title: Synthesis and inhibitory effect of piperine derivates on monoamine oxidase.
abstract: A series of piperine derivates (1-19) have been designed, synthesized and evaluated in vitro for their monoamine oxidase (MAO) A and B inhibitory activity and selectivity. It is worth noting that most of the small amine moieties substituted on the piperidine ring proved to be potent and selective inhibitors of MAO-B rather than of MAO-A. 5-(3,4-methylenedioxyphenyl)-2E,4E-pentadienoic acid n-propyl amide (3) showed the greatest MAO-B inhibitory activity (IC(50)(MAO-B)=0.045 μM) and good selectivity (IC(50)(MAO-A)=3.66 μM). The conjugated double bond and carbonyl group of piperine are proved to be an essential feature for piperine and related alkylamides to exhibit MAO-inhibitory activity. Binding mode of the titled compounds was predicted using FlexX algorithm. The design and optimization of novel small molecule monoamine oxidase inhibitors will be guided by the results of this report.
authors.affiliation: Department of Clinical Pharmacology, General Hospital of PLA, Beijing 100853, China.
authors.forename: Li-Hua
authors.initials: LH
authors.lastname: Mu
authors.forename: Bo
authors.initials: B
authors.lastname: Wang
authors.forename: Hao-Yang
authors.initials: HY
authors.lastname: Ren
authors.forename: Ping
authors.initials: P
authors.lastname: Liu
authors.forename: Dai-Hong
authors.initials: DH
authors.lastname: Guo
authors.forename: Fu-Meng
authors.initials: FM
authors.lastname: Wang
authors.forename: Lin
authors.initials: L
authors.lastname: Bai
authors.forename: Yan-Shen
authors.initials: YS
authors.lastname: Guo
mesh_terms: D000470:Alkaloids / Q000138:chemical synthesis* / Q000494:pharmacology; D052117:Benzodioxoles / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D008995:Monoamine Oxidase / Q000737:chemistry*; D008996:Monoamine Oxidase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D010880:Piperidines / Q000138:chemical synthesis* / Q000494:pharmacology; D053284:Polyunsaturated Alkamides / Q000138:chemical synthesis* / Q000494:pharmacology; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship
chemical_list: D000470:Alkaloids; D052117:Benzodioxoles; D008996:Monoamine Oxidase Inhibitors; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D008995:Monoamine Oxidase; C008922:piperine