The First Chalcone Derivatives of Valine-Based Spiro-Cyclotriphosphazenes: In Vitro Cytotoxic Properties, Molecular Docking and DNA Damage Mechanism Studies

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dc.contributor.authorYucel, Yunus
dc.contributor.authorSeker, Ferhan Sultan
dc.contributor.authorErden, Busra Aksoy
dc.contributor.authorOzdemir, Mucahit
dc.contributor.authorTekin, Cigdem
dc.contributor.authorCaliskan, Eray
dc.contributor.authorTekin, Suat
dc.date.accessioned2026-04-04T13:37:38Z
dc.date.available2026-04-04T13:37:38Z
dc.date.issued2025
dc.departmentİnönü Üniversitesi
dc.description.abstractCancer treatment requires novel compounds with potent cytotoxic and genotoxic properties to effectively target cancer cells. In this study, new hybrid cyclotriphosphazene compounds were synthesized, characterized, and evaluated for their biological activity. Cytotoxicity against A2780 and Caco-2 cancer cell lines was assessed via the MTT assay, while genotoxic effects at 60-70% cell viability were examined using the Comet assay. Apoptotic cells were identified through TUNEL analyses, and reactive oxygen species levels were measured. Results showed that these compounds significantly reduced cell viability through DNA damage mechanisms. At high doses (50-100 mu M), BV, BVK1, BVK2, and BVK4 decreased A2780 cell viability by 30-65%, whereas VPA had a milder effect (15-25%). In Caco-2 cells, viability was reduced by 10-35%. The compounds exhibited varying cytotoxicity across different cancer cell lines, reflecting cancer cell heterogeneity. Significant DNA damage, including changes in tail length, tail density, and tail moment, was observed in A2780 cells, confirming cell death via DNA damage. Molecular docking analyses further supported the potential of cyclotriphosphazene compounds (BV and BVK2) as targeted cancer inhibitors. Molecular docking revealed BVK2's high selectivity for Bcl-2, mutant p53, and VEGFR2. BVK2 and BV demonstrate strong binding affinities with key cancer-related targets, indicating their potential as multi-targeted inhibitors that regulate apoptosis, cell cycle control, and angiogenesis, making them promising candidates for targeted cancer therapy.
dc.description.sponsorshipScientific and Technical Research Council of Turkiye (TUBITAK) [122Z060]
dc.description.sponsorshipThis study was supported by a grant from the Scientific and Technical Research Council of Turkiye (TUBITAK, Grant Number: 122Z060).
dc.identifier.doi10.1002/jbt.70233
dc.identifier.issn1095-6670
dc.identifier.issn1099-0461
dc.identifier.issue4
dc.identifier.orcid0000-0002-2218-7211
dc.identifier.pmid40127203
dc.identifier.scopus2-s2.0-105000944301
dc.identifier.scopusqualityQ2
dc.identifier.urihttps://doi.org/10.1002/jbt.70233
dc.identifier.urihttps://hdl.handle.net/11616/109964
dc.identifier.volume39
dc.identifier.wosWOS:001450544700001
dc.identifier.wosqualityQ2
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherWiley
dc.relation.ispartofJournal of Biochemical and Molecular Toxicology
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/openAccess
dc.snmzKA_WOS_20250329
dc.subjectcyclotriphosphazene
dc.subjectcytotoxicity
dc.subjectgenotoxicity
dc.subjectmolecular docking
dc.subjectTUNEL analysis
dc.titleThe First Chalcone Derivatives of Valine-Based Spiro-Cyclotriphosphazenes: In Vitro Cytotoxic Properties, Molecular Docking and DNA Damage Mechanism Studies
dc.typeArticle

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