bluuebunny/crossref_metadata_2025 huggingface dataset:
Antifungal Activity of (+)-Curcuphenol, a Metabolite from the Marine Sponge Didiscus oxeata
Authors: Gaspar Helena , Feio Sonia  Savluchinske , Rodrigues Ana  Isabel , Van Soest Rob
Published: October 2008

The antifungal activity of the sesquiterpenoids (+)-curcuphenol and (+)-curcudiol isolated from the Caribbean sponge Didiscus oxeata was evaluated against several filamentous fungi.
New Marine Derived Anticancer Therapeutics ─ A Journey from the Sea to Clinical Trials
Authors: Jimeno J. , Faircloth G. , Sousa-Faro JM  Fernández , Scheuer P. , Rinehart K.
Published: October 2008

Nature has been instrumental as a source for therapeutics. Despite the fact that we live in an oceanic planet, a number of technical factors have historically hampered the evolution of a marine-based chamanic medicine. With the implementation of scuba diving tools and the development of sophisticated instruments for the isolation and elucidation of structures of natural products from marine organisms, major advances have been made in the discovery of marine derived therapeutics. The availability of ARA-C, a nucleoside analog that is a basic component in the treatment of acute myeloid leukemia, and its fluorinated analog Gemcitabine, an important therapeutic tool in the treatment of pancreatic cancer and in non small cell lung cancer, is a solid proof and validation of the potential of this approach. As a result of our discovery and developmental program, three innovative compounds with novel mechanisms of action: ET-743, AplidinR and Kahalalide F, have been shown to display a positive therapeutic index and activity in resistant solid tumors that supports the ongoing clinical phase III/II trials. ET-743 represents the first active agent against sarcomas developed in the past 25 years and has demonstrated a therapeutic potential in pretreated ovarian cancer. Several chemical entities are under advanced preclinical testing and additional candidates for clinical development are emerging, including compounds hitting a specific target. Moreover, the development of a given marine candidate implies the collaboration of an interdisciplinary team special focused on supply, formulation, pharmacogenetics and preclinical toxicology.
Identification and Biological Characterization of Angiogenic and Tumor Growth Inhibitors derived from Sinica cetorhinus maximum Cartilage
Authors: Jiao Binghua , Chen Jianhe , Miao Weimin , Wang Lianghua , Zhu Yuping , Miao Huinan
Published: October 2008

Shark (Sinica cetorhinus maximum) cartilage was extracted in 1 mol/L Gu-HCl guanidine. Two purified active proteins with apparent molecular weights of 15.2x103 Da and 8.0×103 Da (designated as Sp15 and Sp8, respectively) were obtained through ultrafiltration and Superdex 75 chromatography. The activities of the samples were studied in terms of their potential inhibition of vascular endothelial cell growth in vitro, of angiogenesis both in rabbit cornea and chick embryo chorioallantoic membrane (CAM) assay models in vivo, and of growth of transplanted S180 sarcoma in mice in vivo. The results showed that Sp15 expressed a typical lysozymatic activity up to 223,000 U/mg and its N-terminus was highly homologous to lysozymes of various mammalian origins. Sp15 exhibited a strong anti-angiogenic activity only in vitro, whereas Sp8 shared this effect both in vitro and in vivo. Both Sp15 and Sp8 provided an effective anti-tumor activity in mice bearing transplanted S180 sarcoma. These results suggest that Sp15 is a shark cartilage-derived lysozyme that participates in the defense to bacterial invasion to the body, while Sp8 is an angiogenic inhibitor that mediates at least part of the anti-tumor activity associated with shark cartilage probably through the inhibition of tumor-induced angiogenesis.
Bioactive Alkaloids from the Sea: A Review
Authors: Kuramoto Makoto , Arimoto Hirokazu , Uemura Daisuke
Published: October 2008

In our ongoing search for bioactive substances from marine organisms, novel alkaloids have been isolated. Pinnatoxins and pinnamine, potent shellfish poisons, were purified from the Okinawan bivalve Pinna muricata. Pinnatoxins activate Ca2+ channels. Halichlorine was isolated from the marine sponge Halichondria okadai. This compound inhibits the induction of VCAM-1. Drugs that block VCAM-1 may be useful for treating coronary artery diseases, angina, and noncardiovascular inflammatory diseases. Pinnaic acids, which are cPLA2 inhibitors, were also obtained from P. muricata. Interestingly, the structures of pinnaic acids are closely related to that of halichlorine. Norzoanthamine hydrochloride, isolated from the colonial zoanthid Zoanthus sp., suppresses decreases in bone weight and strength in ovariectomized mice, and could be a good candidate for an osteoporotic drug. Ircinamine, purified from the marine sponge Ircinia sp., has a reactive thioester. Aburatubolactams, inhibitors of superoxide anion generation, were isolated from Streptomyces sp. This article covers the bioactive marine alkaloids that have been recently isolated by this research group.
Identification of Renieramycin A as an Antileishmanial Substance in a Marine Sponge Neopetrosia sp.
Authors: Nakao Yoichi , Shiroiwa Takeru , Murayama Shuhei , Matsunaga Shigeki , Goto Yasuyuki , Matsumoto Yoshitsugu , Fusetani Nobuhiro
Published: October 2008

The newly developed assay system using recombinant Leishmania amazonensis expressing enhanced green fluorescent protein (La/egfp) has been applied to the screening of Japanese marine sponges for antileishmanial activity. Bioassay-guided fractionation of an active sponge Neopetrosia sp. afforded an active compound which was identified as renieramycin A by spectroscopic analysis. It inhibited La/egfp with an IC50 value of 0.2 μg/mL.
Fucoxanthin and Its Metabolites in Edible Brown Algae Cultivated in Deep Seawater
Authors: Mori Kanami , Ooi Takashi , Hiraoka Masanori , Oka Naohiro , Hamada Hideyuki , Tamura Mitsumasa , Kusumi Takenori
Published: October 2008

