Combined In Silico and In Vitro Analyses to Assess the Anticancer Potential of Thiazolidinedione–Thiosemicarbazone Hybrid Molecules
The number of people affected by cancer and antibiotic-resistant bacterial infections has increased, such that both diseases are already seen as current and future leading causes of death globally. To address this issue, based on a combined in silico and in vitro approach, we explored the anticancer...
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| Format: | Article |
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MDPI AG
2023-12-01
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| Series: | International Journal of Molecular Sciences |
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| author | Agata Paneth Barbara Kaproń Tomasz Plech Roman Paduch Nazar Trotsko Piotr Paneth |
| author_facet | Agata Paneth Barbara Kaproń Tomasz Plech Roman Paduch Nazar Trotsko Piotr Paneth |
| author_sort | Agata Paneth |
| collection | DOAJ |
| description | The number of people affected by cancer and antibiotic-resistant bacterial infections has increased, such that both diseases are already seen as current and future leading causes of death globally. To address this issue, based on a combined in silico and in vitro approach, we explored the anticancer potential of known antibacterials with a thiazolidinedione–thiosemicarbazone (TZD–TSC) core structure. A cytotoxicity assessment showed encouraging results for compounds <b>2</b>–<b>4</b>, with IC<sub>50</sub> values against T98G and HepG2 cells in the low micromolar range. TZD–TSC <b>3</b> proved to be most toxic to cancer cell lines, with IC<sub>50</sub> values of 2.97 ± 0.39 µM against human hepatoma HepG2 cells and IC<sub>50</sub> values of 28.34 ± 2.21 µM against human glioblastoma T98G cells. Additionally, compound <b>3</b> induced apoptosis and showed no specific hemolytic activity. Furthermore, treatment using <b>3</b> on cancer cell lines alters these cells’ morphology and further suppresses migratory activity. Molecular docking, in turn, suggests that <b>3</b> would have the capacity to simultaneously target HDACs and PPARγ, by the activation of PPARγ and the inhibition of both HDAC4 and HDAC8. Thus, the promising preliminary results obtained with TZD–TSC <b>3</b> represent an encouraging starting point for the rational design of novel chemotherapeutics with dual antibacterial and anticancer activities. |
| first_indexed | 2024-03-08T20:41:08Z |
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| id | doaj.art-b5361b31f67646ae881e1f40686da6b7 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-08T20:41:08Z |
| publishDate | 2023-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-b5361b31f67646ae881e1f40686da6b72023-12-22T14:14:56ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-12-0124241752110.3390/ijms242417521Combined In Silico and In Vitro Analyses to Assess the Anticancer Potential of Thiazolidinedione–Thiosemicarbazone Hybrid MoleculesAgata Paneth0Barbara Kaproń1Tomasz Plech2Roman Paduch3Nazar Trotsko4Piotr Paneth5Chair and Department of Organic Chemistry, Faculty of Pharmacy, Medical University of Lublin, 20-059 Lublin, PolandDepartment of Clinical Genetics, Faculty of Medicine, Medical University of Lublin, 20-080 Lublin, PolandDepartment of Pharmacology, Faculty of Health Sciences, Medical University of Lublin, 20-080 Lublin, PolandDepartment of Virology and Immunology, Institute of Biological Sciences, Faculty of Biology and Biotechnology, Maria Curie-Skłodowska University, 20-033 Lublin, PolandChair and Department of Organic Chemistry, Faculty of Pharmacy, Medical University of Lublin, 20-059 Lublin, PolandInstitute of Applied Radiation Chemistry, Faculty of Chemistry, Lodz University of Technology, 90-924 Lodz, PolandThe number of people affected by cancer and antibiotic-resistant bacterial infections has increased, such that both diseases are already seen as current and future leading causes of death globally. To address this issue, based on a combined in silico and in vitro approach, we explored the anticancer potential of known antibacterials with a thiazolidinedione–thiosemicarbazone (TZD–TSC) core structure. A cytotoxicity assessment showed encouraging results for compounds <b>2</b>–<b>4</b>, with IC<sub>50</sub> values against T98G and HepG2 cells in the low micromolar range. TZD–TSC <b>3</b> proved to be most toxic to cancer cell lines, with IC<sub>50</sub> values of 2.97 ± 0.39 µM against human hepatoma HepG2 cells and IC<sub>50</sub> values of 28.34 ± 2.21 µM against human glioblastoma T98G cells. Additionally, compound <b>3</b> induced apoptosis and showed no specific hemolytic activity. Furthermore, treatment using <b>3</b> on cancer cell lines alters these cells’ morphology and further suppresses migratory activity. Molecular docking, in turn, suggests that <b>3</b> would have the capacity to simultaneously target HDACs and PPARγ, by the activation of PPARγ and the inhibition of both HDAC4 and HDAC8. Thus, the promising preliminary results obtained with TZD–TSC <b>3</b> represent an encouraging starting point for the rational design of novel chemotherapeutics with dual antibacterial and anticancer activities.https://www.mdpi.com/1422-0067/24/24/17521thiazolidinedionethiosemicarbazonemolecular dockingHDACsPPARγcytotoxic effect |
| spellingShingle | Agata Paneth Barbara Kaproń Tomasz Plech Roman Paduch Nazar Trotsko Piotr Paneth Combined In Silico and In Vitro Analyses to Assess the Anticancer Potential of Thiazolidinedione–Thiosemicarbazone Hybrid Molecules International Journal of Molecular Sciences thiazolidinedione thiosemicarbazone molecular docking HDACs PPARγ cytotoxic effect |
| title | Combined In Silico and In Vitro Analyses to Assess the Anticancer Potential of Thiazolidinedione–Thiosemicarbazone Hybrid Molecules |
| title_full | Combined In Silico and In Vitro Analyses to Assess the Anticancer Potential of Thiazolidinedione–Thiosemicarbazone Hybrid Molecules |
| title_fullStr | Combined In Silico and In Vitro Analyses to Assess the Anticancer Potential of Thiazolidinedione–Thiosemicarbazone Hybrid Molecules |
| title_full_unstemmed | Combined In Silico and In Vitro Analyses to Assess the Anticancer Potential of Thiazolidinedione–Thiosemicarbazone Hybrid Molecules |
| title_short | Combined In Silico and In Vitro Analyses to Assess the Anticancer Potential of Thiazolidinedione–Thiosemicarbazone Hybrid Molecules |
| title_sort | combined in silico and in vitro analyses to assess the anticancer potential of thiazolidinedione thiosemicarbazone hybrid molecules |
| topic | thiazolidinedione thiosemicarbazone molecular docking HDACs PPARγ cytotoxic effect |
| url | https://www.mdpi.com/1422-0067/24/24/17521 |
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