Novel Imidazo[۱,۲-𝑎]Pyridine Hybrids: Synthesis, Antioxidant Activity, Cytotoxicity against Cancer Cell Lines, and 𝐼𝑛 𝑆𝑖𝑙𝑖𝑐𝑜 Docking Analysis

This study presents the synthesis of ten novel imidazo[۱,۲-a]pyridines HB۱-HB۱۰ through the hybridization of ۴-(imidazo[۱,۲-a]pyridin-۲-yl)benzoic acid with different amines, anilines, and acid hydrazides. The structural characterization of these compounds was accomplished using mass spectrometry (mass), elemental analysis (CHNS), infrared spectroscopy (FTIR), and both ۱H-NMR and ۱۳C-NMR spectroscopy. The cytotoxic potential of the hybrids HB۱-HB۱۰ was assessed against A۵۴۹ (lung cancer) and HepG۲ (liver carcinoma) cell lines after a ۲۴-hour exposure. Among the synthesized hybrids, compound HB۹ exhibited the lowest IC۵۰ value of ۵۰.۵۶ μM against A۵۴۹ cells, outperforming Cisplatin (IC۵۰ of ۵۳.۲۵ μM). Additionally, HB۱۰ demonstrated significant activity against HepG۲ with an IC۵۰ of ۵۱.۵۲ μM, lower than that of Cisplatin (۵۴.۸۱ μM). The antioxidant activity was assessed through the DPPH (۲,۲-diphenyl-۱-picrylhydrazyl) radical scavenging method, which demonstrated a dose-dependent enhancement in activity among the hybrids. Notably, HB۷ reached inhibition values of ۷۹%, ۸۱%, and ۸۳% at concentrations of ۲۵, ۵۰, and ۱۰۰ μg/mL, respectively. Molecular docking simulations with the ۳D structure of human LTA۴H (۳U۹W.pdb) indicated that all hybrids interacted with key amino acid residues in the active site, with HB۷ exhibiting the strongest binding affinity (S score of -۱۱.۲۳۷ Kcal/mol) compared to the original ligand (-۶.۹۰۸ Kcal/mol). RMSD analysis revealed that HB۱ had the lowest RMSD of ۱.۰۴۹ Å, suggesting a close fit to the original ligand, while several hybrids, particularly HB۶ and HB۷, engaged with more residues, indicating their potential for diverse interactions.

Keywords:

Imidazopyridines , Imidazo [۱ , ۲-a]pyridines , Lung cancer , Liver cancer , Molecular docking