Synthesis and anticholinesterase activity of novel non-hepatotoxic naphthyridine-11-amine derivatives

In the present study, 14 novel naphthyridine-11-amine derivatives were synthesized and their inhibitory effects on acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) were evaluated. 12-(4-Fluorophenyl)-1,2,3,4,7,8,9,10-octahydrodibenzo[b,g][1, 8]naphthyridin-11-amine (4a) was found to be the most potent AChE inhibitor with IC50 value of 0.091 mu M, and 12-(2,3-dimethoxyphenyl)-1,2,3,4,7,8,9,10-octahydrodibenzo[b,g][1,8]naphthyridin-11-amine (4h) exhibited the strongest inhibition against BuChE with IC50 value of 0.182 mu M. Additionally, hepatocellular carcinoma (HepG2) cell cytotoxicity assay for the synthesized compounds was investigated and the results showed negligible cell death. Log P values of the synthesized compounds were also calculated using ChemSketch program. Moreover, the blood-brain barrier (BBB) permeability of the potent AChE inhibitor (4a) was assessed by the widely used parallel artificial membrane permeability assay (PAMPA-BBB). The results showed that 4a is capable of crossing the BBB. [GRAPHICS] .