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A Template-Based Approach for Guiding and Refining the Development of Cinnamon-Based Phenylpropanoids as Drugs

Background: Structure-activity relationships describe the relationship between chemical structure and biologic activity and are capable of informing deliberate structural modifications to a molecule in order enhance drug properties. Methods: Here, we present a subtle, yet unique twist on structure-a...

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Autores principales: Nguyen, Ngoc Uy, Stamper, Brendan David
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7587175/
https://www.ncbi.nlm.nih.gov/pubmed/33050677
http://dx.doi.org/10.3390/molecules25204629
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author Nguyen, Ngoc Uy
Stamper, Brendan David
author_facet Nguyen, Ngoc Uy
Stamper, Brendan David
author_sort Nguyen, Ngoc Uy
collection PubMed
description Background: Structure-activity relationships describe the relationship between chemical structure and biologic activity and are capable of informing deliberate structural modifications to a molecule in order enhance drug properties. Methods: Here, we present a subtle, yet unique twist on structure-activity relationships in which a collective biologic activity was measured among five cinnamon constituents with a shared phenylpropanoid template (cinnamic acid, cinnamaldehyde, chlorogenic acid, caffeic acid, and ferulic acid). This template-based approach utilized publicly available transcriptomic data through the Gene Expression Omnibus (GEO) to identify a fundamental biologic effect; in essence, a phenylpropanoid template effect. Results: The recurrent identification of cytokine-cytokine receptor interaction and neuroactive ligand receptor pathways in each individual treatment condition strongly supports the fact that changes in gene expression within these pathways is a hallmark of the phenylpropanoid template. With a template effect identified, future structural modifications can be performed in order to overcome pharmacokinetic barriers to clinical use (i.e., traditional structure-activity relationship experiments). Moreover, these modifications can be implemented with a high degree of confidence knowing that a consistent and robust template effect is likely to persist. Conclusion: We believe this template-based approach offers researchers an attractive and cost-effective means for evaluating multicomponent natural products during drug development.
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spelling pubmed-75871752020-10-29 A Template-Based Approach for Guiding and Refining the Development of Cinnamon-Based Phenylpropanoids as Drugs Nguyen, Ngoc Uy Stamper, Brendan David Molecules Communication Background: Structure-activity relationships describe the relationship between chemical structure and biologic activity and are capable of informing deliberate structural modifications to a molecule in order enhance drug properties. Methods: Here, we present a subtle, yet unique twist on structure-activity relationships in which a collective biologic activity was measured among five cinnamon constituents with a shared phenylpropanoid template (cinnamic acid, cinnamaldehyde, chlorogenic acid, caffeic acid, and ferulic acid). This template-based approach utilized publicly available transcriptomic data through the Gene Expression Omnibus (GEO) to identify a fundamental biologic effect; in essence, a phenylpropanoid template effect. Results: The recurrent identification of cytokine-cytokine receptor interaction and neuroactive ligand receptor pathways in each individual treatment condition strongly supports the fact that changes in gene expression within these pathways is a hallmark of the phenylpropanoid template. With a template effect identified, future structural modifications can be performed in order to overcome pharmacokinetic barriers to clinical use (i.e., traditional structure-activity relationship experiments). Moreover, these modifications can be implemented with a high degree of confidence knowing that a consistent and robust template effect is likely to persist. Conclusion: We believe this template-based approach offers researchers an attractive and cost-effective means for evaluating multicomponent natural products during drug development. MDPI 2020-10-11 /pmc/articles/PMC7587175/ /pubmed/33050677 http://dx.doi.org/10.3390/molecules25204629 Text en © 2020 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 Communication
Nguyen, Ngoc Uy
Stamper, Brendan David
A Template-Based Approach for Guiding and Refining the Development of Cinnamon-Based Phenylpropanoids as Drugs
title A Template-Based Approach for Guiding and Refining the Development of Cinnamon-Based Phenylpropanoids as Drugs
title_full A Template-Based Approach for Guiding and Refining the Development of Cinnamon-Based Phenylpropanoids as Drugs
title_fullStr A Template-Based Approach for Guiding and Refining the Development of Cinnamon-Based Phenylpropanoids as Drugs
title_full_unstemmed A Template-Based Approach for Guiding and Refining the Development of Cinnamon-Based Phenylpropanoids as Drugs
title_short A Template-Based Approach for Guiding and Refining the Development of Cinnamon-Based Phenylpropanoids as Drugs
title_sort template-based approach for guiding and refining the development of cinnamon-based phenylpropanoids as drugs
topic Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7587175/
https://www.ncbi.nlm.nih.gov/pubmed/33050677
http://dx.doi.org/10.3390/molecules25204629
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