Pachon_2020_Int.J.Mol.Sci_21_

We report herein the design, synthesis, biological evaluation, and molecular modelling of new inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), able to block Ca(+2) channels also showing antioxidant and neuroprotective activities. The new MTDL, dialkyl 2,6-dimethyl-4-(4-((5-aminoalkyl)oxy)phenyl)-1,4-dihydropyridine-3,5-dicarboxylate 3a-p, have been obtained via Hantzsch reaction from appropriate and commercially available precursors. Pertinent biological analysis has prompted us to identify MTDL 3h [dimethyl-4-(4-((5-(4-benzylpiperidin-1-yl)pentyl)oxy)phenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate] as an attractive inhibitor of AChE (1.8 microM) and BuChE (2 microM), Ca(+2) channel antagonist (47.72% at 10 microM), and antioxidant (2.54 TE) agent, showing significant neuroprotection 28.68% and 38.29% against H(2)O(2,) and O/R, respectively, at 0.3 M, thus being considered a hit-compound for further investigation in our search for anti-Alzheimer's disease agents.