Unlocking the Diversity of Pyrroloiminoquinones Produced by Latrunculid Sponge Species

Jarmo-Charles J Kalinski,Rosemary A Dorrington,Shirley Parker-Nance,Rui W M Krause,Samantha C Waterworth

doi:10.3390/md19020068

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.

Highlights

The emergence of new and multidrug-resistant pathogens [1,2,3,4] creates an ongoing need to investigate novel compounds from marine organisms, since marine natural products have proven useful for medical and pharmacological applications [5,6] and include potential antimicrobial [7], antiviral [8] and antifungal [9] drug leads
The MS2 data ensemble was deconvoluted into a network, based on spectral similarity using the GNPS feature based molecular networking (FBMN) workflow [37,38]
Four molecular networks were created for subsets of the samples (T. favus and T. nguni, T. pedunculata, T. michaeli and C. bellae and L. apicalis; see Figures S2.1–S2.4) confirming that grouping sponge samples into eight different types and averaging across each type for the ‘holistic’ analysis presented in this article was appropriate and did not combine chemically disparate samples

Summary

Introduction

The emergence of new and multidrug-resistant pathogens [1,2,3,4] creates an ongoing need to investigate novel compounds from marine organisms, since marine natural products have proven useful for medical and pharmacological applications [5,6] and include potential antimicrobial [7], antiviral [8] and antifungal [9] drug leads. Marine sponges of the family Latrunculiidae are known to be prolific producers of cytotoxic pyrroloiminoquinones, a class of alkaloids with potential as leads in anticancer, antiparasite and antibacterial drug development [10,11,12,13]. In nature, these compounds are mostly encountered as makaluvamines, tsitsikammamines, and discorhabdins, all sharing the characteristic tricyclic pyrroloiminoquinone structural motif and they are often isolated alongside related pyrroloquinolines such as damirones (Figure 1) [12,13]. Discorhabdins, exhibiting a peculiar spiro-structure [19,23,24], as well as discorhabdin oligomers [25,26,27,28,29] have to date only been reported from marine sponges with the vast majority of studies focusing on Latrunculia species [12,13]

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