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Inhibition of Angiotensin-Converting Enzyme Activity by Flavonoids: Structure-Activity Relationship Studies

Previous studies have demonstrated that certain flavonoids can have an inhibitory effect on angiotensin-converting enzyme (ACE) activity, which plays a key role in the regulation of arterial blood pressure. In the present study, 17 flavonoids belonging to five structural subtypes were evaluated in v...

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Autores principales: Guerrero, Ligia, Castillo, Julián, Quiñones, Mar, Garcia-Vallvé, Santiago, Arola, Lluis, Pujadas, Gerard, Muguerza, Begoña
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3504033/
https://www.ncbi.nlm.nih.gov/pubmed/23185345
http://dx.doi.org/10.1371/journal.pone.0049493
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author Guerrero, Ligia
Castillo, Julián
Quiñones, Mar
Garcia-Vallvé, Santiago
Arola, Lluis
Pujadas, Gerard
Muguerza, Begoña
author_facet Guerrero, Ligia
Castillo, Julián
Quiñones, Mar
Garcia-Vallvé, Santiago
Arola, Lluis
Pujadas, Gerard
Muguerza, Begoña
author_sort Guerrero, Ligia
collection PubMed
description Previous studies have demonstrated that certain flavonoids can have an inhibitory effect on angiotensin-converting enzyme (ACE) activity, which plays a key role in the regulation of arterial blood pressure. In the present study, 17 flavonoids belonging to five structural subtypes were evaluated in vitro for their ability to inhibit ACE in order to establish the structural basis of their bioactivity. The ACE inhibitory (ACEI) activity of these 17 flavonoids was determined by fluorimetric method at two concentrations (500 µM and 100 µM). Their inhibitory potencies ranged from 17 to 95% at 500 µM and from 0 to 57% at 100 µM. In both cases, the highest ACEI activity was obtained for luteolin. Following the determination of ACEI activity, the flavonoids with higher ACEI activity (i.e., ACEI >60% at 500 µM) were selected for further IC(50) determination. The IC(50) values for luteolin, quercetin, rutin, kaempferol, rhoifolin and apigenin K were 23, 43, 64, 178, 183 and 196 µM, respectively. Our results suggest that flavonoids are an excellent source of functional antihypertensive products. Furthermore, our structure-activity relationship studies show that the combination of sub-structures on the flavonoid skeleton that increase ACEI activity is made up of the following elements: (a) the catechol group in the B-ring, (b) the double bond between C2 and C3 at the C-ring, and (c) the cetone group in C4 at the C-ring. Protein-ligand docking studies are used to understand the molecular basis for these results.
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spelling pubmed-35040332012-11-26 Inhibition of Angiotensin-Converting Enzyme Activity by Flavonoids: Structure-Activity Relationship Studies Guerrero, Ligia Castillo, Julián Quiñones, Mar Garcia-Vallvé, Santiago Arola, Lluis Pujadas, Gerard Muguerza, Begoña PLoS One Research Article Previous studies have demonstrated that certain flavonoids can have an inhibitory effect on angiotensin-converting enzyme (ACE) activity, which plays a key role in the regulation of arterial blood pressure. In the present study, 17 flavonoids belonging to five structural subtypes were evaluated in vitro for their ability to inhibit ACE in order to establish the structural basis of their bioactivity. The ACE inhibitory (ACEI) activity of these 17 flavonoids was determined by fluorimetric method at two concentrations (500 µM and 100 µM). Their inhibitory potencies ranged from 17 to 95% at 500 µM and from 0 to 57% at 100 µM. In both cases, the highest ACEI activity was obtained for luteolin. Following the determination of ACEI activity, the flavonoids with higher ACEI activity (i.e., ACEI >60% at 500 µM) were selected for further IC(50) determination. The IC(50) values for luteolin, quercetin, rutin, kaempferol, rhoifolin and apigenin K were 23, 43, 64, 178, 183 and 196 µM, respectively. Our results suggest that flavonoids are an excellent source of functional antihypertensive products. Furthermore, our structure-activity relationship studies show that the combination of sub-structures on the flavonoid skeleton that increase ACEI activity is made up of the following elements: (a) the catechol group in the B-ring, (b) the double bond between C2 and C3 at the C-ring, and (c) the cetone group in C4 at the C-ring. Protein-ligand docking studies are used to understand the molecular basis for these results. Public Library of Science 2012-11-21 /pmc/articles/PMC3504033/ /pubmed/23185345 http://dx.doi.org/10.1371/journal.pone.0049493 Text en © 2012 Guerrero et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Guerrero, Ligia
Castillo, Julián
Quiñones, Mar
Garcia-Vallvé, Santiago
Arola, Lluis
Pujadas, Gerard
Muguerza, Begoña
Inhibition of Angiotensin-Converting Enzyme Activity by Flavonoids: Structure-Activity Relationship Studies
title Inhibition of Angiotensin-Converting Enzyme Activity by Flavonoids: Structure-Activity Relationship Studies
title_full Inhibition of Angiotensin-Converting Enzyme Activity by Flavonoids: Structure-Activity Relationship Studies
title_fullStr Inhibition of Angiotensin-Converting Enzyme Activity by Flavonoids: Structure-Activity Relationship Studies
title_full_unstemmed Inhibition of Angiotensin-Converting Enzyme Activity by Flavonoids: Structure-Activity Relationship Studies
title_short Inhibition of Angiotensin-Converting Enzyme Activity by Flavonoids: Structure-Activity Relationship Studies
title_sort inhibition of angiotensin-converting enzyme activity by flavonoids: structure-activity relationship studies
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3504033/
https://www.ncbi.nlm.nih.gov/pubmed/23185345
http://dx.doi.org/10.1371/journal.pone.0049493
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