Cholinesterase inhibitory activity versus aromatic core multiplicity: A facile green synthesis and molecular docking study of novel piperidone embedded thiazolopyrimidines

Novel thiazolopyrimidine derivatives have been synthesized via microwave assisted, domino cascade methodology in ionic liquid and evaluated in vitro for their acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities. Among the newly synthesized compounds 6d, 6a, 6e and 6b displayed higher AChE inhibitory activity than standard drug, galanthamine, with IC50 values of 0.53, 1.47, 1.62 and 2.05 μM, respectively. Interestingly, all the compounds except for 6m–r and 6x displayed higher BChE inhibitory potentials than galanthamine with IC50 values ranging from 1.09 to 18.56 μM. Molecular docking simulations for 6d possessing the most potent AChE and BChE inhibitory activities, disclosed its binding interactions at the active site gorge of AChE and BChE enzymes.

Novel piperidone grafted heterocycles comprising three aromatic core synthesized and evaluated for cholinesterases inhibitory activity to disclose the relationship between the activity and aromatic content of inhibitors.Figure optionsDownload as PowerPoint slide