Monoamine oxidase A and B inhibiting effect and molecular modeling of some synthesized coumarin derivatives

New series of bioactive 7-oxycoumarin derivatives were synthesized and tested for their in vitro and in vivo monoamine oxidase (MAO) A and B inhibitory effect. In vitro studies revealed exceptionally potent and selective MAO-A inhibitors with Ki values on a picomolar range. The acetohydrazide (3b) and the dioxopyrrolidine derivative (7b) showed the most potent in vitro and in vivo MAO inhibition activity. Moreover, molecular modeling study of the synthesized compounds into MAO-A (PDB: 2Z5X) and MAO-B (PDB: 2XFN) binding sites exhibited direct correlation between AutoDock binding affinity and% inhibition MAO-A (pM) and MAO-B (μM). In addition, the results of in vivo MAO inhibiting properties (ED50) of the tested compounds revealed better direct correlation.

New series of 7-oxycoumarin derivatives were synthesized and tested for their monoamine oxidase inhibitory effect. Molecular modeling study into MAO-A (2Z5X) and MAO-B (2XFN) binding sites was also demonstrated.Figure optionsDownload as PowerPoint slideHighlights
► Synthesis of hydrazide, pyrazole, pyrrole and indole 7-oxycoumarin derivatives.
► Study of MAO (A&B) inhibition effect of the target compounds in vivo and in vitro.
► Molecular modeling study of the compounds into MAO-A and MAO-B binding sites.