Background: Monoamine oxidase (MAO) is a critical target used for the cure of neuropsychological
Objective: A series of quercetin based derivatives was designed, synthesized, and evaluated as novel
multifunctional agents against monoamine oxidase A and B with antioxidant potential.
Methods: Hybrid derivatives based on quercetin were synthesized and screened for hMAO inhibition
along with antioxidant activity. Molecular docking was performed to explicate the rationale of the different
MAO (IC50) values and to explain the presence of inhibitory activity against specificity, respectively.
Results: The results of in vitro hMAO inhibition showed that compound 8a, 6c, and 4 were found as
potent hMAO-A inhibitors whereas compounds 6b, 6a, and 6d were observed as potent hMAO-B inhibitors.
The DPPH radical scavenging activity showed that compounds 6b, 6a, and 4 exhibited a promising
antioxidant potential with IC50 values 5.931±0.007, 6.421±0.037, and 8.516±0.098 respectively.
Moreover, the compound 6b, 6a, and 4 exhibited remarkable H2O2 scavenging potential with IC50 values
05.80±0.004 µM, 06.20±0.009 µM, and 07.66±0.009 µM respectively.
Conclusion: The results of docking studies were found in good correlation with experimental MAO inhibition
studies. Moreover, the mechanistic insight into the docking poses was also explored by binding
interactions of quercetin based derivatives inside the dynamic site of hMAO-A and hMAO-B. It was
also noticed that the potent MAO inhibitors were also acting as better antioxidants as evaluated through
DPPH radical scavenging activity and H2O2 radical scavenging assay.