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

## TL;DR

A new antiproliferative compound was isolated from a marine sponge using a bioassay and mass spectrometry, showing potential for cancer treatment.

## Contribution

A bromo-tyramine derivative with antiproliferative activity was isolated and its apoptotic mechanism was characterized.

## Key findings

- N,N,N-trimethyl-3,5-dibromotyramine showed antiproliferative activity on HepG2 cells with an IC50 of 37.49 ± 1.94 μg/mL.
- The compound induced apoptosis by upregulating BAX and c-PARP-1 and downregulating BCL-2 and p-AKT.

## Abstract

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 Aplysina cauliformis organic extracts. This procedure combines a bioassay-guided approach with the dereplication of mass data through bioinformatic analysis. This approach identified the compound N,N,N-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. N,N,N-trimethyl-3,5-dibromotyramine increased the expression of pro-apoptotic β-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 N,N,N-trimethyl-3,5-dibromotyramine from Aplysina cauliformis and its antiproliferative activity against the HepG2 cell line.