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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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Springer Berlin Heidelberg
2020
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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. |
format | Online Article Text |
id | pubmed-8102453 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Springer Berlin Heidelberg |
record_format | MEDLINE/PubMed |
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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