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Aggregating Behavior of Phenolic Compounds — A Source of False Bioassay Results?

Previous descriptions of quercetin, a widely studied flavonoid, as a frequently reported nonspecific screening hit due to aggregating behavior has raised questions about the reliability of in vitro bioactivity reports of phenolic compounds. Here a systematic study on 117 phenolic compounds is presen...

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Autores principales: Pohjala, Leena, Tammela, Päivi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6268869/
https://www.ncbi.nlm.nih.gov/pubmed/22960870
http://dx.doi.org/10.3390/molecules170910774
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author Pohjala, Leena
Tammela, Päivi
author_facet Pohjala, Leena
Tammela, Päivi
author_sort Pohjala, Leena
collection PubMed
description Previous descriptions of quercetin, a widely studied flavonoid, as a frequently reported nonspecific screening hit due to aggregating behavior has raised questions about the reliability of in vitro bioactivity reports of phenolic compounds. Here a systematic study on 117 phenolic compounds is presented, concerning their aggregating tendency and the relevance of this phenomenon to obtaining false bioassay results. Fourteen compounds formed aggregates detectable by dynamic light scattering (DLS) when assayed at 10 µM in Tris-HCl pH 7.5. Flavonoids were more prone to aggregation than other phenolic compounds, and the aggregate formation was highly dependent on the vehicle, ionic strength and pH. The compounds were also assayed against three unrelated enzymes in the presence and absence of Triton X-100, and their bioactivity ratios were collected from PubChem database. By comparing these datasets, quercetin and rhamnetin were confirmed as promiscuous inhibitors. In general, flavonoids exhibited also higher bioactivity ratios in the PubChem database than coumarins or organic acids. To conclude, aggregate formation can be controlled with Triton X-100 and this phenomenon needs to be considered when bioassay data is interpreted, but our data indicates that it does not always lead to unspecific inhibition of biological targets.
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spelling pubmed-62688692018-12-12 Aggregating Behavior of Phenolic Compounds — A Source of False Bioassay Results? Pohjala, Leena Tammela, Päivi Molecules Article Previous descriptions of quercetin, a widely studied flavonoid, as a frequently reported nonspecific screening hit due to aggregating behavior has raised questions about the reliability of in vitro bioactivity reports of phenolic compounds. Here a systematic study on 117 phenolic compounds is presented, concerning their aggregating tendency and the relevance of this phenomenon to obtaining false bioassay results. Fourteen compounds formed aggregates detectable by dynamic light scattering (DLS) when assayed at 10 µM in Tris-HCl pH 7.5. Flavonoids were more prone to aggregation than other phenolic compounds, and the aggregate formation was highly dependent on the vehicle, ionic strength and pH. The compounds were also assayed against three unrelated enzymes in the presence and absence of Triton X-100, and their bioactivity ratios were collected from PubChem database. By comparing these datasets, quercetin and rhamnetin were confirmed as promiscuous inhibitors. In general, flavonoids exhibited also higher bioactivity ratios in the PubChem database than coumarins or organic acids. To conclude, aggregate formation can be controlled with Triton X-100 and this phenomenon needs to be considered when bioassay data is interpreted, but our data indicates that it does not always lead to unspecific inhibition of biological targets. MDPI 2012-09-07 /pmc/articles/PMC6268869/ /pubmed/22960870 http://dx.doi.org/10.3390/molecules170910774 Text en © 2012 by the authors; licensee MDPI, Basel, Switzerland. http://creativecommons.org/licenses/by/3.0/ 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
Pohjala, Leena
Tammela, Päivi
Aggregating Behavior of Phenolic Compounds — A Source of False Bioassay Results?
title Aggregating Behavior of Phenolic Compounds — A Source of False Bioassay Results?
title_full Aggregating Behavior of Phenolic Compounds — A Source of False Bioassay Results?
title_fullStr Aggregating Behavior of Phenolic Compounds — A Source of False Bioassay Results?
title_full_unstemmed Aggregating Behavior of Phenolic Compounds — A Source of False Bioassay Results?
title_short Aggregating Behavior of Phenolic Compounds — A Source of False Bioassay Results?
title_sort aggregating behavior of phenolic compounds — a source of false bioassay results?
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6268869/
https://www.ncbi.nlm.nih.gov/pubmed/22960870
http://dx.doi.org/10.3390/molecules170910774
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