Stronger Cytotoxicity for Cancer Cells Than for Fast Proliferating Human Stem Cells by Rationally Designed Dinuclear Complexes

authored by: Sabrina Schwarzbich, Claudia Horstmann Née Gruschka, Jasmin Simon, Lena Siebe, Alexander Moreth, Christiane Wiegand, Antonina Lavrentieva, Thomas Scheper, Anja Stammler, Hartmut Bögge, Gabriele Fischer Von Mollard, Thorsten Glaser
Abstract: Cytostatic metallo-drugs mostly bind to the nucleobases of DNA. A new family of dinuclear transition metal complexes was rationally designed to selectively target the phosphate diesters of the DNA backbone by covalent bonding. The synthesis and characterization of the first dinuclear NiII2 complex of this family are presented, and its DNA binding and interference with DNA synthesis in polymerase chain reaction (PCR) are investigated and compared to those of the analogous CuII2 complex. The NiII2 complex also binds to DNA but forms fewer intermolecular DNA cross-links, while it interferes with DNA synthesis in PCR at lower concentrations than CuII2. To simulate possible competing phosphate-based ligands in vivo, these effects have been studied for both complexes with 100-200-fold excesses of phosphate and ATP, which provided no disturbance. The cytotoxicity of both complexes has been studied for human cancer cells and human stem cells with similar rates of proliferation. CuII2 shows the lowest IC50 values and a remarkable preference for killing the cancer cells. Three different assays show that the CuII2 complex induces apoptosis in cancer cells. These results are discussed to gain insight into the mechanisms of action and demonstrate the potential of this family of dinuclear complexes as anticancer drugs acting by a new binding target.
Organisation(s): Institute of Technical Chemistry
External Organisation(s): Bielefeld University
Type: Article
Journal: Inorganic chemistry
Volume: 59
Pages: 14464-14477
No. of pages: 14
ISSN: 0020-1669
Publication date: 05.10.2020
Publication status: Published
Peer reviewed: Yes
ASJC Scopus subject areas: Physical and Theoretical Chemistry, Inorganic Chemistry
Sustainable Development Goals: SDG 3 - Good Health and Well-being
Electronic version(s): https://doi.org/10.1021/acs.inorgchem.0c02255 (Access: Closed)