Evaluation of natural and synthetic 1,4-naphthoquinones as inhibitors of monoamine oxidase

Abstract

Previous reports have documented that 1,4-naphtho- quinones act as inhibitors of the monoamine oxidase (MAO) enzymes. In particular, fractionation of the extracts of cured tobacco leafs has led to the charac- terization of 2,3,6-trimethyl-1,4-naphthoquinone, a non- selective MAO inhibitor. To derive structure–activity relationships for MAO inhibition by the 1,4-naphthoqui- none class of compounds, this study investigates the human MAO inhibitory activities of fourteen structurally diverse 1,4-naphthoquinones of natural and synthetic origin. Of these, 5,8-dihydroxy-1,4-naphthoquinone was found to be the most potent inhibitor with an IC 50 value of 0.860 l M for the inhibition of MAO-B. A related compound, shikonin, inhibits both the MAO-A and MAO-B isoforms with IC 50 values of 1.50 and 1.01 lM, respectively. It is further shown that MAO-A and MAO- B inhibition by these compounds is reversible by dialy- sis. In this respect, kinetic analysis suggests that the modes of MAO inhibition are competitive. This study contributes to the discovery of novel MAO inhibitors, which may be useful in the treatment for disorders such as Parkinson’s disease, depressive illness, con- gestive heart failure and cancer