Inhibition of monoamine oxidase by derivatives of piperine, an alkaloid from the pepper plant Piper nigrum, for possible use in Parkinson's disease

Osamah B Al-Baghdadi; Natalie I Prater; Cornelis J Van der Schyf; Werner J Geldenhuys

doi:10.1016/j.bmcl.2012.09.056

Inhibition of monoamine oxidase by derivatives of piperine, an alkaloid from the pepper plant Piper nigrum, for possible use in Parkinson's disease

Bioorg Med Chem Lett. 2012 Dec 1;22(23):7183-8. doi: 10.1016/j.bmcl.2012.09.056. Epub 2012 Sep 23.

Authors

Osamah B Al-Baghdadi¹, Natalie I Prater, Cornelis J Van der Schyf, Werner J Geldenhuys

Affiliation

¹ Neurotherapeutics Emphasis Group, Department of Pharmaceutical Sciences, Northeast Ohio Medical University, College of Pharmacy, Rootstown, OH 44272, USA.

PMID: 23102654
DOI: 10.1016/j.bmcl.2012.09.056

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.

MeSH terms

Alkaloids / chemistry*
Alkaloids / isolation & purification
Alkaloids / pharmacology
Animals
Benzodioxoles / chemistry*
Benzodioxoles / isolation & purification
Benzodioxoles / pharmacology
Binding Sites
Blood-Brain Barrier / drug effects
Cattle
Humans
Hydrogen Bonding
Molecular Docking Simulation
Monoamine Oxidase / chemistry*
Monoamine Oxidase / metabolism
Monoamine Oxidase Inhibitors / chemistry*
Monoamine Oxidase Inhibitors / isolation & purification
Monoamine Oxidase Inhibitors / pharmacology
Parkinson Disease / metabolism
Parkinson Disease / pathology
Piper nigrum / chemistry*
Piperidines / chemistry*
Piperidines / isolation & purification
Piperidines / pharmacology
Polyunsaturated Alkamides / chemistry*
Polyunsaturated Alkamides / isolation & purification
Polyunsaturated Alkamides / pharmacology
Protein Binding
Protein Structure, Tertiary
Serum Albumin, Bovine / metabolism

Substances

Alkaloids
Benzodioxoles
Monoamine Oxidase Inhibitors
Piperidines
Polyunsaturated Alkamides
Serum Albumin, Bovine
Monoamine Oxidase
piperine