Synthesis, human monoamine oxidase inhibitory activity and molecular docking studies of 3-heteroarylcoumarin derivatives

Monoamine oxidase (MAO) is an important drug target for the treatment of neurological disorders. Series of 3-indolyl and 3-thiophenylcoumarins were synthesized and evaluated as inhibitors of the two human MAO isoforms, hMAO-A and hMAO-B. In general, the derivatives were found to be selective hMAO-B inhibitors with IC50 values in the nanoMolar (nM) to microMolar (μM) range. Docking experiments were carried out in order to compare the theoretical and experimental affinity of these compounds to the hMAO-B protein. According to our results, docking experiments could be an interesting approach to try to predict the activity of this class of coumarins against MAO-B receptors.

Graphical abstractThree series of 3-heteroarylcoumarin derivatives have been synthesized and evaluated as hMAO inhibitors. The biological data were compared to the molecular docking study.Figure optionsDownload full-size imageDownload as PowerPoint slideResearch highlights► Synthesis of 3-heteroarylcumarins. ► Evaluation of hMAO activity. ► Docking studies. ► Prediction of hMAO-B activity for new derivatives.