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.

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.

The visual pigment xenopsin is widespread in protostome eyes and impacts the view on eye evolution.

Photoreceptor cells in the eyes of Bilateria are often classified into microvillar cells with rhabdomeric opsin and ciliary cells with ciliary opsin, each type having specialized molecular components and physiology. First data on the recently discovered xenopsin point towards a more complex situation in protostomes. In this study, we provide clear evidence that xenopsin enters cilia in the eye of the larval bryozoan Tricellaria inopinata and triggers phototaxis. As reported from a mollusc, we find xenopsin coexpressed with rhabdomeric-opsin in eye photoreceptor cells bearing both microvilli and cilia in larva of the annelid Malacoceros fuliginosus. This is the first organism known to have both xenopsin and ciliary opsin, showing that these opsins are not necessarily mutually exclusive. Compiling existing data, we propose that xenopsin may play an important role in many protostome eyes and provides new insights into the function, evolution, and possible plasticity of animal eye photoreceptor cells.

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.

Preclinical and Clinical Studies on Bryostatins, A Class of Marine-Derived Protein Kinase C Modulators: A Mini-Review.

Bryostatins are complex macrolactones isolated from marine organisms Bryozoan Bugula neritina. They are potent modulators of protein kinase C isozymes (PKCα: ki = 1.3-188 nM), and are one of the most extensively investigated marine natural products in clinical trials. Although ~21 natural bryostatins have been isolated, however only bryostatin-1 (1) has received much interest among medicinal chemists and clinicians. The structure-activity relationship of bryostatins has been well established, with the identification of key pharmacophoric features important for PKC modulation. The low natural abundance and the long synthetic route have prompted medicinal chemists to come-up with simplified analogs. Bryostatin skeleton comprises three pyran rings connected to each other to form a macrocyclic lactone. The simplest analog 27 contains only one pyran, which is also able to modulate the PKCα activity; however, the cyclic framework appears to be essential for the desired level of potency. Another simplified analog 17 ("picolog") exhibited potent and in-vivo efficacy against lymphoma. Bryostatin-1 (1) has shown an acceptable intravenous pharmacokinetic profile in mice and displayed promising in-vivo efficacy in mice models of various cancers and Alzheimer's disease. Bryostatin-1 was investigated in numerous Phase I/II oncology clinical trials; it has shown minimal effect as a single agent, however, provided encouraging results in combination with other chemotherapy agents. FDA has granted orphan drug status to bryostatin-1 in combination with paclitaxel for esophageal cancer. Bryostatin-1 has also received orphan drug status for fragile X syndrome. Bryostatin-1 was also investigated in clinical studies for Alzheimer's disease and HIV infection. In a nutshell, the natural as well as synthetic bryostatins have generated a strong hope to emerge as treatment for cancer along with many other diseases.

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.

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.

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.

Dendrobeaniamine A, a new alkaloid from the Arctic marine bryozoan Dendrobeania murrayana.

The new guanidine alkaloid Dendrobeaniamine A (1) was isolated from the organic extract of the Arctic marine bryozoan Dendrobeania murrayana. The chemical structure of 1 was elucidated by spectroscopic experiments, including 1D and 2D NMR and HRESIMS analysis. Compound 1 is a lipoamino acid, consisting of a C12 fatty acid anchored to the amino acid arginine. The bioactivity of 1 was evaluated using cellular and biochemical assays, but the compound did not show cytotoxic, antimicrobial, anti-inflammatory or antioxidant activities.

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.

Architecture of Anoteropora latirostris (Bryozoa, Cheilostomata) and implications for their biomineralization.

Cheilostome Bryozoa Anoteropora latirostris, a colonial marine invertebrate, constructs its skeleton from calcite and aragonite. This study presents firstly correlated multi-scale electron microscopy, micro-computed tomography, electron backscatter diffraction and NanoSIMS mapping. We show that all primary, coarse-grained platy calcitic lateral walls are covered by fine-grained fibrous aragonite. Vertical lateral walls separating autozooid chambers have aragonite only on their distal side. This type of asymmetric mineralization of lateral walls results from the vertical arrangement of the zooids at the growth margins of the colony and represents a type of biomineralization previously unknown in cheilostome bryozoans. NanoSIMS mapping across the aragonite-calcite interface indicates an organic layer between both mineral phases, likely representing an organic template for biomineralization of aragonite on the calcite layer. Analysis of crystallographic orientations show a moderately strong crystallographic preferred orientation (CPO) for calcite (7.4 times random orientation) and an overall weaker CPO for aragonite (2.4 times random orientation) with a high degree of twinning (45%) of the aragonite grains. The calculated Young's modulus for the CPO map shows a weak mechanical direction perpendicular to the colony's upper surface facilitating this organism's strategy of clonal reproduction by fragmentation along the vertical zooid walls.