Three metabolites of fucoxanthin were isolated from a brown alga, Scytosiphon lomentaria, and the structure of a new compound was determined by NMR. The content of fucoxanthin, a biologically active carotenoid, in four edible brown algae, cultivated in deep seawater, was studied.
Drugs and Cosmetics from the Sea
Authors: Kijjoa Anake , Sawangwong Pichan
Published: October 2008

The marine environment is a rich source of both biological and chemical diversity. This diversity has been the source of unique chemical compounds with the potential for industrial development as pharmaceuticals, cosmetics, nutritional supplements, molecular probes, fine chemicals and agrochemicals. In recent years, a significant number of novel metabolites with potent pharmacological properties has been discovered from the marine organisms. Although there are only a few marine-derived products currently on the market, several robust new compounds derived from marine natural products are now in the clinical pipeline, with more clinical development. While the marine world offers an extremely rich resource for novel compounds, it also represents a great challenge that requires inputs from various scientific areas to bring the marine chemical diversity up to its therapeutic potential.
Amphidinolide C2, New Macrolide from Marine Dinoflagellate Amphidinium Species
Authors: Kubota Takaaki , Sakuma Yusuke , Tsuda Masashi , Kobayashi Jun’ichi
Published: October 2008

A new cytotoxic 25-membered macrolide, amphidinolide C2 (1), has been isolated from marine dinoflagellate Amphidinium sp. (Y-71 strain), and the structure 1 was elucidated on the basis of spectroscopic data and chemical means.
New Alkaloids from the Mediterranean Sponge Hamigera hamigera
Authors: Hassan Wafaa , Edrada RuAngelie , Ebel Rainer , Wray Victor , Proksch Peter
Published: October 2008

The Mediterranean sponge Hamigera hamigera (family Anchinoideae) was studied since its total extract showed deterrent activity in a fish feeding assay. Eight compounds were isolated from the biologically active fractions and four of these proved to be new natural products, hamigeroxalamic acid (1), hamigeramine (2), hamigeramide (3) and hamiguanosinol (5). The structures of the new compounds were elucidated by 1D and 2D NMR spectroscopy and mass spectrometry .
Bioactive Chromodorolide Diterpenes from an Aplysillid Sponge
Authors: Rungprom Wimolpun , Chavasiri Warinthorn , Kokpol Udom , Kotze Andrew , Garson Mary   J.
Published: October 2008

The known chromodorolides A (1) and B (2), and a new derivative chromodorolide C (3) have been isolated from an Australian sponge and characterized by 1D and 2D NMR experiments. The chromodorolides exhibited significant cytotoxicity against the P388 mouse leukaemia cell line, and also showed activity against the freeliving larval stages of the parasitic nematodes Haemonchus contortus and Trichostrongylus colubriformis.
Healing and Preventive Effects of Calcium Alginate on Carbon Tetrachloride Induced Liver Injury in Rats
Authors: Khotimchenko Yuri S. , Khotimchenko Maxim Y.
Published: October 2008

The purpose of this study was to investigate the pharmacological effects of calcium alginate on carbon tetrachloride (CCL4)-induced hepatotoxicity in rats. The study included two experiments. In the first experiment the animals were given daily CCL4 through gavage for 7 days and then 10, 50, or 250 mg/kg b.w. of calcium alginate for 21 days. The increased bilirubin level, enhanced alanine and aspartate aminotransferase activity in plasma and reduced liver glycogen content induced by CCL4 were partly normalized by alginate administration in a dose-dependent manner. In addition, alginate significantly improved CCL4-induced alterations of pro-oxidant and antioxidant biochemical parameters in liver and plasma compared to those of rats administered CCL4. In the second experiment the animals were given daily 10, 50 or 250 mg/kg b.w. of calcium alginate for 21 days before 7-day administration of CCL4. Pretreatment with alginate before CCL4 administration resulted in significantly inhibited increase of the blood enzymatic activities of alanine and aspartate aminotransferases and bilirubin level in a dose-dependent manner. Also, preliminary administration of alginate prevented elevation of lipid peroxidation products and reduction of liver glutathione content in rats given CCL4. These results suggest that calcium alginate exerts healing and preventive effects on CCL4-induced hepatotoxicity in rats.
Biomedical Compounds from Marine organisms
Authors: Jha Rajeev  Kumar , Zi-rong Xu
Published: October 2008

The Ocean, which is called the ‘mother of origin of life’, is also the source of structurally unique natural products that are mainly accumulated in living organisms. Several of these compounds show pharmacological activities and are helpful for the invention and discovery of bioactive compounds, primarily for deadly diseases like cancer, acquired immuno-deficiency syndrome (AIDS), arthritis, etc., while other compounds have been developed as analgesics or to treat inflammation, etc. The lifesaving drugs are mainly found abundantly in microorganisms, algae and invertebrates, while they are scarce in vertebrates. Modern technologies have opened vast areas of research for the extraction of biomedical compounds from oceans and seas.
Antimicrobial Activity of Untenospongin B, a Metabolite from the Marine Sponge Hippospongia communis collected from the Atlantic Coast of Morocco
Authors: Rifai Saida , Fassouane Aziz Fassouane , Kijjoa Anake , Van Soest Rob
Published: October 2008

(-)-Untenospongin B isolated from the marine sponge Hippospongia communis has been tested for its antimicrobial activity against bacteria and human pathogenic fungi using agar disk method and was found to possess a broad and strong activity toward the test organisms. Its antifungal activity was further characterized by determination of the minimum inhibitory concentration (MIC) against five fungal species using broth microdilution method.
Isolation of Araguspongine M, a New Stereoisomer of an Araguspongine/Xestospongin alkaloid, and Dopamine from the Marine Sponge Neopetrosia exigua Collected in Palau
Authors: Liu Hongwei , Mishima Yuri , Fujiwara Takeshi , Nagai Hiroshi , Kitazawa Akira , Mine Yuji , Kobayashi Hisayoshi , Yao Xinsheng , Yamada Junko , Oda Taiko , Namikoshi Michio
Published: October 2008

