Bioactive Brominated Oxindole Alkaloids from the Red Sea Sponge Callyspongia siphonella

Abstract

In the present study, LC-HRESIMS-assisted dereplication along with bioactivity-guided isolation led to targeting two brominated oxindole alkaloids (compounds <b>1</b> and <b>2</b>) which probably play a key role in the previously reported antibacterial, antibiofilm, and cytotoxicity of <i>Callyspongia siphonella</i> crude extracts. Both metabolites showed potent antibacterial activity against Gram-positive bacteria, <i>Staphylococcus aureus</i> (minimum inhibitory concentration (MIC) = 8 and 4 µg/mL) and <i>Bacillus subtilis</i> (MIC = 16 and 4 µg/mL), respectively. Furthermore, they displayed moderate biofilm inhibitory activity in <i>Pseudomonas</i> <i>aeruginosa</i> (49.32% and 41.76% inhibition, respectively), and moderate in vitro antitrypanosomal activity (13.47 and 10.27 µM, respectively). In addition, they revealed a strong cytotoxic effect toward different human cancer cell lines, supposedly through induction of necrosis. This study sheds light on the possible role of these metabolites (compounds <b>1</b> and <b>2</b>) in keeping fouling organisms away from the sponge outer surface, and the possible applications of these defensive molecules in the development of new anti-infective agents.