A Chemo-Ecological Investigation of Dendrilla antarctica Topsent, 1905: Identification of Deceptionin and the Effects of Heat Stress and Predation Pressure on Its Terpene Profiles.

Marine sponges usually host a wide array of secondary metabolites that play crucial roles in their biological interactions. The factors that influence the intraspecific variability in the metabolic profile of organisms, their production or ecological function remain generally unknown. Understanding this may help predict changes in biological relationships due to environmental variations as a consequence of climate change. The sponge Dendrilla antarctica is common in shallow rocky bottoms of the Antarctic Peninsula and is known to produce diterpenes that are supposed to have defensive roles. Here we used GC-MS to determine the major diterpenes in two populations of D. antarctica from two islands, Livingston and Deception Island (South Shetland Islands). To assess the potential effect of heat stress, we exposed the sponge in aquaria to a control temperature (similar to local), heat stress (five degrees higher) and extreme heat stress (ten degrees higher). To test for defence induction by predation pressure, we exposed the sponges to the sea star Odontaster validus and the amphipod Cheirimedon femoratus. Seven major diterpenes were isolated and identified from the samples. While six of them were already reported in the literature, we identified one new aplysulphurane derivative that was more abundant in the samples from Deception Island, so we named it deceptionin (7). The samples were separated in the PCA space according to the island of collection, with 9,11-dihydrogracilin A (1) being more abundant in the samples from Livingston, and deceptionin (7) in the samples from Deception. We found a slight effect of heat stress on the diterpene profiles of D. antarctica, with tetrahydroaplysulphurin-1 (6) and the gracilane norditerpene 2 being more abundant in the group exposed to heat stress. Predation pressure did not seem to influence the metabolite production. Further research on the bioactivity of D. antarctica secondary metabolites, and their responses to environmental changes will help better understand the functioning and fate of the Antarctic benthos.

Computer-Aided Drug Design (CADD) to De-Orphanize Marine Molecules: Finding Potential Therapeutic Agents for Neurodegenerative and Cardiovascular Diseases.

Computer-aided drug design (CADD) techniques allow the identification of compounds capable of modulating protein functions in pathogenesis-related pathways, which is a promising line on drug discovery. Marine natural products (MNPs) are considered a rich source of bioactive compounds, as the oceans are home to much of the planet's biodiversity. Biodiversity is directly related to chemodiversity, which can inspire new drug discoveries. Therefore, natural products (NPs) in general, and MNPs in particular, have been used for decades as a source of inspiration for the design of new drugs. However, NPs present both opportunities and challenges. These difficulties can be technical, such as the need to dive or trawl to collect the organisms possessing the compounds, or biological, due to their particular marine habitats and the fact that they can be uncultivable in the laboratory. For all these difficulties, the contributions of CADD can play a very relevant role in simplifying their study, since, for example, no biological sample is needed to carry out an in-silico analysis. Therefore, the amount of natural product that needs to be used in the entire preclinical and clinical study is significantly reduced. Here, we exemplify how this combination between CADD and MNPs can help unlock their therapeutic potential. In this study, using a set of marine invertebrate molecules, we elucidate their possible molecular targets and associated therapeutic potential, establishing a pipeline that can be replicated in future studies.

Would Antarctic Marine Benthos Survive Alien Species Invasions? What Chemical Ecology May Tell Us.

Many Antarctic marine benthic macroinvertebrates are chemically protected against predation by marine natural products of different types. Antarctic potential predators mostly include sea stars (macropredators) and amphipod crustaceans (micropredators) living in the same areas (sympatric). Recently, alien species (allopatric) have been reported to reach the Antarctic coasts, while deep-water crabs are suggested to be more often present in shallower waters. We decided to investigate the effect of the chemical defenses of 29 representative Antarctic marine benthic macroinvertebrates from seven different phyla against predation by using non-native allopatric generalist predators as a proxy for potential alien species. The Antarctic species tested included 14 Porifera, two Cnidaria, two Annelida, one Nemertea, two Bryozooa, three Echinodermata, and five Chordata (Tunicata). Most of these Antarctic marine benthic macroinvertebrates were chemically protected against an allopatric generalist amphipod but not against an allopatric generalist crab from temperate waters. Therefore, both a possible recolonization of large crabs from deep waters or an invasion of non-native generalist crab species could potentially alter the fundamental nature of these communities forever since chemical defenses would not be effective against them. This, together with the increasing temperatures that elevate the probability of alien species surviving, is a huge threat to Antarctic marine benthos.