A new stereoisomer of an araguspongine/xestospongin alkaloid, named araguspongine M (1), has been isolated together with 12 known compounds, araguspongines B (2) and D (3), dopamine, three galactosyl diacylglycerols, 24-methyl cholesterol, 5,6-dihydrocholesterol, β-sitosterol, and three 5α,8α-epidioxy sterols (11–13), from the marine sponge Neopetrosia exigua (formerly Xestospongia exigua) collected in Palau. The structure of 1 was assigned on the basis of its spectral data analysis. This is the first report on the isolation of dopamine from a marine sponge. This compound may be produced by an endosymbiotic Synechococcus-like cyanobacterium. Compounds 1–3 and 11–13 showed cytotoxicity against HL-60 at IC50’s of 5.5, 5.5, 5.9, 22.4, 9.5, and 9.6 μM, respectively. The possible biosynthesis origin of the isolated metabolites is discussed.
Sporiolides A and B, New Cytotoxic Twelve-Membered Macrolides from a Marine-Derived Fungus Cladosporium Species
Authors: Shigemori Hideyuki , Kasai Yuu , Komatsu Kazusei , Tsuda Masashi , Mikami Yuzuru , Kobayashi Jun’ichi
Published: October 2008

Two new cytotoxic twelve-membered macrolides, sporiolides A (1) and B (2), were isolated from the cultured broth of a fungus Cladosporium sp., which was separated from an Okinawan marine brown alga Actinotrichia fragilis, and the structures were elucidated by spectroscopic data. Sporiolides A (1) and B (2) exhibited cytotoxicity against murine lymphoma L1210 cells. Spoliolide A (1) showed antifungal activity against Cryptococcus neoformans and Neurospora crassa.
Parguerol and Isoparguerol Isolated from the Sea Hare, Aplysia kurodai, Induce Neurite Outgrowth in PC-12 Cells
Authors: Tsukamoto Sachiko , Yamashita Yuko , Yoshida Takushi , Ohta Tomihisa
Published: October 2008

The extract of the sea hare, Aplysia kurodai, showed neurotrophic activity toward rat pheochromocytoma (PC-12) cells. Bioassay-guided purification afforded two active compounds, which were subsequently identified to be parguerol and isoparguerol by spectroscopic analysis. It was found that both parguerol and isoparguerol induced neurite outgrowth in PC-12 cells at concentrations of 25 and 50 μM, respectively.
1-O-Sulfatobastadins-1 and -2 from Ianthella basta (Pallas).Antagonists of the yR1-FKBP12 Ca2+ Channel
Authors: Masuno Makoto N. , Hoepker Alexander C. , Pessah Isaac N. , Molinski Tadeusz F.
Published: October 2008

Two new sulfate monoesters of hemibastadins-1 and -2 were isolated from the marine sponge Ianthella basta (Pallas) from Guam. A third new compound was tentatively assigned the structure 34-O-sulfatobastadin-9. The 1-O-sulfatohemibastadins-1 and –2 were antagonists of the RyR1-FKBP12 Ca2+ channel under conditions where the known compound bastadin-5 exhibits potent agonism (EC50 2μM).
Philinopgenin A, B, and C, Three New Triterpenoid Aglycones from the Sea Cucumber Pentacta quadrangulasis
Authors: Zhang Shi-Long , Li Ling , Yi Yang-Hua , Zou Zheng-Rong , Sun Peng
Published: October 2008

Three new triterpenoid aglycones named Philinopgenin A (1), B (2), and C (3) were isolated from the acid hydrolysate of the crude glycoside mixture prepared from the whole sea cucumber Pentacta quadrangulasis Lesson. The corresponding structures were determined as 16β-acetoxyholosta-8(9), 24(25)-diene-3β-ol (1), 20, 25-epoxy-lanosta-9(11)-ene-3β-ol 18(16)–lactone (2) and 16β-acetoxyholosta-9(11), 24(25)-diene-3β-ol (3), respectively, on the basis of spectral evidence.
Amphidinolides B4 and B5, Potent Cytotoxic 26-Membered Macrolides from Dinoflagellate Amphidinium Species
Authors: Tsuda Masashi , Kariya Yuuko , Iwamoto Rie , Fukushi Eri , Kawabata Jun , Kobayashi Jun’ichi
Published: October 2008

Two new cytotoxic 26-membered macrolides, amphidinolides B4 (1) and B5 (2), have been isolated from a marine dinoflagellate Amphidinium sp. (strain Y-100), and the structures were elucidated on the basis of detailed analyses of 2D NMR data including 13C−13C correlations.
Marine Sponge Dysidea herbacea revisited: Another Brominated Diphenyl Ether
Authors: Agrawal Madhavi S. , Bowden Bruce F.
Published: October 2008

A pentabrominated phenolic diphenyl ether (1) that has not previously been reported from marine sources has been isolated from Dysidea herbacea collected at Pelorus Island, Great Barrier Reef, Australia. The structure was determined by comparison of NMR data with those of known structurally-related metabolites. NMR spectral assignments for (1) are discussed in context with those of three previously reported isomeric pentabrominated phenolic diphenyl ethers.
Cytotoxicity and Inhibition of Lymphocyte Proliferation of Fasciculatin, a Linear Furanosesterterpene Isolated from Ircinia variabilis Collected from the Atlantic Coast of Morocco
Authors: Rifai Saida , Fassouane Aziz , Pinho Paulo   M. , Kijjoa Anake , Nazareth Nair , Nascimento Maria   São José , Herz Werner
Published: October 2008

Fasciculatin, a furanosesterterpene isolated from the marine sponge Ircinia variabilis from the Atlantic Coast of Morocco, has been evaluated for its influence on a mitogen-induced proliferation of human lymphocytes and growth of human tumor cell lines.
New Cytotoxic and Antibacterial Compounds Isolated from the Sea Hare, Aplysia kurodai
Authors: Tsukamoto Sachiko , Yamashita Yuko , Ohta Tomihisa
Published: October 2008

