Tripeptide linked dispiro cyclotriphosphazene conjugates: Synthesis, molecular docking analysis of compounds binding within cancer cell line receptors and in vitro cytotoxic and genotoxic activities

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dc.authoridCAPAN, IRFAN/0000-0002-9555-1555
dc.authorwosidCAPAN, IRFAN/AAE-4102-2022
dc.contributor.authorCaliskan, Eray
dc.contributor.authorCapan, Irfan
dc.contributor.authorTekin, Suat
dc.contributor.authorQaoud, Mohammed T.
dc.contributor.authorBiryan, Fatih
dc.contributor.authorKoran, Kenan
dc.contributor.authorSandal, Suleyman
dc.date.accessioned2024-08-04T20:56:12Z
dc.date.available2024-08-04T20:56:12Z
dc.date.issued2024
dc.departmentİnönü Üniversitesien_US
dc.description.abstractThe novel dioxybiphenyl bridged-cyclotriphosphazenes (DPP) bearing tripeptide were synthesized and investigated for their molecular docking analysis, visualizing their binding profiles within various cancer cell line receptors and in vitro cytotoxic and genotoxic properties. The dipeptide compound (Tyr- Phe) was treated with various amino acids to obtain the tripeptide compounds (Tyr- Phe- Gly, Tyr- Phe- Ala, Tyr- Phe- Val, Tyr- Phe- Phe, and Tyr- Phe- Leu). These synthesized tripeptides were subsequently treated with DPP to obtain novel phosphazene compounds bearing tripeptide structures. As a result, the synthesis of target molecules with phosphazene compound in the center and biphenyl and tripeptide groups in the side arms was obtained for the first time in this study. Examining the cytotoxic studies in vitro of our newly synthesized compounds demonstrated the anticancer properties against four selected human cancer cell lines, including breast (MCF-7), ovarian (A2780), prostate (PC-3), and colon (Caco-2) cancer cells. The Comet Assay analysis determined that the cell death mechanism of most of the compounds with cytotoxic activity stemmed from the DNA damage mechanism. Among the compounds, the DPP-Tyr- Phe- Phe compound seems to have the best anticancer activity against the subjected cell lines (Except for A2780) with IC 50 values equal to 20.18, 72.14, 12.21, and 5.17 mu M against breast, ovarian, prostate, and colon cancer cell lines, respectively. For this reason, the molecular docking analysis was conducted for the DTPP compound to visualize its binding geometry and profile within the target enzyme 's binding site associated with the specific cancer cell line. The analysis revealed that the DTPP derivative exhibited an optimal binding conformation and characteristics within the target enzyme 's binding site, aligning well with the experimental data. Based on the data, these compounds are believed to be strong candidate molecules for both pharmaceutical and clinical applications.en_US
dc.description.sponsorshipScientific and Technical Research Council of Turkiye (TUBITAK) [118Z286]en_US
dc.description.sponsorshipThis work was supported by a grant from the Scientific and Technical Research Council of Turkiye (TUBITAK, Grant Number: 118Z286) . We would like to thank TUBITAK for their contribution.en_US
dc.identifier.doi10.1016/j.bioorg.2024.107621
dc.identifier.issn0045-2068
dc.identifier.issn1090-2120
dc.identifier.pmid38996546en_US
dc.identifier.scopus2-s2.0-85198106561en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.urihttps://doi.org/10.1016/j.bioorg.2024.107621
dc.identifier.urihttps://hdl.handle.net/11616/102112
dc.identifier.volume150en_US
dc.identifier.wosWOS:001270484900001en_US
dc.identifier.wosqualityN/Aen_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherAcademic Press Inc Elsevier Scienceen_US
dc.relation.ispartofBioorganic Chemistryen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectCyclotriphosphazeneen_US
dc.subjectDNA damageen_US
dc.subjectPhosphazeneen_US
dc.subjectTripeptideen_US
dc.subjectCytotoxicityen_US
dc.titleTripeptide linked dispiro cyclotriphosphazene conjugates: Synthesis, molecular docking analysis of compounds binding within cancer cell line receptors and in vitro cytotoxic and genotoxic activitiesen_US
dc.typeArticleen_US

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