Triple-negative breast cancer (TNBC) is an aggressive cancer subtype lacking estrogen, progesterone, and HER-2 receptors, making it highly resistant to conventional therapies and associated with poor prognosis. Despite chemotherapy with taxanes, anthracyclines, and platinum-based agents, side effects and treatment resistance remain a significant challenge. Flavonoids, natural bioactive compounds, have shown anticancer potential, targeting oxidative stress, apoptosis, and resistance pathways. Semi-synthetic chiral derivatives of flavonoids (CDFs) have emerged as promising agents to overcome multidrug resistance. Building on our previous results that support the cytotoxic potential of CDFs, this project aims to elucidate their underlying molecular mechanisms in breast cancer, with a particular focus on TNBC. We will investigate their effects on cell death pathways, antimitotic activity, metabolic alterations, reactive oxygen species generation and resistance mechanisms, aiming to investigate more effective anticancer therapies.