The extract of the sea hare, Aplysia kurodai, showed cytotoxicity against HeLa cells and antibacterial activity against Staphylococcus aureus. Bioassay-guided purification afforded four active compounds, which were identified to be laurinterol, laurinterol acetate, debromolaurinterol, and debromolaurinterol acetate by spectroscopic analysis. Although the acetates were derived from laurinterol and debromolaurinterol before, this is the first isolation of the acetates from natural sources.
Secomycalolide A: A New Proteasome Inhibitor Isolated from a Marine Sponge of the Genus Mycale
Authors: Tsukamoto Sachiko , Koimaru Keiichirou , Ohta Tomihisa
Published: October 2008

A new oxazole-containing proteasome inhibitor, secomycalolide A, together with known mycalolide A and 30-hydroxymycalolide A, was isolated from a marine sponge of the genus Mycale. They showed proteasome inhibitory activities with IC50 values of 11-45 μg/mL.
Quality not Quantity: The Role of Marine Natural Products in Drug Discovery and Reverse Chemical Proteomics
Authors: Piggott Andrew M. , Karuso Peter
Published: October 2008

Reverse chemical proteomics combines affinity chromatography with phage display and promises to be a powerful new platform technology for the isolation of natural product receptors, facilitating the drug discovery process by rapidly linking biologically active small molecules to their cellular receptors and the receptors’ genes. In this paper we review chemical proteomics and reverse chemical proteomics and show how these techniques can add value to natural products research. We also report on techniques for the derivatisation of polystyrene microtitre plates with cleavable linkers and marine natural products that can be used in chemical proteomics or reverse chemical proteomics. Specifically, we have derivatised polystyrene with palau’amine and used reverse chemical proteomics to try and isolate the human receptors for this potent anticancer marine drug.
Verrucarin A Inhibition of MAP Kinase Activation in a PMA-stimulated Promyelocytic Leukemia Cell Line
Authors: Oda Taiko , Namikoshi Michio , Akano Kyoko , Kobayashi Hisayoshi , Honma Yoshio , Kasahara Tadashi
Published: October 2008

Verrucarin A is an inhibitor of protein synthesis. In this study, we examined the inhibitory action of verrucarin A on signal molecules. Verrucarin A partially inhibited the IL-8 production of a PMA-stimulated promyelocytic leukemia cell line (HL-60 cells), and the effect was related to the inhibition of NF-κB activation at noncytotoxic concentrations. Moreover, the inhibition of mitogen activated protein (MAP) kinase by verrucarin A was especially strong with p38- and JNK-phosphorylation. The findings show a new action of verrucarin A, and it is expected that this action relaxes the signal activation in response to stress.
Polycitorols A and B, New Tricyclic Alkaloids from an Ascidian
Authors: Issa Hamad H. , Tanaka Junichi , Rachmat Rachmaniar , Setiawan Andi , Trianto Agus , Higa Tatsuo
Published: October 2008

Two new tricyclic alkaloids, polycitorols A (1) and B (2) have been isolated along with the known lepadiformine (3) from a marine ascidian of the family Polycitoridae. The structures of the new compounds were elucidated by analysis of NMR data and comparison with those of 3 and other related compounds [1-5]. Compounds 1 and 2 are closely related to cylindricines A and B, lacking C-4 oxygenation found in cylindricines and having a butyl instead of a hexyl appendage. NOE experiments on compounds 1 and 2 suggested the A/B ring fusion to be cis.
Sterol Ring System Oxidation Pattern in Marine Sponges
Authors: Sarma Nittala  S. , Krishna M.   Sri Rama , Rao S.  Ramakrishna
Published: October 2008

The marine sponges (Porifera) are a unique group of sedentary organisms from which several novel natural products are reported, many of which have useful biological activities. In producing unusual sterols, they occupy a preeminent position among the various groups of organisms. The polar sterols of sponges reported as at the end of the year 2002 number about 250; their ring structure changing a hundred times. The oxidation pattern in the sterol ring system, from the point of view of biogenesis seems to be mainly of four types. Each sponge species is able to produce sterols fitting into one of the four main biogenetic pathways viz., (i) 3β-hydroxy-Δ5-sterol pathway, (ii) 3β-hydroxy-Δ7-sterol pathway, (iii) 3β-hydroxy-Δ5,7-sterol pathway, and (iv) 3α-hydroxy sterol pathway.
Withdrawn Paper: Rajeev Kumar Jha * and Xu Zi-Rong. Review: Biomedical Compounds from Marine Organisms, Marine Drugs 2004, 2, 123-146
Authors: Proksch Peter , McPhee Derek , Lin Shu-Kun
Published: October 2008

It has been brought to our attention by a member of our Editorial Board that substantial portions of this review article have been copied verbatim from earlier publications without credit.[...]
Luteophanol D, New Polyhydroxyl Metabolite from Marine Dinoflagellate Amphidinium sp.
Authors: Kubota Takaaki , Takahashi Ayako , Tsuda Masashi , Kobayashi Jun'ichi
Published: October 2008

Luteophanol D (1), a new polyhydroxyl linear carbon-chain metabolite, has been isolated from the cultured marine dinoflagellate Amphidinium sp., which was isolated from Okinawan marine acoel flatworm Pseudaphanostoma luteocoloris. The structure of 1 was elucidated by detailed analyses of 2D NMR spectra. Luteophanol D (1) possesses two tetrahydropyran rings and twenty-three hydroxyl groups on C63-linear aliphatic chain with one exo-methylene and two methyl branches.
Effects of Polybrominated Diphenol Ethers from a Marine Sponge Phyllospongia dendyi on IL-8 Production in a PMAstimulated Promyelocytic Leukemia Cell Line
Authors: Oda Taiko , Liu Hongwei , Namikoshi Michio
Published: October 2008

