Chemodiversified Brazilin Derivatives Suppress Migration and FAK Signaling in Breast Cancer Cells

Breast cancer is the most frequently diagnosed malignancy in women and remains the leading cause of cancer-related mortality worldwide. The treatment of invasive forms of this disease is particularly problematic due to the toxicity and side effects associated with conventional chemotherapeutic agents. Natural products have therefore gained attention as promising candidates for anticancer drug development; among them, the homoisoflavonoid brazilin has been reported to exhibit several biological activities, including anti-tumor and anti-inflammatory effects. In this work, brazilin was isolated from the heartwood of Haematoxylum brasiletto. Subsequently, structural modification was achieved by semi-synthesis, introducing three methyl or acetyl groups onto the parent brazilin scaffold. The chemical identities of brazilin and its derivatives were confirmed by spectroscopic analyses (¹H NMR and ¹³C NMR), and their purities were determined by optical rotation measurements. The biological activity of brazilin and its derivatives was then investigated in three mammary-derived cell lines: the triple-negative breast cancer (TNBC) line MDA-MB-231, the estrogen receptor-positive ERα(+) MCF7 line, and the non-tumorigenic MCF10A epithelial cell line. Cell viability was assessed using MTT assays, migratory behavior was analyzed through wound-healing assays, and focal adhesion kinase (FAK) activation was examined by Western blotting. The MTT results demonstrated that both MCF7 and MDA-MB-231 cancer cells were sensitive to the compounds at 20 µM, whereas no cytotoxicity was observed in MCF10A cells. The strongest response was observed in MDA-MB-231 cells, where brazilin exhibited an IC50 value of 49.92 μM, while in MCF7 cells, the brazilin-(OAc)3 derivative showed an IC50 of 49.97 μM. These effects were dependent on both dose and exposure time and were accompanied by reduced cell migration and suppression of FAK activation.