We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Cytotoxic platinum(II) complexes derived from saccharinate and phosphine ligands: synthesis, structures, DNA cleavage, and oxidative stress-induced apoptosis.
- Authors
Icsel, Ceyda; Yilmaz, Veysel T.; Cevatemre, Buse; Aygun, Muhittin; Ulukaya, Engin
- Abstract
A series of the structurally related platinum(II) saccharinate (sac) complexes with alkylphenylphosphines, namely cis-[Pt(sac)2(PPh2Me)2]·DMSO (1), cis-[Pt(sac)2(PPhMe2)2] (2), cis-[Pt(sac)2(PPh2Et)2] (3), and cis-[Pt(sac)2(PPhEt2)2]·2DMSO (4), were synthesized and fully characterized; their structures were determined by X-ray crystallography. All the complexes were investigated for their anticancer potentials on three human cancer cells including A549 (lung), MCF-7 (breast), and HCT116 (colon) in addition to a noncancerous human bronchial epithelial cells (BEAS-2B). Specifically, 1 and 3 showed significant cytotoxic effects against MCF-7 and HCT116 cell lines in comparison to cisplatin, and were considered as the most potent ones in the series. The cytotoxic complexes were found to cleave DNA efficiently. In addition, the binding interactions of the complexes with DNA were confirmed by enzyme inhibition and molecular docking studies. Complexes 1 and 3 were capable of inducing apoptosis and arrested the cell cycle at the DNA synthesis (S) phase in MCF-7 cells. Furthermore, 1 and 3 caused the excessive generation of reactive oxygen species (ROS), leading to mitochondrial dysfunction and double-strand DNA breaks.
- Subjects
PHOSPHINE synthesis; DOUBLE-strand DNA breaks; DNA synthesis; DNA; PLATINUM; X-ray crystallography
- Publication
Journal of Biological Inorganic Chemistry (JBIC), 2020, Vol 25, Issue 1, p75
- ISSN
0949-8257
- Publication type
Article
- DOI
10.1007/s00775-019-01736-4