Unlocking the Diversity of Pyrroloiminoquinones Produced by Latrunculid Sponge Species

Abstract

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 Tsitsikamma favus, Tsitsikamma pedunculata, Cyclacanthia bellae, and Latrunculia apicalis as well as the recently discovered species, Tsitsikamma nguni and Tsitsikamma michaeli. 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 T. nguni closely resembled those of the known T. favus (chemotype I), but with a higher abundance of tsitsikammamines vs. discorhabdins. T. michaeli sponges displayed two distinct chemical profiles, either producing mostly the same discorhabdins as T. favus (chemotype I) or non- or monobrominated, hydroxylated discorhabdins. C. bellae and L. apicalis 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.

Marine natural products

“…519 A large study of 43 individual Latrunculid sponges has assessed variability of pyrroloiminoquinone metabolites, an important and commonly encountered class of MNP from this family, with distinctive species-dependent proles across over 200 individually detected metabolites. 520 A MS-based protocol for discovery of proline-rich cyclic peptides has been described. The method utilises a biomimetic enzymatic synthesis to provide standards for the analysis, showing that proline-rich peptides are much more common in marine sponges than isolation studies would suggest.…”

A Quarter Century of Marine Biodiscovery in Algoa Bay, South Africa

“… Compounds 61 and 62 were previously isolated from T. favus. A recent liquid chromatography tandem mass spectrometry (LCMS 2 ) molecular networking analysis by Kalinski et al of 43 specimens from six different species of South African and sub-Antarctic latrunculid sponges included four species, viz., T . pedunculata , C .…”

“…The comparative networking analysis confirmed species-specific pyrroloiminoquinone specialized metabolite profiles in each of the six latrunculid species including identifying two “regiospecific” chemotypes of T. michaeli , separately inhabiting two different reefs. The tribrominated discorhabdin C dominated metabolite profile of T. michaeli chemotype I (Riy Banks Reef) was consistent with that of T. favus chemotype I and differed only in the absence of tsitsikammamines . The chemical profile of T. michaeli c hemotype II (Evans Peak Reef) incorporated a series of brominated and hydroxylated discorhabdin C analogues which were absent from chemotype I.…”

“…The pyrroloiminoquinone metabolite profiles of both chemotypes of T. michaeli differed from that of T. pedunculata , with the latter characterized by mono- and dibrominated discorhabin V type pyrroloiminoquinones. Kalinski et al consequently suggested that the reported co-occurrence of T. favus discorhabdin-type metabolites in the original natural products investigation of T. pedunculata by Antunes et al may have been as a result of contamination with specimens of the pedunculated and morphologically similar T. michaeli chemotype I …”

Anticancer Activities of Marine-Derived Phenolic Compounds and Their Derivatives

“…Many studies were performed on interesting pyrroloiminoquinone alkaloids containing a makaluvamine-type scaffold and phenolic substituent, which were isolated from the two sponge genera of Zyzzya and Latrunculia collected in the Pacific-Oceania region. In addition, a significant cytotoxicity of makaluvamines has been reported through interaction with topoisomerase II resulting in DNA cleavage [201,202]. Among them, makaluvamines D (64), K (65), J (66) and P (67) were found to be the most active against the PANC-1 cell line, exhibiting IC 50 values of 0.29, 0.56, 0.054 and 0.3 µM, respectively.…”