Alkaloids from marine ascidians

About 300 alkaloid structures isolated from marine ascidians are discussed in term of their occurrence, structural type and reported pharmacol. activity. Some major groups (e.g., the lamellarins and the ecteinascidins) are discussed in detail, highlighting their potential as therapeutic agents for the treatment of cancer or viral infections

Marine Antimalarials

Malaria is an infectious disease causing at least 1 million deaths per year, and, unfortunately, the chemical entities available to treat malaria are still too limited. In this review we highlight the contribution of marine chemistry in the field of antimalarial research by reporting the most important results obtained until the beginning of 2009, with particular emphasis on recent discoveries. About 60 secondary metabolites produced by marine organisms have been grouped into three structural types and discussed in terms of their reported antimalarial activities. The major groups of metabolites include isonitrile derivatives, alkaloids and endoperoxide derivatives. The following discussion evidences that antimalarial marine molecules can efficiently integrate the panel of lead compounds isolated from terrestrial sources with new chemical backbones and, sometimes, with unique functional groups

Further Investigation of the Mediterranean Sponge Axinella polypoides: Isolation of a New Cyclonucleoside and a New Betaine

An exhaustive exploration into the metabolic content of the Mediterranean sponge Axinella-polypoides resulted in the isolation of the new betaine 5 and the new cyclonucleoside 8. The structures of the new metabolites were elucidated by spectroscopic methods assisted by computational methods. The analysis also provided evidence that the sponge does not elaborate pyrrole-imidazole alkaloids (PIAs) but, interestingly, it was shown to contain two already known cyclodipeptides, compounds 9 (verpacamide A) and 10

Aurantoside J: a New Tetramic Acid Glycoside from Theonella swinhoei. Insights into the Antifungal Potential of Aurantosides

The chemical investigation of an Indonesian specimen of Theonella swinhoei afforded four aurantosides, one of which, aurantoside J (5), is a new compound. The structure of this metabolite, exhibiting the unprecedented N-α-glycosidic linkage between the pentose and the tetramate units, has been determined through detailed spectroscopic analysis. The four obtained aurantosides have been tested against five fungal strains (four Candida and one Fusarium) responsible of invasive infections in immuno-compromised patients. The non-cytotoxic aurantoside I (4) was the single compound to show an excellent potency against all the tested strains, thus providing valuable insights about the antifungal potential of this class of compounds and the structure-activity relationships

The dual impact of Ostreopsis cf. ovata on Mytilus galloprovincialis and Paracentrotus lividus: Toxin accumulation and pathological aspects

Blooms of the toxic dinoflagellates Ostreopsis have become common along rocky shores of the Mediterranean Sea. In addition to health problems for beach-goers, Ostreopsis toxins may accumulate in benthic marine animals used for human consumption, which however at times have shown signals of stress and even mortality. In order to elucidate the actual relationships between Ostreopsis and benthic invertebrates, we exposed mussels Mytilus galloprovincialis and sea urchins Paracentrotus lividus from the Gulf of Naples to cultures and natural material of O. cf. ovata and assessed feeding and adverse effects on the animals, along with their acquired toxicity. Mussels exposed to O. cf. ovata for 24 hours filtered the microalgae at different rates, depending on both mussel size and microalgal density, and became weakly toxic in some cases. Under longer exposure most animals died and all survivors were toxic. Detoxification of a naturally toxic mussel populations from an area affected by O. cf. ovata blooms took more than two weeks. Sea urchins fed with the red alga Asparagopsis taxiformis epiphytised by O. cf. ovata did not show damages and became mildly toxic in some cases. However, the direct exposure of sea urchins to O. cf. ovata cultures caused the partial or total loss of the spines in a density-dependent way, with the death of the animals at the highest microalgal concentrations. Milder effects were registered with sonicated cultures or toxin extracts. Our results indicate that the balance between toxicity and animal health in these invertebrates depends on the mode and intensity of exposure to the toxic microalga, while the response varies between the two species but also within the same species. This scenario matches the variety of responses of benthic populations recorded in the natural environment in areas affected by O. cf. ovata blooms

Mumijo Traditional Medicine: Fossil Deposits from Antarctica (Chemical Composition and Beneficial Bioactivity)

