Design, synthesis, and biological evaluation of tetrahydroquinolinones and tetrahydroquinolines with anticancer activity
Abstract Colorectal cancer (CRC) is the most commonly diagnosed cancer in Europe and the United States and the second leading cause of cancer related mortality. A therapeutic strategy used for the treatment of CRC involves targeting the intracellular levels of reactive oxygen species (ROS). In this...
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| Format: | Article |
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Nature Portfolio
2022-06-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-13867-x |
| _version_ | 1811343667948945408 |
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| author | Małgorzata Ryczkowska Natalia Maciejewska Mateusz Olszewski Milena Witkowska Sławomir Makowiec |
| author_facet | Małgorzata Ryczkowska Natalia Maciejewska Mateusz Olszewski Milena Witkowska Sławomir Makowiec |
| author_sort | Małgorzata Ryczkowska |
| collection | DOAJ |
| description | Abstract Colorectal cancer (CRC) is the most commonly diagnosed cancer in Europe and the United States and the second leading cause of cancer related mortality. A therapeutic strategy used for the treatment of CRC involves targeting the intracellular levels of reactive oxygen species (ROS). In this study, we synthesized a series of novel tetrahydroquinolinones and assessed their ability to inhibit CRC growth and proliferation by evoking cellular stress through ROS. Our results revealed that (2-oxo-4-phenyl-5,6,7,8-tetrahydroquinolin-8-yl) N-(3-fluorophenyl)carbamate (20d) exhibited in vitro antiproliferative activity at micromolar concentrations. The compound also suppressed colony formation and the migration of HCT-116 cells, as well as deregulated the expression of several proteins involved in cell proliferation and metastasis. Furthermore, 20d induced massive oxidative stress by disrupting the balance of cells survival resulting in autophagy via the PI3K/AKT/mTOR signaling pathway. These findings suggest that this tetrahydroquinolinone can be an ideal lead compound for drug discovery based on quinone derivatives. |
| first_indexed | 2024-04-13T19:34:00Z |
| format | Article |
| id | doaj.art-fb224a41963143b185f729852d6f25eb |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-13T19:34:00Z |
| publishDate | 2022-06-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-fb224a41963143b185f729852d6f25eb2022-12-22T02:33:07ZengNature PortfolioScientific Reports2045-23222022-06-0112111710.1038/s41598-022-13867-xDesign, synthesis, and biological evaluation of tetrahydroquinolinones and tetrahydroquinolines with anticancer activityMałgorzata Ryczkowska0Natalia Maciejewska1Mateusz Olszewski2Milena Witkowska3Sławomir Makowiec4Department of Organic Chemistry, Faculty of Chemistry, Gdansk University of TechnologyDepartment of Pharmaceutical Technology and Biochemistry, Faculty of Chemistry, Gdansk University of TechnologyDepartment of Pharmaceutical Technology and Biochemistry, Faculty of Chemistry, Gdansk University of TechnologyDepartment of Organic Chemistry, Faculty of Chemistry, Gdansk University of TechnologyDepartment of Organic Chemistry, Faculty of Chemistry, Gdansk University of TechnologyAbstract Colorectal cancer (CRC) is the most commonly diagnosed cancer in Europe and the United States and the second leading cause of cancer related mortality. A therapeutic strategy used for the treatment of CRC involves targeting the intracellular levels of reactive oxygen species (ROS). In this study, we synthesized a series of novel tetrahydroquinolinones and assessed their ability to inhibit CRC growth and proliferation by evoking cellular stress through ROS. Our results revealed that (2-oxo-4-phenyl-5,6,7,8-tetrahydroquinolin-8-yl) N-(3-fluorophenyl)carbamate (20d) exhibited in vitro antiproliferative activity at micromolar concentrations. The compound also suppressed colony formation and the migration of HCT-116 cells, as well as deregulated the expression of several proteins involved in cell proliferation and metastasis. Furthermore, 20d induced massive oxidative stress by disrupting the balance of cells survival resulting in autophagy via the PI3K/AKT/mTOR signaling pathway. These findings suggest that this tetrahydroquinolinone can be an ideal lead compound for drug discovery based on quinone derivatives.https://doi.org/10.1038/s41598-022-13867-x |
| spellingShingle | Małgorzata Ryczkowska Natalia Maciejewska Mateusz Olszewski Milena Witkowska Sławomir Makowiec Design, synthesis, and biological evaluation of tetrahydroquinolinones and tetrahydroquinolines with anticancer activity Scientific Reports |
| title | Design, synthesis, and biological evaluation of tetrahydroquinolinones and tetrahydroquinolines with anticancer activity |
| title_full | Design, synthesis, and biological evaluation of tetrahydroquinolinones and tetrahydroquinolines with anticancer activity |
| title_fullStr | Design, synthesis, and biological evaluation of tetrahydroquinolinones and tetrahydroquinolines with anticancer activity |
| title_full_unstemmed | Design, synthesis, and biological evaluation of tetrahydroquinolinones and tetrahydroquinolines with anticancer activity |
| title_short | Design, synthesis, and biological evaluation of tetrahydroquinolinones and tetrahydroquinolines with anticancer activity |
| title_sort | design synthesis and biological evaluation of tetrahydroquinolinones and tetrahydroquinolines with anticancer activity |
| url | https://doi.org/10.1038/s41598-022-13867-x |
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