Insights on cyclophosphamide metabolism and anticancer mechanism of action : A computational study
© 2023 The Authors. Journal of Computational Chemistry published by Wiley Periodicals LLC.
| Veröffentlicht in: | Journal of computational chemistry. - 1984. - 45(2024), 10 vom: 15. März, Seite 663-670 |
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| 1. Verfasser: | |
| Weitere Verfasser: | , , , , , |
| Format: | Online-Aufsatz |
| Sprache: | English |
| Veröffentlicht: |
2024
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| Zugriff auf das übergeordnete Werk: | Journal of computational chemistry |
| Schlagworte: | Journal Article DFT DNA alkylating agents cyclophosphamide Cyclophosphamide 8N3DW7272P Acrolein 7864XYD3JJ 9007-49-2 |
| Zusammenfassung: | © 2023 The Authors. Journal of Computational Chemistry published by Wiley Periodicals LLC. The oxazaphosphorine cyclophosphamide (CP) is a DNA-alkylating agent commonly used in cancer chemotherapy. This anticancer agent is administered as a prodrug activated by a liver cytochrome P450-catalyzed 4-hydroxylation reaction that yields the active, cytotoxic metabolite. The primary metabolite, 4-hydroxycyclophosphamide, equilibrates with the ring-open aldophosphamide that undergoes β-elimination to yield the therapeutically active DNA cross-linking phosphoramide mustard and the byproduct acrolein. The present paper presents a DFT investigation of the different metabolic phases and an insight into the mechanism by which CP exerts its cytotoxic action. A detailed computational analysis of the energy profiles describing all the involved transformations and the mechanism of DNA alkylation is given with the aim to contribute to an increase of knowledge that, after more than 60 years of unsuccessful attempts, can lead to the design and development of a new generation of oxazaphosphorines |
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| Beschreibung: | Date Completed 04.03.2024 Date Revised 04.03.2024 published: Print-Electronic Citation Status MEDLINE |
| ISSN: | 1096-987X |
| DOI: | 10.1002/jcc.27280 |