The present study examines the
monoamine oxidase (
MAO) inhibitory properties of a series of 20
3-coumaranone [
benzofuran-3(2H)-one] derivatives. The
3-coumaranone derivatives are structurally related to series of α-tetralone and 1-indanone derivatives, which have recently been shown to potently inhibit
MAO, with selectivity for
MAO-B (in preference to the
MAO-A isoform). 3-Coumaranones are similarly found to selectively inhibit human
MAO-B with half-maximal inhibitory concentration (IC50) values of 0.004-1.05 µM. Nine compounds exhibited IC50<0.05 µM for the inhibition of
MAO-B. For the inhibition of human
MAO-A, IC50 values ranged from 0.586 to >100 µM, with only one compound possessing an IC50<1 µM. For selected
3-coumaranone derivatives, it is established that
MAO-A and
MAO-B inhibition are reversible since dialysis of
enzyme-inhibitor mixtures almost completely restores
enzyme activity. On the basis of the selectivity profiles and potent action, it may be concluded that the
3-coumaranone derivatives are suitable leads for the development of selective
MAO-B inhibitors as potential treatment for disorders such as
Parkinson's disease and
Alzheimer's disease.