Novel small molecules were synthesized in the quest to search for multi-target directed ligand for Alzheimer's disease. From the preliminary synthesis, ethyl 4-((cyclohexylmethyl)amino)-3nitrobenzoate (2 h) showed good butyrylcholinesterase (BChE) inhibitory activity. Modifications carried out on compound 2 h by removing the nitro group resulted in the identification of ethyl 4-((cyclohexylmethyl)amino)benzoate (3 h) as a selective and potent BChE inhibitor (IC 50 = 0.735 μM; BChE selectivity > 100-fold over acetylcholinesterase (AChE)). Furthermore, compound 3 h was shown to be able to promote neurite outgrowth in SH-SY5Y cells. No significant cytotoxicity was exhibited by compound 3 h, up till the highest concentration tested (25 μM). The compound was also predicted to have good permeability across the lipid infused bilayer, indicating its potential to cross the blood-brain barrier. These results warrant further investigations on compound 3 h as a potential treatment for Alzheimer's disease.
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