title: Synthesis and biological evaluation of 2-phenoxyacetamide analogues, a novel class of potent and selective monoamine oxidase inhibitors.
abstract: Monoamine oxidases (EC 1.4.3.4; MAOs), a family of FAD-containing enzymes, is an important target for antidepressant drugs. In this paper, a series of 2-phenoxyacetamide analogues were synthesized, and their inhibitory potency towards monoamine oxidases A (MAO-A) and B (MAO-B) were evaluated using enzyme and cancer cell lysate. 2-(4-Methoxyphenoxy)acetamide (compound 12) (SI=245) and (2-(4-((prop-2-ynylimino)methyl)phenoxy)acetamide (compound 21) (IC50MAO-A=0.018 μM, IC50MAO-B=0.07 μM) were successfully identified as the most specific MAO-A inhibitor, and the most potent MAO-A/-B inhibitor, respectively. The inhibitory activities of these two compounds in living cells were also further evaluated utilizing HepG2 and SHSY-5Y cell lysates.
authors.affiliation: Department of General Surgery, Jinhua Central Hospital, Jinhua 321000, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Shen
authors.affiliation: Department of General Surgery, Jinhua Central Hospital, Jinhua 321000, China.
authors.forename: Shian
authors.initials: S
authors.lastname: Yu
authors.affiliation: Department of General Surgery, Jinhua Central Hospital, Jinhua 321000, China.
authors.forename: Jiaming
authors.initials: J
authors.lastname: Zhang
authors.affiliation: College of Biological and Environmental Engineering, Zhejiang University of Technology, 18 Chaowang Road, Hangzhou 310014, China.
authors.forename: Weizheng
authors.initials: W
authors.lastname: Jia
authors.affiliation: College of Biological and Environmental Engineering, Zhejiang University of Technology, 18 Chaowang Road, Hangzhou 310014, China. chmzhuq@hotmail.com.
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhu
mesh_terms: D056945:Hep G2 Cells; D006801:Humans; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D010642:Phenoxyacetates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: D008996:Monoamine Oxidase Inhibitors; D010642:Phenoxyacetates; D008995:Monoamine Oxidase; C579458:monoamine oxidase A, human