title: New 2H-chromene-3-carboxamide derivatives: design, synthesis and use as inhibitors of hMAO.
abstract: A series new 2H-chromene-3-carboxamide derivatives 4a-4t were synthesized and evaluated as monoamine oxidase A and B (MAO-A and MAO-B) inhibitors. Among them, compound 4d (IC50 = 0.93 μM, IC(50 iproniazid) = 7.80 μM) showed the most activity and higher MAO-B selectivity (64.5-fold vs. 1-fold) with respect to the MAO-A isoform. The active compound 4d was also docked into the hMAO-B complex structure active site to determine the probable binding model. The results indicated that conserved residue CYSA 172 was important for ligand binding via hydrogen bond interaction, Pi-Pi interaction was found between the benzene-ring of compound 4d and residue ILEA 199.
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: 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: Wen-Jian
authors.initials: WJ
authors.lastname: Tang
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: Yu-Lan
authors.initials: YL
authors.lastname: Tang
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.
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: D001578:Benzopyrans / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D060326:Chemistry Techniques, Synthetic; D015195:Drug Design; D006801:Humans; D020128:Inhibitory Concentration 50; D062105:Molecular Docking Simulation; D008995:Monoamine Oxidase / Q000737:chemistry / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D001578:Benzopyrans; D008996:Monoamine Oxidase Inhibitors; D008995:Monoamine Oxidase
keywords: Coumarin; Design; Inhibitors; Synthesis; hMAO-B