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Combining supramolecular cylinders with a platinum anticancer agent

Sadovnikova, Viktoriia (2012)
Ph.D. thesis, University of Birmingham.

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Abstract

Chapter 1 reviews DNA structure and DNA molecular recognition by synthetic agents, including supramolecular helicates and cisplatin. An overview of various types of helicates and cisplatin anticancer drugs and their mechanisms of action is discussed. Examples of non-platinum anticancer drugs are also presented. In Chapter 2, the synthesis of novel metal-based supramolecular helicates and attempts to combine them with the cisplatin anticancer agent are described. In some cases X-ray crystallography data are presented and discussed in detail. In addition, the synthesis of the fluorescent europium helicate is described. In Chapter 3, stability and DNA binding properties of the synthesised metallo-helicates are investigated using UV/Vis spectroscopy, CD and LD techniques. The ability of the complexes to unwind plasmid DNA and stabilise DNA three-way junction formation is explored by gel electrophoresis experiments. The results demonstrate that the geometry and size of the helicates are crucial for DNA three-way junction recognition. In Chapter 4, biological evaluation of antineoplastic activity of the metallo-helicates synthesised in this work, as well as of the compounds supplied by other members of the group, is studied using an MTT colorimetric assay. The results of the study reveal that some of the complexes exhibit a potent cytotoxic activity.

Type of Work:Ph.D. thesis.
Supervisor(s):Hannon, Michael J.
School/Faculty:Colleges (2008 onwards) > College of Engineering & Physical Sciences
Department:School of Chemistry
Subjects:QD Chemistry
QH426 Genetics
RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Institution:University of Birmingham
ID Code:3517
This unpublished thesis/dissertation is copyright of the author and/or third parties. The intellectual property rights of the author or third parties in respect of this work are as defined by The Copyright Designs and Patents Act 1988 or as modified by any successor legislation. Any use made of information contained in this thesis/dissertation must be in accordance with that legislation and must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the permission of the copyright holder.
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