Marine Drugs

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Open AccessArticle

Synthesis and Neuroprotective Action of Xyloketal Derivatives in Parkinson’s Disease Models

by Shichang Li, Cunzhou Shen, Wenyuan Guo, Xuefei Zhang, Shixin Liu, Fengyin Liang, Zhongliang Xu, Zhong Pei, Huacan Song, Liqin Qiu, Yongcheng Lin and Jiyan Pang

Mar. Drugs 2013, 11(12), 5159-5189; https://doi.org/10.3390/md11125159 - 18 Dec 2013

Cited by 36 | Viewed by 8636

Abstract

Parkinson’s disease (PD) is the second most common neurodegenerative disease affecting people over age 55. Oxidative stress actively participates in the dopaminergic (DA) neuron degeneration of PD. Xyloketals are a series of natural compounds from marine mangrove fungus strain No. 2508 that have [...] Read more.

Parkinson’s disease (PD) is the second most common neurodegenerative disease affecting people over age 55. Oxidative stress actively participates in the dopaminergic (DA) neuron degeneration of PD. Xyloketals are a series of natural compounds from marine mangrove fungus strain No. 2508 that have been reported to protect against neurotoxicity through their antioxidant properties. However, their protection versus 1-methyl-4-phenylpyridinium (MPP+)-induced neurotoxicity is only modest, and appropriate structural modifications are necessary to discover better candidates for treating PD. In this work, we designed and synthesized 39 novel xyloketal derivatives (1–39) in addition to the previously reported compound, xyloketal B. The neuroprotective activities of all 40 compounds were evaluated in vivo via respiratory burst assays and longevity-extending assays. During the zebrafish respiratory burst assay, compounds 1, 9, 23, 24, 36 and 39 strongly attenuated reactive oxygen species (ROS) generation at 50 μM. In the Caenorhabditis elegans longevity-extending assay, compounds 1, 8, 15, 16 and 36 significantly extended the survival rates (p < 0.005 vs. dimethyl sulfoxide (DMSO)). A total of 15 compounds were tested for the treatment of Parkinson’s disease using the MPP+-induced C. elegans model, and compounds 1 and 8 exhibited the highest activities (p < 0.005 vs. MPP⁺). In the MPP+-induced C57BL/6 mouse PD model, 40 mg/kg of 1 and 8 protected against MPP+-induced dopaminergic neurodegeneration and increased the number of DA neurons from 53% for the MPP+ group to 78% and 74%, respectively (p < 0.001 vs. MPP+ group). Thus, these derivatives are novel candidates for the treatment of PD. Full article

(This article belongs to the Special Issue Bioactivity-Focused Syntheses of Marine Natural Products and Congeners)

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969 KiB

Open AccessArticle

Bone Regeneration of Rat Tibial Defect by Zinc-Tricalcium Phosphate (Zn-TCP) Synthesized from Porous Foraminifera Carbonate Macrospheres

by Joshua Chou, Jia Hao, Shinji Kuroda, David Bishop, Besim Ben-Nissan, Bruce Milthorpe and Makoto Otsuka

Mar. Drugs 2013, 11(12), 5148-5158; https://doi.org/10.3390/md11125148 - 16 Dec 2013

Cited by 30 | Viewed by 8738

Abstract

Foraminifera carbonate exoskeleton was hydrothermally converted to biocompatible and biodegradable zinc-tricalcium phosphate (Zn-TCP) as an alternative biomimetic material for bone fracture repair. Zn-TCP samples implanted in a rat tibial defect model for eight weeks were compared with unfilled defect and beta-tricalcium phosphate showing [...] Read more.

Foraminifera carbonate exoskeleton was hydrothermally converted to biocompatible and biodegradable zinc-tricalcium phosphate (Zn-TCP) as an alternative biomimetic material for bone fracture repair. Zn-TCP samples implanted in a rat tibial defect model for eight weeks were compared with unfilled defect and beta-tricalcium phosphate showing accelerated bone regeneration compared with the control groups, with statistically significant bone mineral density and bone mineral content growth. CT images of the defect showed restoration of cancellous bone in Zn-TCP and only minimal growth in control group. Histological slices reveal bone in-growth within the pores and porous chamber of the material detailing good bone-material integration with the presence of blood vessels. These results exhibit the future potential of biomimetic Zn-TCP as bone grafts for bone fracture repair. Full article

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Open AccessReview

Fucoxanthin: A Marine Carotenoid Exerting Anti-Cancer Effects by Affecting Multiple Mechanisms

by Sangeetha Ravi Kumar, Masashi Hosokawa and Kazuo Miyashita

Mar. Drugs 2013, 11(12), 5130-5147; https://doi.org/10.3390/md11125130 - 16 Dec 2013

Cited by 201 | Viewed by 13391

Abstract

Fucoxanthin is a marine carotenoid exhibiting several health benefits. The anti-cancer effect of fucoxanthin and its deacetylated metabolite, fucoxanthinol, is well documented. In view of its potent anti-carcinogenic activity, the need to understand the underlying mechanisms has gained prominence. Towards achieving this goal, [...] Read more.

