Synthesis, structures and anticancer potentials of platinum(II) saccharinate complexes of tertiary phosphines with phenyl and cyclohexyl groups targeting mitochondria and DNA

View/ Open
Date
2018Author
Yilmaz, Veysel T.Icsel, Ceyda
Turgut, Omer R.
Aygun, Muhittin
Erkisa Genel, Merve
Turkdemir, Mehmet H.
Ulukaya, Engin
Metadata
Show full item recordCitation
Yilmaz, 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.2018.06.035Abstract
A 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.
Source
European Journal of Medicinal ChemistryVolume
155Collections
- Ar-Ge [27]
- Makale Koleksiyonu [208]
- PubMed İndeksli Yayınlar Koleksiyonu [890]
- Scopus İndeksli Yayınlar Koleksiyonu [1274]
- WoS İndeksli Yayınlar Koleksiyonu [1330]