Antiplasmodial Metabolites from Two Verongida Marine Sponges and Structure Revision for Caissarine A

Abstract Marine sponges of the order Verongida constitute a rich source of bioactive secondary metabolites, mainly bromotyrosine-derived compounds. Our ongoing search for bioactive marine natural products led us to investigate the chemistry of the marine sponge Aplysina alcicornis Pinheiro, Hajdu & Custódio, Aplysinidae, collected at the Rio de Janeiro coastline. Caissarine A ( 1a ) was isolated from extracts of A. alcicornis and its revised correct structure of the previously reported 1b from the sponge A. caissara was defined by analysis of spectroscopic data. Additionally, ( R , R ) 5 [3,5-dibromo-4-[(2-oxo-5-oxazolidinyl)]methoxyphenyl]-2-oxazolidinone, fistularin-3, (3,5-dibromo-1-hydroxy-4-oxocyclohexa-2,5-dien-1-yl)acetic acid and methyl 2-(3,5-dibromo-1-hydroxy-4-oxocyclohexa-2,5-dien-1-yl)acetate were also isolated from extracts of A. alcicornis . A simultaneous re-investigation of a Bahia-de-Todos-os-Santos sample of Aiolochroia crassa MeOH extract led to the isolation of pseudoceratinazole A. All isolated compounds were identified by analysis of spectroscopic data. Antiplasmodial evaluation revealed that fistularin-3 and pseudoceratinazole A were active against Plasmodium falciparum 3D7 strain, with IC 50 values of 2.3 and 7.6 µM, respectively. Both compounds exhibited low cytotoxicity against HepG2 cells (CC₅₀ > 50 µM for fistularin-3 and > 100 µM for pseudoceratinazole A), resulting in selectivity indices higher than 22 and 13, respectively. Fistularin-3 represents a unique antiplasmodial scaffold among bromotyrosine-derived Verongida metabolites.