Marine natural products.

Covering: 2020This review covers the literature published in 2020 for marine natural products (MNPs), with 757 citations (747 for the period January to December 2020) referring to compounds isolated from marine microorganisms and phytoplankton, green, brown and red algae, sponges, cnidarians, bryozoans, molluscs, tunicates, echinoderms, mangroves and other intertidal plants and microorganisms. The emphasis is on new compounds (1407 in 420 papers for 2020), together with the relevant biological activities, source organisms and country of origin. Pertinent reviews, biosynthetic studies, first syntheses, and syntheses that led to the revision of structures or stereochemistries, have been included. A meta analysis of bioactivity data relating to new MNPs reported over the last five years is also presented.

Marine natural products.

This review covers the literature published in 2019 for marine natural products (MNPs), with 719 citations (701 for the period January to December 2019) referring to compounds isolated from marine microorganisms and phytoplankton, green, brown and red algae, sponges, cnidarians, bryozoans, molluscs, tunicates, echinoderms, mangroves and other intertidal plants and microorganisms. The emphasis is on new compounds (1490 in 440 papers for 2019), together with the relevant biological activities, source organisms and country of origin. Pertinent reviews, biosynthetic studies, first syntheses, and syntheses that led to the revision of structures or stereochemistries, have been included. Methods used to study marine fungi and their chemical diversity have also been discussed.

Marine natural products.

This review covers the literature published between January and December in 2018 for marine natural products (MNPs), with 717 citations (706 for the period January to December 2018) referring to compounds isolated from marine microorganisms and phytoplankton, green, brown and red algae, sponges, cnidarians, bryozoans, molluscs, tunicates, echinoderms, mangroves and other intertidal plants and microorganisms. The emphasis is on new compounds (1554 in 469 papers for 2018), together with the relevant biological activities, source organisms and country of origin. Reviews, biosynthetic studies, first syntheses, and syntheses that led to the revision of structures or stereochemistries, have been included. The proportion of MNPs assigned absolute configuration over the last decade is also surveyed.

Bromotryptamine and Imidazole Alkaloids with Anti-inflammatory Activity from the Bryozoan Flustra foliacea.

Chemical investigation of the marine bryozoan Flustra foliacea collected in Iceland resulted in isolation of 13 new bromotryptamine alkaloids, flustramines Q-W (1-7) and flustraminols C-H (8-13), and two new imidazole alkaloids, flustrimidazoles A and B (14 and 15), together with 12 previously described compounds (16-27). Their structures were established by detailed spectroscopic analysis using 1D and 2D NMR and HRESIMS. Structure 2 was verified by calculations of the 13C and 1H NMR chemical shifts using density functional theory. The relative and absolute configurations of the new compounds were elucidated on the basis of coupling constant analysis, NOESY, [α]D, and ECD spectroscopic data, in addition to chemical derivatization. The compounds were tested for in vitro anti-inflammatory activity using a dendritic cell model. Eight compounds (1, 3, 5, 13, 16, 18, 26, and 27) decreased dendritic cell secretion of the pro-inflammatory cytokine IL-12p40, and two compounds (4 and 14) increased secretion of the anti-inflammatory cytokine IL-10. Deformylflustrabromine B (27) showed the most potent anti-inflammatory effect (IC50 2.9 µM). These results demonstrate that F. foliacea from Iceland expresses a broad range of brominated alkaloids, many without structural precedents. The potent anti-inflammatory activity in vitro of metabolite 27 warrants further investigations into its potential as a lead for inflammation-related diseases.

Orthoscuticellines A-E, ß-Carboline Alkaloids from the Bryozoan Orthoscuticella ventricosa Collected in Australia.

Antiplasmodial high-throughput screening of extracts derived from marine invertebrates collected from northern NSW, Australia, resulted in the methanol extract of the bryozoan Orthoscuticella ventricosa being identified as inhibitory toward the 3D7 strain of Plasmodium falciparum. Purification of this extract resulted in two new bis-ß-carbolines that possess a cyclobutane moiety, orthoscuticellines A and B (1 and 2), three new ß-carboline alkaloids, orthoscuticellines C-E (3-5), and six known compounds, 1-ethyl-4-methylsulfone-ß-carboline (6), 1-ethyl-ß-carboline (7), 1-acetyl-ß-carboline (8) 1-(1'-hydroxyethyl)-ß-carboline (9), 1-methoxycarbonyl-ß-carboline (10), and 1-vinyl-ß-carboline (11). The structures of all compounds were determined from analysis of MS and 1D and 2D NMR data. The compounds showed modest antiplasmodial activity against P. falciparum in the range of 12-21 µM.

