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Factors Influencing the Antifolate Activity of Synthetic Tea-Derived Catechins

Novel tea catechin derivatives have been synthesized, and a structure-activity study, related to the capacity of these and other polyphenols to bind dihydrofolate reductase (DHFR), has been performed. The data showed an effective binding between all molecules and the free enzyme, and the dissociatio...

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Autores principales: Sáez-Ayala, Magalí, Fernández-Pérez, María Piedad, Chazarra, Soledad, Mchedlishvili, Nani, Tárraga-Tomás, Alberto, Rodríguez-López, José Neptuno
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6270263/
https://www.ncbi.nlm.nih.gov/pubmed/23863773
http://dx.doi.org/10.3390/molecules18078319
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author Sáez-Ayala, Magalí
Fernández-Pérez, María Piedad
Chazarra, Soledad
Mchedlishvili, Nani
Tárraga-Tomás, Alberto
Rodríguez-López, José Neptuno
author_facet Sáez-Ayala, Magalí
Fernández-Pérez, María Piedad
Chazarra, Soledad
Mchedlishvili, Nani
Tárraga-Tomás, Alberto
Rodríguez-López, José Neptuno
author_sort Sáez-Ayala, Magalí
collection PubMed
description Novel tea catechin derivatives have been synthesized, and a structure-activity study, related to the capacity of these and other polyphenols to bind dihydrofolate reductase (DHFR), has been performed. The data showed an effective binding between all molecules and the free enzyme, and the dissociation constants of the synthetic compounds and of the natural analogues were on the same order. Polyphenols with a catechin configuration were better DHFR inhibitors than those with an epicatechin configuration. Antiproliferative activity was also studied in cultured tumour cells, and the data showed that the activity of the novel derivatives was higher in catechin isomers. Derivatives with a hydroxyl group para on the ester-bonded gallate moiety presented a high in vitro binding to DHFR, but exhibited transport problems in cell culture due to ionization at physiologic pHs. The impact of the binding of catechins to serum albumin on their biological activity was also evaluated. The information provided in this study could be important for the design of novel medicinal active compounds derived from tea catechins. The data suggest that changes in their structure to avoid serum albumin interactions and to facilitate plasmatic membrane transport are essential for the intracellular functions of catechins.
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spelling pubmed-62702632018-12-17 Factors Influencing the Antifolate Activity of Synthetic Tea-Derived Catechins Sáez-Ayala, Magalí Fernández-Pérez, María Piedad Chazarra, Soledad Mchedlishvili, Nani Tárraga-Tomás, Alberto Rodríguez-López, José Neptuno Molecules Article Novel tea catechin derivatives have been synthesized, and a structure-activity study, related to the capacity of these and other polyphenols to bind dihydrofolate reductase (DHFR), has been performed. The data showed an effective binding between all molecules and the free enzyme, and the dissociation constants of the synthetic compounds and of the natural analogues were on the same order. Polyphenols with a catechin configuration were better DHFR inhibitors than those with an epicatechin configuration. Antiproliferative activity was also studied in cultured tumour cells, and the data showed that the activity of the novel derivatives was higher in catechin isomers. Derivatives with a hydroxyl group para on the ester-bonded gallate moiety presented a high in vitro binding to DHFR, but exhibited transport problems in cell culture due to ionization at physiologic pHs. The impact of the binding of catechins to serum albumin on their biological activity was also evaluated. The information provided in this study could be important for the design of novel medicinal active compounds derived from tea catechins. The data suggest that changes in their structure to avoid serum albumin interactions and to facilitate plasmatic membrane transport are essential for the intracellular functions of catechins. MDPI 2013-07-16 /pmc/articles/PMC6270263/ /pubmed/23863773 http://dx.doi.org/10.3390/molecules18078319 Text en © 2013 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 license (http://creativecommons.org/licenses/by/3.0/).
spellingShingle Article
Sáez-Ayala, Magalí
Fernández-Pérez, María Piedad
Chazarra, Soledad
Mchedlishvili, Nani
Tárraga-Tomás, Alberto
Rodríguez-López, José Neptuno
Factors Influencing the Antifolate Activity of Synthetic Tea-Derived Catechins
title Factors Influencing the Antifolate Activity of Synthetic Tea-Derived Catechins
title_full Factors Influencing the Antifolate Activity of Synthetic Tea-Derived Catechins
title_fullStr Factors Influencing the Antifolate Activity of Synthetic Tea-Derived Catechins
title_full_unstemmed Factors Influencing the Antifolate Activity of Synthetic Tea-Derived Catechins
title_short Factors Influencing the Antifolate Activity of Synthetic Tea-Derived Catechins
title_sort factors influencing the antifolate activity of synthetic tea-derived catechins
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6270263/
https://www.ncbi.nlm.nih.gov/pubmed/23863773
http://dx.doi.org/10.3390/molecules18078319
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