Induction of Cyp450 enzymes by 4-thiazolidinone-based derivatives in 3T3-L1 cells in vitro
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ORIGINAL ARTICLE
Induction of Cyp450 enzymes by 4-thiazolidinone-based derivatives in 3T3-L1 cells in vitro Konrad A. Szychowski 1 & Bartosz Skóra 1 & Anna Kryshchyshyn-Dylevych 2 Kamila Rybczyńska-Tkaczyk 3 & Roman Lesyk 1,2 & Jan Gmiński 1
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Danylo Kaminskyy 2
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Received: 18 September 2020 / Accepted: 15 November 2020 # The Author(s) 2020
Abstract 4-Thiazolidinones and related derivatives are regarded as privileged structures in medicinal chemistry and a source of new druglike 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 Les6166. Moreover, the Les-2194 and Les-5935 compounds were shown to increase the activity of EROD, MROD, and PROD. Les3640 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. Keywords CYP450 . 4-Thiazolidinone . Cyp1a1 . 3T3-L1 cells . Cyp1b1 . AhR Highlights • Les-2194, Les-3640, Les-5935, and Les-6166 do not affect cell viability in the range from 100 nM to 1 μM. • Compounds Les-3640 and Les-6166 at the 50 and 100 μM concentrations activate caspase-3 in 3T3-L1 cells. • Les-2194 increases the activity of EROD, MROD, and PROD and the Cyp1a2 mRNA expression in 3T3-L1 cells. • Les-2194 and Les-3640 increase the Cyp1a1 mRNA expression in 3T3L1 cells. • Les-6166 increases the activity of EROD and decreases the activity of MROD and PROD in 3T3-L1 cells. * Konrad A. Szychowski [email protected] Bartosz Skóra [email protected]
Jan Gmiński [email protected]
1
Department of Lifestyle Disorders and Regenerative Medicine, University of Information Technology and Management in Rzeszow, Sucharskiego 2, 35-225 Rzeszow, Poland
2
Department of Pharmaceutical, Organic and Bioorganic Chemistry, Danylo Halytsky Lviv National Medical University, Pekarska 69, Lviv 79010, Ukraine
3
Department of Environmental Microbiology, University of Life Sciences, Leszczyńskiego 7, 20-069 Lublin, Poland
Anna Kryshchyshyn-Dylevych [email protected] Danylo Kaminskyy [email protected] Kamila Rybczyńska-Tkaczyk [email protected] Roman Lesyk [email protected]
Naunyn-Schmiedeberg's Arch Pharmacol
Abbreviations AhR Aryl hydrocarbon r
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