title: Synthesis, pharmacological study and docking calculations of new benzo[f]coumarin derivatives as dual inhibitors of enzymatic systems involved in neurodegenerative diseases.
abstract: BACKGROUND
  Due to the complex etiology of neurodegenerative diseases, there is growing interest in multitarget drugs. In this study we synthesized and evaluated a new series of compounds, with benzo[f]coumarin structure, as potential inhibitors of MAO-A, MAO-B, AChE and BuChE.
  
  
  RESULTS
  In vitro studies show that most of the studied compounds inhibited the activity of MAO-B in the nano- to micro-molar range. 3-(3´-methoxyphenyl)benzo[f]coumarin is the most active compound with an IC50 value against MAO-B of 2.44 nM. Most of the derivatives exhibited an important selectivity profile against the MAO-B isoform. Some of them also acted as in vitro inhibitors of BuChE, with 3-(2´-hydroxyphenyl)benzo[f]coumarin being the most active with an IC50 value of 1.13 µM. In addition, a theoretical study of the physicochemical properties of the new compounds, as well as a docking study in both MAO isoforms, were carried out. Important structure-activity relationships were obtained.
  
  
  CONCLUSIONS
  Important preliminary structure-activity relationships were concluded from the experimental results. These results encourage us to further explore the potential of this chemical family as potential drug candidates for the treatment of Alzheimer's disease.
authors.affiliation: Department of Organic Chemistry, Faculty of Pharmacy, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain.
authors.forename: Maria João
authors.initials: MJ
authors.lastname: Matos
authors.forename: Patricia
authors.initials: P
authors.lastname: Janeiro
authors.forename: Rosa María
authors.initials: RM
authors.lastname: González Franco
authors.forename: Santiago
authors.initials: S
authors.lastname: Vilar
authors.forename: Nicholas P
authors.initials: NP
authors.lastname: Tatonetti
authors.forename: Lourdes
authors.initials: L
authors.lastname: Santana
authors.forename: Eugenio
authors.initials: E
authors.lastname: Uriarte
authors.forename: Fernanda
authors.initials: F
authors.lastname: Borges
authors.forename: José Angel
authors.initials: JA
authors.lastname: Fontenla
authors.forename: Dolores
authors.initials: D
authors.lastname: Viña
mesh_terms: D000110:Acetylcholinesterase / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites; D002091:Butyrylcholinesterase / Q000737:chemistry / Q000378:metabolism; D020134:Catalytic Domain; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D003374:Coumarins / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D062105:Molecular Docking Simulation; D008995:Monoamine Oxidase / Q000737:chemistry / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D019636:Neurodegenerative Diseases / Q000188:drug therapy / Q000201:enzymology*; D018696:Neuroprotective Agents / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D011485:Protein Binding / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D002800:Cholinesterase Inhibitors; D003374:Coumarins; D008996:Monoamine Oxidase Inhibitors; D018696:Neuroprotective Agents; C030123:coumarin; D008995:Monoamine Oxidase; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase