title: Effect of scopoletin on monoamine oxidases and brain amines.
abstract: Naturally, occurring compounds with MAO inhibitory property may provide promising lead molecules against neurodegenerative disorders. We report MAO inhibitory activity of a naturally occurring coumarin (validated chemical scaffold as MAO inhibitors), scopoletin. It selectively (and reversibly) inhibits human (Ki = 20.7 μM) and mouse (Ki = 22 μM) MAO-B, ∼3.5 times more selective towards MAO-B than MAO-A. Docking studies revealed its molecular recognition and explained the selectivity mechanism towards MAO isoforms. Scopoletin occupied the hydrophobic aromatic pockets showing favorable interactions for MAO-B; experimental Ki agreed with the predicted Ki. In vivo, scopoletin (80 mg/kg, i.p.) treatment significantly increases dopamine level and decreases its metabolite DOPAC in striatum. Overall, scopoletin is a partially selective MAO-B inhibitor that increases brain dopamine level.
authors.affiliation: St. Xavier's College 30, Mother Teresa Sarani, Kolkata, 700016, India.
authors.forename: Mahua
authors.initials: M
authors.lastname: Basu
authors.affiliation: Department of Pharmaceutical Sciences, Birla Institute of Technology, Mesra, 835215, India.
authors.forename: Kamlesh
authors.initials: K
authors.lastname: Mayana
authors.affiliation: St. Xavier's College 30, Mother Teresa Sarani, Kolkata, 700016, India.
authors.forename: S
authors.initials: S
authors.lastname: Xavier
authors.affiliation: Department of Environmental Studies, Siksha Bhavana, Visva Bharati, India. Electronic address: s.balachandran@visva-bharti.ac.in.
authors.forename: S
authors.initials: S
authors.lastname: Balachandran
authors.affiliation: Department of Pharmaceutical Sciences, Birla Institute of Technology, Mesra, 835215, India. Electronic address: nmishra@bitmesra.ac.in.
authors.forename: Nibha
authors.initials: N
authors.lastname: Mishra
mesh_terms: D000588:Amines / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D062105:Molecular Docking Simulation; D008995:Monoamine Oxidase / Q000187:drug effects*; D012603:Scopoletin / Q000494:pharmacology*
chemical_list: D000588:Amines; D008995:Monoamine Oxidase; D012603:Scopoletin
keywords: Docking; Dopamine; Monoamine oxidase; Scopoletin