- Title
- Substituted 9-aminoacridine-4-carboxamides tethered to platinum(II)diamine complexes: Chemistry, cytotoxicity and DNA sequence selectivity
- Creator
- Carland, Michael; Grannas, Martin J.; Cairns, Murray J.; Roknic, Vanessa J.; Denny, William A.; McFadyen, W. David; Murray, Vincent
- Relation
- Journal of Inorganic Biochemistry Vol. 104, Issue 8, p. 815-819
- Publisher Link
- http://dx.doi.org/10.1016/j.jinorgbio.2010.03.011
- Publisher
- Elsevier
- Resource Type
- journal article
- Date
- 2010
- Description
- Three platinum complexes in which substituted (7-OMe, 9-NH₂; 7-F, 9-NH₂; and 7-H, 9-NH(CH₂)₂OH) 9-aminoacridine-4-carboxamides were tethered to a platinum(II)diamine moiety were synthesised and characterised at the chemical and biological level. These variants showed a decrease in cytotoxicity, as measured by IC₅₀ values in HeLa cells, when compared with the parent 7-H, 9-NH₂ compound. The 7-F and 9-NH(CH₂)₂OH substituents gave rise to a small decrease in cytotoxicity, and the 7-OMe substituent resulted in a larger decrease in cytotoxicity. Their binding to purified pUC19 plasmid DNA was investigated and it was found that the addition of 7-F, 9-NH(CH₂)₂OH and especially the 7-OMe substituents, resulted in reduced DNA binding. This correlated well with the IC₅₀ cytotoxicity values. However, the DNA sequence selectivity was unaffected by the addition of these moieties.
- Subject
- acridine-4-carboxamides; substituents; platinum(II); synthesis; cytotoxicity; DNA sequence selectivity
- Identifier
- uon:9530
- Identifier
- http://hdl.handle.net/1959.13/922289
- Identifier
- ISSN:0162-0134
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