Meridianins Inhibit GSK3ß In Vivo and Improve Behavioral Alterations Induced by Chronic Stress.

Major depression disorder (MDD) is a severe mental alteration with a multifactorial origin, and chronic stress is one of the most relevant environmental risk factors associated with MDD. Although there exist some therapeutical options, 30% of patients are still resistant to any type of treatment. GSK3ß inhibitors are considered very promising therapeutic tools to counteract stress-related affectations. However, they are often associated with excessive off-target effects and undesired secondary alterations. Meridianins are alkaloids with an indole framework linked to an aminopyrimidine ring from Antarctic marine ascidians. Meridianins could overcome several of the aforementioned limitations since we previously demonstrated that they can inhibit GSK3ß activity without the associated neurotoxic or off-target effects in rodents. Here, we show that meridianins delivered into the lateral ventricle inhibited GSK3ß in several brain regions involved with stress-related symptoms. We also observed changes in major signaling pathways in the prefrontal cortex (Akt and PKA) and hippocampus (PKC and GluR1). Moreover, meridianins increased synaptic activity, specifically in the CA1 but not in the CA3 or other hippocampal subfields. Finally, we chronically treated the mice subjected to an unpredictable mild chronic stress (CUMS) paradigm with meridianins. Our results showed improvements produced by meridianins in behavioral alterations provoked by CUMS. In conclusion, meridianins could be of therapeutic interest to patients with stress-related disorders such as MDD.

Terpenoids in Marine Heterobranch Molluscs.

Heterobranch molluscs are rich in natural products. As other marine organisms, these gastropods are still quite unexplored, but they provide a stunning arsenal of compounds with interesting activities. Among their natural products, terpenoids are particularly abundant and diverse, including monoterpenoids, sesquiterpenoids, diterpenoids, sesterterpenoids, triterpenoids, tetraterpenoids, and steroids. This review evaluates the different kinds of terpenoids found in heterobranchs and reports on their bioactivity. It includes more than 330 metabolites isolated from ca. 70 species of heterobranchs. The monoterpenoids reported may be linear or monocyclic, while sesquiterpenoids may include linear, monocyclic, bicyclic, or tricyclic molecules. Diterpenoids in heterobranchs may include linear, monocyclic, bicyclic, tricyclic, or tetracyclic compounds. Sesterterpenoids, instead, are linear, bicyclic, or tetracyclic. Triterpenoids, tetraterpenoids, and steroids are not as abundant as the previously mentioned types. Within heterobranch molluscs, no terpenoids have been described in this period in tylodinoideans, cephalaspideans, or pteropods, and most terpenoids have been found in nudibranchs, anaspideans, and sacoglossans, with very few compounds in pleurobranchoideans and pulmonates. Monoterpenoids are present mostly in anaspidea, and less abundant in sacoglossa. Nudibranchs are especially rich in sesquiterpenes, which are also present in anaspidea, and in less numbers in sacoglossa and pulmonata. Diterpenoids are also very abundant in nudibranchs, present also in anaspidea, and scarce in pleurobranchoidea, sacoglossa, and pulmonata. Sesterterpenoids are only found in nudibranchia, while triterpenoids, carotenoids, and steroids are only reported for nudibranchia, pleurobranchoidea, and anaspidea. Many of these compounds are obtained from their diet, while others are biotransformed, or de novo biosynthesized by the molluscs. Overall, a huge variety of structures is found, indicating that chemodiversity correlates to the amazing biodiversity of this fascinating group of molluscs.

Bioactive Compounds from Marine Heterobranchs.

The natural products of heterobranch molluscs display a huge variability both in structure and in their bioactivity. Despite the considerable lack of information, it can be observed from the recent literature that this group of animals possesses an astonishing arsenal of molecules from different origins that provide the molluscs with potent chemicals that are ecologically and pharmacologically relevant. In this review, we analyze the bioactivity of more than 450 compounds from ca. 400 species of heterobranch molluscs that are useful for the snails to protect themselves in different ways and/or that may be useful to us because of their pharmacological activities. Their ecological activities include predator avoidance, toxicity, antimicrobials, antifouling, trail-following and alarm pheromones, sunscreens and UV protection, tissue regeneration, and others. The most studied ecological activity is predation avoidance, followed by toxicity. Their pharmacological activities consist of cytotoxicity and antitumoral activity; antibiotic, antiparasitic, antiviral, and anti-inflammatory activity; and activity against neurodegenerative diseases and others. The most studied pharmacological activities are cytotoxicity and anticancer activities, followed by antibiotic activity. Overall, it can be observed that heterobranch molluscs are extremely interesting in regard to the study of marine natural products in terms of both chemical ecology and biotechnology studies, providing many leads for further detailed research in these fields in the near future.

