Marmaricines A-C: Antimicrobial Brominated Pyrrole Alkaloids from the Red Sea Marine Sponge Agelas sp. aff. marmarica

The Red Sea is the home of a rich diversity of sponge species with unique ecological adaptations that thrive in its saline, warm, and nutrient-poor waters. Red Sea sponges offer potential as sources of bioactive compounds and novel drugs. The organic extract of the Red Sea sponge <i>Agelas</i> sp. <i>aff. marmarica</i> was investigated for its antimicrobial constituents. Through bioassay-guided fractionation of the antimicrobial fraction of the extract on SiO₂ and Sephadex LH-20, as well as HPLC purification, three bioactive compounds, marmaricines A-C (<b>1</b>-<b>3</b>), were isolated. Structural elucidation of the compounds was performed using 1D (¹H and ¹³C) and 2D (COSY, HSQC, HMBC, and NOESY) NMR, as well as (+)-HRESIMS, leading to the identification of the compounds. The antimicrobial activities of the compounds were assessed through evaluation of their inhibition zones, MIC, MBC, and MFC, against Methicillin-Resistant <i>Staphylococcus aureus</i> (MRSA), <i>Escherichia coli</i>, and <i>Candida albicans</i>. Marmaricines A and B exhibited the strongest antibacterial effects against MRSA, with inhibition zones ranging from 14.00 to 15.00 mm, MIC values of 8 µg/mL, and MBC values of 16 µg/mL. In comparison, marmaracine C showed slightly weaker activity (inhibition zone: 12 mm, MIC: 16 µg/mL, MBC: 32 µg/mL). In terms of antifungal activity, marmaricines B and C demonstrated the greatest effect against <i>C. albicans</i>, with inhibition zones of 14-15 mm, MIC values of 8 µg/mL, and MFCs of 16 µg/mL. Interestingly, none of the compounds showed any inhibitory effect against <i>E. coli</i>. The results indicate that marmaricines A-C are selectively active against MRSA, and marmaricines B and C demonstrate potential against <i>C. albicans</i>, making them promising candidates for the development of novel antimicrobial agents targeting resistant pathogens.