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Identification of Interleukin-8-Reducing Lead Compounds Based on SAR Studies on Dihydrochalcone-Related Compounds in Human Gingival Fibroblasts (HGF-1 cells) In Vitro

Background: In order to identify potential activities against periodontal diseases, eighteen dihydrochalcones and structurally related compounds were tested in an established biological in vitro cell model of periodontal inflammation using human gingival fibroblasts (HGF-1 cells). Methods: Subsequen...

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Autores principales: Schueller, Katharina, Hans, Joachim, Pfeiffer, Stefanie, Walker, Jessica, Ley, Jakob P., Somoza, Veronika
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7144391/
https://www.ncbi.nlm.nih.gov/pubmed/32197426
http://dx.doi.org/10.3390/molecules25061382
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author Schueller, Katharina
Hans, Joachim
Pfeiffer, Stefanie
Walker, Jessica
Ley, Jakob P.
Somoza, Veronika
author_facet Schueller, Katharina
Hans, Joachim
Pfeiffer, Stefanie
Walker, Jessica
Ley, Jakob P.
Somoza, Veronika
author_sort Schueller, Katharina
collection PubMed
description Background: In order to identify potential activities against periodontal diseases, eighteen dihydrochalcones and structurally related compounds were tested in an established biological in vitro cell model of periodontal inflammation using human gingival fibroblasts (HGF-1 cells). Methods: Subsequently to co-incubation of HGF-1 cells with a bacterial endotoxin (Porphyromonas gingivalis lipopolysaccharide, pgLPS) and each individual dihydrochalcone in a concentration range of 1 µM to 100 µM, gene expression of interleukin-8 (IL-8) was determined by qPCR and cellular interleukin-8 (IL-8) release by ELISA. Results: Structure–activity analysis based on the dihydrochalcone backbone and various substitution patterns at its aromatic ring revealed moieties 2′,4,4′,6′-tetrahydroxy 3-methoxydihydrochalcone (7) to be the most effective anti-inflammatory compound, reducing the pgLPS-induced IL-8 release concentration between 1 µM and 100 µM up to 94%. In general, a 2,4,6-trihydroxy substitution at the A-ring and concomitant vanilloyl (4-hydroxy-3-methoxy) pattern at the B-ring revealed to be preferable for IL-8 release inhibition. Furthermore, the introduction of an electronegative atom in the A,B-linker chain led to an increased anti-inflammatory activity, shown by the potency of 4-hydroxybenzoic acid N-vanillylamide (13). Conclusions: Our data may be feasible to be used for further lead structure designs for the development of potent anti-inflammatory additives in oral care products.
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spelling pubmed-71443912020-04-13 Identification of Interleukin-8-Reducing Lead Compounds Based on SAR Studies on Dihydrochalcone-Related Compounds in Human Gingival Fibroblasts (HGF-1 cells) In Vitro Schueller, Katharina Hans, Joachim Pfeiffer, Stefanie Walker, Jessica Ley, Jakob P. Somoza, Veronika Molecules Article Background: In order to identify potential activities against periodontal diseases, eighteen dihydrochalcones and structurally related compounds were tested in an established biological in vitro cell model of periodontal inflammation using human gingival fibroblasts (HGF-1 cells). Methods: Subsequently to co-incubation of HGF-1 cells with a bacterial endotoxin (Porphyromonas gingivalis lipopolysaccharide, pgLPS) and each individual dihydrochalcone in a concentration range of 1 µM to 100 µM, gene expression of interleukin-8 (IL-8) was determined by qPCR and cellular interleukin-8 (IL-8) release by ELISA. Results: Structure–activity analysis based on the dihydrochalcone backbone and various substitution patterns at its aromatic ring revealed moieties 2′,4,4′,6′-tetrahydroxy 3-methoxydihydrochalcone (7) to be the most effective anti-inflammatory compound, reducing the pgLPS-induced IL-8 release concentration between 1 µM and 100 µM up to 94%. In general, a 2,4,6-trihydroxy substitution at the A-ring and concomitant vanilloyl (4-hydroxy-3-methoxy) pattern at the B-ring revealed to be preferable for IL-8 release inhibition. Furthermore, the introduction of an electronegative atom in the A,B-linker chain led to an increased anti-inflammatory activity, shown by the potency of 4-hydroxybenzoic acid N-vanillylamide (13). Conclusions: Our data may be feasible to be used for further lead structure designs for the development of potent anti-inflammatory additives in oral care products. MDPI 2020-03-18 /pmc/articles/PMC7144391/ /pubmed/32197426 http://dx.doi.org/10.3390/molecules25061382 Text en © 2020 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 (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Schueller, Katharina
Hans, Joachim
Pfeiffer, Stefanie
Walker, Jessica
Ley, Jakob P.
Somoza, Veronika
Identification of Interleukin-8-Reducing Lead Compounds Based on SAR Studies on Dihydrochalcone-Related Compounds in Human Gingival Fibroblasts (HGF-1 cells) In Vitro
title Identification of Interleukin-8-Reducing Lead Compounds Based on SAR Studies on Dihydrochalcone-Related Compounds in Human Gingival Fibroblasts (HGF-1 cells) In Vitro
title_full Identification of Interleukin-8-Reducing Lead Compounds Based on SAR Studies on Dihydrochalcone-Related Compounds in Human Gingival Fibroblasts (HGF-1 cells) In Vitro
title_fullStr Identification of Interleukin-8-Reducing Lead Compounds Based on SAR Studies on Dihydrochalcone-Related Compounds in Human Gingival Fibroblasts (HGF-1 cells) In Vitro
title_full_unstemmed Identification of Interleukin-8-Reducing Lead Compounds Based on SAR Studies on Dihydrochalcone-Related Compounds in Human Gingival Fibroblasts (HGF-1 cells) In Vitro
title_short Identification of Interleukin-8-Reducing Lead Compounds Based on SAR Studies on Dihydrochalcone-Related Compounds in Human Gingival Fibroblasts (HGF-1 cells) In Vitro
title_sort identification of interleukin-8-reducing lead compounds based on sar studies on dihydrochalcone-related compounds in human gingival fibroblasts (hgf-1 cells) in vitro
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7144391/
https://www.ncbi.nlm.nih.gov/pubmed/32197426
http://dx.doi.org/10.3390/molecules25061382
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