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

Abstract

This study investigates the inhibitory potential of 2-aminothiazole derivatives on α-glucosidase (α-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 α-Glu inhibition, with 2-amino-4-(4-bromophenyl) thiazole showing the highest potency (K_i: 56.61 ± 1.31 µM). 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 µg/mL) and the highest TPTZ-Fe³⁺ reducing capacity among the derivatives (λ₅₉₃ = 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 α-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.