α-Synuclein aggregation inhibitory activity of the bromotyrosine derivatives aerothionin and aerophobin-2 from the subtropical marine sponge Aplysinella sp

The neuronal protein α-synuclein (α-syn) is one of the main constituents of intracellular amyloid aggregations found in the post-mortem brains of Parkinson’s disease (PD) patients. Recently, we screened the MEOH extracts obtained from 300 sub-tropical marine invertebrates for α-syn binding activity using affinity MS and this resulted in the extract of the Verongida marine sponge Aplysinella sp. 1194, (QM G339263) displaying molecules that bind to the protein. The subsequent bioassay-guided separation of the Aplysinella sp. extract led to the isolation of the known bromotyrosine derivatives (+)-aerothionin (1) and (+)-aerophobin-2 (2). Both compounds bind to α-syn as detected by a MS affinity assay and inhibit α-syn aggregation in an assay that uses the fluorescence probe, thioflavin T, to detect aggregation. (+)-Aerothionin (1) was toxic to primary dopaminergic neurons at its expected α-syn aggregation inhibitory concentration and so could not be tested for pSyn aggregates in this functional assay. (+)-Aerophobin-2 (2) was not toxic and shown to weakly inhibit pSyn aggregation in primary dopaminergic neurons at 10 µM.Peer reviewe

Hesperine, a new imidazole alkaloid and α-synuclein binding activity of 1-methyl-1,2,7,8-tetrahydro-2,8-dioxoadenosine from the marine sponge Clathria (Thalysias) cf. hesperia

During a high-throughput screen of 300 Australian marine invertebrate extracts, the extract of the marine sponge Clathria (Thalysias) cf. hesperia was identified with α-synuclein binding activity. The bioassay-guided purification of this extract resulted in the isolation of 1-methyl-1,2,7,8-tetrahydro-2,8-dioxoadenosine (2) as the α-syn binder along with one new compound, hesperine (1), and five known compounds, indole-3-carboxaldehyde (3), (Z)-2'-demethylaplysinopsin (4), 2-amino-4'-hydroxyacetophenone (5), 4-hydroxybenzoic acid (6) and 4-hydroxybenzaldehyde (7). Herein, we report the structure elucidation of hesperine (1) and α-syn binding activity of 1-methyl-1,2,7,8-tetrahydro-2,8-dioxoadenosine (2).Peer reviewe

A new deep-water Tethya (Porifera, Tethyida, Tethyidae) from the Great Australian Bight and an updated Tethyida phylogeny

A new species of Tethya Lamarck, 1815 is described from a depth of 1000 m on the continental slope of the Great Australian Bight (GAB), southern Australia. The GAB slope was explored as part of systematic benthic surveys to understand unexplored communities in the light of current oil and gas exploration activity in the area. Tethya irisae sp. nov. was present at 1000 m in six of eight longitudinal depth surveys. Three molecular markers were obtained: COI, 28S (D3–D5) and ITS1-5.8S-ITS2. COI and 28S phylogenetic analyses show that the new species fits clearly within the genus Tethya. This is the 28th species of Tethya reported from Australia; it is unusual in that it has a stalk. The presence of a stalk as a morphological character to split genera in this family is questioned. The description of this new species is an opportunity to revisit the molecular phylogeny of the Tethyida Morrow & Cárdenas, 2015 using comprehensive datasets of COI and 28S markers. As in previous analyses, four Tethya clades were retrieved; we discuss the possibility of using external colour to support some of these clades. Despite unclear phylogenetic relationships amongst Tethyidae Gray, 1848 from Australia, our results suggest that tethyid genera Tethytimea Laubenfels, 1936, Tectitethya Sarà, 1994, Laxotethya Sarà & Sarà, 2002, Stellitethya Sarà, 1994, and Xenospongia Gray, 1858 derive from species of Tethya. We show that asters have been secondarily lost at least twice in the Hemiasterellidae Lendenfeld, 1889: in Liosina Thiele, 1899 and a potential new genus from northern Australia. We formally propose the reallocation of Liosina from Dictyonellidae van Soest, Diaz & Pomponi, 1990 to Hemiasterellidae Lendenfeld, 1889

Data from: Age and area predict patterns of species richness in pumice rafts contingent on oceanic climatic zone encountered

