title: Design of novel nicotinamides as potent and selective monoamine oxidase a inhibitors.
abstract: A series of N-(2-morpholinoethyl)nicotinamide (1-13) and N-(3-morpholinopropyl)nicotinamide derivatives (14-26) have been designed, synthesized and evaluated in vitro for their monoamine oxidase (MAO) A and B inhibitory activity and selectivity. Most of these synthesized compounds proved to be potent, and selective inhibitors of MAO-A rather than of MAO-B. 5-Chloro-6-hydroxy-N-(2-morpholinoethyl)nicotinamide (13) displayed the highest MAO-A inhibitory potency (IC(50)=0.045 microM) and a good selectivity. 2-Bromo-N-(2-morpholinoethyl)nicotinamide (3) was the most potent MAO-B inhibitor with the IC(50) value of 0.32 microM, but it was not selective. Molecular dockings of compound 13 were performed in order to give structural insights regarding the MAO-A selectivity.
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Shi
authors.forename: Ying
authors.initials: Y
authors.lastname: Yang
authors.forename: Zi-Lin
authors.initials: ZL
authors.lastname: Li
authors.forename: Zhen-Wei
authors.initials: ZW
authors.lastname: Zhu
authors.forename: Chang-Hong
authors.initials: CH
authors.lastname: Liu
authors.forename: Hai-Liang
authors.initials: HL
authors.lastname: Zhu
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D009682:Magnetic Resonance Spectroscopy; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology; D008958:Models, Molecular; D008995:Monoamine Oxidase / Q000187:drug effects*; D008996:Monoamine Oxidase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D009536:Niacinamide / Q000737:chemistry* / Q000494:pharmacology*; D051381:Rats; D021241:Spectrometry, Mass, Electrospray Ionization; D013329:Structure-Activity Relationship
chemical_list: D008996:Monoamine Oxidase Inhibitors; D009536:Niacinamide; D008995:Monoamine Oxidase