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

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

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

Bioorganic & medicinal chemistry letters

2012

2012-12

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 muM 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.

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

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