Evaluation of 2-Aminothiazoles as α-Glucosidase Inhibitors: DFT, Molecular Docking, and Antioxidant Studies

This study investigates the inhibitory potential of 2-aminothiazole derivatives on alpha-glucosidase (alpha-Glu) activity and their antioxidant properties using a combination of in vitro and in silico methods. Diabetes mellitus, characterized by chronic hyperglycemia, necessitates effective enzyme inhibitors to manage postprandial glucose levels. Among the studied compounds, structural variations significantly influenced alpha-Glu inhibition, with 2-amino-4-(4-bromophenyl) thiazole showing the highest potency (K i: 56.61 +/- 1.31 mu M). Molecular docking analyses revealed critical interactions within the enzyme's active site, emphasizing the importance of electron-withdrawing groups for enhancing inhibitory activity. Antioxidant properties were assessed using Fe3(+), Cu2(+), and ABTS radical scavenging assays, where specific derivatives, particularly compound 5 demonstrated strong radical scavenging activity (ABTS IC50 = 8.5-9 mu g/mL) and the highest TPTZ-Fe3(+) reducing capacity among the derivatives (lambda 593 = 0.637 +/- 0.005). Density functional theory (DFT) analysis further elucidated the electronic properties of these derivatives, identifying low HOMO-LUMO energy gaps as a determinant of reactivity. These findings underscore the therapeutic potential of 2-aminothiazoles as alpha-Glu inhibitors and antioxidants, paving the way for developing novel treatments for diabetes and oxidative stress-related disorders. This research contributes to the rational design of bioactive molecules with enhanced efficacy and reduced side effects.

Journal

BIOTECHNOLOGY AND APPLIED BIOCHEMISTRY

Year

2026

Volume

73

Issue

2

Pages

645-654

ISSN

0885-4513

eISSN

1470-8744

DOI

10.1002/bab.70054

WoS UID

WOS:001572129900001

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