DESIGN, SYNTHESIS, AND IN VITRO EVALUATION OF NOVEL ACRIDINE DERIVATIVES AS MONOAMINE OXIDASE INHIBITORS

Alzheimer's disease (AD) is a complex neurodegenerative ailment, which demands the use of multifunctional agents for its therapy. Currently, FDA-approved drugs for AD are only palliative. The current research focused on adding a flavone nucleus to the amino group of the acridine nucleus to provide it with Monoamine oxidase (MAO)-B inhibitory properties. Method: We designed and synthesized ten flavone substituted acridine derivatives and evaluated for Invitro MAO B inhibitory activity. Molecular modeling studies were conducted in AutoDock Vina with hMAO B (PDB ID: 2V60). Compounds exhibited MAO B inhibition with IC50 values in 3.24 µM to 9.48 µM concentration. Compounds AF6 and AF14 showed the highest activity with an IC50 value of 3.24 µM for MAO B. The results highlighted the MAO B inhibitory effect of the novel Acridine-Flavone hybrids and they can be promising multitarget directed ligands for AD.