Combining supramolecular cylinders with a platinum anticancer agent

Sadovnikova, Viktoriia (2012). Combining supramolecular cylinders with a platinum anticancer agent. University of Birmingham. Ph.D.

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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:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):