Phosphazene Tripeptide Conjugates: Design, Synthesis, In Vitro Cytotoxicity and Genotoxicity, Molecular Interactions in Binding Pockets on Human Breast and Colon Cancer Cell Lines

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dc.contributor.authorCaliskan, Eray
dc.contributor.authorYuksel, Furkan
dc.contributor.authorCapan, Irfan
dc.contributor.authorTekin, Suat
dc.contributor.authorBouzidi, Reda
dc.contributor.authorQaoud, Mohammed T.
dc.contributor.authorBiryan, Fatih
dc.date.accessioned2026-04-04T13:37:41Z
dc.date.available2026-04-04T13:37:41Z
dc.date.issued2025
dc.departmentİnönü Üniversitesi
dc.description.abstractThe biological activity of both cyclophosphazenes and peptides makes these compounds important for new studies in medicinal chemistry. For this purpose, five different phosphazene-peptide conjugates synthesized from dichlorocyclotriphosphazene and tyrosine-containing tripeptides. The synthesized compounds were evaluated for their in vitro cytotoxic activities against human breast (MCF-7) and colon (Caco-2) cancer cell lines using MTT assay. The derivatives induced cell death through DNA damage, with notable effects in Caco-2 cell lines. Specifically, DTVV, DTVG, and DTVA were cytotoxic at 50 and 100 mu M, while DTVP and DTVM were effective at 25, 50, and 100 mu M. DTVM outperformed Tamoxifen at 50 mu M in the MCF-7 cell line. DNA damage studies of the compounds were performed using the comet assay method, evaluating tail length, tail density, olive tail moment, head length, and head density parameters. The findings indicated that cell death occurred via a DNA damage mechanism. The molecular intricacies of DTVA, DTVG, DTVM, DTVP and DTVV within the VEGFR2 kinase domain (3VHE) and Cyclophilin_CeCYP16-Like Domain (2HQ6) binding pockets and various interactions, docking scores and potential activities of these derivatives were investigated. The differences in docking scores and interaction profiles highlight the potential efficacy and specificity of these compounds in targeting breast and colon cancer cells. These findings highlight the potential of phosphazene-peptide derivatives as therapeutic agents in cancer treatment.
dc.description.sponsorshipScientific and Technological Research Council of Turkey [118Z286]; Scientific and Technological Research Council of Turkey (TUBITAK); TUBITAK
dc.description.sponsorshipThis study was supported by the Scientific and Technological Research Council of Turkey (TUBITAK) under Project No. 118Z286. We would like to thank TUBITAK for its support to the project.
dc.identifier.doi10.1002/cmdc.202400570
dc.identifier.issn1860-7179
dc.identifier.issn1860-7187
dc.identifier.issue3
dc.identifier.orcid0000-0002-2218-7211
dc.identifier.orcid0000-0002-1503-265X
dc.identifier.pmid39450534
dc.identifier.scopus2-s2.0-85209632637
dc.identifier.scopusqualityQ1
dc.identifier.urihttps://doi.org/10.1002/cmdc.202400570
dc.identifier.urihttps://hdl.handle.net/11616/109992
dc.identifier.volume20
dc.identifier.wosWOS:001359067900001
dc.identifier.wosqualityQ2
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherWiley-V C H Verlag Gmbh
dc.relation.ispartofChemmedchem
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/openAccess
dc.snmzKA_WOS_20250329
dc.subjectTripeptides
dc.subjectPhosphazene
dc.subjectMolecular docking
dc.subjectCytotoxicity
dc.subjectGenotoxicity
dc.titlePhosphazene Tripeptide Conjugates: Design, Synthesis, In Vitro Cytotoxicity and Genotoxicity, Molecular Interactions in Binding Pockets on Human Breast and Colon Cancer Cell Lines
dc.typeArticle

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