Amino acid–modified chalcone derivatives with in vitro and in vivo efficacy against colon cancer

A novel series of chalcone derivatives was developed with potent anticancer activity against colon cancer. Sixteen amino acid–based compounds, incorporating phenylalanine or tryptophan to improve aqueous solubility, were evaluated by the NCI on its 60-cell line panel. Eleven showed notable growth inhibition potencies, with five exhibiting high activity, particularly against the HCT116 colon cancer cell line, and no significant toxicity on WI-38 fibroblasts. Compounds 5f and 5g were selected for further evaluation; both induced SubG₀-G₁ cell cycle arrest, secondary necrosis, and upregulation of caspase-3, p53, and Bax/Bcl-2. Kinome inhibition profiling across 340 human kinases revealed that these compounds may act as PKC inhibitors, making them the first chalcones reported with such activity. In vivo, both compounds significantly reduced tumor growth, with efficacy comparable to doxorubicin. These results highlight these compounds as promising candidates for further development as anticancer agents, particularly for colon cancer treatment.