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

• Published in: Inorganic chemistry Vol. 57; no. 9; pp. 5004 - 5012
• Main Authors: Hormann, Jan, Malina, Jaroslav, Lemke, Oliver, Hülsey, Max J, Wedepohl, Stefanie, Potthoff, Jan, Schmidt, Claudia, Ott, Ingo, Keller, Bettina G, Brabec, Viktor, Kulak, Nora
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 07.05.2018
• ISSN: 0020-1669; 1520-510X
• DOI: 10.1021/acs.inorgchem.8b00027

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.