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Induction of Cyp450 enzymes by 4-thiazolidinone-based derivatives in 3T3-L1 cells in vitro

4-Thiazolidinones and related derivatives are regarded as privileged structures in medicinal chemistry and a source of new drug-like compounds. To date it is known that thiazolidinones are able to induce CYP1A1 activity in 3T3-L1 cells. Therefore, to extend the knowledge of the mechanism of thiazoli...

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Autores principales: Szychowski, Konrad A., Skóra, Bartosz, Kryshchyshyn-Dylevych, Anna, Kaminskyy, Danylo, Rybczyńska-Tkaczyk, Kamila, Lesyk, Roman, Gmiński, Jan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102453/
https://www.ncbi.nlm.nih.gov/pubmed/33219472
http://dx.doi.org/10.1007/s00210-020-02025-7
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author Szychowski, Konrad A.
Skóra, Bartosz
Kryshchyshyn-Dylevych, Anna
Kaminskyy, Danylo
Rybczyńska-Tkaczyk, Kamila
Lesyk, Roman
Gmiński, Jan
author_facet Szychowski, Konrad A.
Skóra, Bartosz
Kryshchyshyn-Dylevych, Anna
Kaminskyy, Danylo
Rybczyńska-Tkaczyk, Kamila
Lesyk, Roman
Gmiński, Jan
author_sort Szychowski, Konrad A.
collection PubMed
description 4-Thiazolidinones and related derivatives are regarded as privileged structures in medicinal chemistry and a source of new drug-like compounds. To date it is known that thiazolidinones are able to induce CYP1A1 activity in 3T3-L1 cells. Therefore, to extend the knowledge of the mechanism of thiazolidinones in the cell, four chemically synthesized heterocycles were tested on 3T3-L1 cells. The 3T3-L1 cells were exposed to Les-2194, Les-3640, Les-5935, and Les-6166. Our study showed that 1 μM βNF, Les-2194, and Les-6166 decreased the expression of Ahr mRNA. In turn, βNF, Les-2194, and Les-3640 increased the Cyp1a1 mRNA expression at the same time interval. On the other hand, Les-5935 was found to decrease the Cyp1a1 mRNA expression. Interestingly, the expression of Cyp1a2 mRNA was activated only by βNF and Les-2194. The expression of Cyp1b1 mRNA in the 3T3 cell line increased after the βNF and Les-2194 treatment but declined after the exposure to Les-5935 and Les-6166. Moreover, the Les-2194 and Les-5935 compounds were shown to increase the activity of EROD, MROD, and PROD. Les-3640 increased the activity of EROD and decreased the activity of PROD. In turn, the treatment with Les-6166 resulted in an increase in the activity of EROD and a decrease in the activity of MROD and PROD in the 3T3-L1 cells. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00210-020-02025-7.
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spelling pubmed-81024532021-05-11 Induction of Cyp450 enzymes by 4-thiazolidinone-based derivatives in 3T3-L1 cells in vitro Szychowski, Konrad A. Skóra, Bartosz Kryshchyshyn-Dylevych, Anna Kaminskyy, Danylo Rybczyńska-Tkaczyk, Kamila Lesyk, Roman Gmiński, Jan Naunyn Schmiedebergs Arch Pharmacol Original Article 4-Thiazolidinones and related derivatives are regarded as privileged structures in medicinal chemistry and a source of new drug-like compounds. To date it is known that thiazolidinones are able to induce CYP1A1 activity in 3T3-L1 cells. Therefore, to extend the knowledge of the mechanism of thiazolidinones in the cell, four chemically synthesized heterocycles were tested on 3T3-L1 cells. The 3T3-L1 cells were exposed to Les-2194, Les-3640, Les-5935, and Les-6166. Our study showed that 1 μM βNF, Les-2194, and Les-6166 decreased the expression of Ahr mRNA. In turn, βNF, Les-2194, and Les-3640 increased the Cyp1a1 mRNA expression at the same time interval. On the other hand, Les-5935 was found to decrease the Cyp1a1 mRNA expression. Interestingly, the expression of Cyp1a2 mRNA was activated only by βNF and Les-2194. The expression of Cyp1b1 mRNA in the 3T3 cell line increased after the βNF and Les-2194 treatment but declined after the exposure to Les-5935 and Les-6166. Moreover, the Les-2194 and Les-5935 compounds were shown to increase the activity of EROD, MROD, and PROD. Les-3640 increased the activity of EROD and decreased the activity of PROD. In turn, the treatment with Les-6166 resulted in an increase in the activity of EROD and a decrease in the activity of MROD and PROD in the 3T3-L1 cells. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00210-020-02025-7. Springer Berlin Heidelberg 2020-11-21 2021 /pmc/articles/PMC8102453/ /pubmed/33219472 http://dx.doi.org/10.1007/s00210-020-02025-7 Text en © The Author(s) 2020 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Original Article
Szychowski, Konrad A.
Skóra, Bartosz
Kryshchyshyn-Dylevych, Anna
Kaminskyy, Danylo
Rybczyńska-Tkaczyk, Kamila
Lesyk, Roman
Gmiński, Jan
Induction of Cyp450 enzymes by 4-thiazolidinone-based derivatives in 3T3-L1 cells in vitro
title Induction of Cyp450 enzymes by 4-thiazolidinone-based derivatives in 3T3-L1 cells in vitro
title_full Induction of Cyp450 enzymes by 4-thiazolidinone-based derivatives in 3T3-L1 cells in vitro
title_fullStr Induction of Cyp450 enzymes by 4-thiazolidinone-based derivatives in 3T3-L1 cells in vitro
title_full_unstemmed Induction of Cyp450 enzymes by 4-thiazolidinone-based derivatives in 3T3-L1 cells in vitro
title_short Induction of Cyp450 enzymes by 4-thiazolidinone-based derivatives in 3T3-L1 cells in vitro
title_sort induction of cyp450 enzymes by 4-thiazolidinone-based derivatives in 3t3-l1 cells in vitro
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102453/
https://www.ncbi.nlm.nih.gov/pubmed/33219472
http://dx.doi.org/10.1007/s00210-020-02025-7
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