Heteronemin and Other Cytotoxic Compounds from the Red Sea Sponge Hyrtios erectus : Isolation, Characterization, and Lipid Nanoparticle Formulation for Improved Cancer Therapy

The marine sponge Hyrtios erectus is one of the most widely distributed and extensively studied species worldwide, known for its bioactive compounds. Investigation of the cytotoxic nonpolar fractions of the alcoholic extract of the Red Sea sponge Hyrtios erectus afforded four new natural compounds, erectine A (1), 5-hydroxy-1H-indol-3-carboxamide (2), erectine B (3) and hyrtiosol (4), together with the previously reported compounds 5-hydroxyindole-3-aldehyde (5), hyrtiosine A (6), hyrtiosulawesine (7), heteronemin (8), 3-oxo-12-O-deacetyle-12-epi-scalarin (9), 3-acetylsesterstatin 1 (10), and scalarfuran (11). The chemical structures of the compounds were elucidated using 1D and 2D NMR and HRESIMS. Heteronemin (8) demonstrated outstanding cytotoxic potency with an IC50 value of 0.0419 μg/mL against HCT-116 cells, while other compounds showed weak to moderate activity. To enhance the therapeutic potential of heteronemin, it was successfully encapsulated in lipid nanoformulations. These formulations, designed for high activity against HCT-116, have key features such as negative zeta potential values, nanometer range, and efficient encapsulation. The lipid nanoparticle formulations exhibited potent cytotoxic activity against HCT-116 cells, underscoring their potential as anticancer drug carriers. These findings support the need for additional clinical trials to assess their safety and effectiveness in cancer treatment.