Resistance to drugs is often the cause of cancer treatment failure. Our previous results showed that chiral derivatives of flavonoids have the potential to overcome this multidrug resistance (MDR) phenotype. Flavonoids are bioactive compounds found in plants, increasingly used for the synthesis of chiral derivatives. Several studies have already demonstrated that some of these compounds have a high cytotoxicity for cancer cells. Additionally, our preliminary results indicated that these compounds potentiated the cytotoxicity of doxorubicin. However, the molecular mechanisms responsible for these effects are yet to be elucidated. Therefore, the aims of this work are to continue the screening of a library of chiral synthetic flavonoids and further explore some of the most promising compounds, namely concerning the role of the stereochemistry in their activity, the mechanisms inducing cell death, anti-mitotic activity and their effect on metabolism, microenvironment and MDR proteins, aiming to unravel their mechanism of action in different cellular models. It is also objective of the project to analyze their ability to sensitize tumor cells to other conventional anticancer agents.