Evaluation of Natural and Synthetic 1,4‐naphthoquinones as Inhibitors of Monoamine Oxidase

Abstract

Previous reports have documented that 1,4-naphthoquinones act as inhibitors of the monoamine oxidase (MAO) enzymes. In particular, fractionation of the extracts of cured tobacco leafs has led to the characterization 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-naphthoquinone 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 IC50 value of 0.860 μm for the inhibition of MAO-B. A related compound, shikonin, inhibits both the MAO-A and MAO-B isoforms with IC50 values of 1.50 and 1.01 μm, respectively. It is further shown that MAO-A and MAO-B inhibition by these compounds is reversible by dialysis. 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, congestive heart failure and cancer.

1,4-Naphthoquinones: Some Biological Properties and Application

“…87) It was later found that echinochrome (20) is a non-competitive acetylcholinesterase inhibitor, which opens up prospects for the use of echinochrome for the treatment of neuromuscular disorders, as well as Alzheimer's and Parkinson's diseases. 88) The monoamine oxidase (MAO) enzymes are of considerable pharmacological interest and inhibitors are used in the clinic for the treatment of major depressive disorder and neurodegenerative diseases. 2,3,6-trimethyl-1,4-naphthoquinone (70) (Fig.…”

Monoamine oxidase‐B inhibitors as potential neurotherapeutic agents: An overview and update

“…Literatures have documented the MAO inhibitory activity of 1,4‐naphthoquinones. In this view, Mostert et al investigated the recombinant hMAO‐B inhibitory activities of several structurally diverse 1,4‐naphthoquinones of natural and synthetic origin ( 134‐138 ; Figure ). The hMAO‐B inhibition potencies ranged from 0.860 to 24.8 µM.…”

“…1,4‐Naphthoquinone derivatives ( 134‐138 ) . hMAO, human monoamine oxidase; IC 50 , half maximal inhibitory concentration…”

“…Naphthoquinone derivatives(134)(135)(136)(137)(138) 200. hMAO, human monoamine oxidase; IC50 , half maximal inhibitory concentration TRIPATHI AND AYYANNAN | 1651 F I G U R E 5 7 5-(Azole)methyl oxazolidinones(139)(140)(141) 201.…”

“…C6-and C7-Substituted 3,4-dihydro-2(1H)-quinolinones (198a-g, 199a-g, and[200][201] 216. IC 50 , half maximal inhibitory concentration; MAO, monoamine oxidase TRIPATHI AND AYYANNAN | 1665 Sesamol and benzodioxane derivatives Engelbrecht et al 218 synthesized a series of sesamol (1,3-benzodioxol-5-ol; 204a-h) and benzodioxane (2,3-dihydro-1,4-benzodioxine; 205a-h) derivatives and evaluated them for hMAO-B inhibitory activity (Figures 75 and 76).…”