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Mar. Drugs, Volume 2, Issue 1 (March 2004), Pages 1-54

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Research

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Open AccessArticle An Improved Synthesis of 7, 8-Epoxy-1,3,11-cembratriene-15R(α), 16-diol, a Cembranoid of Marine Origin with a Potent Cancer Chemopreventive Activity
Mar. Drugs 2004, 2(1), 1-7; doi:10.3390/md201001
Received: 29 October 2003 / Accepted: 20 November 2003 / Published: 25 February 2004
Cited by 17 | PDF Full-text (135 KB) | HTML Full-text | XML Full-text
Abstract
An effective method for the synthesis of 7,8-epoxy-1,3,11-cembratriene-15R(α), 16-diol and its in vitro Epstein-Barr Virus Early Antigen (EBV-EA) Activation Chemopreventive Assay are reported. This semisynthetic product is a new cembranoid with a potent tumor inhibitory activity that is expected to be a lead
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An effective method for the synthesis of 7,8-epoxy-1,3,11-cembratriene-15R(α), 16-diol and its in vitro Epstein-Barr Virus Early Antigen (EBV-EA) Activation Chemopreventive Assay are reported. This semisynthetic product is a new cembranoid with a potent tumor inhibitory activity that is expected to be a lead compound for a new class of chemopreventive agents of marine origin. Full article
Open AccessArticle Antifungal Activity of (+)-Curcuphenol, a Metabolite from the Marine Sponge Didiscus oxeata
Mar. Drugs 2004, 2(1), 8-13; doi:10.3390/md201008
Received: 17 October 2003 / Accepted: 26 November 2003 / Published: 25 February 2004
Cited by 6 | PDF Full-text (35 KB) | HTML Full-text | XML Full-text
Abstract The antifungal activity of the sesquiterpenoids (+)-curcuphenol and (+)-curcudiol isolated from the Caribbean sponge Didiscus oxeata was evaluated against several filamentous fungi. Full article
Open AccessArticle Identification and Biological Characterization of Angiogenic and Tumor Growth Inhibitors derived from Sinica cetorhinus maximum Cartilage
Mar. Drugs 2004, 2(1), 30-38; doi:10.3390/md201030
Received: 25 March 2003 / Accepted: 31 January 2004 / Published: 25 February 2004
Cited by 1 | PDF Full-text (123 KB) | HTML Full-text | XML Full-text
Abstract
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
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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. Full article
Open AccessArticle Bioactive Alkaloids from the Sea: A Review
Mar. Drugs 2004, 2(1), 39-54; doi:10.3390/md201039
Received: 29 October 2003 / Accepted: 31 January 2004 / Published: 25 February 2004
Cited by 35 | PDF Full-text (329 KB) | HTML Full-text | XML Full-text
Abstract
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.
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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. Full article

Review

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Open AccessReview New Marine Derived Anticancer Therapeutics ─ A Journey from the Sea to Clinical Trials
Mar. Drugs 2004, 2(1), 14-29; doi:10.3390/md201014
Received: 12 November 2003 / Accepted: 23 January 2004 / Published: 25 February 2004
Cited by 44 | PDF Full-text (215 KB) | HTML Full-text | XML Full-text
Abstract
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
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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. Full article

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