Unmasking Antarctic mollusc lineages: novel evidence from philinoid snails (Gastropoda: Cephalaspidea).

Since its introduction, the genus Philine has epitomized numerous mollusc snails with strong morphological convergence. Recently, a molecular analysis including a wide taxon sampling split this group into four non-sister families. Although they are especially diverse in cold and deep waters, no comprehensive studies are available for the Antarctic counterparts. Here, our morpho-anatomical and molecular data suggest major changes in the systematics of the group. From the eight known species, two are synonymized, Antarctophiline amoena with A. alata, and A. gouldi with A. gibba, and two are transferred to the genus Antarctophiline, namely A. apertissima comb.n. and A. falklandica comb.n. Two new species are described, A. easmithi sp.n. and A. amundseni sp.n. from different depths in the eastern Weddell Sea. The elusive P. antarctica from the Ross Sea was found in the Weddell Sea and Waegelea gen.n. is erected to place this species. Both phylogenetic and morphological data support the erection of Antarctophilinidae fam.n. to embrace most of the Philinoidea species described in the Southern Ocean. Only two species of Philinidae are found in Antarctic waters, Spiraphiline bathyalis gen. et sp.n. from bathyal depths in the Weddell Sea and S. kerguelensis comb.n. from the Kerguelen Islands. In light of the new data provided for all described species and the phylogenetic framework proposed herein, we briefly discuss the diversification and biogeographical patterns of Antarctic philinoid snails. Overall, antarctophilinid species seem to have restricted and grossly nonoverlapping distributions suggesting allopatric speciation connected possibly to geographical or bathymetric isolation.

The Phylum Bryozoa as a Promising Source of Anticancer Drugs.

Recent advances in sampling and novel techniques in drug synthesis and isolation have promoted the discovery of anticancer agents from marine organisms to combat this major threat to public health worldwide. Bryozoans, which are filter-feeding, aquatic invertebrates often characterized by a calcified skeleton, are an excellent source of pharmacologically interesting compounds including well-known chemical classes such as alkaloids and polyketides. This review covers the literature for secondary metabolites isolated from marine cheilostome and ctenostome bryozoans that have shown potential as cancer drugs. Moreover, we highlight examples such as bryostatins, the most known class of marine-derived compounds from this animal phylum, which are advancing through anticancer clinical trials due to their low toxicity and antineoplastic activity. The bryozoan antitumor compounds discovered until now show a wide range of chemical diversity and biological activities. Therefore, more research focusing on the isolation of secondary metabolites with potential anticancer properties from bryozoans and other overlooked taxa covering wider geographic areas is needed for an efficient bioprospecting of natural products.

Kororamides, Convolutamines, and Indole Derivatives as Possible Tau and Dual-Specificity Kinase Inhibitors for Alzheimer's Disease: A Computational Study.

Alzheimer's disease (AD) is becoming one of the most disturbing health and socioeconomic problems nowadays, as it is a neurodegenerative pathology with no treatment, which is expected to grow further due to population ageing. Actual treatments for AD produce only a modest amelioration of symptoms, although there is a constant ongoing research of new therapeutic strategies oriented to improve the amelioration of the symptoms, and even to completely cure the disease. A principal feature of AD is the presence of neurofibrillary tangles (NFT) induced by the aberrant phosphorylation of the microtubule-associated protein tau in the brains of affected individuals. Glycogen synthetase kinase-3 beta (GSK3ß), casein kinase 1 delta (CK1δ), dual-specificity tyrosine phosphorylation regulated kinase 1A (DYRK1A) and dual-specificity kinase cdc2-like kinase 1 (CLK1) have been identified as the principal proteins involved in this process. Due to this, the inhibition of these kinases has been proposed as a plausible therapeutic strategy to fight AD. In this study, we tested in silico the inhibitory activity of different marine natural compounds, as well as newly-designed molecules from some of them, over the mentioned protein kinases, finding some new possible inhibitors with potential therapeutic application.

UV-Protective Compounds in Marine Organisms from the Southern Ocean.

