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

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Authors

  • 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

Research Organisations

External Research Organisations

  • Bielefeld University
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Details

Original languageEnglish
Pages (from-to)14464-14477
Number of pages14
JournalInorganic chemistry
Volume59
Issue number19
Early online date21 Sept 2020
Publication statusPublished - 5 Oct 2020

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.

ASJC Scopus subject areas

Sustainable Development Goals

Cite this

Stronger Cytotoxicity for Cancer Cells Than for Fast Proliferating Human Stem Cells by Rationally Designed Dinuclear Complexes. / Schwarzbich, Sabrina; Horstmann Née Gruschka, Claudia; Simon, Jasmin et al.
In: Inorganic chemistry, Vol. 59, No. 19, 05.10.2020, p. 14464-14477.

Research output: Contribution to journalArticleResearchpeer review

Schwarzbich, S, Horstmann Née Gruschka, C, Simon, J, Siebe, L, Moreth, A, Wiegand, C, Lavrentieva, A, Scheper, T, Stammler, A, Bögge, H, Fischer Von Mollard, G & Glaser, T 2020, 'Stronger Cytotoxicity for Cancer Cells Than for Fast Proliferating Human Stem Cells by Rationally Designed Dinuclear Complexes', Inorganic chemistry, vol. 59, no. 19, pp. 14464-14477. https://doi.org/10.1021/acs.inorgchem.0c02255
Schwarzbich, S., Horstmann Née Gruschka, C., Simon, J., Siebe, L., Moreth, A., Wiegand, C., Lavrentieva, A., Scheper, T., Stammler, A., Bögge, H., Fischer Von Mollard, G., & Glaser, T. (2020). Stronger Cytotoxicity for Cancer Cells Than for Fast Proliferating Human Stem Cells by Rationally Designed Dinuclear Complexes. Inorganic chemistry, 59(19), 14464-14477. https://doi.org/10.1021/acs.inorgchem.0c02255
Schwarzbich S, Horstmann Née Gruschka C, Simon J, Siebe L, Moreth A, Wiegand C et al. Stronger Cytotoxicity for Cancer Cells Than for Fast Proliferating Human Stem Cells by Rationally Designed Dinuclear Complexes. Inorganic chemistry. 2020 Oct 5;59(19):14464-14477. Epub 2020 Sept 21. doi: 10.1021/acs.inorgchem.0c02255
Schwarzbich, Sabrina ; Horstmann Née Gruschka, Claudia ; Simon, Jasmin et al. / Stronger Cytotoxicity for Cancer Cells Than for Fast Proliferating Human Stem Cells by Rationally Designed Dinuclear Complexes. In: Inorganic chemistry. 2020 ; Vol. 59, No. 19. pp. 14464-14477.
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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.",
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AU - Schwarzbich, Sabrina

AU - Horstmann Née Gruschka, Claudia

AU - Simon, Jasmin

AU - Siebe, Lena

AU - Moreth, Alexander

AU - Wiegand, Christiane

AU - Lavrentieva, Antonina

AU - Scheper, Thomas

AU - Stammler, Anja

AU - Bögge, Hartmut

AU - Fischer Von Mollard, Gabriele

AU - Glaser, Thorsten

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N2 - 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.

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