Slim and scum: Natural products from land and sea

To a natural-products chemist, the term "natural products" does not refer to all compounds from natural sources, as the name might imply. It is specifically used to refer to compounds known as secondary metabolites, structurally complex molecules, often of unknown function, with very limited biological distribution

MALDI-TOF mass spectrometry of Cyanobacteria: a global approach to the discovery of novel secondary metabolites

Cyanobacteria (blue-green algae) are a group of ancient prokaryotic organisms dating back between three and four billion years.¹ They have been attributed with oxygenating the earth’s atmosphere² but, since the anthropogenic euthrophication of lakes, ponds and oceans, they have become synonymous with water hygiene issues.³ This is due to the alteration of the nutrient composition of their habitat to one which is optimal for growth (or blooms). Cyanobacterial blooms may simply cause foul tastes and odours,⁴ but they can also lead to the production of toxic secondary metabolites poisonous to humans and animals upon ingestion.⁵ NZ has yet to suffer a human fatality, but the deaths of several dogs in Wellington was attributed to homoanatoxin-a 1 (Chart 1) from a Phormidium species.

Review: Marine natural products

This review covers the literature published in 2003 for marine natural products, with 619 citations (413 for the period January to December 2003) referring to compounds isolated from marine microorganisms and phytoplankton, green algae, brown algae, red algae, sponges, coelenterates, bryozoans, molluscs, tunicates and echinoderms. The emphasis is on new compounds (656 for 2003), together with their relevant biological activities, source organisms and country of origin. Biosynthetic studies or syntheses that lead to the revision of structures or stereochemistries have been included (78), including any first total syntheses of a marine natural product

Further characterization of glycine-containing microcystins from the McMurdo Dry Valleys of Antarctica

Microcystins are hepatotoxic cyclic peptides produced by several cyanobacterial genera worldwide. In 2008, our research group identified eight new glycine-containing microcystin congeners in two hydro-terrestrial mat samples from the McMurdo Dry Valleys of Eastern Antarctica. During the present study, high-resolution mass spectrometry, amino acid analysis and micro-scale thiol derivatization were used to further elucidate their structures. The Antarctic microcystin congeners contained the rare substitution of the position-1 D-alanine for glycine, as well as the acetyl desmethyl modification of the position-5 Adda moiety (3S-amino-9S-methoxy-2S,6,8S-trimethyl-10-phenyldeca-4E,6E-dienoic acid). Amino acid analysis was used to determine the stereochemistry of several of the amino acids and conclusively demonstrated the presence of glycine in the microcystins. A recently developed thiol derivatization technique showed that each microcystin contained dehydrobutyrine in position-7 instead of the commonly observed N-methyl dehydroalanine

Pterocellin A isolated from marine bryozoan Pterocella vesiculosa is cytotoxic to human HeLa cells via mitochondrial apoptotic processes

Pterocellin A is a novel bioactive alkaloid isolated from the New Zealand marine bryozoan Pterocella vesiculosa. It exhibits potent antitumour activity towards the P388 (murine leukaemia) cell line in vitro and is selectively sensitive towards certain non-small cell lung, melanoma, and breast cancer cell lines, however, the biological mode of action of pterocellin A is unknown. Using the human cervical cancer cell line HeLa, we show that pterocellin A exhibited cytotoxicity against HeLa cells with an IC50 of 886 ng/mL. Time-course MTT and LDH assays were carried out and the results showed only a low level of cytosolic LDH was detected in the supernatant after all the cells have died from pterocellin A treatment at 2000 ng/mL. This indicated the cells maintained membrane integrity upon cell death which suggested apoptotic cell death. Additionally, morphological changes were observed under the microscope after 6 h of treatment. Cell shrinkage and nucleus condensation were observed, as well as apparent membrane blebbing, a key feature of apoptosis. The MTT data was also indicative of mitochondria impairment which could suggest that pterocellin A targets the mitochondria. This idea was supported by the observed changes in the morphology and location of the mitochondria after exposure to pterocellin A. Furthermore, the level of activated caspase-3 in HeLa cells increased after treatment with pterocellin A; activated caspase-3 can only be detected after a series of signalling events following the induction of apoptosis. These data support the notion that pterocellin A is an inducer of apoptosis in HeLa cells possibly via mitochondria related processes

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

The effect of cyanobacterial biomass enrichment by centrifugation and GF/C filtration on subsequent microcystin measurement

Microcystins are cyclic peptides produced by multiple cyanobacterial genera. After accumulation in the liver of animals they inhibit eukaryotic serine/threonine protein phosphatases, causing liver disease or death. Accurate detection/quantification of microcystins is essential to ensure safe water resources and to enable research on this toxin. Previous methodological comparisons have focused on detection and extraction techniques, but have not investigated the commonly used biomass enrichment steps. These enrichment steps could modulate toxin production as recent studies have demonstrated that high cyanobacterial cell densities cause increased microcystin levels. In this study, three microcystin-producing strains were processed using no cell enrichment steps (by direct freezing at three temperatures) and with biomass enrichment (by centrifugation or GF/C filtration). After extraction, microcystins were analyzed using liquid chromatography-tandem mass spectrometry. All processing methods tested, except GF/C filtration, resulted in comparable microcystin quotas for all strains. The low yields observed for the filtration samples were caused by adsorption of arginine-containing microcystins to the GF/C filters. Whilst biomass enrichment did not affect microcystin metabolism over the time-frame of normal sample processing, problems associated with GF/C filtration were identified. The most widely applicable processing method was direct freezing of samples as it could be utilized in both field and laboratory environments

Identification and structure elucidation of epoxyjanthitrems from Lolium perenne infected with the endophytic fungus Epichloë festucae var. lolii and determination of the tremorgenic and anti-insect activity of epoxyjanthitrem I.

Epoxyjanthitrems I-IV (1-4) and epoxyjanthitriol (5) were isolated from seed of perennial ryegrass (Lolium perenne) infected with the endophytic fungus Epichloë festucae var. lolii. Although structures for epoxyjanthitrems I-IV have previously been proposed in the literature, this is the first report of a full structural elucidation yielding NMR (Nuclear magnetic resonance) assignments for all five epoxyjanthitrem compounds, and additionally, it is the first isolation of epoxyjanthitriol (5). Epoxyjanthitrem I induced tremors in mice and gave a dose dependent reduction in weight gain and feeding for porina (Wiseana cervinata), a common pasture pest in New Zealand. These data suggest that epoxyjanthitrems are involved in the observed effects of the AR37 endophyte on livestock and insect pests

Further pterocellins from the New Zealand marine bryozoan Pterocella vesiculosa

Four new alkaloids, pterocellins C−F (1–4), have been isolated from the New Zealand marine bryozoan Pterocella vesiculosa. Structural elucidation was achieved through NMR spectroscopic and mass spectrometric analysis and comparison of spectroscopic data with that of the known compounds pterocellins A and B. The biological activities of 1–4 were assessed in a number of different assay systems and compared with those of pterocellins A and B

5-Bromo-8-methoxy-1-methyl-β-carboline, an alkaloid from the New Zealand marine bryozoan Pterocella vesiculosa

A new alkaloid, 5-bromo-8-methoxy-1-methyl-β-carboline (1), has been isolated from the New Zealand marine bryozoan Pterocella vesiculosa. Structural elucidation was achieved through NMR spectroscopic and mass spectrometric analysis, and a single-crystal X-ray diffraction analysis of 1 was performed. The biological activity of 1 was assessed against P388 murine leukemia cells and three microorganisms and compared with that of a number of related β-carboline alkaloids