Kinase-Inhibitory Nucleoside Derivatives from the Pacific Bryozoan Nelliella nelliiformis.

Marine organisms are a valuable source of bioactive natural products, yet bryozoan invertebrates have been relatively understudied. Herein, we report nelliellosides A and B, new secondary metabolites of the Pacific bryozoan Nelliella nelliiformis, found using NMR-guided isolation. Their structures, including absolute configurations, were elucidated using spectroscopic and chromatographic techniques. Total synthesis of the natural products and four analogues was also achieved, in addition to an assessment of their biological activity, especially kinase inhibition.

The Phylum Bryozoa: From Biology to Biomedical Potential.

Less than one percent of marine natural products characterized since 1963 have been obtained from the phylum Bryozoa which, therefore, still represents a huge reservoir for the discovery of bioactive metabolites with its ~6000 described species. The current review is designed to highlight how bryozoans use sophisticated chemical defenses against their numerous predators and competitors, and which can be harbored for medicinal uses. This review collates all currently available chemoecological data about bryozoans and lists potential applications/benefits for human health. The core of the current review relates to the potential of bryozoan metabolites in human diseases with particular attention to viral, brain, and parasitic diseases. It additionally weighs the pros and cons of total syntheses of some bryozoan metabolites versus the synthesis of non-natural analogues, and explores the hopes put into the development of biotechnological approaches to provide sustainable amounts of bryozoan metabolites without harming the natural environment.

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.

Parallel lives of symbionts and hosts: chemical mutualism in marine animals.

Covering: up to 2018 Symbiotic microbes interact with animals, often by producing natural products (specialized metabolites; secondary metabolites) that exert a biological role. A major goal is to determine which microbes produce biologically important compounds, a deceptively challenging task that often rests on correlative results, rather than hypothesis testing. Here, we examine the challenges and successes from the perspective of marine animal-bacterial mutualisms. These animals have historically provided a useful model because of their technical accessibility. By comparing biological systems, we suggest a common framework for establishing chemical interactions between animals and microbes.

Marine natural products.

Covering: 2016. Previous review: Nat. Prod. Rep., 2017, 34, 235-294This review covers the literature published in 2016 for marine natural products (MNPs), with 757 citations (643 for the period January to December 2016) referring to compounds isolated from marine microorganisms and phytoplankton, green, brown and red algae, sponges, cnidarians, bryozoans, molluscs, tunicates, echinoderms, mangroves and other intertidal plants and microorganisms. The emphasis is on new compounds (1277 in 432 papers for 2016), together with the relevant biological activities, source organisms and country of origin. Reviews, biosynthetic studies, first syntheses, and syntheses that led to the revision of structures or stereochemistries, have been included.

Ponasterone A and F, Ecdysteroids from the Arctic Bryozoan Alcyonidium gelatinosum.

A new ecdysteroid, ponasterone F (1) and the previously reported compound ponasterone A (2) were isolated from specimens of the Arctic marine bryozoan Alcyonidium gelatinosum collected at Hopenbanken, off the coast of Edgeøya, Svalbard. The structure of 1 was elucidated, and the structure of 2 confirmed by spectroscopic methods including 1D and 2D NMR and analysis of HR-MS data. The compounds were evaluated for their ability to affect bacterial survival and cell viability, as well as their agonistic activities towards the estrogen receptors α and ß. The compounds were not active in these assays. Compound 2 is an arthropod hormone controlling molting and are known to act as an allelochemical when produced by plants. Even though its structure has been previously reported, this is the first time a ponasterone has been isolated from a bryozoan. A. gelatinosum produced 1 and 2 in concentrations surpassing those expected of hormonal molecules, indicating their function as defence molecules against molting predators. This work adds to the chemical diversity reported from marine bryozoans and expanded our knowledge of the chemical modifications of the ponasterones.

