İçsel, CeydaYılmaz, Veysel T.Cevatemre, BuseAygün, MuhittinUlukaya, Engin2020-08-302020-08-302019Icsel, C., Yilmaz, V. T., Cevatemre, B., Aygun, M., & Ulukaya, E. (2019). Structures and anticancer activity of chlorido platinum(II) saccharinate complexes with mono- and dialkylphenylphosphines. Journal of Inorganic Biochemistry, 195, 39–50. https://doi.org/10.1016/j.jinorgbio.2019.03.0080162-01341873-3344https://doi.org/10.1016/j.jinorgbio.2019.03.008https://hdl.handle.net/20.500.12713/623cis-[PtCl(sac)(PPh2Me)(2)] (1), cis-[PtCl(sac)(PPhMe2)(2)] (2), trans-[PtCl(sac)(PPh2Et)(2)] (3) and trans- [PtCl(sac) (PPhEt2)(2)] (4) complexes (sac = saccharinate) were synthesized and characterized by elemental analysis and spectroscopic methods. The structures of 2-4 were determined by X-ray single-crystal diffraction. The interaction of the complexes with DNA was studied various biochemical, biophysical and molecular docking methods. Only the cis-configured complexes (1 and 2) showed nuclease activity and their binding affinity towards DNA was considerably higher than those of their trans-congeners (3 and 4). The chlorido ligand in the cis-configured complexes underwent aquation, making them more reactive towards DNA. Furthermore, 1 and 2 exhibited anticancer potency on breast (MCF-7) and colon (HCT116) cancer cells similar to cisplatin, whereas 3 and 4 were biologicallly inactive. Mechanistic studies on MCF-7 cells showed that higher nuclear uptake, cell cycle arrest at the S phase, dramatically increased DNA double-strand breaks, apoptosis induction, elevated levels of reactive oxygen species (ROS) and high mitochondrial membrane depolarization greatly contribute to the anticancer potency of 1 and 2.eninfo:eu-repo/semantics/closedAccessPt(Ii) ComplexSaccharinatePhosphineDna BindingCytotoxicityAnticancer MechanismArticle195395030889415WOS:0004694085000052-s2.0-85062936854Q110.1016/j.jinorgbio.2019.03.008Q1