Abstract
This investigation centres on the design, synthesis and computational evaluation of novel N-heterocyclic hybrid molecules that possess three-in-one functionalities: quinoline-indole chalcone (QIC). These hybrids have been successfully synthesized using Claisen-Schmidt condensation reaction between 3-acetyl-2-methyl-4-phenylquinoline (3a) (AcQ)/ 1-(6-bromo-2-methyl-4-phenylquinolin-3-yl)ethan-1-one (B-AcQ) (3b) and indole-3-aldehyde (4a-e) precursors. Structural integrity and purity of all the compounds were confirmed by 1H-NMR, 13C-NMR, FTIR, HRMS and HPLC. The computational study was executed using ADMETlab 3.0 online tool favoring drug-likeness and pharmacokinetic properties for all the compounds, adhering to Lipinski's Rule of Five. Molecular docking was performed using key protein targets to evaluate antibacterial (PDB IDs: 3TTZ and 7C7O), anticancer (PDB IDs: 4HJO and 3W2S) and antineurodegenerative (PDB IDs: 2V5Z and 2Z5X) properties of all the synthesized compounds. The results indicated stronger binding interactions of 5f (- 11.86 kcal/mol) and 5g (- 9.71 kcal/mol) with antibacterial, 5d (- 11.89 kcal/mol) and 5h (- 11.72 kcal/mol) with anticancer and 5h (- 14.89 kcal/mol) and 5a (- 8.53 kcal/mol) with antineurodegenerative protein targets compared with the co-crystal ligands 07N and FKU for antibacterial (- 8.67 kcal/mol and - 10.95 kcal/mol) respectively, co-crystal ligand W2R (- 13.73 kcal/mol) and reference drug erlotinib (- 7.87 kcal/mol) for anticancer, safinamide (- 9.64 kcal/mol) and harmine (- 7.61 kcal/mol) for antineurodegenerative targets. These compounds showed comparable or stronger predicted binding affinities under the applied docking conditions.Supplementary information
The online version contains supplementary material available at https://doi.org/10.1007/s40203-026-00735-z.