The discovery and development of effective chemotherapeutic agents in the past few decades
have immensely enhanced the treatment and management of human cancer. However, because
these drugs are associated with adverse side effects, high genotoxicity, risk for secondary cancers
and devastating effects on the patients’ immune system; the need for developing more effective
anticancer agents remains. A priority Research shows that 9-aminoacridine (9AA) derivatives
have substantial anticancer properties. The pharmacological properties of this agent are well
characterized and this scaffold has been widely used to treat different diseases for decades.
Quinacrine is a 9AA derivative, which was first discovered as an antimalarial compound in
1930’s and since then had been widely used in treating a variety of parasitic infections and
demonstrated potential for cancer treatment. Importantly, the polypharmacology of Quinacrine
makes it an attractive drug to treat a variety of cancers. Quinacrine acts by specifically targeting
cellular signaling pathways that play an important role in cell survival. Given the distinctive
cancer treating abilities of Quinacrine by specifically targeting cellular signaling pathways, it
was the objective of this study to develop a compound that has similar properties as Quinacrine
but has better efficacy and selectivity in targeting tumor cells. Therefore, for this project we
created derivatives of 9AA compound using hybrid pharmapore approach and examined one of
the derivatives of Quinacrine compound named VR118. After performing a series of experiments
to test the efficacy and selectivity of the Quinacrine derivative VR118, I came to the conclusion
that VR118 is highly effective in treating cancer cells and have the potential to selectively target
cancer cells without causing severe harm to normal cells at concentrations applicable for
malignant cell lines. This report discusses the efficacy and selectivity of VR118 compound in
targeting cellular signaling pathways and the mechanisms through which VR118 kills cancer
cells.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:OSUL.10219/2149 |
| Date | 17 March 2014 |
| Creators | Almnayan, Danah |
| Publisher | Laurentian University of Sudbury |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Thesis |
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