Chalcones with N‐Methylpiperazine Moiety: Synthesis, Monoamine Oxidase Inhibition, Neuroprotective Effect and Computer Simulation Study

Eleven derivatives of chalcones (PZ1–PZ11) were synthesized by incorporating N-methyl piperazine on the para position of the aromatic B ring of chalcones. The A ring is substituted with different electron-donating and withdrawing groups. All the final derivatives were evaluated for their monoamine oxidase A and B inhibition studies. From the series of compounds PZ-7 was found to possess good MAO-B inhibitory activity with an IC50 value of 2.60±0.22 μM, followed by PZ-9 with an IC50 value of 3.44±0.20 μM, when compared with reference compound pargyline 2.69±0.48 μM. PZ-7 also considerably reduced the cell mortality triggered by rotenone in SH-SY5Y neuroblastoma cells. The docking study found that PZ-7 showed a docking score of −10.809 kCal/mol, with a polar interaction with Gln206, and π-π stacking interaction between the B ring of chalcone. A molecular dynamics simulation study showed higher stability of the protein–ligand complex. Overall, compound PZ-7 could serve as a promising MAO-B inhibitor with neuroprotective action.