In the present study, series of eight
sesamol (1,3-benzodioxol-5-ol) and eight benzodioxane (2,3-dihydro-1,4-benzodioxine) derivatives were synthesised and evaluated as inhibitors of recombinant human
monoamine oxidase (
MAO) A and B. The
sesamol and benzodioxane derivatives are structurally related to series of
phthalide derivatives, which have previously been found to act as potent reversible
MAO inhibitors. The results document that the benzodioxane derivatives, in particular, are potent
MAO-B inhibitors with IC50 values ranging from 0.045 to 0.947 μM. IC50 values for the inhibition of
MAO-B by the homologous series of
sesamol derivatives ranged from 0.164 to 7.29 μM. All compounds evaluated are selective for the
MAO-B isoform, with IC50 values for the inhibition of
MAO-A ranging from 13.2 to >100 μM. It is further shown that for the most potent
MAO-B inhibitor, 6-[(3-bromophenyl)methoxy]-2,3-dihydro-1,4-benzodioxine, inhibition is almost completely reversed by dialysis of
enzyme-inhibitor mixtures. It may be concluded that benzodioxane derivatives are promising leads for the design of selective
MAO-B inhibitors for the treatment of
Parkinson's disease.