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Mar. Drugs, Volume 7, Issue 1 (March 2009) – 6 articles , Pages 1-70

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215 KiB  
Article
Phase II Randomized Study of Plitidepsin (Aplidin), Alone or in Association with L-carnitine, in Patients with Unresectable Advanced Renal Cell Carcinoma
by Patrick Schöffski, Vincente Guillem, Margarita Garcia, Fernando Rivera, Josep Tabernero, Martin Cullell, Jose Antonio Lopez-Martin, Patricia Pollard, Herlinde Dumez, Xavier Garcia del Muro and Luis Paz-Ares
Mar. Drugs 2009, 7(1), 57-70; https://doi.org/10.3390/md7010057 - 05 Mar 2009
Cited by 35 | Viewed by 11493
Abstract
This randomized phase II study evaluated two schedules of the marine compound Plitidepsin with or without co-administration of L-carnitine in patients with renal cell carcinoma. Patients had adequate performance status and organ function.The primary endpoint was the rate of disease control (no progression) [...] Read more.
This randomized phase II study evaluated two schedules of the marine compound Plitidepsin with or without co-administration of L-carnitine in patients with renal cell carcinoma. Patients had adequate performance status and organ function.The primary endpoint was the rate of disease control (no progression) at 12 weeks (RECIST).Other endpoints included the response rate and time dependent efficacy measures.The trial also assessed the efficacy of L-carnitine to prevent Plitidepsin-related toxicity. The two regimes given as 24 hour infusion every two weeks showed hints of antitumoral activity. Disease control at 12 weeks was 15.8% in Arm A (5mg/m2, no L-carnitine) and 11,1% in Arm B (7mg/m2 with L-carnitine). Two partial responses were observed in Arm A (19 patients), none in Arm B (20 patients). Both schedules had the same progression-free interval (2.1 months).The median overall survival was 7.0 and 7.6 months.The safety profile was similar in both arms of the trial and adverse events were mainly mild to moderate (NCI CTC version 2.0). Increasing the dose to 7mg/m2 did not increase the treatment efficacy but the incidence of transaminase and CPK elevations and serious AEs. Coadministration of L-carnitine did not prevent muscular toxicity or CPK-elevation associated with Plitidepsin. Full article
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485 KiB  
Article
The Carotenogenesis Pathway via the Isoprenoid-β-carotene Interference Approach in a New Strain of Dunaliella salina Isolated from Baja California Mexico
by J. Paniagua-Michel, Willian Capa-Robles, Jorge Olmos-Soto and Luis Enrique Gutierrez-Millan
Mar. Drugs 2009, 7(1), 45-56; https://doi.org/10.3390/md7010045 - 10 Feb 2009
Cited by 29 | Viewed by 14173
Abstract
D. salina is one of the recognized natural sources to produce β-carotene, and an useful model for studying the role of inhibitors and enhancers of carotenogenesis. However there is little information in D. salina regarding whether the isoprenoid substrate can be influenced [...] Read more.
D. salina is one of the recognized natural sources to produce β-carotene, and an useful model for studying the role of inhibitors and enhancers of carotenogenesis. However there is little information in D. salina regarding whether the isoprenoid substrate can be influenced by stress factors (carotenogenic) or selective inhibitors which in turn may further contribute to elucidate the early steps of carotenogenesis and biosynthesis of β-carotene. In this study,Dunaliella salina (BC02) isolated from La Salina BC Mexico, was subjected to the method of isoprenoids-β-carotene interference in order to promote the interruption or accumulation of the programmed biosynthesis of carotenoids. When Carotenogenic and non-carotenogenic cells of D. salina BC02 were grown under photoautotrophicgrowth conditions in the presence of 200 µM fosmidomycin, carotenogenesis and the synthesis of β-carotene were interrupted after two days in cultured D. salina cells. This result is an indirect consequence of the inhibition of the synthesis of isoprenoids and activity of the recombinant DXR enzyme thereby preventing the conversionof 1-deoxy-D-xylulose 5-phosphate (DXP) to 2-C-methyl-D-erythritol (MEP) and consequently interrupts the early steps of carotenogenesis in D. salina. The effect at the level of proteins and RNA was not evident. Mevinolin treated D. salina cells exhibited carotenogenesis and β-carotene levels very similar to those of control cell cultures indicating that mevinolin not pursued any indirect action in the biosynthesis of isoprenoids and had no effect at the level of the HMG-CoA reductase, the key enzyme of the Ac/MVA pathway. Full article
(This article belongs to the Special Issue Bioactive Compounds from Marine Microorganisms)
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94 KiB  
Editorial
Special Issue on Marine Toxins
by Alejandro M.S. Mayer
Mar. Drugs 2009, 7(1), 19-23; https://doi.org/10.3390/md7010019 - 29 Jan 2009
Cited by 2 | Viewed by 9010
Abstract
The special issue on Marine Toxins of the Open Access journal Marine Drugs (ISSN 1660-3397, https://www.mdpi.com/journal/marinedrugs/) presents twenty four contributions which were received from distinguished investigators currently working in Canada, China, France, Germany, Iran, Italy, Japan, Portugal, Russian Federation, Slovenia, South Africa, Spain, [...] Read more.
