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Cited by 391Flavonoids in Medical ResearchBioactive natural compoundsRenin-Angiotensin System Studies

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

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Guerrero, Ligia, Castillo, Julián, Quiñones, Mar, Garcia-Vallvé, Santiago, Arola, Lluis, Pujadas, Gerard, Muguerza, Begoña·2012·PLoS ONE
DOI 10.1371/journal.pone.0049493PMC PMC3504033
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Abstract

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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Authors
Guerrero, L., Castillo, J., Quiñones, M., Garcia-Vallvé, S., Arola, L., Pujadas, G., & Muguerza, B.
Affiliations
  • Universitat Rovira i Virgili (ES)
  • Technological Center of Nutrition and Health (ES)
Corresponding author
Muguerza, Begoña
ORCID
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2012-11-21
Volume
7
Issue
11
Pages
e49493
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0049493
PMC
PMC3504033
OpenAlex
W1992203795
Cited by
391
References
3
Citations by year
2026: 23 · 2025: 33 · 2024: 34 · 2023: 38 · 2022: 34 · 2021: 38 · 2020: 35 · 2019: 33 · 2018: 28 · 2017: 23 · 2016: 25 · 2015: 27 · 2014: 14 · 2013: 5
FWCI
11.06
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Rovira & Virgili repository (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Banco Santander
Topics
  • Health Sciences › Medicine › Pharmacology › Flavonoids in Medical Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioactive natural compounds
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
Keywords
angiotensin-converting enzyme inhibition, flavonoids, structure-activity relationship, luteolin, quercetin, rutin, kaempferol, rhoifolin, apigenin, antihypertensive drugs, catechol groups, protein-ligand docking, IC50
MeSH terms
Angiotensin-Converting Enzyme Inhibitors, Cardiovascular Diseases, Catechols, Chromatography, High Pressure Liquid, Dose-Response Relationship, Drug, Flavonoids, Humans, Peptidyl-Dipeptidase A, Ligands, Models, Chemical, Models, Molecular, Molecular Conformation, Risk Factors, Structure-Activity Relationship, Temperature, Inhibitory Concentration 50

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