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

Abstract 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 IC 50 value of 2.60±0.22 μM, followed by PZ‐9 with an IC 50 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.