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Synthesis, Characterization, and Biological Evaluation of Novel Azo-Based Imidazo[1,2- a ]pyridine Derivatives: In Vitro and In Silico Investigations

Year: 2025

Type: article

Abstract: High Resolution Image Download MS PowerPoint Slide In this study, a series of azo-linked imidazo[1,2- a ]pyridine derivatives ( 4a – f ) was synthesized and fully characterized using FTIR, NMR ( 1 H and 13 C), and mass spectrometry. Structural and electronic properties were investigated through Density Functional Theory (DFT) at the B3LYP/6-311++G(d,p) level, revealing key insights into charge distribution, molecular orbitals, and reactivity indices. The antibacterial and antibiofilm activities were assessed in vitro against Gram-positive and Gram-negative strains, including multidrug-resistant isolates. 4e exhibited the most potent antibacterial activity, with minimum inhibitory concentrations (MICs) of 0.5–1.0 mg/mL, and retained activity against resistant strains, showing MICs of 0.5–0.7 mg/mL against Escherichia coli CTXM and Klebsiella pneumoniae NDM . 4b and 4c notably inhibited biofilm formation at concentrations as low as 0.4 mg/mL against E. coli . Molecular docking studies indicated strong binding affinities for the active compounds, with 4b achieving the most favorable docking score (−10.4 kcal/mol) against the bacterial target GyrB. These binding interactions were further corroborated by molecular dynamics simulations, which demonstrated stable protein–ligand complexes over a 100 ns trajectory with minimal structural deviations. Additionally, ADME-T and drug-likeness evaluations predicted favorable pharmacokinetic profiles for the majority of the compounds, highlighting their viability for further development. Overall, this study establishes azo-based imidazo[1,2- a ]pyridine derivatives as promising scaffolds for future antibacterial drug discovery.

Source: ACS Omega

DOI: 10.1021/acsomega.5c07351