Chalcones with N‐Methylpiperazine Moiety: Synthesis, Monoamine Oxidase Inhibition, Neuroprotective Effect and Computer Simulation Study
Jayalakshmi Jayan, Daniela Trisciuzzi, Feba Benny, Sunil Kumar, Nicola Gambacorta, Marco Catto, Mohamed A. Abdelgawad, Mohammed M. Ghoneim, Rasha Hamed Al‐Serwi, Prashant Gahtori, Subin Mary Zachariah, Orazio Nicolotti, Bijo Mathew- General Chemistry
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 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.