New 2-Chloroimidazo[1,2-a]pyridine induced Schiff bases: synthesis, characterization, antimicrobial and A-498 and A-549 anticancer activity, molecular modeling, in-silico pharmacokinetics, and DFT studies

The novel 1-(2-chloroimidazo[1,2-a]pyridin-3-yl)-N-(substitutedphenyl) methanimines have been synthesized and characterized by spectral (IR, MS, 1H, and 13C NMR) and elemental analysis. Molecular docking studies were conducted with three cancer target proteins (PDB IDs: 1M17, 2OF4, and 3LCK) and assorted microbial target proteins (1KZN, 2XCT, 1D7U, 1BAG, and 1EA1) to explore their binding interactions. Further in-silico target prediction study suggested a 26.7% probability that VIf acts on kinases. The synthesized analogs were subjected to in-vitro anticancer activity assessments against A-498 (kidney carcinoma) and A-549 (lung carcinoma) cell lines and compound VIf exhibited good inhibition (GI50<10) of the A-498 cell line. Additionally, all analogs showed moderate to good in-vitro antimicrobial activity against S. aureus, B. subtilis, E. coli, K. pneumoniae (bacterial strains), and C. albicans (fungal strain). The optimized geometries, FMO energies, MEP plots, and global reactivity descriptors (µ, ɳ, S, and ω) were achieved employing DFT at B3LYP/6-31G (d) level to explore structural features and probable reactivity and toxicity of the synthesized compounds. Compound VIg exhibited high reactivity (ɳ: 1.8218 eV, S: 0.2744 eV) and low toxicity (ω: 3.2061 eV) among all analogs. These findings collectively underscore the potential of the synthesized compounds, with VIf and VIg standing out as particularly promising candidates for further exploration.