Objective

Cancer is a devastating disease worldwide, with millions of diagnoses per year and many people living with this disease. Breast cancer is the most frequent type of malignancy in women and due to the increasing cancer incidence, research in this area has been growing at the same rate. The chromene scaffold has been identified in several compounds with anticancer activity. The substitution pattern highly influences the mode of action and synthesis of new derivatives and is an important element in the search for improved drug candidates. This work addresses the synthesis of new chromene derivatives with enhanced anticancer activity.

New chalcone and chromene derivatives were synthesized in good yield through simple and effective reactions using innocuous solvents such as water and ethanol and high yielding aldol condensations. These compounds were tested on breast cancer cells (MCF-7 and Hs578T) and breast non-neoplastic cells (MCF-10A). After determination of IC₅₀ values and selectivity index, specific assays were performed to analyse the potential of these compounds.

Generally, compounds with halogenated substituents presented enhanced activity compared to those with methoxy or methyl groups. The bromine atom was often present in the bioactive molecules that proceeded to the final assays and showed to be promising candidates. A particular chromene acted as a cell migration inhibitory agent and triggered regulated cell death associated with G₂/M cell-arrest and microtubule destabilization. Finally, combining these compounds with the currently used chemotherapeutic drug doxorubicin, potentiated its antitumor effect and decreased the cytotoxicity in non-neoplastic cells, anticipating a potential reduction of side effects. Therefore, we have developed an efficient apoptotic-inducer and microtubule destabilizer agent that can potentially be applied to future cancer therapy.