This study aims to evaluate the therapeutic potential of five novel tetraoxane
compounds and one novel tetraoxane-naphthalimide hybrid compound for chronic
lymphocytic leukaemia. These novel compounds are predicted to deliver targeted
toxicity to cancer cells with reduced activity on non-cancer, healthy tissue. This
selectivity is expected due to a number of properties associated with tetraoxane
compounds, including the affinity of the cleavage of the endoperoxide bridge by the
elevated levels of iron associated with cancer cells, and the expected production of
reactive oxygen species (ROS) by cancer cells on exposure to the cytotoxic compounds.
The study focuses on Chronic Lymphocytic Leukaemia, as it the most prevalent type of
leukaemia in adults in the western world. However, these compounds have the potential
to be equally as effective against other cancer types.
The six test compounds, along with two reference compounds, Chlorambucil and
Dihydroartemisinin, were evaluated on two leukaemia cell lines, HL-60 and MEC-1, and
a non-cancer peripheral blood cell line, BL-2052. The anti-proliferation potential of the
compounds on the leukaemia cell lines was determined and the selectivity of each
compound toward the cancer cell lines over the non-cancerous BL-2052 cell line was
established. Initial screening involved determination of compound IC50 values, cell
membrane permeability, and analysis of mechanism of cell death, via flow cytometric
analysis.
The results show promising anti-cancer properties of all six compounds, with IC50 values
in the low micromolar range. A comparative study of the selectivity of the compounds
for leukaemic cells shows compound selectivity, with all six novel tetraoxanes less
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potent against the non-cancer cell line than HL-60s. The novel compounds showed
higher activity towards both leukaemic cell lines analysed in comparison to the currently
utilised chemotherapeutic drug Chlorambucil. These findings show potential for these
novel compounds in the endless search to provide more effective treatment options for
patients while reducing adverse effects. However, further investigation of these
tetraoxane compounds is required to determine their full potentia
