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

0491177 - BFÚ 2019 RIV US eng J - Journal Article
Hormann, J. - Malina, Jaroslav - Lemke, O. - Huelsey, M.J. - Wedepohl, S. - Potthoff, J. - Schmidt, C. - Ott, I. - Keller, B.G. - Brabec, Viktor - Kulak, N.
Multiply Intercalator-Substituted Cu(II) Cyclen Complexes as DNA Condensers and DNA/RNA Synthesis Inhibitors.
Inorganic Chemistry. Roč. 57, č. 9 (2018), s. 5004-5012. ISSN 0020-1669. E-ISSN 1520-510X
R&D Projects: GA ČR GA17-09436S
Institutional support: RVO:68081707
Keywords : nucleic-acids * metal-ions * selective recognition
OECD category: Inorganic and nuclear chemistry
Impact factor: 4.850, year: 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.
Permanent Link: http://hdl.handle.net/11104/0285221