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.

Skeletal carbonate mineralogy of Scottish bryozoans.

This paper describes the skeletal carbonate mineralogy of 156 bryozoan species collected from Scotland (sourced both from museum collections and from waters around Scotland) and collated from literature. This collection represents 79% of the species which inhabit Scottish waters and is a greater number and proportion of extant species than any previous regional study. The study is also of significance globally where the data augment the growing database of mineralogical analyses and offers first analyses for 26 genera and four families. Specimens were collated through a combination of field sampling and existing collections and were analysed by X-ray diffraction (XRD) and micro-XRD to determine wt% MgCO3 in calcite and wt% aragonite. Species distribution data and phylogenetic organisation were applied to understand distributional, taxonomic and phylo-mineralogical patterns. Analysis of the skeletal composition of Scottish bryozoans shows that the group is statistically different from neighbouring Arctic fauna but features a range of mineralogy comparable to other temperate regions. As has been previously reported, cyclostomes feature low Mg in calcite and very little aragonite, whereas cheilostomes show much more variability, including bimineralic species. Scotland is a highly variable region, open to biological and environmental influx from all directions, and bryozoans exhibit this in the wide range of within-species mineralogical variability they present. This plasticity in skeletal composition may be driven by a combination of environmentally-induced phenotypic variation, or physiological factors. A flexible response to environment, as manifested in a wide range of skeletal mineralogy within a species, may be one characteristic of successful invasive bryozoans.

Review of bioactive secondary metabolites from marine bryozoans in the progress of new drugs discovery.

Marine bryozoans play an important role for the discovery of novel bioactive compounds among marine organisms. In this review, we summarize 164 new secondary metabolites including macrocyclic lactones, sterols, alkaloids, sphingolipids and so forth from 24 marine bryozoans in the last two decades. The structural features, bioactivity, structure-activity relationship, mechanism and strategies to address the resupply of these scarce secondary metabolites are discussed. The structural and bioactive diversity of the secondary metabolites from marine bryozoans indicated the possibility of using these compounds, especially bryostatin 1 (1), bryostatin analog (BA1), alkaloids (50, 53, 127-128 and 134-139), sphingolipids sulfates (148 and 149) and sulfur-containing aromatic compound (160), as the starting points for new drug discovery.

Lipidomic Study of Precursors of Endocannabinoids in Freshwater Bryozoan Pectinatella magnifica.

Freshwater bryozoan Pectinatella magnifica was collected from a sand pit (South Bohemia). The total lipids after extraction from lyophilized bryozoans were analyzed using high-performance liquid chromatography/high-resolution negative tandem electrospray mass spectrometry. A total of 19 lipid classes were identified, including N-acyl-substituted phospholipids, that is, N-acylphosphatidylethanolamine and N-acylphosphatidylserine in their plasmenyl forms. Based on gas chromatography/mass spectrometry of 3-pyridylcarbonyl (picolinyl) esters, a very unusual fatty acid was identified, namely 24:7n-3 (all-cis-3,6,9,12,15,18,21-tetracosaheptaenoic acid). The presence of polyunsaturated fatty acids in individual classes is very specific: arachidonic and eicosapentaenoic acids being predominantly bound as amides in N-acyl phospholipids, that is, diacyl-N-acylphosphatidylethanolamines (NAPtdEtn), plasmenyl-N-acylphosphatidyl ethanolamines (PlsNAPtdEtn), diacyl-N-acylphosphatidylserines (NAPtdSer), and plasmenyl-N-acylphosphatidylserines (PlsNAPtdSer). While 24:6n-3 was identified in the sn-2 position of several phospholipids, 24:7n-3 was identified in only two plasmalogens, that is, PlsNAPtdEtn and PlsNAPtdSer. Thanks to the tandem mass spectrometry, we managed to identify the position of all acyl groups in both diacyl- and also in alkenyl-acyl-(plasmenyl) molecular species of N-acylphospholipids. The identification of the molecular species of N-acyl-substituted phosphatidylethanolamine and phosphatidylserine, including their plasmalogen forms, in the freshwater bryozoan P. magnifica has enabled the identification of endogenous cannabinoid precursors.

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.

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.