Methylpiperate derivatives from Piper longum and their inhibition of monoamine oxidase.
We have previously reported that piperine, a known piperidine alkaloid from Piper longum, competitively inhibited mouse brain MAO-A and MAO-B activities. Piperine also showed in vivo antidepressant-like activity against the tail suspension test. In the present study, we further expanded on the identification of MAO inhibitors from the fruit of P. longum. Activity-guided fractionation of a methylene chloride soluble extract led to the isolation of three known piperine-related compounds, methylpiperate (1), guineensine (2), and piperlonguminine (3). Of these, methylpiperate (1) and guineensine (2) showed significant MAO inhibitory activities with IC50 values of 3.6 and 139.2 microM, respectively. Furthermore, methylpiperate (1) exhibited a selective inhibitory effect against MAO-B (IC50 value: 1.6 microM) than MAO-A (IC50 value: 27.1 microM). The kinetic study using the Lineweaver-Burk plots analysis suggested that methylpiperate (1) competitively inhibits MAO-A and MAO-B activities with the Ki values of 23.5 and 1.3 microM, respectively.
College of Pharmacy, Chungbuk National University, Cheongju, 361-763, Korea.
Seon A
SA
Lee
Ji Sang
JS
Hwang
Xiang Hua
XH
Han
Chul
C
Lee
Min Hee
MH
Lee
Sang Gil
SG
Choe
Seong Su
SS
Hong
Dongho
D
Lee
Myung Koo
MK
Lee
Bang Yeon
BY
Hwang
D000475:Alkenes / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000201:enzymology; D004148:Dioxolanes / Q000302:isolation & purification / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005638:Fruit; D006574:Heterocyclic Compounds, 2-Ring / Q000302:isolation & purification / Q000494:pharmacology*; D007700:Kinetics; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000302:isolation & purification / Q000494:pharmacology*; D031701:Piper / Q000737:chemistry; D010881:Piperidones
D000475:Alkenes; D004148:Dioxolanes; D006574:Heterocyclic Compounds, 2-Ring; D008995:Monoamine Oxidase; D008996:Monoamine Oxidase Inhibitors; C492480:guineensine; C531425:methylpiperate; C498077:piperlongumine; D010881:Piperidones