Background: A series of perimidinone derivatives (7H-benzo[e]perimidin-7-one) were synthesized
and assessed by means of in vitro assays as human MAO inhibitors. These compounds inhibited
reversibly the enzymes with inhibitory constants in the range of 2 to 20 μM. In addition, the selectivity
of inhibition of the MAO isoforms seems to be significantly dependent of the presence either of
heteroatom or electron donating and withdrawing groups on the perimidinone framework, which was
verified by using molecular docking simulation with the crystallized MAO receptors. Most of these inhibitors
were highly selective: 9 and 11 inhibited selectively the MAO-B isoform while 12 had 10-fold
selectivity for MAO-A isoform. Moreover, the compound 12 was both the most selective and potent
MAO-A inhibitor among perimidinones.
Result: These results have important implications for the drug design of molecules targeting depression
and movement-related disorders.