Design, synthesis and bioactivity evaluation of phosphinanes as potential anticancer agents
Abstract The development of novel anticancer agents is crucial to the ongoing effort to combat cancer. In this study, six-membered phosphorus heterocycles (phosphinanes) were designed, synthesized, and evaluated as potential antiproliferative agents. A series of novel phosphinane derivatives was obt...
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| Format: | Article |
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Nature Portfolio
2025-08-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-025-10692-w |
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| author | Elżbieta Łastawiecka Paulina Strzyga-Łach Ewelina Kiernozek-Kalińska Marta Struga Anna Bielenica |
| author_facet | Elżbieta Łastawiecka Paulina Strzyga-Łach Ewelina Kiernozek-Kalińska Marta Struga Anna Bielenica |
| author_sort | Elżbieta Łastawiecka |
| collection | DOAJ |
| description | Abstract The development of novel anticancer agents is crucial to the ongoing effort to combat cancer. In this study, six-membered phosphorus heterocycles (phosphinanes) were designed, synthesized, and evaluated as potential antiproliferative agents. A series of novel phosphinane derivatives was obtained through structural modifications of 1-phenylphosphinane 1-oxide and 1-phenylphosphinan-4-one 1-oxide, achieving high overall yields. The dearomatization of the phenyl group attached to the phosphorus atom is a pivotal step in the P-substituent modification. The synthesized compounds, differing in steric and electronic properties, were assessed for in vitro cytotoxicity against colon (SW480, SW620, HCT116) and prostate (PC3) cancer cell lines. Among them, three compounds (2, 8, and 11) exhibited activity at ≤ 10 µM, with compound 11 outperforming cisplatin in all assays. This compound was the most potent activator of late apoptosis in PC3, SW480, and HCT116 cells (by 87.5–95.5%) and inhibited IL-6 secretion from all studied tumor cells by 71.8–96.8%. These results position phosphinanes as a tractable scaffold for further development in anticancer drug discovery. |
| format | Article |
| id | doaj-art-ad52aa5e9d794becb23db2c6e15774ec |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Nature Portfolio |
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| series | Scientific Reports |
| spelling | doaj-art-ad52aa5e9d794becb23db2c6e15774ec2025-08-20T04:03:06ZengNature PortfolioScientific Reports2045-23222025-08-0115111710.1038/s41598-025-10692-wDesign, synthesis and bioactivity evaluation of phosphinanes as potential anticancer agentsElżbieta Łastawiecka0Paulina Strzyga-Łach1Ewelina Kiernozek-Kalińska2Marta Struga3Anna Bielenica4Department of Organic Chemistry and Crystal Chemistry, Institute of Chemical Sciences, Faculty of Chemistry, Maria Curie-Sklodowska UniversityChair and Department of Biochemistry, Medical University of WarsawDepartment of Immunology, Faculty of Biology, University of WarsawChair and Department of Biochemistry, Medical University of WarsawChair and Department of Biochemistry, Medical University of WarsawAbstract The development of novel anticancer agents is crucial to the ongoing effort to combat cancer. In this study, six-membered phosphorus heterocycles (phosphinanes) were designed, synthesized, and evaluated as potential antiproliferative agents. A series of novel phosphinane derivatives was obtained through structural modifications of 1-phenylphosphinane 1-oxide and 1-phenylphosphinan-4-one 1-oxide, achieving high overall yields. The dearomatization of the phenyl group attached to the phosphorus atom is a pivotal step in the P-substituent modification. The synthesized compounds, differing in steric and electronic properties, were assessed for in vitro cytotoxicity against colon (SW480, SW620, HCT116) and prostate (PC3) cancer cell lines. Among them, three compounds (2, 8, and 11) exhibited activity at ≤ 10 µM, with compound 11 outperforming cisplatin in all assays. This compound was the most potent activator of late apoptosis in PC3, SW480, and HCT116 cells (by 87.5–95.5%) and inhibited IL-6 secretion from all studied tumor cells by 71.8–96.8%. These results position phosphinanes as a tractable scaffold for further development in anticancer drug discovery.https://doi.org/10.1038/s41598-025-10692-wPhosphinaneSix-membered heterocyclic compoundsApoptosisAntiproliferative activityCytotoxic activity |
| spellingShingle | Elżbieta Łastawiecka Paulina Strzyga-Łach Ewelina Kiernozek-Kalińska Marta Struga Anna Bielenica Design, synthesis and bioactivity evaluation of phosphinanes as potential anticancer agents Scientific Reports Phosphinane Six-membered heterocyclic compounds Apoptosis Antiproliferative activity Cytotoxic activity |
| title | Design, synthesis and bioactivity evaluation of phosphinanes as potential anticancer agents |
| title_full | Design, synthesis and bioactivity evaluation of phosphinanes as potential anticancer agents |
| title_fullStr | Design, synthesis and bioactivity evaluation of phosphinanes as potential anticancer agents |
| title_full_unstemmed | Design, synthesis and bioactivity evaluation of phosphinanes as potential anticancer agents |
| title_short | Design, synthesis and bioactivity evaluation of phosphinanes as potential anticancer agents |
| title_sort | design synthesis and bioactivity evaluation of phosphinanes as potential anticancer agents |
| topic | Phosphinane Six-membered heterocyclic compounds Apoptosis Antiproliferative activity Cytotoxic activity |
| url | https://doi.org/10.1038/s41598-025-10692-w |
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