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Synthesis and Evaluation of Thymol-Based Synthetic Derivatives as Dual-Action Inhibitors against Different Strains of H. pylori and AGS Cell Line

Following a similar approach on carvacrol-based derivatives, we investigated the synthesis and the microbiological screening against eight strains of H. pylori, and the cytotoxic activity against human gastric adenocarcinoma (AGS) cells of a new series of ether compounds based on the structure of th...

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Autores principales: Sisto, Francesca, Carradori, Simone, Guglielmi, Paolo, Spano, Mattia, Secci, Daniela, Granese, Arianna, Sobolev, Anatoly P., Grande, Rossella, Campestre, Cristina, Di Marcantonio, Maria Carmela, Mincione, Gabriella
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8037164/
https://www.ncbi.nlm.nih.gov/pubmed/33805064
http://dx.doi.org/10.3390/molecules26071829
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author Sisto, Francesca
Carradori, Simone
Guglielmi, Paolo
Spano, Mattia
Secci, Daniela
Granese, Arianna
Sobolev, Anatoly P.
Grande, Rossella
Campestre, Cristina
Di Marcantonio, Maria Carmela
Mincione, Gabriella
author_facet Sisto, Francesca
Carradori, Simone
Guglielmi, Paolo
Spano, Mattia
Secci, Daniela
Granese, Arianna
Sobolev, Anatoly P.
Grande, Rossella
Campestre, Cristina
Di Marcantonio, Maria Carmela
Mincione, Gabriella
author_sort Sisto, Francesca
collection PubMed
description Following a similar approach on carvacrol-based derivatives, we investigated the synthesis and the microbiological screening against eight strains of H. pylori, and the cytotoxic activity against human gastric adenocarcinoma (AGS) cells of a new series of ether compounds based on the structure of thymol. Structural analysis comprehended elemental analysis and (1)H/(13)C/(19)F NMR spectra. The analysis of structure–activity relationships within this molecular library of 38 structurally-related compounds reported that some chemical modifications of the OH group of thymol led to broad-spectrum growth inhibition on all isolates. Preferred substitutions were benzyl groups compared to alkyl chains, and the specific presence of functional groups at para position of the benzyl moiety such as 4-CN and 4-Ph endowed the most anti-H. pylori activity toward all the strains with minimum inhibitory concentration (MIC) values up to 4 µg/mL. Poly-substitution on the benzyl ring was not essential. Moreover, several compounds characterized by the lowest minimum inhibitory concentration/minimum bactericidal concentration (MIC/MBC) values against H. pylori were also tested in order to verify a cytotoxic effect against AGS cells with respect to 5-fluorouracil and carvacrol. Three derivatives can be considered as new lead compounds alternative to current therapy to manage H. pylori infection, preventing the occurrence of severe gastric diseases. The present work confirms the possibility to use natural compounds as templates for the medicinal semi-synthesis.
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spelling pubmed-80371642021-04-12 Synthesis and Evaluation of Thymol-Based Synthetic Derivatives as Dual-Action Inhibitors against Different Strains of H. pylori and AGS Cell Line Sisto, Francesca Carradori, Simone Guglielmi, Paolo Spano, Mattia Secci, Daniela Granese, Arianna Sobolev, Anatoly P. Grande, Rossella Campestre, Cristina Di Marcantonio, Maria Carmela Mincione, Gabriella Molecules Article Following a similar approach on carvacrol-based derivatives, we investigated the synthesis and the microbiological screening against eight strains of H. pylori, and the cytotoxic activity against human gastric adenocarcinoma (AGS) cells of a new series of ether compounds based on the structure of thymol. Structural analysis comprehended elemental analysis and (1)H/(13)C/(19)F NMR spectra. The analysis of structure–activity relationships within this molecular library of 38 structurally-related compounds reported that some chemical modifications of the OH group of thymol led to broad-spectrum growth inhibition on all isolates. Preferred substitutions were benzyl groups compared to alkyl chains, and the specific presence of functional groups at para position of the benzyl moiety such as 4-CN and 4-Ph endowed the most anti-H. pylori activity toward all the strains with minimum inhibitory concentration (MIC) values up to 4 µg/mL. Poly-substitution on the benzyl ring was not essential. Moreover, several compounds characterized by the lowest minimum inhibitory concentration/minimum bactericidal concentration (MIC/MBC) values against H. pylori were also tested in order to verify a cytotoxic effect against AGS cells with respect to 5-fluorouracil and carvacrol. Three derivatives can be considered as new lead compounds alternative to current therapy to manage H. pylori infection, preventing the occurrence of severe gastric diseases. The present work confirms the possibility to use natural compounds as templates for the medicinal semi-synthesis. MDPI 2021-03-24 /pmc/articles/PMC8037164/ /pubmed/33805064 http://dx.doi.org/10.3390/molecules26071829 Text en © 2021 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 (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ).
spellingShingle Article
Sisto, Francesca
Carradori, Simone
Guglielmi, Paolo
Spano, Mattia
Secci, Daniela
Granese, Arianna
Sobolev, Anatoly P.
Grande, Rossella
Campestre, Cristina
Di Marcantonio, Maria Carmela
Mincione, Gabriella
Synthesis and Evaluation of Thymol-Based Synthetic Derivatives as Dual-Action Inhibitors against Different Strains of H. pylori and AGS Cell Line
title Synthesis and Evaluation of Thymol-Based Synthetic Derivatives as Dual-Action Inhibitors against Different Strains of H. pylori and AGS Cell Line
title_full Synthesis and Evaluation of Thymol-Based Synthetic Derivatives as Dual-Action Inhibitors against Different Strains of H. pylori and AGS Cell Line
title_fullStr Synthesis and Evaluation of Thymol-Based Synthetic Derivatives as Dual-Action Inhibitors against Different Strains of H. pylori and AGS Cell Line
title_full_unstemmed Synthesis and Evaluation of Thymol-Based Synthetic Derivatives as Dual-Action Inhibitors against Different Strains of H. pylori and AGS Cell Line
title_short Synthesis and Evaluation of Thymol-Based Synthetic Derivatives as Dual-Action Inhibitors against Different Strains of H. pylori and AGS Cell Line
title_sort synthesis and evaluation of thymol-based synthetic derivatives as dual-action inhibitors against different strains of h. pylori and ags cell line
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8037164/
https://www.ncbi.nlm.nih.gov/pubmed/33805064
http://dx.doi.org/10.3390/molecules26071829
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