A series of (E)-3-heteroarylidenechroman-4-ones (1a-r) was designed, synthesized and investigated
in vitro for their ability to inhibit the enzymatic activity of both human monoamine oxidase (hMAO)
isoforms, hMAO-A and hMAO-B. All the compounds were found to be selective hMAO-B inhibitors
showing IC50 values in the nanomolar or micromolar range. (E)-5,7-Dichloro-3-{[(2-(dimethylamino)
pyrimidin-5-yl]methylene}chroman-4-one (1c) was the most interesting compound identified in this
study, endowed with higher hMAO-B potency (IC50 ¼ 10.58 nM) and selectivity (SI > 9452) with respect
to the reference selective inhibitor selegiline (IC50 ¼ 19.60 nM, IC50 > 3431). Molecular modelling studies
were performed for rationalizing at molecular level the target selective inhibition of our compounds,
revealing a remarkable contribution of hydrogen bond network and water solvent