The effects of five polybrominated diphenol ethers from a Marine Sponge, Phyllospongia dendyi, on the relative plating efficiencies in V79 cells and the cell proliferation and IL-8 production in PMA-stimulated HL-60 cells were examined. Three compounds, possessing two phenol units, were reported to inhibit the assembly of microtubule proteins and showed the inhibition of colony formation of V79 cells and increase in IL-8 production. Interestingly, a monomethoxy compound exhibited the stronger activity than the three active compounds in both bioassays. This compound did not inhibit the assembly of microtubule proteins. A dimethoxy compound was not active in either bioassays. In these experimental conditions, the biological activities were not high, but in future, these compounds will be expected to be made stronger by structural modifications.
Farewell Address of Marine Drugs Executive Editor-in-Chief
Authors: Proksch Peter
Published: October 2008

After serving as the Executive Editor-in-Chief for Marine Drugs for almost three years I am now stepping back from this position but will remain attached to the Journal by serving on the Editorial Board.[...]
Antimicrobial and Antimycobacterial Activity of Cyclostellettamine Alkaloids from Sponge Pachychalina sp.
Authors: De Oliveira Jaine   H. H. L. , Seleghim Mirna   H. R. , Timm Christoph , Grube Achim , Köck Matthias , Nascimento Gislene  G.F. , Martins Ana   Claudia T. , Silva Elissa   G. O. , De Souza Ana   Olívia , Minarini Paulo   R. R. , Galetti Fabio   C. S. , Silva Célio   L. , Hajdu Eduardo , Berlinck Roberto   G. S.
Published: October 2008

Cyclostellettamines A – F (1 – 6) isolated from the sponge Pachychalina sp. and cyclostellettamines G - I, K and L (7 – 11) obtained by synthesis were evaluated in bioassays of antimicrobial activity against susceptible and antibiotic-resistant Staphylococcus aureus, Pseudomonas aeruginosa and antibiotic-susceptible Escherichia coli and Candida albicans, as well as in antimycobacterial activity against Mycobacterium tuberculosis H37Rv bioassays. The results obtained indicated that cyclostellettamines display different antimicrobial activity depending on the alkyl-chain size, suggesting that, if a mechanism-of action is implied, it is dependent on the distance between the two pyridinium moieties of cyclostellettamines.
Manzamenones Inhibit T-Cell Protein Tyrosine Phosphatase
Authors: Wakuda Yusuke , Kubota Takaaki , Shima Hiroshi , Okada Tadashi , Mitsuhashi Shinya , Aoki Naohito , Kikuchi Kunimi , Kobayashi Jun'ichi
Published: October 2008

Manzamenones A~C (1~3) and E~F (5~6), unique oxylipin metabolites isolated from a marine sponge Plakortis sp., have been found to exhibit inhibitory activity against Tcell protein tyrosine phosphatase (TCPTP). The inhibitory activity of 2 and 5 against TCPTP was 4 times more potent than that against protein tyrosine phosphatase-1B (PTP1B).
Effects of Lissoclibadins and Lissoclinotoxins, Isolated from a Tropical Ascidian Lissoclinum cf. badium, on IL-8 production in a PMA-stimulated Promyelocytic Leukemia Cell Line
Authors: Oda Taiko , Fujiwara Takeshi , Liu Hongwei , Ukai Kazuyo , Mangindaan Remy E. P. , Mochizuki Masataka , Namikoshi Michio
Published: October 2008

The effects of seven compounds 1-7, isolated from a tropical ascidian Lissoclinum cf. badium, on IL-8 production in PMA-stimulated HL-60 cells were examined. Lissoclibadins 2 (2) and 3 (3) and lissoclinotoxin F (5) increased the IL-8 production in a dose-dependent manner. Compounds 2 and 5 are structural isomers possessing dimeric structures of trans and cis-orientations, respectively, and showed a very similar activity on the induction of IL-8 levels. Compound 3 and lissoclinotoxin E (4) are also structural isomers having dimeric trans and cis-structures, respectively, but 4 did not induce the IL-8 production. Lissoclibadin 1 (1, trimeric compound) and two monomeric compounds (6 and 7) did not increase the IL-8 level. Therefore, the differences in their structures remarkably affected the IL-8 production activity, the inhibition of cell proliferation, and the survival of HL-60 cells. Lissoclibadin 2 was the most interesting compound of the seven metabolites tested in this study.
Effects of bistheonellide A, an Actin-polymerization Inhibitor, on Chinese Hamster V79 Cells and on IL-8 Production in PMA-stimulated HL-60 Cells
Authors: Oda Taiko , Xu Jinzhong , Fujita Ayako , Mochizuki Masataka , Namikoshi Michio
Published: October 2008

Bioassay-guided isolation from the ethanol extract of a marine sponge Theonella sp. collected in Palau yielded bistheonellide A, which strongly inhibited the colony formation of Chinese hamster V79 cells (EC50 = 6.8 nM). Bistheonellide A is an actinpolymerization inhibitor and was suggested to control cytokine production. Therefore, we attempted to detect an effect of this compound on IL-8 production in PMA-stimulated HL- 60 cells. Interestingly, bistheonellide A did not modulate the production of IL-8 under cytotoxic concentrations as determined by LDH analysis. Although the correlation between the inhibition of microtubule assembly and the stimulation of IL-8 production has been observed for several compounds, the polymerization of actin was not related to an IL-8 production in the case of bistheonellide A. It will be suggested that the actin polymerization is not involved in the IL-8 production system.
Potent Skin Cancer Chemopreventing Activity of Some Novel Semi-synthetic Cembranoids from Marine Sources
Authors: Fahmy Hesham , Zjawiony Jordan K. , Konoshima Takao , Tokuda Harukuni , Khan Shabana , Khalifa Sherief
Published: October 2008