Mumijo is a widely used traditional medicine, especially in Russia, Altai Mountains, Mongolia, Iran Kasachstan and in Kirgistan. Mumijo preparations have been successfully used for the prevention and treatment of infectious diseases; they display immune-stimulating and antiallergic activity as well. In the present study, we investigate the chemical composition and the biomedical potential of a Mumijo(-related) product collected from the Antarctica. The yellow material originates from the snow petrels, Pagodroma nivea. Extensive purification and chemical analysis revealed that the fossil samples are a mixture of glycerol derivatives. In vitro experiments showed that the Mumijo extract caused in cortical neurons a strong neuroprotective effect against the apoptosis-inducing amyloid peptide fragment β-fragment 25–35 (Aβ25–35). In addition, the fraction rich in glycerol ethers/wax esters displayed a significant growth-promoting activity in permanent neuronal PC12 cells. It is concluded that this new Mumijo preparation has distinct and marked neuroprotective activity, very likely due to the content of glycerol ether derivatives

Cytotoxic Activity of Crude Extracts as well as of Pure Components from Jatropha Species, Plants Used Extensively in African Traditional Medicine

Extracts from Jatropha curcas, a plant used in African traditional medicine for various diseases, were tested for cytotoxic activity. The root extracts strongly reduced cell growth of tumor cells in vitro, a result consistent with the knowledge of the application of these plant extracts in traditional medicine, especially to cure/ameliorate cancer. A selection of pure diterpenoids existing in extracts from Jatropha species and isolated from J. curcas, for example, curcusone C, curcusone D, multidione, 15-epi-4Z-jatrogrossidentadion, 4Z-jatrogrossidentadion, 4E-jatrogrossidentadion, 2-hydroxyisojatrogrossidion, and 2-epi-hydroxyisojatrogrossidion, were likewise tested, and they also showed strong cytotoxic activity. It turned out that these extracts are highly active against L5178y mouse lymphoma cells and HeLa human cervix carcinoma cells, while they cause none or only very low activity against neuronal cell, for example, PC12. These data underscore that extracts from J. curcas or pure secondary metabolites from the plant are promising candidates to be anticancer drug, combined with low neuroactive effects

Palytoxin and an Ostreopsis Toxin Extract Increase the Levels of mRNAs Encoding Inflammation-Related Proteins in Human Macrophages via p38 MAPK and NF-κB

BACKGROUND: Palytoxin and, likely, its analogues produced by the dinoflagellate genus Ostreopsis, represent a class of non-proteinaceous compounds displaying high toxicity in animals. Owing to the wide distribution and the poisonous effects of these toxins in humans, their chemistry and mechanism of action have generated a growing scientific interest. Depending on the exposure route, palytoxin and its Ostreopsis analogues may cause several adverse effects on human health, including acute inflammatory reactions which seem more typical of cutaneous and inhalation contact. These observations have led us to hypothesize that these toxins may activate pro-inflammatory signalling cascades. METHODOLOGY AND PRINCIPAL FINDINGS: Here we demonstrate that palytoxin and a semi-purified Ostreopsis cf. ovata toxin extract obtained from a cultured strain isolated in the NW Adriatic Sea and containing a putative palytoxin and all the ovatoxins so far known--including the recently identified ovatoxin-f--significantly increase the levels of mRNAs encoding inflammation-related proteins in immune cells, i.e. monocyte-derived human macrophages, as assessed by Real-Time PCR analysis. Western immunoblot and electrophoretic mobility shift assays revealed that nuclear transcription factor -κB (NF-κB) is activated in cells exposed to toxins in coincidence with reduced levels of the inhibitory protein IκB-α. Moreover, Mitogen-Activated Protein Kinases (MAPK) were phosphorylated in response to palytoxin, as also reported by others, and to the Ostreopsis toxin extract, as shown here for the first time. By using specific chemical inhibitors, the involvement of NF-κB and p38 MAPK in the toxin-induced transcription and accumulation of Cycloxigenase-2, Tumor Necrosis Factor-α, and Interleukin-8 transcripts has been demonstrated. CONCLUSIONS AND SIGNIFICANCE: The identification of specific molecular targets of palytoxin and its Ostreopsis analogues, besides contributing to expand the still limited knowledge of the intracellular signalling cascades affected by these toxins, may have important implications in setting up focused pharmacological interventions, replacing currently used symptomatic treatments

Iodocionin, a Cytotoxic Iodinated Metabolite from the Mediterranean Ascidian Ciona edwardsii

Chemical investigation of the Mediterranean ascidian Ciona edwardsii has been performed, leading to the isolation of two halogenated compounds: a new tyrosineiodinated derivative iodocionin (1) and the relevant brominated analogue (2), previously isolated from a Caribbean sponge. The structure of the new compound 1 has been assigned on the basis of spectroscopic analysis. Both compounds were tested for cytotoxicity in vitro against two different cancer cell lines, L5178Y (mouse lymphoma) and PC-12 (rat pheochromocytoma). Iodocionin was shown to possess significant and selective activity against lymphoma cells with an IC50 of 7.75 μg/mL