Multiply Intercalator-Substituted Cu(II) Cyclen Complexes as DNA Condensers and DNA/RNA Synthesis Inhibitors

J. Hormann, J. Malina, O. Lemke, M. J. Hülsey, S. Wedepohl, J. Potthoff, C. Schmidt, I. Ott, B. G. Keller, V. Brabec, N. Kulak – 2018

Many drugs that are applied in anticancer therapy such as the anthracycline doxorubicin contain DNA-intercalating 9,10-anthraquinone (AQ) moieties. When Cu(II) cyclen complexes were functionalized with up to three (2-anthraquinonyl)methyl substituents, they efficiently inhibited DNA and RNA synthesis resulting in high cytotoxicity (selective for cancer cells) accompanied by DNA condensation/aggregation phenomena. Molecular modeling suggests an unusual bisintercalation mode with only one base pair between the two AQ moieties and the metal complex as a linker. A regioisomer, in which the AQ moieties point in directions unfavorable for such an interaction, had a much weaker biological activity. The ligands alone and corresponding Zn(II) complexes (used as redox inert control compounds) also exhibited lower activity.

Titel
Multiply Intercalator-Substituted Cu(II) Cyclen Complexes as DNA Condensers and DNA/RNA Synthesis Inhibitors
Verfasser
J. Hormann, J. Malina, O. Lemke, M. J. Hülsey, S. Wedepohl, J. Potthoff, C. Schmidt, I. Ott, B. G. Keller, V. Brabec, N. Kulak
Datum
2018
Kennung
10.1021/acs.inorgchem.8b00027
Zitierweise
Inorg. Chem., 2018, 57 (9), pp 5004–5012
Art
Text
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