title: The Benzopyrone Biochanin-A as a reversible, competitive, and selective monoamine oxidase B inhibitor.
abstract: BACKGROUND
  Monoamine oxidase-B (MAO-B) inhibitors are widely used in the treatment of Parkinson's disease. They increase vital monoamine neurotransmitters in the brain. However, there is a need for safer natural reversible MAO inhibitors with MAO-B selectivity. Our previous studies showed that Psoralea corylifolia seeds (PCS) extract contains compounds that inhibit monoamine oxidase-B.
  
  
  METHODS
  In this study, six of PCS constituents sharing a benzopyrone structure were investigated. The compounds Biochanin-A (BIO-A), isopsoralen, 6-prenylnaringenin, neobavaisoflavone, psoralen, and psoralidin, were tested for their ability to inhibit recombinant human MAO-A and B (hMAO-A and hMAO-B) isozymes. The ability of these compounds to inhibit MAO-A and MAO-B were compared to that of PCS ethanolic extract (PCSEE) using spectrophotometric assays and confirmed by luminescence assays. The highly potent and selective MAO-B inhibitor, BIO-A, was further investigated for both isozymes reversibility and enzyme kinetics. Molecular docking studies were used to predict the bioactive conformation and molecular interactions of BIO-A with both isozymes.
  
  
  RESULTS
  The data obtained indicate that benzopyrones inhibited hMAO-A and hMAO-B with different degrees as confirmed with the luminescence assay. BIO-A inhibited hMAO-B with high potency and selectivity in the present study (IC50= 0.003 μg/mL) and showing 38-fold more selectivity than PCSEE (hMAO-B IC50= 3.03 μg/mL, 17-fold selectivity) without affecting hydrogen peroxide. Furthermore, BIO-A reversibly and competitively inhibited both hMAOs with significantly lower inhibitory constant (Ki) in hMAO-B (3.8 nM) than hMAO-A (99.3 nM). Our docking studies indicated that the H-bonds and hydrophobic interactions at the human MAO-A and MAO-B active sites contributed to the reversibility and selectivity of BIO-A.
  
  
  CONCLUSIONS
  The data obtained indicate that BIO-A is a potent, reversible and selective MAO-B inhibitor and may be recommended for further investigation in its possible use in the therapeutic management of Parkinson's and Alzheimer's diseases.
authors.affiliation: College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, FL, 32307, USA.
authors.forename: Najla O
authors.initials: NO
authors.lastname: Zarmouh
authors.affiliation: College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, FL, 32307, USA.
authors.forename: Suresh K
authors.initials: SK
authors.lastname: Eyunni
authors.affiliation: College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, FL, 32307, USA. karam.soliman@famu.edu.
authors.forename: Karam F A
authors.initials: KF
authors.lastname: Soliman
mesh_terms: D016227:Benzoquinones / Q000737:chemistry*; D001667:Binding, Competitive; D019833:Genistein / Q000737:chemistry*; D006801:Humans; D007700:Kinetics; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D008995:Monoamine Oxidase / Q000737:chemistry* / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors / Q000737:chemistry*; D010936:Plant Extracts / Q000737:chemistry*; D029907:Psoralea / Q000737:chemistry*
chemical_list: D016227:Benzoquinones; D008996:Monoamine Oxidase Inhibitors; D010936:Plant Extracts; C004532:quinone; D019833:Genistein; D008995:Monoamine Oxidase; C004541:biochanin A
keywords: Benzopyrone; Biochanin-A; Coumarins; Docking studies; Flavonoids; Human monoamine oxidase-A; Human monoamine oxidase-B; Psoralea corylifolia ethanolic extract; Reversible competitive inhibition