In the course of our continuing research in development and evaluation of novel skin cancer chemopreventive agents from marine sources, five semi-synthetic cembranoids derived from the marine natural product sarcophine, isolated from the soft coral Sarcophyton glaucum, were synthesized and shown to exhibit a remarkable chemopreventive activity in the in-vitro Epstein Barr Virus Early Antigen (EBV-EA) activation assay. These compounds were assayed in vivo using the two-stage carcinogenesis test of mouse skin tumors induced by 7,12-dimethylbenz[a]anthracene (DMBA) as an initiator, and 12-O-tetradecanoylphorbol-13-acetate (TPA) as a promoter by topical administration. They showed potent inhibition of both percentage incidence of skin tumor as well asthe multiplicity of skin tumors per mouse compared to untreated controls.Semi-synthetic Cembranoids from Marine Sources
Marine Toxins Targeting Ion Channels
Authors: Arias Hugo R.
Published: October 2008

This introductory minireview points out the importance of ion channels for cell communication. The basic concepts on the structure and function of ion channels triggered by membrane voltage changes, the so-called voltage-gated ion channels (VGICs), as well as those activated by neurotransmitters, the so-called ligand-gated ion channel (LGICs), are introduced. Among the most important VGIC superfamiles, we can name the voltage-gated Na+ (NaV), Ca2+ (CaV), and K+ (KV) channels. Among the most important LGIC super families, we can include the Cys-loop or nicotinicoid, the glutamate-activated (GluR), and the ATP-activated (P2XnR) receptor superfamilies. Ion channels are transmembrane proteins that allow the passage of different ions in a specific or unspecific manner. For instance, the activation of NaV, CaV, or KV channels opens a pore that is specific for Na+, Ca2+, or K+, respectively. On the other hand, the activation of certain LGICs such as nicotinic acetylcholine receptors, GluRs, and P2XnRs allows the passage of cations (e.g., Na+, K+, and/or Ca2+), whereas the activation of other LGICs such as type A γ-butyric acid and glycine receptors allows the passage of anions (e.g., Cl− and/or HCO3−). In this regard, the activation of NaV and CaV as well as ligand-gated cation channels produce membrane depolarization, which finally leads to stimulatory effects in the cell, whereas the activation of KV as well as ligand-gated anion channels induce membrane hyperpolarization that finally leads to inhibitory effects in the cell. The importance of these ion channel superfamilies is emphasized by considering their physiological functions throughout the body as well as their pathophysiological implicance in several neuronal diseases. In this regard, natural molecules, and especially marine toxins, can be potentially used as modulators (e.g., inhibitors or prolongers) of ion channel functions to treat or to alleviate a specific ion channel-linked disease (e.g., channelopaties).
Cnidarian Toxins Acting on Voltage-Gated Ion Channels
Authors: Messerli Shanta M. , Greenberg Robert M.
Published: October 2008

Voltage-gated ion channels generate electrical activity in excitable cells. As such, they are essential components of neuromuscular and neuronal systems, and are targeted by toxins from a wide variety of phyla, including the cnidarians. Here, we review cnidarian toxins known to target voltage-gated ion channels, the specific channel types targeted, and, where known, the sites of action of cnidarian toxins on different channels.
Ciguatoxins: Cyclic Polyether Modulators of Voltage-gated Iion Channel Function
Authors: Nicholson Graham M. , Lewis Richard J.
Published: October 2008

Ciguatoxins are cyclic polyether toxins, derived from marine dinoflagellates, which are responsible for the symptoms of ciguatera poisoning. Ingestion of tropical and subtropical fin fish contaminated by ciguatoxins results in an illness characterised by neurological, cardiovascular and gastrointestinal disorders. The pharmacology of ciguatoxins is characterised by their ability to cause persistent activation of voltage-gated sodium channels, to increase neuronal excitability and neurotransmitter release, to impair synaptic vesicle recycling, and to cause cell swelling. It is these effects, in combination with an action to block voltage-gated potassium channels at high doses, which are believed to underlie the complex of symptoms associated with ciguatera. This review examines the sources, structures and pharmacology of ciguatoxins. In particular, attention is placed on their cellular modes of actions to modulate voltage-gated ion channels and other Na+-dependent mechanisms in numerous cell types and to current approaches for detection and treatment of ciguatera.
Conotoxins: Therapeutic Potential and Application
Authors: Layer Richard T. , McIntosh J. Michael
Published: October 2008

The pharmacological variety of conotoxins, diverse peptides found in the venoms of marine cone snails, is well recognized. Venoms from each of the estimated 500 species of cone snails contain 50 to 200 distinct biologically active peptides. Most conotoxins characterized to date target receptors and ion channels of excitable tissues, such as ligandgated nicotinic acetylcholine, N-methyl-D-aspartate, and type 3 serotonin receptors, as well as voltage-gated calcium, sodium, and potassium channels, and G-protein-coupled receptors including α-adrenergic, neurotensin, and vasopressin receptors, and the norepinephrine transporter. Several conotoxins have shown promise in preclinical models of pain, convulsive disorders, stroke, neuromuscular block, and cardioprotection. The pharmacological selectivity of the conotoxins, coupled with the safety and efficacy demonstrated in preclinical models, has led to their investigation as human therapeutic agents. In the following review, we will survey the pharmacology and therapeutic rationale of those conotoxins with potential clinical application, and discuss the unique challenges that each will face in the course of their transition from venom component to human therapeutic.
The Structural Basis and Functional Consequences of Interactions Between Tetrodotoxin and Voltage-Gated Sodium Channels
Authors: Geffeney Shana L. , Ruben C.
Published: October 2008

Tetrodotoxin (TTX) is a highly specific blocker of voltage-gated sodium channels. The dissociation constant of block varies with different channel isoforms. Until recently, channel resistance was thought to be primarily imparted by amino acid substitutions at a single position in domain I. Recent work reveals a novel site for tetrodotoxin resistance in the P-region of domain IV.
Marine Toxins That Target Voltage-gated Sodium Channels
Authors: Al-Sabi Ahmed , McArthur Jeff , Ostroumov Vitaly , French Robert J.
Published: October 2008

