title: 2-Azolylchromone Derivatives as Potent and Selective Inhibitors of Monoamine Oxidases A and B.
abstract: A series of 2-azolylchromone derivatives were synthesized and their monoamine oxidase (MAO) A and B inhibitory activities were evaluated. Of the synthesized compounds, compounds 1b, 2b, 4a-c, 5b and 7b showed potent inhibitory activities against MAO-A (IC50values, 1b: 0.32 µM; 2b: 0.14 µM; 4a: 0.11 µM; 4b: 0.023 µM; 4c: 0.15 µM; 5b: 0.59 µM; 7b: 0.19 µM) and 4a, c, 5a, c, 6c and 8c for MAO-B (IC50values, 4a: 0.028 µM; 4c: 0.019 µM; 5a: 0.73 µM; 5c: 0.28 µM; 6c: 0.28 µM; 8c: 0.27 µM). These data suggest that 6-methoxy substitution favors MAO-A inhibition and 7-methoxy substitution favors MAO-B inhibition. In addition, compound 4b was the most potent inhibitor for MAO-A, and compound 4c for MAO-B. This is the first report identifying 2-azolylchromone derivatives as potent monoamine oxidase inhibitors. These results suggest that the 2-triazolylchromone structure may be a useful scaffold for the design and development of novel monoamine oxidase inhibitors, as evidenced by the activities of 4a-c and 5a-c.
authors.affiliation: Laboratory of Bioorganic Chemistry, Department of Pharmaceutical and Health Sciences, Faculty of Pharmaceutical Sciences, Josai University.
authors.forename: Koichi
authors.initials: K
authors.lastname: Takao
authors.forename: Takayuki
authors.initials: T
authors.lastname: Saito
authors.forename: Daisuke
authors.initials: D
authors.lastname: Chikuda
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Sugita
mesh_terms: D001393:Azoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002867:Chromones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015394:Molecular Structure; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D001393:Azoles; D002867:Chromones; D008996:Monoamine Oxidase Inhibitors; D011994:Recombinant Proteins; D008995:Monoamine Oxidase; C579458:monoamine oxidase A, human