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dc.contributor.authorYilmaz, Veysel T.
dc.contributor.authorIcsel, Ceyda
dc.contributor.authorTurgut, Omer R.
dc.contributor.authorAygun, Muhittin
dc.contributor.authorErkisa Genel, Merve
dc.contributor.authorTurkdemir, Mehmet H.
dc.contributor.authorUlukaya, Engin
dc.date.accessioned2020-08-30T20:07:28Z
dc.date.available2020-08-30T20:07:28Z
dc.date.issued2018
dc.identifier.citationYilmaz, V. T., Icsel, C., Turgut, O. R., Aygun, M., Erkisa, M., Turkdemir, M. H., & Ulukaya, E. (2018). Synthesis, structures and anticancer potentials of platinum(II) saccharinate complexes of tertiary phosphines with phenyl and cyclohexyl groups targeting mitochondria and DNA. European Journal of Medicinal Chemistry, 155, 609–622. https://doi.org/10.1016/j.ejmech.2018.06.035en_US
dc.identifier.issn0223-5234
dc.identifier.issn1768-3254
dc.identifier.urihttps://doi.org/10.1016/j.ejmech.2018.06.035
dc.identifier.urihttps://hdl.handle.net/20.500.12713/770
dc.descriptionErkisa, Merve/0000-0002-3127-742X; Yilmaz, Veysel T./0000-0002-2849-3332en_US
dc.descriptionWOS: 000441856300048en_US
dc.descriptionPubMed: 29920455en_US
dc.descriptionErkisa Genel, Merve ; Ulukaya, Engin (isu author)
dc.description.abstractA series of new Pt(II) saccharinate complexes containing PR3 ligands (PPh3, PPh2Cy, PPhCy2 and PCy3) with progressive phenyl (Ph) replacement by cyclohexyl (Cy) were synthesized and structurally characterized by lR, NMR, ESI-MS and X-ray diffraction. The anticancer activity of the complexes was tested against human breast (MCF-7), lung (A549), colon (HCT116), and prostate (DU145) cancer cell lines as well as against normal bronchial epithelial (BEAS-2B) cells. Trans-configured complexes 1, 3 and 5 emerged as potential anticancer drug candidates. The mechanism of action of the potent complexes was then investigated in detail. The three complexes interacted with DNA by groove binding and with HSA via hydrophobic IIA subdomain. Furthermore, the complexes cleaved plasmid DNA efficiently. Cellular uptake studies in MCF-7 cells showed that the biologically active complexes were mainly localized in cytoplasm. The cytotoxic activity was a function of the lipophilicity and cellular accumulation of the complexes. As determined by M30, Annexin V and Caspase 3/7 activity assays, the complexes induced apoptosis in MCF-7 and HCT116 cells. Mechanistic studies showed that the potent complexes cause excessive generation of reactive oxygen species (ROS) and display a dual action, concurrently targeting both mitochondria and genomic DNA. (C) 2018 Elsevier Masson SAS. All rights reserved.en_US
dc.description.sponsorshipTUBITAKTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [215Z230]en_US
dc.description.sponsorshipThe authors thank TUBITAK for the financial support given to the research project 215Z230 and are also grateful to Dr. S. Aydinlik for her help with the cellular uptake studies.en_US
dc.language.isoengen_US
dc.publisherElsevier France-Editions Scientifiques Medicales Elsevieren_US
dc.relation.isversionof10.1016/j.ejmech.2018.06.035en_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectPlatinum(Ii)en_US
dc.subjectSaccharinateen_US
dc.subjectTertiary Phosphineen_US
dc.subjectAnticancer Activityen_US
dc.subjectApoptosisen_US
dc.titleSynthesis, structures and anticancer potentials of platinum(II) saccharinate complexes of tertiary phosphines with phenyl and cyclohexyl groups targeting mitochondria and DNAen_US
dc.typearticleen_US
dc.contributor.departmentİstinye Üniversitesi, Rektörlüken_US
dc.contributor.authorID0000-0002-9992-833Xen_US
dc.contributor.institutionauthorErkisa Genel, Merveen_US
dc.contributor.institutionauthorUlukaya, Enginen_US
dc.identifier.volume155en_US
dc.identifier.startpage609en_US
dc.identifier.endpage622en_US
dc.relation.journalEuropean Journal of Medicinal Chemistryen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US


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