Tetrahydroquinolinone derivatives exert antiproliferative effect on lung cancer cells through apoptosis induction
Abstract The anticancer properties of quinolones is a topic of interest among researchers in the scientific world. Because these compounds do not cause side effects, unlike the commonly used cytostatics, they are considered a promising source of new anticancer drugs. In this work, we designed a brie...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2022-11-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-23640-9 |
| _version_ | 1798018228322041856 |
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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 The anticancer properties of quinolones is a topic of interest among researchers in the scientific world. Because these compounds do not cause side effects, unlike the commonly used cytostatics, they are considered a promising source of new anticancer drugs. In this work, we designed a brief synthetic pathway and obtained a series of novel 8-phenyltetrahydroquinolinone derivatives functionalized with benzyl-type moieties at position 3. The compounds were synthesized via classical reactions such as nucleophilic substitution, solvent lysis, and condensation. Biological evaluation revealed that 3-(1-naphthylmethyl)-4-phenyl-5,6,7,8-tetrahydro-1H-quinolin-2-one (4a) exhibited potent cytotoxicity toward colon (HTC-116) and lung (A549) cancer cell lines. Analysis of the mechanism of action of compounds showed that compound 4a induced cell cycle arrest at the G2/M phase, leading to apoptotic cell death via intrinsic and extrinsic pathways. Taken together, the findings of the study suggest that tetrahydroquinolinone derivatives bearing a carbonyl group at position 2 could be potential lead compounds to develop anticancer agents for the treatment of lung cancers. |
| first_indexed | 2024-04-11T16:20:24Z |
| format | Article |
| id | doaj.art-e14121f0571f4930bf5c2ae8b0ece9d0 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-11T16:20:24Z |
| publishDate | 2022-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-e14121f0571f4930bf5c2ae8b0ece9d02022-12-22T04:14:24ZengNature PortfolioScientific Reports2045-23222022-11-0112111010.1038/s41598-022-23640-9Tetrahydroquinolinone derivatives exert antiproliferative effect on lung cancer cells through apoptosis inductionMałgorzata 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 The anticancer properties of quinolones is a topic of interest among researchers in the scientific world. Because these compounds do not cause side effects, unlike the commonly used cytostatics, they are considered a promising source of new anticancer drugs. In this work, we designed a brief synthetic pathway and obtained a series of novel 8-phenyltetrahydroquinolinone derivatives functionalized with benzyl-type moieties at position 3. The compounds were synthesized via classical reactions such as nucleophilic substitution, solvent lysis, and condensation. Biological evaluation revealed that 3-(1-naphthylmethyl)-4-phenyl-5,6,7,8-tetrahydro-1H-quinolin-2-one (4a) exhibited potent cytotoxicity toward colon (HTC-116) and lung (A549) cancer cell lines. Analysis of the mechanism of action of compounds showed that compound 4a induced cell cycle arrest at the G2/M phase, leading to apoptotic cell death via intrinsic and extrinsic pathways. Taken together, the findings of the study suggest that tetrahydroquinolinone derivatives bearing a carbonyl group at position 2 could be potential lead compounds to develop anticancer agents for the treatment of lung cancers.https://doi.org/10.1038/s41598-022-23640-9 |
| spellingShingle | Małgorzata Ryczkowska Natalia Maciejewska Mateusz Olszewski Milena Witkowska Sławomir Makowiec Tetrahydroquinolinone derivatives exert antiproliferative effect on lung cancer cells through apoptosis induction Scientific Reports |
| title | Tetrahydroquinolinone derivatives exert antiproliferative effect on lung cancer cells through apoptosis induction |
| title_full | Tetrahydroquinolinone derivatives exert antiproliferative effect on lung cancer cells through apoptosis induction |
| title_fullStr | Tetrahydroquinolinone derivatives exert antiproliferative effect on lung cancer cells through apoptosis induction |
| title_full_unstemmed | Tetrahydroquinolinone derivatives exert antiproliferative effect on lung cancer cells through apoptosis induction |
| title_short | Tetrahydroquinolinone derivatives exert antiproliferative effect on lung cancer cells through apoptosis induction |
| title_sort | tetrahydroquinolinone derivatives exert antiproliferative effect on lung cancer cells through apoptosis induction |
| url | https://doi.org/10.1038/s41598-022-23640-9 |
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