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Synthesis and anticancer activity of metallocene-containing nucleoside and DNA analogues

After the discovery of cisplatin, the development of metal-containing anticancer drugs has been the subject of much research, with the aim of achieving high activities with minimal side effects. Metallocene derivatives are now common place within this field. Building on work previously published work by the Tucker group on ferrocene-containing nucleoside analogues, further research has now been undertaken to explore structure activity relationships. Firstly, the study has involved changing the substitution pattern through the synthesis of a series of regioisomeric derivatives, while maintaining other parameters. Secondly, the central metal ion has been changed to ruthenium from iron. The series of compounds have been characterised both spectroscopically and electrochemically and have, also been assessed for their anticancer activity in various cell lines. The latter show that both the substitution pattern and the metal ion play an important role in determining the biological properties. The other metallocene compounds, a tetrasubstituted dicytosine ferrocene and two disubstituted ruthenocene derivatives have also been prepared for incorporation into DNA strands by automated synthesis. The resulting oligoes have been characterised by HPLC and mass spectrometry.

Identiferoai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:760505
Date January 2018
CreatorsIsmail, Media K.
PublisherUniversity of Birmingham
Source SetsEthos UK
Detected LanguageEnglish
TypeElectronic Thesis or Dissertation
Sourcehttp://etheses.bham.ac.uk//id/eprint/8644/

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