Eukaryotic, voltage-gated sodium (NaV) channels are large membrane proteins which underlie generation and propagation of rapid electrical signals in nerve, muscle and heart. Nine different NaV receptor sites, for natural ligands and/or drugs, have been identified, based on functional analyses and site-directed mutagenesis. In the marine ecosystem, numerous toxins have evolved to disrupt NaV channel function, either by inhibition of current flow through the channels, or by modifying the activation and inactivation gating processes by which the channels open and close. These toxins function in their native environment as offensive or defensive weapons in prey capture or deterrence of predators. In composition, they range from organic molecules of varying size and complexity to peptides consisting of ~10-70 amino acids. We review the variety of known NaV-targeted marine toxins, outlining, where known, their sites of interaction with the channel protein and their functional effects. In a number of cases, these natural ligands have the potential applications as drugs in clinical settings, or as models for drug development.
ω-Conotoxins GVIA, MVIIA and CVID: SAR and Clinical Potential
Authors: Schroeder Christina I. , Lewis Richard J.
Published: October 2008

Highly selective N-type voltage-gated calcium (CaV) channel inhibitors from cone snail venom (the ω-conotoxins) have emerged as a new class of therapeutics for the treatment of chronic and neuropathic pain. Earlier in 2005, Prialt (Elan) or synthetic ω-conotoxin MVIIA, was the first ω-conotoxin to be approved by Food and Drug Administration for human use. This review compares the action of three ω-conotoxins, GVIA, MVIIA and CVID, describing their structure-activity relationships and potential as leads for the design of improved N-type therapeutics that are more useful in the treatment of chronic pain.
New Conotoxin SO-3 Targeting N-type Voltage-Sensitive Calcium Channels
Authors: Wen Lei , Yang Sheng , Zhou Wenxia , Zhang Yongxiang , Huang Peitang
Published: October 2008

Selective blockers of the N-type voltage-sensitive calcium (CaV) channels are useful in the management of severe chronic pain. Here, the structure and function characteristics of a novel N-type CaV channel blocker, SO-3, are reviewed. SO-3 is a 25-amino acid conopeptide originally derived from the venom of Conus striatus, and contains the same 4-loop, 6-cysteine framework (C-C-CC-C-C) as O-superfamily conotoxins. The synthetic SO-3 has high analgesic activity similar to ω-conotoxin MVIIA (MVIIA), a selective N-type CaV channel blocker approved in the USA and Europe for the alleviation of persistent pain states. In electrophysiological studies, SO-3 shows more selectivity towards the N-type CaV channels than MVIIA. The dissimilarity between SO-3 and MVIIA in the primary and tertiary structures is further discussed in an attempt to illustrate the difference in selectivity of SO-3 and MVIIA towards N-type CaV channels.
The Chemistry and Pharmacology of Anatoxin-a and Related Homotropanes with respect to Nicotinic Acetylcholine Receptors
Authors: Wonnacott Susan , Gallagher Timothy
Published: October 2008

This chapter covers the chemistry and nicotinic pharmacology of naturally occurring homotropane alkaloids, with an emphasis of anatoxin-a. In addition to anatoxin-a, homoanatoxin and pinnamine, as well as the major classes of synthetic derivatives of anatoxin-a including UB-165, are discussed.
The Nemertine Toxin Anabaseine and Its Derivative DMXBA (GTS-21): Chemical and Pharmacological Properties
Authors: Kem William , Soti Ferenc , Wildeboer Kristin , LeFrancois Susan , MacDougall Kelly , Wei Dong-Qing , Chou Kuo-Chen , Arias Hugo R.
Published: October 2008

Nemertines are a phylum of carnivorous marine worms that possess a variety of alkaloidal, peptidic or proteinaceous toxins that serve as chemical defenses against potential predators. The hoplonemertines additionally envenomate their prey with a mixture of proboscis alkaloids delivered with the help of a calcareous stylet that punctures the skin of the victim. Anabaseine, the first of these alkaloids to be identified, stimulates a wide variety of animal nicotinic acetylcholine receptors (AChRs), especially the neuromuscular [e.g., α12β1γδ (embryogenic) or α12β1γε (adult)] and α7 AChRs that are inhibited by the snake peptide α-bungarotoxin. A synthetic derivative, 3-(2,4-Dimethoxybenzylidene)-Anabaseine (DMXBA; also called GTS-21), improves memory in experimental animals and humans and is currently in clinical trials to determine whether it can ameliorate cognitive problems associated with schizophrenia. Here we summarize present knowledge concerning the chemistry and mechanisms of action of these two substances (anabaseine and DMXBA) on AChRs, especially those found in the mammalian brain.
A Possible Mechanism of Action of the Chemopreventive Effects of Sarcotriol on Skin Tumor Development in CD-1 Mice
Authors: Kundoor Vipra , Zhang Xiaoying , Khalifa Sherief , Fahmy Hesham , Dwivedi Chandradhar
Published: October 2008

Sarcophine derivatives have been suggested to be chemopreventive in nature. One of its derivatives, Sarcotriol (ST), was investigated to study the skin cancer chemopreventive effects in female CD-1 mice. Three groups (control, promotion, initiation) of 30 female CD-1 mice each were taken. Carcinogenesis was initiated with 7, 12-dimethylbenz (a) anthracene (DMBA) and promoted with 12-O-tetradecanoylphorbol-13-acetate (TPA). One hour before treating with DMBA (200 nmol/100 μl acetone), control and promotion groups were treated with acetone (100 μl) and initiation group with ST (30μg/100μl of acetone). Beginning one week after initiation with DMBA, control and initiation groups were treated with acetone and promotion group with ST (30μg/100μl of acetone), one hour before treating with TPA (5 nmol/100 μl acetone). This was carried out twice a week for the next 20 weeks. The effects of ST on 3H-thymidine incorporation in epidermal DNA, the possible role of apoptotic proteins and COX-2 involved in the prevention of skin tumor development of CD-1 mice were investigated. Tumor incidence and multiplicity was found to be 100%, 73%, 100% and 8.2, 4.8, 9.7 in control, promotion and initiation groups respectively. ST treatment resulted in a significant (P < 0.05) inhibition in the incorporation of 3H-thymidine in epidermal DNA. The promotion group showed higher levels of caspase-3, -8 and –9 compared to the control. COX-2 expression was significantly lower (P < 0.05) in the promotion group as compared to the control. No significant difference in caspase-3, -8, -9 and COX-2 levels were observed in the initiation group compared to control. Together, this study confirms the chemopreventive effects of ST, and for the first time identifies the stage of carcinogenesis at which ST exerts its chemopreventive effect, and elucidates the mechanism possibly by inducing apoptosis and decreasing the COX-2 levels, contributing to its overall cancer chemopreventive effects in the mouse skin cancer model.
Synthesis of Acetylhomoagmatine
Authors: Castellanos Leonardo , Duque Carmenza , Rodríguez Jaime , Jiménez Carlos
Published: October 2008

