Inhibition of monoamine oxidases by coumarin-3-acyl derivatives: biological activity and computational study

A series of coumarin-3-acyl derivatives have been synthesized and investigated for the ability to inhibit selectively monoamine oxidases. The coumarin-3-carboxylic acids, 2a–e, proved to be reversible and selective inhibitors of the MAO-B isoform, displaying pIC50 values of particular interest: 2a shows pIC50 7.76 and a selectivity index (pS.I.) 2.94 and 2b shows pIC50 7.72 and a pS.I. of 2.80. The coumarin-3-acyl chlorides 3a–e showed high pIC50 values against both MAO-A and MAO-B isoforms, 3d being the highest against MAO-B with a pIC50 value of 8.00. In order to rationalize the activity/selectivity results, molecular descriptors were generated. Further insight about enzyme–inhibitor interaction was obtained by docking experiments with the MAO-B isoform.