Synthesis, Biological Evaluation, Molecular Docking and Kinetic Investigation of New 2,4,5‐Trisubstituted Imidazole Derivatives as Antidiabetic Agents

Abstract

A series of novel 2,4,5‐trisubstituted imidazole motifs have been synthesized by a magnetically‐tuned halloysite‐supported sulfonic acid catalyst. The prepared supported sulfonic acid catalyst was well characterized by High‐resolution transmission electron microscopy (HR‐TEM), Scanning electron microscopy (SEM), Energy dispersive X‐rays spectroscopy (EDS), Fourier transform infrared (FTIR), X‐ray powder diffraction (XRD), Thermogravimetric analysis (TGA), Brunauer–Emmett–Teller (BET), and Vibrating–sample magnetometry (VSM) techniques; and compounds were confirmed by ¹H, ¹³C‐Nuclear magnetic resonance (NMR) and High resolution mass spectrometry (HRMS) techniques. The purity of compounds was established by High performance liquid chromatography (HPLC). All the prepared compounds were screened for their in vitro antidiabetic activity by using α‐amylase and α‐glucosidase inhibition assay taking acarbose as a reference standard and were found to exhibit significant α‐amylase inhibitory potentials, whereas for α‐glucosidase inhibition, compounds were equipotent to the reference standard. Compound bearing ferrocene moiety was identified as the strongest α‐amylase inhibitor of the series with IC₅₀=47.83±0.63 μM, a five‐fold more potency compared to acarbose (IC₅₀ =269.39±0.29 μM). The presence of substituents in the second position of imidazole pharmacophore plays a key role in inhibitory activity. To find the possible binding interaction of compounds, in silico molecular docking study was performed.