methanone (CD-40)With basic skeleton, coumarin contains methoxy group at 7th position, 2-methyl groups present at ortho position of phenyl ring of benzophenone and iodo group is present at para position of benzoyl ring of benzophenone4-((5-(7-methoxy-2H-chromen-2-one)-1,3,4-oxadiazol-2yl)methoxy)-3,5-dimethylphenyl)(4-tbutylphenyl)methanone (CD-38)With basic skeleton, coumarin contains methoxy group at 7th position, 2-methyl groups present at ortho position of phenyl ring of benzophenone and t-butyl group is prese...…”

Inhibitory Effect of Polyphenols from the Whole Green Jackfruit Flour against α-Glucosidase, α-Amylase, Aldose Reductase and Glycation at Multiple Stages and Their Interaction: Inhibition Kinetics and Molecular Simulations

“…Conversely, both caffeic acid and acarbose were not able to bind to all three catalytic residues. Binding to these catalytic residues would effectively reduce the activity of α-amylase, as indicated in recent studies [ 52 , 53 ]. Therefore, syringic acid proves to be a more efficient inhibitor than caffeic acid and acarbose.…”

Phyto-Computational Intervention of Diabetes Mellitus at Multiple Stages Using Isoeugenol from Ocimum tenuiflorum: A Combination of Pharmacokinetics and Molecular Modelling Approaches

“…The MD trajectories obtained were the root mean square deviation (RMSD), root mean square fluctuation (RMSF), radius of gyration (Rg), SASA (solvent accessible surface area), and the ligand hydrogen bonds. The MD trajectories were plotted and analyzed using XMGRACE, based on the previous studies by the authors [ 28 , 29 ].…”