Acetylcholinesterase inhibition, molecular docking and ADME prediction studies of new dihydrofuran-piperazine hybrid compounds

Novel acrylamide and methacryloyl carrying piperazine-dihydrofuran derivatives (3a-p) were designed and obtained from radical cyclizations of unsaturated piperazine derivatives (1a-f) with 1,3-dicarbonyl compounds (2a-c) mediated by Mn(OAc)(3). Obtained compounds were characterized by spectroscopic methods. In vitro AChE inhibitory activites of 3a-p were evaluated against AChE (Acetylcholinesterase) by Ellman method and test results showed that 3a, 3c, 3j, and 3l are the most active AChEI's (AChE inhibitors) of our work with IC50 (half-maximal inhibitory concentration) values of 2.62, 5.29, 1.17, and 3.90 mu M, respectively. Furthermore, ligand-protein interactions and inhibitory activity mechanisms of 3a and 3j were investigated by molecular docking. Finally, in silico molecular property and ADME predictions (absorption, distribution, metabolism and excretion) of potential AChEI's were predicted by PreADMET and Molinspiration webservers. It can be concluded that the lead compound 3j show excellent inhibiton and satisfactory druglike characteristics.