Novel Urolithin Derivative Molecules as Dual MAO and Cholinesterase Inhibitor Agents

The number of drugs used for the treatment of Alzheimer‟s disease is quite limited. These drugs (e.g., cholinesterase inhibitors and N-methyl-D-aspartate receptor antagonist) provide symptomatic treatment rather than a total cure. Therefore, there has been great scientific interest worldwide for the design and development of novel drug candidates for the treatment of this neurodegenerative disease. Previous studies indicated that the urolithin (hydroxy substituted benzo[c]chromen - 6-one) scaffold can be employed to design molecules promising to act as multi target ligands against Alzheimer‟s disease. Within the scope of this research study, we have aimed to synthesis 3-subsitiuted benzo[c]chromen-6-one, and 3-subsistuted 7,8,9,10- tetrahydrobenzo[c]chromen-6-one derivatives connected to an amide function with a spacer. The enzyme inhibitor activities (i.e., acetylcholinesterase, butyrylcholinesterase, and monoamine oxidase B) concomitant to antioxidant and amyloid beta aggregation inhibitor characteristics of the title molecules have been planned to be screened. The results pointed out several drug candidate molecules possessing multi target ligand feature in terms of inhibiting the aforementioned enzymes with anti-oxidant properties in ORAC assay conditions. Moreover, the computer aided docking studies revealed out the predicted binding modes of the most active compounds displaying the possible interactions with the receptors. Keywords: Urolithin derivatives, Cholinesterase inhibitors, Monoamine oxidase B, Antioxidant.