The first total synthesis of acetylhomoagmatine, a natural product isolated form the methanolic extracts from the sponge Cliona celata, is performed in four steps in a very high yield.
Natural Abundance 14C Content of Dibutyl Phthalate (DBP) from Three Marine Algae
Authors: Namikoshi Michio , Fujiwara Takeshi , Nishikawa Teruaki , Ukai Kazuyo
Published: October 2008

Analysis of the natural abundance 14C content of dibutyl phthalate (DBP) from two edible brown algae, Undaria pinnatifida and Laminaria japonica, and a green alga, Ulva sp., revealed that the DBP was naturally produced. The natural abundance 14C content of di-(2-ethylhexyl) phthalate (DEHP) obtained from the same algae was about 50-80% of the standard sample and the 14C content of the petrochemical (industrial) products of DBP and DEHP were below the detection limit.
Effects of Melophlins on Colony Formation of Chinese Hamster V79 Cells and IL-8 Production in PMA-stimulated HL-60 Cells
Authors: Oda Taiko , Fujita Ayako , Xu Jinzhong , Mochizuki Masataka , Ukai Kazuyo , Namikoshi Michio
Published: October 2008

We have recently isolated four new melophlins P (1), Q (2), R (3), and S (4) together with seven known melophlins A (5), D (6), E (7), G (8), H (9), I (10), and O (11) from two marine sponges of the genus Melophlus collected in Palau. In this study, the influence of these compounds on the colony formation of Chinese hamster V79 cells and the production of IL-8 in PMA-stimulated HL-60 cells were examined. These 11 compounds did not show any effect on IL-8 production. The EC50 values of compounds 2, 3, 4, 5, 7, 9, 10, and 11 against V79 cells were 44.0, 13.3, 16.7, 27.2, 19.8, 8.5, 23.1, and 9.6 μM, respectively. The linear-chain-type compounds (1, 6, and 8) were not active against V79 cells at 50 μM. Although the growth inhibitory activity of these melophlins was not remarkable, some structure-activity relationships of these compounds against V79 and murine leukemia L1210 cells were observed.
Anticancer Activity Evaluation of Kuanoniamines A and C Isolated from the Marine Sponge Oceanapia sagittaria, Collected from the Gulf of Thailand
Authors: Kijjoa Anake , Wattanadilok Rawiwan , Herz Werner , Campos Nair , Nascimento Maria São José , Pinto Madalena
Published: October 2008

The pyridoacridine alkaloids kuanoniamines A and C were isolated together with 24α-methylcholestanol, p-hydroxybenzaldehyde, p-hydroxybenzoic acid, phenylacetic acid and 3-formylindole from the ethyl acetate extract of the marine sponge Oceanapia sagittaria (Sollas), collected from the Gulf of Thailand. Kuanoniamines A and C were evaluated for their effect on the growth of five human tumour and a non-tumour cell lines, as well as on the proliferation of human lymphocytes. Kuanoniamine A was found to be a potent growth inhibitor of all the tumour and a non-tumour cell lines while kuanoniamine C was less potent but showed high selectivity toward the estrogen dependent (ER+) breast cancer cell line. Kuanoniamine A has shown to be a more potent inhibitor of DNA synthesis than kuanoniamine C. Kuanoniamine A was also found to cause an extensive reduction of the MCF-7 cells in G2/M phase as well as an increase in the apoptotic cells.
Large-Scale Biotechnological Production of the Antileukemic Marine Natural Product Sorbicillactone A
Authors: Bringmann Gerhard , Gulder Tobias A. M. , Lang Gerhard , Schmitt Stefanie , Stöhr Rüdiger , Wiese Jutta , Nagel Kerstin , Imhoff Johannes F.
Published: October 2008

In the search for novel bioactive compounds from sponge-derived microorganisms, we have recently identified two structurally and biosynthetically unprecedented fungal metabolites, the novel-type alkaloids sorbicillactone A and sorbicillactone B. Sorbicillactone A is active against leukemia cells without showing notable cytotoxicity. Therefore, we have developed an efficient process for its biotechnological production and isolation on a large scale supplying sufficient material for the ongoing preclinical investigations and structure-activity relationship (SAR) studies.
Monoindole Alkaloids from a Marine Sponge Spongosorites sp.
Authors: Bao Baoquan , Zhang Ping , Lee Yoonmi , Hong Jongki , Lee Chong-O. , Jung Jee H.
Published: October 2008

Seven (1−7) monoindole derivatives were isolated from the MeOH extract of a marine sponge Spongosorites sp. by bioactivity-guided fractionation. The planar structures were established on the basis of NMR and MS spectroscopic analyses. Compounds 1−5 are unique indole pyruvic acid derivatives. Compounds 1−2 and 4−6 are isolated for the first time from a natural source although they were previously reported as synthetic intermediates. Compound 3 was defined as a new compound. Co-occurring bisindoles such as hamacanthins and topsentins might be biosynthesized by condensation of two units of these compounds. The compounds were tested for cytotoxicity against a panel of five human solid tumor cell lines, and compound 7 displayed weak activity.