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

被引：51

作者：

Al-Baghdadi, Osamah B. ^{[1
]}

Prater, Natalie I. ^{[1
]}

Van der Schyf, Cornelis J. ^{[1
]}

Geldenhuys, Werner J. ^{[1
]}

机构：

[1] NE Ohio Med Univ, Coll Pharm, Dept Pharmaceut Sci, Neurotherapeut Emphasis Grp, Rootstown, OH 44272 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2012年 / 22卷 / 23期

关键词：

High-throughput (HTS) screening; Monomine oxidase; Piperine derivatives; Serum albumin; BLACK PEPPER; LONGUM;

D O I：

10.1016/j.bmcl.2012.09.056

中图分类号：

R914 [药物化学];

学科分类号：

100705 [微生物与生化药学];

摘要：

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 IC50 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 mu M 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. (C) 2012 Elsevier Ltd. All rights reserved.

引用

页码：7183 / 7188

页数：6

共 25 条

[1]

Piperine, a major constituent of black pepper, inhibits human P-glycoprotein and CYP3A4 [J].