Design and synthesis of Morinda citrifolia inspired anthraquinone derivatives as potential treatment for colon cancer / Nurhaliza Wati Mekzali

Nurhaliza Wati , Mekzali (2023) Design and synthesis of Morinda citrifolia inspired anthraquinone derivatives as potential treatment for colon cancer / Nurhaliza Wati Mekzali. Masters thesis, Universiti Malaya.

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Abstract

Colorectal cancer (CRC) is one of the most fatal malignancies, with only a 5% chance of survival. Early surgical resection and chemotherapy can improve CRC patients' survival rates. Natural phytochemicals have been shown to be effective for preventing and treating CRC. However, isolation and purification of the active phytochemical ingredients from plants are time-consuming and labour-intensive. Thus, in this study, a series of anthraquinone derivatives (6a-j) inspired from Morinda citrifolia were designed, synthesised and evaluated as potential KRAS and p53 inhibitors. Molecular docking was conducted on CRC mutated proteins, i.e., p53 (PDB ID: 7B4N) and KRAS (PDB ID: 6P0Z) to obtain ligand-binding interactions. Synthesis of the ten compounds (6a-j) produced yields between 42-66%. Anti-proliferation of the synthesised anthraquinone derivatives was evaluated against two colorectal cancer cell lines, HCT116 and HT29, respectively. The results showed good IC50 values at micromolar range. Among all tested compounds, 6b (IC50 = 3.828 ± 0.05 μM) exhibited the highest potency as compared to the positive control 5-Fluorouracil (IC50 = 5.00 ± 0.04 μM) against HCT116 cells. Thus, this work suggests 6b for further investigation as colorectal cancer inhibitor.

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