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Synthesis of Carvone Derivatives and In Silico and In Vitro Screening of Anti-Inflammatory Activity in Murine Macrophages

The chemical modification of natural compounds is a promising strategy to improve their frequently poor bioavailability and low potency. This study aimed at synthesizing chemical derivatives of carvone, a natural monoterpene with anti-inflammatory properties, which we recently identified, and evalua...

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Autores principales: Moço, Gabriela, Sousa, Cátia, Capitão, Ana, MacKinnon, Stephen Scott, Leitão, Alcino Jorge, Mendes, Alexandrina Ferreira
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9916994/
https://www.ncbi.nlm.nih.gov/pubmed/36768590
http://dx.doi.org/10.3390/ijms24032263
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author Moço, Gabriela
Sousa, Cátia
Capitão, Ana
MacKinnon, Stephen Scott
Leitão, Alcino Jorge
Mendes, Alexandrina Ferreira
author_facet Moço, Gabriela
Sousa, Cátia
Capitão, Ana
MacKinnon, Stephen Scott
Leitão, Alcino Jorge
Mendes, Alexandrina Ferreira
author_sort Moço, Gabriela
collection PubMed
description The chemical modification of natural compounds is a promising strategy to improve their frequently poor bioavailability and low potency. This study aimed at synthesizing chemical derivatives of carvone, a natural monoterpene with anti-inflammatory properties, which we recently identified, and evaluating their potential anti-inflammatory activity. Fourteen chemical derivatives of carvone were synthesized, purified and their chemical structures confirmed. Noncytotoxic concentrations of the test compounds were selected based on the resazurin reduction assay. Among the tested compounds, four significantly reduced the lipopolysaccharides-induced protein levels of the inducible isoform of the nitric oxide synthase and nitric oxide production and showed a dual effect on pro-IL-1 protein levels in the Raw 264.7 cell line. The Ligand Express drug discovery platform was used to predict the targets of the test compounds, and an enrichment analysis was performed to group the different biological processes and molecular and cellular functions of the tested compounds. Moreover, Ligand Express also predicted that all chemicals evaluated have intestinal and blood–brain barrier permeability, do not inhibit P-gp and do not interact with major receptors. Although presenting anti-inflammatory and some advantageous ADME properties, the tested compounds still have low potency and specificity but may provide novel structures the further chemical modification of which may yield more promising drugs.
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spelling pubmed-99169942023-02-11 Synthesis of Carvone Derivatives and In Silico and In Vitro Screening of Anti-Inflammatory Activity in Murine Macrophages Moço, Gabriela Sousa, Cátia Capitão, Ana MacKinnon, Stephen Scott Leitão, Alcino Jorge Mendes, Alexandrina Ferreira Int J Mol Sci Article The chemical modification of natural compounds is a promising strategy to improve their frequently poor bioavailability and low potency. This study aimed at synthesizing chemical derivatives of carvone, a natural monoterpene with anti-inflammatory properties, which we recently identified, and evaluating their potential anti-inflammatory activity. Fourteen chemical derivatives of carvone were synthesized, purified and their chemical structures confirmed. Noncytotoxic concentrations of the test compounds were selected based on the resazurin reduction assay. Among the tested compounds, four significantly reduced the lipopolysaccharides-induced protein levels of the inducible isoform of the nitric oxide synthase and nitric oxide production and showed a dual effect on pro-IL-1 protein levels in the Raw 264.7 cell line. The Ligand Express drug discovery platform was used to predict the targets of the test compounds, and an enrichment analysis was performed to group the different biological processes and molecular and cellular functions of the tested compounds. Moreover, Ligand Express also predicted that all chemicals evaluated have intestinal and blood–brain barrier permeability, do not inhibit P-gp and do not interact with major receptors. Although presenting anti-inflammatory and some advantageous ADME properties, the tested compounds still have low potency and specificity but may provide novel structures the further chemical modification of which may yield more promising drugs. MDPI 2023-01-23 /pmc/articles/PMC9916994/ /pubmed/36768590 http://dx.doi.org/10.3390/ijms24032263 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Moço, Gabriela
Sousa, Cátia
Capitão, Ana
MacKinnon, Stephen Scott
Leitão, Alcino Jorge
Mendes, Alexandrina Ferreira
Synthesis of Carvone Derivatives and In Silico and In Vitro Screening of Anti-Inflammatory Activity in Murine Macrophages
title Synthesis of Carvone Derivatives and In Silico and In Vitro Screening of Anti-Inflammatory Activity in Murine Macrophages
title_full Synthesis of Carvone Derivatives and In Silico and In Vitro Screening of Anti-Inflammatory Activity in Murine Macrophages
title_fullStr Synthesis of Carvone Derivatives and In Silico and In Vitro Screening of Anti-Inflammatory Activity in Murine Macrophages
title_full_unstemmed Synthesis of Carvone Derivatives and In Silico and In Vitro Screening of Anti-Inflammatory Activity in Murine Macrophages
title_short Synthesis of Carvone Derivatives and In Silico and In Vitro Screening of Anti-Inflammatory Activity in Murine Macrophages
title_sort synthesis of carvone derivatives and in silico and in vitro screening of anti-inflammatory activity in murine macrophages
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9916994/
https://www.ncbi.nlm.nih.gov/pubmed/36768590
http://dx.doi.org/10.3390/ijms24032263
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