Unlocking the Diversity of Pyrroloiminoquinones Produced by Latrunculid Sponge Species.

Sponges of the Latrunculiidae family produce bioactive pyrroloiminoquinone alkaloids including makaluvamines, discorhabdins, and tsitsikammamines. The aim of this study was to use LC-ESI-MS/MS-driven molecular networking to characterize the pyrroloiminoquinone secondary metabolites produced by six latrunculid species. These are , , and as well as the recently discovered species, and . Organic extracts of 43 sponges were analyzed, revealing distinct species-specific chemical profiles. More than 200 known and unknown putative pyrroloiminoquinones and related compounds were detected, including unprecedented makaluvamine-discorhabdin adducts and hydroxylated discorhabdin I derivatives. The chemical profiles of the new species closely resembled those of the known (chemotype I), but with a higher abundance of tsitsikammamines vs. discorhabdins. sponges displayed two distinct chemical profiles, either producing mostly the same discorhabdins as (chemotype I) or non- or monobrominated, hydroxylated discorhabdins. and produced similar pyrroloiminoquinone chemistry to one another, characterized by sulfur-containing discorhabdins and related adducts and oligomers. This study highlights the variability of pyrroloiminoquinone production by latrunculid species, identifies novel isolation targets, and offers fundamental insights into the collision-induced dissociation of pyrroloiminoquinones.