Novel Imidazo[1,2-α]Pyridine Hybrids: Synthesis, Antioxidant Activity, Cytotoxicity against Cancer Cell Lines, and In Silico Docking Analysis
نویسندگان
1 Department of Organic Chemistry, Faculty of Chemistry, University of Mazandaran, Babolsar, Iran
2 Department of Chemistry, College of Education for Pure Science, University of Kerbala, Karbala, Iraq
3 Department of Organic Chemistry, Faculty of Chemistry, University of Mazandaran, Babolsar, Iran
4 Department of Organic Chemistry, Faculty of Chemistry, University of Mazandaran, Babolsar, Iran
doi
10.48309/chemm.2025.525913.1965چکیده
This study presents the synthesis of ten novel imidazo[1,2-a]pyridines HB1-HB10 through the hybridization of 4-(imidazo[1,2-a]pyridin-2-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 1H-NMR and 13C-NMR spectroscopy. The cytotoxic potential of the hybrids HB1-HB10 was assessed against A549 (lung cancer) and HepG2 (liver carcinoma) cell lines after a 24-hour exposure. Among the synthesized hybrids, compound HB9 exhibited the lowest IC50 value of 50.56 μM against A549 cells, outperforming Cisplatin (IC50 of 53.25 μM). Additionally, HB10 demonstrated significant activity against HepG2 with an IC50 of 51.52 μM, lower than that of Cisplatin (54.81 μM). The antioxidant activity was assessed through the DPPH (2,2-diphenyl-1-picrylhydrazyl) radical scavenging method, which demonstrated a dose-dependent enhancement in activity among the hybrids. Notably, HB7 reached inhibition values of 79%, 81%, and 83% at concentrations of 25, 50, and 100 μg/mL, respectively. Molecular docking simulations with the 3D structure of human LTA4H (3U9W.pdb) indicated that all hybrids interacted with key amino acid residues in the active site, with HB7 exhibiting the strongest binding affinity (S score of -11.237 Kcal/mol) compared to the original ligand (-6.908 Kcal/mol). RMSD analysis revealed that HB1 had the lowest RMSD of 1.049 Å, suggesting a close fit to the original ligand, while several hybrids, particularly HB6 and HB7, engaged with more residues, indicating their potential for diverse interactions.
