Synthesis, biological and computational evaluation of benzoxazole hybrid analogs as potential anti-Alzheimer's agents

<b>Aim:</b> Current study aims exploration of <i>bis</i>-benzoxazole bearing <i>bis</i>-Schiff base scaffolds (<b>1-16</b>) as anti-Alzheimer's agents.<b>Materials & methods:</b> 2-aminophenol is used as starting materials which react with different reagents in different step to give us <i>bis</i>-benzoxazole bearing <i>bis</i>-Schiff base analogs. NMR and HREI-MS techniques were used for characterization. All derivatives demonstrated varied range of activities with IC₅₀ values 1.10 ± 0.40-24.50 ± 0.90 μM against acetylcholinesterase (AChE) and 1.90 ± 0.70-28.60 ± 0.60 μM against butyrylcholinesterase (BuChE) in contrast to donepezil. In both cases, analog-<b>3</b> was found most potent. Molecular docking explored modes of interactions between scaffolds and receptor sites of targeted enzymes.<b>Conclusion:</b> This study offering promising approach for optimization and development of potent inhibitors of cholinesterase enzymes.