Bioassay-Guided Procedure Coupled with HR-ESIMS Dereplication for Isolation of Antiproliferative Bromo-Tyramine Derivative from Aplysina cauliformis

The marine environment is vital for sustaining life on Earth and offers a significant, untapped source of bioresources that could enhance the blue economy. The present investigation used our protocol to quickly identify bioactive molecules in <i>Aplysina cauliformis</i> organic extracts. This procedure combines a bioassay-guided approach with the dereplication of mass data through bioinformatic analysis. This approach identified the compound <i>N</i>,<i>N</i>,<i>N</i>-trimethyl-3,5-dibromotyramine, a bromo-tyramine analog that showed promising antiproliferative activity on HepG2 cell lines, with an IC₅₀ value of 37.49 ± 1.94 μg/mL after 24 h. Furthermore, the evaluation of related gene expression confirmed the mechanism of cell death to be apoptosis. <i>N</i>,<i>N</i>,<i>N</i>-trimethyl-3,5-dibromotyramine increased the expression of pro-apoptotic <i>β</i>-cell lymphoma 2-associated X protein (BAX) and Poly (ADP-ribose) polymerase (PARP-1) cleavage (c-PARP-1) and downregulated the anti-apoptotic β-cell lymphoma 2 (BCL-2) and phospho-Akt (p-AKT). This report presents <i>N</i>,<i>N</i>,<i>N</i>-trimethyl-3,5-dibromotyramine from <i>Aplysina cauliformis</i> and its antiproliferative activity against the HepG2 cell line.