Synthesis and Biological Evaluation of Novel Glycomimetics

Carbohydrate molecules play important roles in the biology of the cell as sources of energy and as a constituent of glycoproteins. In many diseases, such as cancer, energy production and biosynthesis of glycoproteins are dysregulated. This thesis explores two methods for the synthesis of molecules that interfere with these processes and, therefore, can be potential starting points in a drug discovery programme. The first method is to change the main skeleton core of the sugar by synthesising a carbasugar, using the cycloaddition of a novel 2H-pyran-2-one. The second method is changing the groups that decorate the sugar molecule by preparing two novel classes of glucose derivatives. In the first chapter, recent methodologies for synthesising carbasugars are described. The second chapter explored using pyrone cycloaddition to synthesise pseudodisaccharides as potential Golgi α-mannosidase II inhibitors. The synthesis is performed over seven steps. Further optimisation is needed to increase the overall yield. Also, an enzyme assay has to be performed to confirm the biological activity of the synthesised compound. The third chapter describes the synthesis of glucose-6-phosphoramidic acid and glucose-6-triazole derivatives as inhibitors of HK II and the biological evaluation of the synthesised compounds on cancer cells. The triazoloderivatives are synthesised in fewer steps and have shown comparable inhibitory activity against cancer cells to the phosphoramidic acid derivatives. An enzyme assay has to be performed to confirm the mode of action of the synthesised compound against HKII. The last chapter explored the experimental procedures, characterisation of chemical compounds, and details of biological evaluations.

Grantor dc:publisher.institution

University of Bradford

Author dc:creator

• Mohamed, Yasser M.O.

Advisors dc:contributor.advisor

• Afarinkia, Kamyar
• Martin, William H.C.

• Carbasugars
• Hexokinase inhibitors
• Pyrone
• Cycloaddition
• Triazole
• Pseudo-disaccharide
• Golgi Alpha Mannosidase II inhibitors
• Drug synthesis

Statement dc:rights

• <a rel="license" href="http://creativecommons.org/licenses/by-nc-nd/3.0/"><img alt="Creative Commons License" style="border-width:0" src="http://i.creativecommons.org/l/by-nc-nd/3.0/88x31.png" /></a><br />The University of Bradford theses are licenced under a <a rel="license" href="http://creativecommons.org/licenses/by-nc-nd/3.0/">Creative Commons Licence</a>.

Language dc:language.iso

en

Repository record dc:identifier.uri

https://bradscholars.brad.ac.uk/handle/10454/20663

OAI identifier oai:identifier

oai:bradscholars.brad.ac.uk:10454/20663