The Theory of Island Biogeography predicts that area and age explain species richness patterns (or alpha diversity) in insular habitats. Using a unique natural phenomenon, pumice rafting, we measured the influence of area, age and oceanic climate on patterns of species richness. Pumice rafts are formed simultaneously when submarine volcanoes erupt, the pumice clasts break-up irregularly, forming irregularly shaped pumice stones which while floating through the ocean are colonised by marine biota. We analyse two eruption events and more than 5000 pumice clasts collected from 29 sites and three climatic zones. Overall the older and larger pumice clasts held more species. Pumice clasts arriving in tropical and subtropical climates showed this same trend, where in temperate locations species richness (alpha diversity) increased with area but decreased with age. Beta diversity analysis of the communities forming on pumice clasts that arrived in different climatic zones showed that tropical and subtropical clasts transported similar communities while species composition on temperate clasts differed significantly from both tropical and subtropical arrivals. Using these thousands of insular habitats, we find strong evidence that area and age but also climatic conditions predict the fundamental dynamics of species richness colonising pumice clasts

Effects of exposure, depth and aspect on sponge communities on a coral reef

Coral reef benthic communities include a wide range of taxa, but most attention has been given to hard coral assemblages, and how their cover and composition vary over strong spatial gradients. Much less is known about the spatial distribution and composition of coral reef sponge communities, which may become increasingly important on reefs with declining coral cover. Here, we examined the effects of exposure, depth, aspect and location on the cover and composition of sponge assemblages on a coral reef in Kimbe Bay, Papua New Guinea. We quantified sponge cover and species composition along replicate line transects on 6 inshore reefs, sampling exposed (seaward) and sheltered (landward) sides of reefs at 5, 10 and 15 m depth, with reef aspect subdivided into slopes or walls along each transect. Although the substratum was generally dominated by corals and algae, sponges ranked 3rd, with an average of 13.1% cover, including 63 recognisable species. Morphologically there were 38 encrusting, 21 erect and 4 massive sponge species, with the encrusting sponges Lamellodysidea cf. chlorea and Dysidea sp1 exhibiting the highest cover. Sponge cover, species richness and species composition all exhibited complex interactions among depth, exposure and location. Sponge cover and species richness increased in transects with higher percentages of wall aspects, and assemblage structure differed between slopes and walls. Sponges are a diverse component of the benthos, with exposure, depth and reef aspect all contributing to explain spatial variation in assemblage structure

Rhodocomatulin-type anthraquinones from the Australian marine invertebrates Clathria hirsuta and Comatula rotalaria

Chemical investigations of an Australian sponge, Clathria hirsuta, from the Great Barrier Reef, have resulted in the isolation of two known anthraquinones, rhodocomatulin 5,7-dimethyl ether (1) and rhodocomatulin 7-methyl ether (2). Additionally, four new anthraquinone metabolites, 6-methoxyrhodocomatulin 7-methyl ether, 3-bromo-6-methoxy-12-desethylrhodocomatulin 7-methyl ether, 3-bromo-6-methoxyrhodocomatulin 7-methyl ether, and 3-bromorhodocomatulin 7-methyl ether (3-6), were also isolated and characterized. This is the first report of the rhodocomatulin-type anthraquinones from a marine sponge, as 1 and 2 were previously isolated from the marine crinoid genus Comatula. An additional chemical investigation of the marine crinoid Comatula rotalaria enabled the isolation of further quantities of 1 and 2, as well as two additional new crinoid metabolites, 12-desethylrhodocomatulin 5,7-dimethyl ether and 12-desethylrhodocomatulin 7-methyl ether (7 and 8). An NMR spectroscopic analysis of compounds 7 and 8 provided further insight into the rhodocomatulin planar structure and, together with the successful implementation of DFT-NMR calculations, confirmed that the rhodocomatulin metabolites existed as para rather than ortho quinones

Rhodocomatulin-Type Anthraquinones from the Australian Marine Invertebrates <i>Clathria hirsuta</i> and <i>Comatula rotalaria</i>

