Multiply Intercalator-Substituted Cu(II) Cyclen Complexes as DNA Condensers and DNA/RNA Synthesis Inhibitors
| Autor: | Ingo Ott, Stefanie Wedepohl, Viktor Brabec, Bettina G. Keller, Jan Potthoff, Jan Hormann, Jaroslav Malina, Max J. Hülsey, Nora Kulak, Claudia Schmidt, Oliver Lemke |
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| Rok vydání: | 2018 |
| Předmět: |
DNA Replication
Models Molecular 0301 basic medicine Molecular model Cell Survival Base pair Intercalation (chemistry) Crystallography X-Ray DNA condensation 01 natural sciences Cell Line Inorganic Chemistry Structure-Activity Relationship 03 medical and health sciences chemistry.chemical_compound Cyclen Coordination Complexes Humans Physical and Theoretical Chemistry Dose-Response Relationship Drug Molecular Structure 010405 organic chemistry Biological activity DNA Combinatorial chemistry 0104 chemical sciences 030104 developmental biology chemistry RNA Linker Copper Plasmids |
| Zdroj: | Inorganic Chemistry. 57:5004-5012 |
| ISSN: | 1520-510X 0020-1669 |
| DOI: | 10.1021/acs.inorgchem.8b00027 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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