Solar radiation represents a key abiotic factor in the evolution of life in the oceans. In general, marine, biota-particularly in euphotic and dysphotic zones-depends directly or indirectly on light, but ultraviolet radiation (UV-R) can damage vital molecular machineries. UV-R induces the formation of reactive oxygen species (ROS) and impairs intracellular structures and enzymatic reactions. It can also affect organismal physiologies and eventually alter trophic chains at the ecosystem level. In Antarctica, physical drivers, such as sunlight, sea-ice, seasonality and low temperature are particularly influencing as compared to other regions. The springtime ozone depletion over the Southern Ocean makes organisms be more vulnerable to UV-R. Nonetheless, Antarctic species seem to possess analogous UV photoprotection and repair mechanisms as those found in organisms from other latitudes. The lack of data on species-specific responses towards increased UV-B still limits the understanding about the ecological impact and the tolerance levels related to ozone depletion in this region. The photobiology of Antarctic biota is largely unknown, in spite of representing a highly promising reservoir in the discovery of novel cosmeceutical products. This review compiles the most relevant information on photoprotection and UV-repair processes described in organisms from the Southern Ocean, in the context of this unique marine polar environment.

Computer-Aided Drug Design Applied to Marine Drug Discovery: Meridianins as Alzheimer's Disease Therapeutic Agents.

Computer-aided drug discovery/design (CADD) techniques allow the identification of natural products that are capable of modulating protein functions in pathogenesis-related pathways, constituting one of the most promising lines followed in drug discovery. In this paper, we computationally evaluated and reported the inhibitory activity found in meridianins A-G, a group of marine indole alkaloids isolated from the marine tunicate Aplidium, against various protein kinases involved in Alzheimer's disease (AD), a neurodegenerative pathology characterized by the presence of neurofibrillary tangles (NFT). Balance splitting between tau kinase and phosphate activities caused tau hyperphosphorylation and, thereby, its aggregation and NTF formation. Inhibition of specific kinases involved in its phosphorylation pathway could be one of the key strategies to reverse tau hyperphosphorylation and would represent an approach to develop drugs to palliate AD symptoms. Meridianins bind to the adenosine triphosphate (ATP) binding site of certain protein kinases, acting as ATP competitive inhibitors. These compounds show very promising scaffolds to design new drugs against AD, which could act over tau protein kinases Glycogen synthetase kinase-3 Beta (GSK3ß) and Casein kinase 1 delta (CK1δ, CK1D or KC1D), and dual specificity kinases as dual specificity tyrosine phosphorylation regulated kinase 1 (DYRK1A) and cdc2-like kinases (CLK1). This work is aimed to highlight the role of CADD techniques in marine drug discovery and to provide precise information regarding the binding mode and strength of meridianins against several protein kinases that could help in the future development of anti-AD drugs.

Gersemiols A-C and Eunicellol A, Diterpenoids from the Arctic Soft Coral Gersemia fruticosa.

Three new diterpenes named gersemiols A-C (1-3) and a new eunicellane diterpene, eunicellol A (4), have been isolated together with the known sesquiterpene (+)-α-muurolene (5) from the Arctic soft coral Gersemia fruticosa. The name gersemiane was assigned to the rare and unnamed diterpene skeleton of compounds 1-3 corresponding to 4-isopropyl-1,5,8a-trimethyltetradecahydrophenanthrene. The chemical structures were elucidated on the basis of extensive spectroscopic analysis (HR-ESIMS, 1D and 2D NMR) as well as coupling constant calculations for the determination of the relative configurations. All compounds were tested for their antimicrobial activity against several bacteria and fungi and eunicellol A was found to exhibit moderate and selective antibacterial activity.

Ecological and Pharmacological Activities of Antarctic Marine Natural Products.

Antarctic benthic communities are regulated by abundant interactions of different types among organisms, such as predation, competition, etc. Predators are usually sea stars, with omnivorous habits, as well as other invertebrates. Against this strong predation pressure, many organisms have developed all sorts of defensive strategies, including chemical defenses. Natural products are thus quite common in Antarctic organisms with an important ecological and pharmacological potential. In this paper, the chemical defenses of the Antarctic organisms studied during the ECOQUIM and ACTIQUIM projects, as well as their pharmacological potential, are reviewed. For the ecological defenses, predation against the sea star Odontaster validus is analyzed and evaluated along depth gradients as well as considering the lifestyle of the organisms. For the pharmacological activity, the anticancer, anti-inflammatory, and antibacterial activities tested are evaluated here. Very often, only crude extracts or fractions have been tested so far, and therefore, the natural products responsible for such activities remain yet to be identified. Even if the sampling efforts are not uniform along depth, most ecologically active organisms are found between 200 and 500 m depth. Also, from the samples studied, about four times more sessile organisms possess chemical defenses against the sea star than the vagile ones; these represent 50 % of sessile organisms and 35 % of the vagile ones, out of the total tested, being active. Pharmacological activity has not been tested uniformly in all groups, but the results show that relevant activity is found in different phyla, especially in Porifera, Cnidaria, Bryozoa, and Tunicata, but also in others. No relationship between depth and pharmacological activity can be established with the samples tested so far. More studies are needed in order to better understand the ecological relationships among Antarctic invertebrates mediated by natural products and to fully explore their pharmacological potential.

