Evaluation of In Vitro Biological Activity of Flavanone/Chromanone Derivatives: Molecular Analysis of Anticancer Mechanisms in Colorectal Cancer

The primary objective of this study was to evaluate the anticancer activity of six flavanone/chromanone derivatives: <i>3</i>-benzylideneflavanones/<i>3</i>-benzylidenechroman-4-ones and their <i>3</i>-spiro-<i>1</i>-pirazolines analogs. We employed five colon cancer cell lines with varying degrees of metastasis and genetic profiles as our research model. Our investigation focused primarily on assessing the pro-oxidant properties of the tested derivatives and their impact on overall antiproliferative activity. To comprehensively evaluate the cytotoxic properties of these compounds, we analyzed their genotoxic, pro-apoptotic, and autophagy-inducing effects. Our findings indicate that three of the six analyzed derivatives exhibited promising antiproliferative activity against cancer cells, with IC₅₀ values ranging from 10 to 30 μM. Strong pro-oxidant properties were identified as a key mechanism underlying their cytotoxic activity. The generation of oxidative stress, which varied depending on the specific flavanone/chromanone derivative, resulted from increased intracellular reactive oxygen species (ROS) levels and decreased glutathione (GSH) concentrations. Furthermore, oxidative stress likely contributed to the induction of apoptosis/autophagy in cancer cells and the emergence of significant DNA damage.