title: New coumarin derivatives: design, synthesis and use as inhibitors of hMAO.
abstract: A series new 2H-chromene-3-carboxamides (4a-4i) and S-2H-chromene-3-carbothioates (5j-5t) were synthesized and evaluated as monoamine oxidase A and B inhibitors. Among them, compound 5k (IC50=0.21μM, IC50 iproniazid=7.65μM) showed the most activity and higher MAO-B selectivity (189.2-fold vs 1-fold) with respect to the MAO-A isoform. The need to clarify at a 3D level some important molecular aspects of discussed SAR, we undertaked a number of docking simulations to better assess. The steric effect was analyzed interms of both posing and scoring by investigating the nature of the binding interactions. The docking results of active compound 5k with hMAO-B complex indicated that conserved residue ILE 199 was important for ligand binding via Sigma-Pi interaction.
authors.affiliation: School of Pharmacy, Anhui Medical University, Hefei 230032, PR China.
authors.forename: Xu
authors.initials: X
authors.lastname: He
authors.affiliation: School of Pharmacy, Anhui Medical University, Hefei 230032, PR China.
authors.forename: Yan-Yan
authors.initials: YY
authors.lastname: Chen
authors.affiliation: School of Pharmacy, Anhui Medical University, Hefei 230032, PR China.
authors.forename: Jing-Bo
authors.initials: JB
authors.lastname: Shi
authors.affiliation: School of Pharmacy, Anhui Medical University, Hefei 230032, PR China.
authors.forename: Wen-Jiang
authors.initials: WJ
authors.lastname: Tang
authors.affiliation: School of Pharmacy, Anhui Medical University, Hefei 230032, PR China.
authors.forename: Zhi-Xiang
authors.initials: ZX
authors.lastname: Pan
authors.affiliation: School of Pharmacy, Anhui Medical University, Hefei 230032, PR China.
authors.forename: Zhi-Qiang
authors.initials: ZQ
authors.lastname: Dong
authors.affiliation: Key Laboratory of Green Pesticide and Agriculture Bioengineering, Ministry of Education, Guizhou University, Guiyang 550025, PR China.
authors.forename: Bao-An
authors.initials: BA
authors.lastname: Song
authors.affiliation: School of Pharmacy, Anhui Medical University, Hefei 230032, PR China. Electronic address: lijun@ahmu.edu.cn.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.affiliation: School of Pharmacy, Anhui Medical University, Hefei 230032, PR China; Key Laboratory of Green Pesticide and Agriculture Bioengineering, Ministry of Education, Guizhou University, Guiyang 550025, PR China; State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, PR China. Electronic address: xhliuhx@163.com.
authors.forename: Xin-Hua
authors.initials: XH
authors.lastname: Liu
mesh_terms: D003374:Coumarins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D003374:Coumarins; D008996:Monoamine Oxidase Inhibitors; C030123:coumarin; D008995:Monoamine Oxidase
keywords: Coumarin; Design; Inhibitors; Synthesis; hMAO-B