Marine natural products.

Covering: 2015. Previous review: Nat. Prod. Rep., 2016, 33, 382-431This review covers the literature published in 2015 for marine natural products (MNPs), with 1220 citations (792 for the period January to December 2015) referring to compounds isolated from marine microorganisms and phytoplankton, green, brown and red algae, sponges, cnidarians, bryozoans, molluscs, tunicates, echinoderms, mangroves and other intertidal plants and microorganisms. The emphasis is on new compounds (1340 in 429 papers for 2015), together with the relevant biological activities, source organisms and country of origin. Reviews, biosynthetic studies, first syntheses, and syntheses that lead to the revision of structures or stereochemistries, have been included.

Interactive effects of temperature, food and skeletal mineralogy mediate biological responses to ocean acidification in a widely distributed bryozoan.

Marine invertebrates with skeletons made of high-magnesium calcite may be especially susceptible to ocean acidification (OA) due to the elevated solubility of this form of calcium carbonate. However, skeletal composition can vary plastically within some species, and it is largely unknown how concurrent changes in multiple oceanographic parameters will interact to affect skeletal mineralogy, growth and vulnerability to future OA. We explored these interactive effects by culturing genetic clones of the bryozoan Jellyella tuberculata (formerly Membranipora tuberculata) under factorial combinations of dissolved carbon dioxide (CO2), temperature and food concentrations. High CO2 and cold temperature induced degeneration of zooids in colonies. However, colonies still maintained high growth efficiencies under these adverse conditions, indicating a compensatory trade-off whereby colonies degenerate more zooids under stress, redirecting energy to the growth and maintenance of new zooids. Low-food concentration and elevated temperatures also had interactive effects on skeletal mineralogy, resulting in skeletal calcite with higher concentrations of magnesium, which readily dissolved under high CO2 For taxa that weakly regulate skeletal magnesium concentration, skeletal dissolution may be a more widespread phenomenon than is currently documented and is a growing concern as oceans continue to warm and acidify.

Securamine Derivatives from the Arctic Bryozoan Securiflustra securifrons.

Bryozoans belonging to the Flustridae family have proven to be a rich source of structurally unique secondary metabolites. As part of our continuing search for bioactive secondary metabolites from Arctic marine invertebrates, the organic extract of Securiflustra securifrons was examined. This resulted in the isolation of three new halogenated, hexacyclic indole-imidazole alkaloids, securamines H-J (1-3), together with the previously reported compounds securamines C (4) and E (5). The structures of the new compounds were elucidated by spectroscopic methods including 1D and 2D NMR and analysis of HRMS data. Through NMR and HRMS analysis, we were also able to prove that 1, 2, 4, and 5, when dissolved in MeOH, were converted into their corresponding artifacts, the securamine MeOH adducts m1, m2, m4, and m5. When redissolved in a non-nucleophilic solvent, the native variants were re-formed. We also found that 3 was a MeOH addition product of a native variant. Even though the structures of several securamines have been reported, their bioactivities were not examined. The securamines displayed various degrees of cytotoxicity against the human cancer cell lines A2058 (skin), HT-29 (colon), and MCF-7 (breast), as well as against nonmalignant human MRC-5 lung fibroblasts. Compounds 1, 2, and 5 were found to be active, with IC50 values against the cancer cell lines ranging from 1.4 ± 0.1 to 10 ± 1 µM. The cytotoxicity of 1 was further evaluated and found to be time-dependent.

A Novel Brominated Alkaloid Securidine A, Isolated from the Marine Bryozoan Securiflustra securifrons.

A novel brominated alkaloid, Securidine A, was isolated from the cold water marine bryozoan Securiflustra securifrons. Securidine A was isolated using semi-preparative HPLC, and the structure was elucidated by spectroscopic methods. The isolated Securidine A was tested for cytotoxic, antibacterial, and anti-diabetic activities as well as for its potential for inhibition of biofilm formation. No significant biological activity was observed in the applied bioassays, thus expanded bioactivity profiling is required, in order to reveal any potential applications for Securidine A.

Marine natural products.