Granuloside, A Unique Linear Homosesterterpene from the Antarctic Nudibranch Charcotia granulosa.

A new homosesterterpene with a unique linear skeleton, named granuloside (1), has been fully characterized from the Antarctic nudibranch Charcotia granulosa Vayssière, 1906 (Mollusca: Gastropoda). The planar structure of 1 was determined by extensive spectroscopic techniques on the methyl derivatives (1a and 1b), and the R absolute configuration at C-4 is suggested by comparison of experimental and calculated ECD spectra of 1b. Granuloside (1) is the first linear homosesterterpene skeleton ever reported and, despite the low molecular complexity, its chemical structure poses many questions about its biogenesis and origin in the nudibranch.

Defensive metabolites from Antarctic invertebrates: does energetic content interfere with feeding repellence?

Many bioactive products from benthic invertebrates mediating ecological interactions have proved to reduce predation, but their mechanisms of action, and their molecular identities, are usually unknown. It was suggested, yet scarcely investigated, that nutritional quality interferes with defensive metabolites. This means that antifeedants would be less effective when combined with energetically rich prey, and that higher amounts of defensive compounds would be needed for predator avoidance. We evaluated the effects of five types of repellents obtained from Antarctic invertebrates, in combination with diets of different energetic values. The compounds came from soft corals, ascidians and hexactinellid sponges; they included wax esters, alkaloids, a meroterpenoid, a steroid, and the recently described organic acid, glassponsine. Feeding repellency was tested through preference assays by preparing diets (alginate pearls) combining different energetic content and inorganic material. Experimental diets contained various concentrations of each repellent product, and were offered along with control compound-free pearls, to the Antarctic omnivore amphipod Cheirimedon femoratus. Meridianin alkaloids were the most active repellents, and wax esters were the least active when combined with foods of distinct energetic content. Our data show that levels of repellency vary for each compound, and that they perform differently when mixed with distinct assay foods. The natural products that interacted the most with energetic content were those occurring in nature at higher concentrations. The bioactivity of the remaining metabolites tested was found to depend on a threshold concentration, enough to elicit feeding repellence, independently from nutritional quality.

Skeletal Mg content in common echinoderm species from Deception and Livingston Islands (South Shetland Islands, Antarctica) in the context of global change.

Echinoderms with high levels of magnesium (Mg) in their skeletons may be especially sensitive to ocean acidification, as the solubility of calcite increases with its Mg content. However, other structural characteristics and environmental/biological factors may affect skeletal solubility. To better understand which factors can influence skeletal mineralogy, we analyzed the Mg content of Antarctic echinoderms from Deception Island, an active volcano with reduced pH and relatively warm water temperatures, and Livingston Island. We found significant interclass and inter- and intraspecific differences in the Mg content, with asteroids exhibiting the highest levels, followed by ophiuroids and echinoids. Specimens exposed to hydrothermal fluids showed lower Mg levels, which may indicate local environmental effects. These patterns suggest that environmental factors such as seawater Mg2+/Ca2+ ratio and temperature may influence the Mg content of some echinoderms and affect their susceptibility to future environmental changes.

Do Antarctic bivalves present microdebris? The case of Livingston Island.

