title: Inhibition of monoamine oxidase by derivatives of piperine, an alkaloid from the pepper plant Piper nigrum, for possible use in Parkinson's disease.
abstract: A series of compounds related to piperine and antiepilepsirine was screened in a monoamine oxidase A and B assay. Piperine is an alkaloid from the source plant of both black and white pepper grains, Piper nigrum. Piperine has been shown to have a wide range of activity, including MAO inhibitory activity. The z-factor for the screening assay was found to be greater than 0.8 for both assays. Notably, the compounds tested were selective towards MAO-B, with the most potent compound having an IC(50) of 498 nM. To estimate blood-brain barrier (BBB) permeability, we used a PAMPA assay, which suggested that the compounds are likely to penetrate the BBB. A fluorescent bovine serum albumin (BSA) high-throughput screening (HTS) binding assay showed an affinity of 8 μM for piperine, with more modest binding for other test compounds. Taken together, the data described here may be useful in gaining insight towards the design of selective MAO-B inhibitory compounds devoid of MAO-A activity.
authors.affiliation: Neurotherapeutics Emphasis Group, Department of Pharmaceutical Sciences, Northeast Ohio Medical University, College of Pharmacy, Rootstown, OH 44272, USA.
authors.forename: Osamah B
authors.initials: OB
authors.lastname: Al-Baghdadi
authors.forename: Natalie I
authors.initials: NI
authors.lastname: Prater
authors.forename: Cornelis J
authors.initials: CJ
authors.lastname: Van der Schyf
authors.forename: Werner J
authors.initials: WJ
authors.lastname: Geldenhuys
mesh_terms: D000470:Alkaloids / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D000818:Animals; D052117:Benzodioxoles / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D001665:Binding Sites; D001812:Blood-Brain Barrier / Q000187:drug effects; D002417:Cattle; D006801:Humans; D006860:Hydrogen Bonding; D062105:Molecular Docking Simulation; D008995:Monoamine Oxidase / Q000737:chemistry* / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D010300:Parkinson Disease / Q000378:metabolism / Q000473:pathology; D029222:Piper nigrum / Q000737:chemistry*; D010880:Piperidines / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D053284:Polyunsaturated Alkamides / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012710:Serum Albumin, Bovine / Q000378:metabolism
chemical_list: D000470:Alkaloids; D052117:Benzodioxoles; D008996:Monoamine Oxidase Inhibitors; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D012710:Serum Albumin, Bovine; D008995:Monoamine Oxidase; C008922:piperine