Structure–activity relationship investigation of coumarin–chalcone hybrids with diverse side-chains as acetylcholinesterase and butyrylcholinesterase inhibitors

摘要: Chalcones containing tertiary amine side-chains have potent activity as acetylcholinesterase (AChE) inhibitors. However, the effects of location groups well other on AChE and butyrylcholinesterase (BChE) not been reported. Here, we report synthesis testing 36 new coumarin–chalcone hybrids (5d–7j, 9d–11f, 12k–13m) against BChE. The nature position chalcone substituents had major inhibitory selectivity for over Compounds with para-substituted fragments in which were choline-like poor BChE, while ortho-substituted analogs exhibited an opposite effect. Replacement terminal by amide, alkyl or alkenyl abrogated activity. Compound 5e showed $$(\hbox {IC}_{50} = 0.15 \pm 0.01\, \upmu \hbox {mol}{/}\hbox {L}$$ ) good BChE (ratio 27.4), a kinetic study that mixed-type inhibition AChE. Computational docking results indicate binds to Trp 279, Tyr334 84 AChE, but only 82 Overall, show promising be therapeutic leads Alzheimer’s disease.