Synthesis and inhibitory effect of piperine derivates on monoamine oxidase

doi:10.1016/j.bmcl.2012.02.090

Bioorganic & Medicinal Chemistry Letters

Volume 22, Issue 9, 1 May 2012, Pages 3343-3348

https://doi.org/10.1016/j.bmcl.2012.02.090 Get rights and content

Abstract

A series of piperine derivates (1–19) have been designed, synthesized and evaluated in vitro for their monoamine oxidase (MAO) A and B inhibitory activity and selectivity. It is worth noting that most of the small amine moieties substituted on the piperidine ring proved to be potent and selective inhibitors of MAO-B rather than of MAO-A. 5-(3,4-methylenedioxyphenyl)-2E,4E-pentadienoic acid n-propyl amide (3) showed the greatest MAO-B inhibitory activity (IC₅₀(MAO-B) = 0.045 μM) and good selectivity (IC₅₀(MAO-A) = 3.66 μM). The conjugated double bond and carbonyl group of piperine are proved to be an essential feature for piperine and related alkylamides to exhibit MAO-inhibitory activity. Binding mode of the titled compounds was predicted using FlexX algorithm. The design and optimization of novel small molecule monoamine oxidase inhibitors will be guided by the results of this report.

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Acknowledgments

We are grateful to Mr Li-Ping Kang for the NMR and HR-EI-MS measurement in the Instrumentation Center of the Academy of Military Medical Sciences.

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^†: These authors contributed equally to this work.

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Synthesis and inhibitory effect of piperine derivates on monoamine oxidase

Abstract

Graphical abstract

Section snippets

Acknowledgments

Life Sci.

Arch. Biochem. Biophys.

Food Chem. Toxicol.

J. Asian Nat. Prod. Res.