Schiff Base Derivatives Based on Ampyrone as Promising Acetylcholinesterase Inhibitors: Synthesis, Spectral Characterization, Biological Activity, and SwissADME Predictions

摘要

In this research, a series of ampyrone-based Schiff base derivatives bearing the biologically active an aryl sulfonate moiety (X-XVIII) were successfully synthesized and screened for their acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities. These molecules, most of which were synthesized for the first time (compounds V, XI-XV, XVII and XVIII are new, others are known), were completely characterized by elemental analysis and some spectroscopic methods such as mass spectroscopy, FT-IR, 1D NMR (H-1- and C-13- NMR) and 2D NMR (COSY and HMQC). The results indicated that all tested molecules inhibited these enzymes at concentrations ranging from 80.4 to 247.1 mu M. All tested molecules exhibited higher activities than the standard compound rivastigmine (IC50 = 501 & PLUSMN; 3.08 mu M) against AChE. Among the synthesized molecules, the most active molecule was compound (XIII) (IC50 = 92.7 & PLUSMN; 0.9 mu M) against AChE. The same molecules displayed lower activities than the standard compounds galanthamine (IC50 =7.96 & PLUSMN; 0.59 mu M) and rivastigmine (IC50 = 19.95 & PLUSMN; 0.20 mu M) against BChE. Also, physicochemical properties, pharmacokinetic properties, and drug-likeness of all tested molecules (I-XVIII) were calculated by using SwissADME.