Marine microdebris (MD) seem to be widespread in benthic invertebrates, even in the most remote areas of the planet such as Antarctica, although the information available is still very scarce. Here we provide a detailed quantification and characterization of the MD found on three common bivalve species (Aequiyoldia eightsii, Thracia cf. meridionalis, and Cyclocardia astartoides) inhabiting shallow areas in Johnsons' Bay, Livingston Island (South Shetland Islands, Antarctica) as a snapshot of the MD present. On average, these bivalves contained 0.71 ± 0.89 items per individual and 1.49 ± 2.35 items per gram, being comparable to the few previous existing studies in other Antarctic areas. Nearly half of the organisms analysed here (45.6 %), contained at least one item. No significant differences were found in the three bivalve species. As far as we know, this is the first study to analyse and compare MD in three bivalve species in the Antarctic Peninsula. Although our results indicate bivalves are as not as polluted as in other areas of the planet, this is remarkable since this is considered one of the last pristine areas of the world. Our results point to local activities as the main source of MD pollution in Livingston Island, although global pollution cannot be discarded. We believe this research provides a useful baseline for future studies and will contribute to develop policies and strategies to preserve Antarctic marine ecosystems from MD pollution.

Peptide Toxins from Antarctica: The Nemertean Predator and Scavenger Parborlasia corrugatus (McIntosh, 1876).

Peptide toxins from marine invertebrates have found use as drugs and in biotechnological applications. Many marine habitats, however, remain underexplored for natural products, and the Southern Ocean is among them. Here, we report toxins from one of the top predators in Antarctic waters: the nemertean worm Parborlasia corrugatus (McIntosh, 1876). Transcriptome mining revealed a total of ten putative toxins with a cysteine pattern similar to that of alpha nemertides, four nemertide-beta-type sequences, and two novel full-length parborlysins. Nemertean worms express toxins in the epidermal mucus. Here, the expression was determined by liquid chromatography combined with mass spectrometry. The findings include a new type of nemertide, 8750 Da, containing eight cysteines. In addition, we report the presence of six cysteine-containing peptides. The toxicity of tissue extracts and mucus fractions was tested in an Artemia assay. Notably, significant activity was observed both in tissue and the high-molecular-weight mucus fraction, as well as in a parborlysin fraction. Membrane permeabilization experiments display the membranolytic activity of some peptides, most prominently the parborlysin fraction, with an estimated EC50 of 70 nM.

Bone-eating worms from the Antarctic: the contrasting fate of whale and wood remains on the Southern Ocean seafloor.

We report the results from the first experimental study of the fate of whale and wood remains on the Antarctic seafloor. Using a baited free-vehicle lander design, we show that whale-falls in the Antarctic are heavily infested by at least two new species of bone-eating worm, Osedax antarcticus sp. nov. and Osedax deceptionensis sp. nov. In stark contrast, wood remains are remarkably well preserved with the absence of typical wood-eating fauna such as the xylophagainid bivalves. The combined whale-fall and wood-fall experiment provides support to the hypothesis that the Antarctic circumpolar current is a barrier to the larvae of deep-water species that are broadly distributed in other ocean basins. Since humans first started exploring the Antarctic, wood has been deposited on the seafloor in the form of shipwrecks and waste; our data suggest that this anthropogenic wood may be exceptionally well preserved. Alongside the new species descriptions, we conducted a comprehensive phylogenetic analyses of Osedax, suggesting the clade is most closely related to the frenulate tubeworms, not the vestimentiferans as previous reported.

Feeding repellence in Antarctic bryozoans.

The Antarctic sea star Odontaster validus and the amphipod Cheirimedon femoratus are important predators in benthic communities. Some bryozoans are part of the diet of the asteroid and represent both potential host biosubstrata and prey for this omnivorous lysianassid amphipod. In response to such ecological pressure, bryozoans are expected to develop strategies to deter potential predators, ranging from physical to chemical mechanisms. However, the chemical ecology of Antarctic bryozoans has been scarcely studied. In this study we evaluated the presence of defenses against predation in selected species of Antarctic bryozoans. The sympatric omnivorous consumers O. validus and C. femoratus were selected to perform feeding assays with 16 ether extracts (EE) and 16 butanol extracts (BE) obtained from 16 samples that belonged to 13 different bryozoan species. Most species (9) were active (12 EE and 1 BE) in sea star bioassays. Only 1 BE displayed repellence, indicating that repellents against the sea star are mainly lipophilic. Repellence toward C. femoratus was found in all species in different extracts (10 EE and 12 BE), suggesting that defenses against the amphipod might be both lipophilic and hydrophilic. Interspecific and intraspecific variability of bioactivity was occasionally detected, suggesting possible environmental inductive responses, symbiotic associations, and/or genetic variability. Multivariate analysis revealed similarities among species in relation to bioactivities of EE and/or BE. These findings support the hypothesis that, while in some cases alternative chemical or physical mechanisms may also provide protection, repellent compounds play an important role in Antarctic bryozoans as defenses against predators.