Enhanced Thymidylate Synthase Inhibition via Imination and Metalation of

Fluoropyrimidine 5-Fluorouracil (5-Fu) and Capecitabine in Colorectal Cancer

G.I. Adebayo-Gege, B.J. Okoli, U.D. Ejike, A.BAlexander B. Adelaiye

{Insert affiliation}

Objectives: The study will investigate the role of capecitabine, fluorouracil derivative and their
copper (II) complexes on polymorphism of different nuclei in colon cancer cell line (COLO-
320). Evaluation on cell viability and its metabolic activities, apoptotic pathway, apoptotic nuclei
count and C-Jun N-terminal kinase (JNK) cascade (cell migration) during exposure of colon
cancer cell line to the synthesised derivatives.
Motivation: Studies have shown that 30% of patient on fluoropyrimidine 5-fluorouracil (5-Fu)
and capecitabine are prone to high rate of cardiac-toxicity, neutropenia and hyperammonaemia
encephalopathy. However, drugs based on hydrazone and copper-templates show little or no
side-effect but effective in the inhibition thymidylate synthase. The use of Spark Cyto Real-
Time Cytometry will provide a better understanding into the molecular mechanism and
biomarkers in the inhibition thymidylate synthase.

Method: Template compounds will be synthesised by imination and metalation reactions.

COLO-320 will be obtained from patient undergoing colon cancer treatment and
cultured in the presence of the synthesised compounds. Cell proliferation assay will be
carried out to obtain the rate of cell growth, assess cell viability, metabolic activity,
apoptotic nuclei count and pathway, migration of c-Jun N-terminal cascade during cell migration
with evaluation of cell cycle.
Data obtained will be helpful in understanding the mode of action and mechanism of
the template drugs during the clinical administration. At large, it will improve the
health condition of colon cancer patients.