Chemical investigations of an Australian sponge, <i>Clathria hirsuta</i>, from the Great Barrier Reef, have resulted in the isolation of two known anthraquinones, rhodocomatulin 5,7-dimethyl ether (<b>1</b>) and rhodocomatulin 7-methyl ether (<b>2</b>). Additionally, four new anthraquinone metabolites, 6-methoxy­rhodocomatulin 7-methyl ether, 3-bromo-6-methoxy-12-desethyl­rhodocomatulin 7-methyl ether, 3-bromo-6-methoxy­rhodocomatulin 7-methyl ether, and 3-bromo­rhodocomatulin 7-methyl ether (<b>3</b>–<b>6</b>), were also isolated and characterized. This is the first report of the rhodocomatulin-type anthraquinones from a marine sponge, as <b>1</b> and <b>2</b> were previously isolated from the marine crinoid genus <i>Comatula</i>. An additional chemical investigation of the marine crinoid <i>Comatula rotalaria</i> enabled the isolation of further quantities of <b>1</b> and <b>2</b>, as well as two additional new crinoid metabolites, 12-desethyl­rhodocomatulin 5,7-dimethyl ether and 12-desethyl­rhodocomatulin 7-methyl ether (<b>7</b> and <b>8</b>). An NMR spectroscopic analysis of compounds <b>7</b> and <b>8</b> provided further insight into the rhodocomatulin planar structure and, together with the successful implementation of DFT-NMR calculations, confirmed that the rhodocomatulin metabolites existed as <i>para</i> rather than <i>ortho</i> quinones

Trikentramides A–D, Indole Alkaloids from the Australian Sponge <i>Trikentrion flabelliforme</i>

Chemical investigations of two specimens of <i>Trikentrion flabelliforme</i> collected from Australian waters have resulted in the identification of four new indole alkaloids, trikentramides A–D (<b>9</b>–<b>12</b>). The planar chemical structures for <b>9</b>–<b>12</b> were established following analysis of 1D/2D NMR and MS data. The relative configurations for <b>9</b>–<b>12</b> were determined following the comparison of ¹H NMR data with data previously reported for related natural products. The application of a quantum mechanical modeling method, density functional theory, confirmed the relative configurations and also validated the downfield carbon chemical shift observed for one of the quaternary carbons (C-5a) in the cyclopenta­[<i>g</i>]­indole series. The indole-2,3-dione motif present in trikentramides A–C is rare in nature, and this is the first report of these oxidized indole derivatives from a marine sponge

Dysidenin from the Marine Sponge <i>Citronia</i> sp. Affects the Motility and Morphology of <i>Haemonchus contortus</i> Larvae In Vitro

High-throughput screening of the NatureBank marine extract library (n = 7616) using a phenotypic assay for the parasitic nematode Haemonchus contortus identified an active extract derived from the Australian marine sponge Citronia sp. Bioassay-guided fractionation of the CH2Cl2/MeOH extract from Citronia sp. resulted in the purification of two known hexachlorinated peptides, dysidenin (1) and dysideathiazole (2). Compound 1 inhibited the growth/development of H. contortus larvae and induced multiple phenotypic changes, including a lethal evisceration (Evi) phenotype and/or somatic cell and tissue destruction. This is the first report of anthelmintic activity for these rare and unique polychlorinated peptides

High Throughput Screening of the NatureBank ‘Marine Collection’ in a Haemonchus Bioassay Identifies Anthelmintic Activity in Extracts from a Range of Sponges from Australian Waters

Widespread resistance in parasitic nematodes to most classes of anthelmintic drugs demands the discovery and development of novel compounds with distinct mechanisms of action to complement strategic or integrated parasite control programs. Products from nature—which assume a diverse ‘chemical space’—have significant potential as a source of anthelmintic compounds. In the present study, we screened a collection of extracts (n = 7616) derived from marine invertebrates sampled from Australian waters in a high throughput bioassay for in vitro anti-parasitic activity against the barber’s pole worm (Haemonchus contortus)—an economically important parasitic nematode of livestock animals. In this high throughput screen (HTS), we identified 58 active extracts that reduced larval motility by ≥70% (at 90 h), equating to an overall ‘hit rate’ of ~0.8%. Of these 58 extracts, 16 also inhibited larval development by ≥80% (at 168 h) and/or induced ‘non-wild-type’ (abnormal) larval phenotypes with reference to ‘wild-type’ (normal) larvae not exposed to extract (negative controls). Most active extracts (54 of 58) originated from sponges, three from chordates (tunicates) and one from a coral; these extracts represented 37 distinct species/taxa of 23 families. An analysis of samples by 1H NMR fingerprinting was utilised to dereplicate hits and to prioritise a set of 29 sponge samples for future chemical investigation. Overall, these results indicate that a range of sponge species from Australian waters represents a rich source of natural compounds with nematocidal or nematostatic properties. Our plan now is to focus on in-depth chemical investigations of the sample set prioritised herein