The special issue on Marine Toxins of the Open Access journal Marine Drugs (ISSN 1660-3397, https://www.mdpi.com/journal/marinedrugs/) presents twenty four contributions which were received from distinguished investigators currently working in Canada, China, France, Germany, Iran, Italy, Japan, Portugal, Russian Federation, Slovenia, South Africa, Spain, and the United States. The reviews and research articles provide the interested reader with a global view of marine toxins research during 2007-2008. [...] Full article
(This article belongs to the Special Issue Marine Toxins)
278 KiB  
Article
Protective Effects of Squid Ink Extract Towards Hemopoietic Injuries Induced by Cyclophosphamine
by Jie-Ping Zhong, Guang Wang, Jiang-Hua Shang, Jiang-Qiu Pan, Kun Li, Yan Huang and Hua-Zhong Liu
Mar. Drugs 2009, 7(1), 9-18; https://doi.org/10.3390/md7010009 - 14 Jan 2009
Cited by 43 | Viewed by 13029
Abstract
To investigate the protective effects of squid ink in chemotherapy, BALB/c mice were used as animal models of injuries induced by cyclophosphamine, a well known chemotherapeutic drug. The mice were randomly divided into five groups with the same number of males and females [...] Read more.
To investigate the protective effects of squid ink in chemotherapy, BALB/c mice were used as animal models of injuries induced by cyclophosphamine, a well known chemotherapeutic drug. The mice were randomly divided into five groups with the same number of males and females in each group. At the end of the experiment, animals were sacrificed to investigate organ indexes and antioxidant ability of the spleen, peripheral blood profile and quantities of bone marrow nucleated cells. Results showed that the hemopoietic function of mice was injured by cyclophosphamine, as indicated by decreases of contents of erythrocytes, leukocytes, hemoglobin and bone marrow nucleated cells (P<0.01), while platelets were not affected (P>0.05), as well as modification of organ indexes (P<0.05) and spleen antioxidant ability (P<0.05 or P<0.01), whereas sepia extract markedly increased the levels of erythrocytes, leukocytes, hemoglobin and bone marrow nucleated cells (P<0.01), but not platelets (P>0.05), and reversed the effects of cyclophosphamine on organ indexes and antioxidant ability of spleen (P<0.01 or P<0.05). In addition, squid ink extract did not change marrow hemopoiesis but improved the antioxidant ability of spleen in the animals. The data suggest that squid ink extract can protect the hemopoietic system from chemotherapeutic injury and could be employed to develop cell-protective drugs for use in clinical treatment of tumours. Full article
(This article belongs to the Special Issue Marine Drugs Studies in China)
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542 KiB  
Article
Actinomycetes for Marine Drug Discovery Isolated from Mangrove Soils and Plants in China
by Kui Hong, An-Hui Gao, Qing-Yi Xie, Hao Gao Gao, Ling Zhuang, Hai-Peng Lin, Hai-Ping Yu, Jia Li, Xin-Sheng Yao, Michael Goodfellow and Ji-Sheng Ruan
Mar. Drugs 2009, 7(1), 24-44; https://doi.org/10.3390/md7010024 - 03 Jan 2009
Cited by 279 | Viewed by 23529 | Correction
Abstract
The mangrove ecosystem is a largely unexplored source for actinomycetes with the potential to produce biologically active secondary metabolites. Consequently, we set out to isolate, characterize and screen actinomycetes from soil and plant material collected from eight mangrove sites in China. Over 2,000 [...] Read more.
The mangrove ecosystem is a largely unexplored source for actinomycetes with the potential to produce biologically active secondary metabolites. Consequently, we set out to isolate, characterize and screen actinomycetes from soil and plant material collected from eight mangrove sites in China. Over 2,000 actinomycetes were isolated and of these approximately 20%, 5%, and 10% inhibited the growth of Human Colon Tumor 116 cells, Candida albicans and Staphylococcus aureus, respectively, while 3% inhibited protein tyrosine phosphatase 1B (PTP1B), a protein related to diabetes. In addition, nine isolates inhibited aurora kinase A, an anti-cancer related protein, and three inhibited caspase 3, a protein related to neurodegenerative diseases. Representative bioactive isolates were characterized using genotypic and phenotypic procedures and classified to thirteen genera, notably to the genera Micromonospora and Streptomyces. Actinomycetes showing cytotoxic activity were assigned to seven genera whereas only Micromonospora and Streptomyces strains showed anti-PTP1B activity. We conclude that actinomycetes isolated from mangrove habitats are a potentially rich source for the discovery of anti-infection and anti-tumor compounds, and of agents for treating neurodegenerative diseases and diabetes. Full article
(This article belongs to the Special Issue Marine Drugs Studies in China)
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183 KiB  
Article
Cytotoxic Aaptamines from Malaysian Aaptos aaptos
by Khozirah Shaari, Kee Cheng Ling, Zalilawati Mat Rashid, Tan Pei Jean, Faridah Abas, Salahudin Mohd. Raof, Zurina Zainal, Nordin Hj. Lajis, Habsah Mohamad and Abdul Manaf Ali
Mar. Drugs 2009, 7(1), 1-8; https://doi.org/10.3390/md7010001 - 28 Dec 2008
Cited by 44 | Viewed by 11760
Abstract
In a preliminary screen, Aaptos aaptos showed significant cytotoxic activity towards a panel of cell lines and was thus subjected to bioassay-guided isolation of the bioactive constituents. In addition to the known aaptamine, two new derivatives of the alkaloid were isolated from the [...] Read more.
In a preliminary screen, Aaptos aaptos showed significant cytotoxic activity towards a panel of cell lines and was thus subjected to bioassay-guided isolation of the bioactive constituents. In addition to the known aaptamine, two new derivatives of the alkaloid were isolated from the bioactive chloroform fraction of the crude methanolic extract. Detailed analysis by NMR and mass spectroscopy enabled their identification to be 3-(phenethylamino)demethyl(oxy)aaptamine and 3-(isopentylamino)demethyl(oxy) aaptamine. The cytotoxic activities of the three alkaloids were further evaluated against CEM-SS cells. Full article
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