Natural and Synthetic Xanthones as Monoamine Oxidase Inhibitors: Biological Assay and 3D‐QSAR

Fifty-nine xanthones (= 9H-xanthen-9-ones) of natural or synthetic origin were investigated for their inhibitory activity toward monoamine-oxidase A (MAO-A) and MAO-B. The compounds demonstrated reversible. time-independent activities, with selectivity toward MAO-A. The most active inhibitor had an IC50 of 40 nM. Electron absorption spectroscopy revealed the formation of a 1:1 charge-transfer complex between lumiflavine and xanthones. 3D-QSAR Studies according to the CoMFA/GOLPE procedure provided information on the relationship between steric and electrostatic fields and MAO-A inhibition. The ALMOND procedure yielded additional topographical information on structural factors favoring activity