Design, synthesis, and biological evaluation of naphthoaurones against colon cancer cells

Abstract

To identify compounds with potent inhibitory effects on HCT116 colon cancer cells, naphthoaurone compounds were designed and synthesized. A clonogenic survival assay was performed for the 16 synthesized compounds as an initial investigation, and compound 8 was selected based on its half-maximal HCT116 colon cancer cell growth inhibitory effect (1.11 μM). Further biological experiments for compound 8 demonstrated a significant decrease in the survival rate of HCT116 cells at the dose exceeded 10 μM, reaching an effective dose for a 50 % reduction in viability (ED₅₀) of 24.62 μM. Cell cycle analysis revealed that the sub-G1 cell population, a common feature of cells undergoing apoptosis, increased with a decrease in the G1 phase and an increase in G2/M phase cells after exposure to compound 8. Moreover, over time, compound 8 activated caspase-2, caspase-9, and caspase-3 via proteolytic cleavage. These results indicated that compound 8 triggered apoptotic cell death in HCT116 colon cancer cells by activating caspase-mediated apoptosis. In conclusion, a novel naphthoaurone derivative, (Z)-6-methoxy-2-((2-methoxynaphthalen-1-yl)methylene)benzofuran-3(2H)-one), shows potential for use in colon cancer therapy.