title: Novel (coumarin-3-yl)carbamates as selective MAO-B inhibitors: synthesis, in vitro and in vivo assays, theoretical evaluation of ADME properties and docking study.
abstract: A series of (coumarin-3-yl)carbamates was synthesized and evaluated in vitro as monoamine oxidase (MAO-A and MAO-B) inhibitors. Most of the new compounds selectively inhibited MAO-B isoenzyme with IC50 values in the micro or nanoMolar ranges. Since these compounds must achieve the brain cells, theoretical evaluation of ADME properties were also carried out. Compound 8 (benzyl(coumarin-3-yl)carbamate), which presented the most interesting in vitro MAO-B inhibitory profile (IC50 against MAO-B = 45 nM), was subjected to further studies. This in vitro MAO-B inhibitory activity is comparable with that of the selegiline, the reference compound (IC50 against MAO-B = 20 nM). Taking into account the in vitro results of compound 8, in vivo assays and docking calculations were also carried out for this derivative.
authors.affiliation: Department of Organic Chemistry, Faculty of Pharmacy, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain. mariacmatos@gmail.com
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Matos
authors.forename: Santiago
authors.initials: S
authors.lastname: Vilar
authors.forename: Rosa Ma
authors.initials: RM
authors.lastname: Gonzalez-Franco
authors.forename: Eugenio
authors.initials: E
authors.lastname: Uriarte
authors.forename: Lourdes
authors.initials: L
authors.lastname: Santana
authors.forename: Carol
authors.initials: C
authors.lastname: Friedman
authors.forename: Nicholas P
authors.initials: NP
authors.lastname: Tatonetti
authors.forename: Dolores
authors.initials: D
authors.lastname: Viña
authors.forename: Jose A
authors.initials: JA
authors.lastname: Fontenla
mesh_terms: D000818:Animals; D055162:Biocatalysis / Q000187:drug effects; D002219:Carbamates / Q000138:chemical synthesis / Q000737:chemistry*; D003374:Coumarins / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D051379:Mice; D008958:Models, Molecular; D015394:Molecular Structure; D008995:Monoamine Oxidase / Q000737:chemistry* / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012642:Selegiline / Q000494:pharmacology; D013379:Substrate Specificity; D014439:Tyramine / Q000378:metabolism
chemical_list: D002219:Carbamates; D003374:Coumarins; D008996:Monoamine Oxidase Inhibitors; D012642:Selegiline; C030123:coumarin; D006861:Hydrogen Peroxide; D008995:Monoamine Oxidase; D014439:Tyramine