First evidence of bioactive compounds from the sponge Agelas oroides (Schmidt, 1864) against pancreatic carcinoma

Pancreatic cancer is one of the most aggressive tumours with poor prognosis and low year survival rate. Marine sponges are considered a challenging source of bioactive compounds, as potential drugs for cancer treatments. Here we report a bioassay-guided investigation of the methanolic extract of the sponge Agelas oroides (Schmidt, 1864), which displayed a potent cytotoxic activity against pancreatic adenocarcinoma (MIA PaCa-2 cells with <40% viability at 1 µg/ml). Two-step fractionation of the extract by SPE-HRX and RP-HPLC led to the identification of brominated pyrrole alkaloids as the chemical constituents of one of the most active fractions (IC₅₀ = 34 µg/ml). Among these, we identified the 4,5-dibromopyrrole-2-carboxylic acid as the bioactive product (IC₅₀ = 10 µg/ml). Our results disclose for the first time the sponge A. oroides as a source of cytotoxic alkaloids targeting pancreatic cancer and provide a contribute to the development of alternative strategies for the treatment of these severe pathologies.