Cargando…
Bioinspired Honokiol Analogs and Their Evaluation for Activity on the Norepinephrine Transporter
In traditional Asian medicinal systems, preparations of the root and stem bark of Magnolia species are widely used to treat anxiety and other nervous disturbances. The biphenyl-type neolignans honokiol and magnolol are the main constituents of Magnolia bark extracts. In the central nervous system, M...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2018
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6222891/ https://www.ncbi.nlm.nih.gov/pubmed/30287800 http://dx.doi.org/10.3390/molecules23102536 |
_version_ | 1783369312880295936 |
---|---|
author | Stout, Kristen Bernaskova, Marketa Miller, Gary W. Hufner, Antje Schuehly, Wolfgang |
author_facet | Stout, Kristen Bernaskova, Marketa Miller, Gary W. Hufner, Antje Schuehly, Wolfgang |
author_sort | Stout, Kristen |
collection | PubMed |
description | In traditional Asian medicinal systems, preparations of the root and stem bark of Magnolia species are widely used to treat anxiety and other nervous disturbances. The biphenyl-type neolignans honokiol and magnolol are the main constituents of Magnolia bark extracts. In the central nervous system, Magnolia bark preparations that contain honokiol are thought to primarily interact with γ-aminobutyric acid A (GABA(A)) receptors. However, stress responses inherently involve the noradrenergic system, which has not been investigated in the pharmacological mechanism of honokiol. We present here interactions of honokiol and other synthesized biphenyl-type neolignans and diphenylmethane analogs with the norepinephrine transporter (NET), which is responsible for the synaptic clearance of norepinephrine and the target of many anxiolytics. Of the synthesized compounds, 16 are new chemical entities, which are fully characterized. The 52 compounds tested show mild, non-potent interactions with NET (IC(50) > 100 µM). It is thus likely that the observed anxiolytic effects of, e.g., Magnolia preparations, are not due to direct interaction with the noradrenergic system. |
format | Online Article Text |
id | pubmed-6222891 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-62228912018-11-13 Bioinspired Honokiol Analogs and Their Evaluation for Activity on the Norepinephrine Transporter Stout, Kristen Bernaskova, Marketa Miller, Gary W. Hufner, Antje Schuehly, Wolfgang Molecules Article In traditional Asian medicinal systems, preparations of the root and stem bark of Magnolia species are widely used to treat anxiety and other nervous disturbances. The biphenyl-type neolignans honokiol and magnolol are the main constituents of Magnolia bark extracts. In the central nervous system, Magnolia bark preparations that contain honokiol are thought to primarily interact with γ-aminobutyric acid A (GABA(A)) receptors. However, stress responses inherently involve the noradrenergic system, which has not been investigated in the pharmacological mechanism of honokiol. We present here interactions of honokiol and other synthesized biphenyl-type neolignans and diphenylmethane analogs with the norepinephrine transporter (NET), which is responsible for the synaptic clearance of norepinephrine and the target of many anxiolytics. Of the synthesized compounds, 16 are new chemical entities, which are fully characterized. The 52 compounds tested show mild, non-potent interactions with NET (IC(50) > 100 µM). It is thus likely that the observed anxiolytic effects of, e.g., Magnolia preparations, are not due to direct interaction with the noradrenergic system. MDPI 2018-10-04 /pmc/articles/PMC6222891/ /pubmed/30287800 http://dx.doi.org/10.3390/molecules23102536 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Stout, Kristen Bernaskova, Marketa Miller, Gary W. Hufner, Antje Schuehly, Wolfgang Bioinspired Honokiol Analogs and Their Evaluation for Activity on the Norepinephrine Transporter |
title | Bioinspired Honokiol Analogs and Their Evaluation for Activity on the Norepinephrine Transporter |
title_full | Bioinspired Honokiol Analogs and Their Evaluation for Activity on the Norepinephrine Transporter |
title_fullStr | Bioinspired Honokiol Analogs and Their Evaluation for Activity on the Norepinephrine Transporter |
title_full_unstemmed | Bioinspired Honokiol Analogs and Their Evaluation for Activity on the Norepinephrine Transporter |
title_short | Bioinspired Honokiol Analogs and Their Evaluation for Activity on the Norepinephrine Transporter |
title_sort | bioinspired honokiol analogs and their evaluation for activity on the norepinephrine transporter |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6222891/ https://www.ncbi.nlm.nih.gov/pubmed/30287800 http://dx.doi.org/10.3390/molecules23102536 |
work_keys_str_mv | AT stoutkristen bioinspiredhonokiolanalogsandtheirevaluationforactivityonthenorepinephrinetransporter AT bernaskovamarketa bioinspiredhonokiolanalogsandtheirevaluationforactivityonthenorepinephrinetransporter AT millergaryw bioinspiredhonokiolanalogsandtheirevaluationforactivityonthenorepinephrinetransporter AT hufnerantje bioinspiredhonokiolanalogsandtheirevaluationforactivityonthenorepinephrinetransporter AT schuehlywolfgang bioinspiredhonokiolanalogsandtheirevaluationforactivityonthenorepinephrinetransporter |