This review covers the literature published in 2014 for marine natural products (MNPs), with 1116 citations (753 for the period January to December 2014) referring to compounds isolated from marine microorganisms and phytoplankton, green, brown and red algae, sponges, cnidarians, bryozoans, molluscs, tunicates, echinoderms, mangroves and other intertidal plants and microorganisms. The emphasis is on new compounds (1378 in 456 papers for 2014), together with the relevant biological activities, source organisms and country of origin. Reviews, biosynthetic studies, first syntheses, and syntheses that lead to the revision of structures or stereochemistries, have been included.

Assessment of Chemical Impact of Invasive Bryozoan Pectinatella magnifica on the Environment: Cytotoxicity and Antimicrobial Activity of P. magnifica Extracts.

Pectinatella magnifica, an invasive bryozoan, might significantly affect ecosystem balance due to its massive occurrence in many areas in Europe and other parts of the world. Biological and chemical analyses are needed to get complete information about the impact of the animal on the environment. In this paper, we aimed to evaluate in vitro cytotoxic effects of five extracts prepared from P. magnifica using LDH assay on THP-1 cell line. Antimicrobial activities of extracts against 22 different bacterial strains were tested by microdilution method. Our study showed that all extracts tested, except aqueous portion, demonstrated LD50 values below 100 µg/mL, which indicates potential toxicity. The water extract of P. magnifica with LD50 value of 250 µg/mL also shows potentially harmful effects. Also, an environmental risk resulting from the presence and increasing biomass of potentially toxic benthic cyanobacteria in old colonies should not be underestimated. Toxicity of Pectinatella extracts could be partially caused by presence of Aeromonas species in material, since we found members of these genera as most abundant bacteria associated with P. magnifica. Furthermore, P. magnifica seems to be a promising source of certain antimicrobial agents. Its methanolic extract, hexane, and chloroform fractions possessed selective inhibitory effect on some potential pathogens and food spoiling bacteria in the range of MIC 0.5-10 mg/mL. Future effort should be made to isolate and characterize the content compounds derived from P. magnifica, which could help to identify the substance(s) responsible for the toxic effects of P. magnifica extracts.

Marine natural products.

This review covers the literature published in 2013 for marine natural products (MNPs), with 982 citations (644 for the period January to December 2013) referring to compounds isolated from marine microorganisms and phytoplankton, green, brown and red algae, sponges, cnidarians, bryozoans, molluscs, tunicates, echinoderms, mangroves and other intertidal plants and microorganisms. The emphasis is on new compounds (1163 for 2013), together with the relevant biological activities, source organisms and country of origin. Reviews, biosynthetic studies, first syntheses, and syntheses that lead to the revision of structures or stereochemistries, have been included.

Isolation and stereospecific synthesis of janolusimide B from a New Zealand collection of the bryozoan Bugula flabellata.

NMR-directed screening of New Zealand marine organisms has led to the isolation of the modified tripeptide janolusimide B from the common invasive bryozoan Bugula flabellata. The structure was established by NMR and MS analysis, degradative hydrolysis and derivatization, and stereoselective fragment synthesis. The bryozoan natural product is an N-methyl analogue of janolusimide, previously reported from the Mediterranean nudibranch Janolus cristatus, a species known to prey upon bryozoa.

Neristatin 1 provides critical insight into bryostatin 1 structure-function relationships.

Bryostatin 1, a complex macrocyclic lactone isolated from Bugula neritina, has been the subject of multiple clinical trials for cancer. Although it functions as an activator of protein kinase C (PKC) in vitro, bryostatin 1 paradoxically antagonizes most responses to the prototypical PKC activator, the phorbol esters. The bottom half of the bryostatin 1 structure has been shown to be sufficient to confer binding to PKC. In contrast, we have previously shown that the top half of the bryostatin 1 structure is necessary for its unique biological behavior to antagonize phorbol ester responses. Neristatin 1 comprises a top half similar to that of bryostatin 1 together with a distinct bottom half that confers PKC binding. We report here that neristatin 1 is bryostatin 1-like, not phorbol ester-like, in its biological activity on U937 promyelocytic leukemia cells. We conclude that the top half of the bryostatin 1 structure is largely sufficient for bryostatin 1-like activity, provided the molecule also possesses an appropriate PKC binding domain.