Fucoxanthin is a marine carotenoid exhibiting several health benefits. The anti-cancer effect of fucoxanthin and its deacetylated metabolite, fucoxanthinol, is well documented. In view of its potent anti-carcinogenic activity, the need to understand the underlying mechanisms has gained prominence. Towards achieving this goal, several researchers have carried out studies in various cell lines and in vivo and have deciphered that fucoxanthin exerts its anti-proliferative and cancer preventing influence via different molecules and pathways including the Bcl-2 proteins, MAPK, NFκB, Caspases, GADD45, and several other molecules that are involved in either cell cycle arrest, apoptosis, or metastasis. Thus, in addition to decreasing the frequency of occurrence and growth of tumours, fucoxanthin has a cytotoxic effect on cancer cells. Some studies show that this effect is selective, i.e., fucoxanthin has the capability to target cancer cells only, leaving normal physiological cells unaffected/less affected. Hence, fucoxanthin and its metabolites show great promise as chemotherapeutic agents in cancer. Full article

(This article belongs to the Collection Marine Compounds and Cancer)

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Open AccessArticle

Identification and Functional Characterization of Genes Encoding Omega-3 Polyunsaturated Fatty Acid Biosynthetic Activities from Unicellular Microalgae

by Royah Vaezi, Johnathan A. Napier and Olga Sayanova

Mar. Drugs 2013, 11(12), 5116-5129; https://doi.org/10.3390/md11125116 - 16 Dec 2013

Cited by 41 | Viewed by 10306

Abstract

In order to identify novel genes encoding enzymes involved in the biosynthesis of nutritionally important omega-3 long chain polyunsaturated fatty acids, a database search was carried out in the genomes of the unicellular photoautotrophic green alga Ostreococcus RCC809 and cold-water diatom Fragilariopsis cylindrus [...] Read more.

In order to identify novel genes encoding enzymes involved in the biosynthesis of nutritionally important omega-3 long chain polyunsaturated fatty acids, a database search was carried out in the genomes of the unicellular photoautotrophic green alga Ostreococcus RCC809 and cold-water diatom Fragilariopsis cylindrus. The search led to the identification of two putative “front-end” desaturases (Δ6 and Δ4) from Ostreococcus RCC809 and one Δ6-elongase from F. cylindrus. Heterologous expression of putative open reading frames (ORFs) in yeast revealed that the encoded enzyme activities efficiently convert their respective substrates: 54.1% conversion of α-linolenic acid for Δ6-desaturase, 15.1% conversion of 22:5n-3 for Δ4-desaturase and 38.1% conversion of γ-linolenic acid for Δ6-elongase. The Δ6-desaturase from Ostreococcus RCC809 displays a very strong substrate preference resulting in the predominant synthesis of stearidonic acid (C18:4Δ^6,9,12,15). These data confirm the functional characterization of omega-3 long chain polyunsaturated fatty acid biosynthetic genes from these two species which have until now not been investigated for such activities. The identification of these new genes will also serve to expand the repertoire of activities available for metabolically engineering the omega-3 trait in heterologous hosts as well as providing better insights into the synthesis of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in marine microalgae. Full article

(This article belongs to the Special Issue Marine Fatty Acids-2013)

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Open AccessArticle

Polypeptide Modulators of TRPV1 Produce Analgesia without Hyperthermia

by Yaroslav A. Andreev, Sergey A. Kozlov, Yuliya V. Korolkova, Igor A. Dyachenko, Dmitrii A. Bondarenko, Denis I. Skobtsov, Arkadii N. Murashev, Polina D. Kotova, Olga A. Rogachevskaja, Natalia V. Kabanova, Stanislav S. Kolesnikov and Eugene V. Grishin

Mar. Drugs 2013, 11(12), 5100-5115; https://doi.org/10.3390/md11125100 - 16 Dec 2013

Cited by 68 | Viewed by 8031

Abstract

Transient receptor potential vanilloid 1 receptors (TRPV1) play a significant physiological role. The study of novel TRPV1 agonists and antagonists is essential. Here, we report on the characterization of polypeptide antagonists of TRPV1 based on in vitro and in vivo experiments. We evaluated [...] Read more.

Transient receptor potential vanilloid 1 receptors (TRPV1) play a significant physiological role. The study of novel TRPV1 agonists and antagonists is essential. Here, we report on the characterization of polypeptide antagonists of TRPV1 based on in vitro and in vivo experiments. We evaluated the ability of APHC1 and APHC3 to inhibit TRPV1 using the whole-cell patch clamp approach and single cell Ca²⁺ imaging. In vivo tests were performed to assess the biological effects of APHC1 and APHC3 on temperature sensation, inflammation and core body temperature. In the electrophysiological study, both polypeptides partially blocked the capsaicin-induced response of TRPV1, but only APHC3 inhibited acid-induced (pH 5.5) activation of the receptor. APHC1 and APHC3 showed significant antinociceptive and analgesic activity in vivo at reasonable doses (0.01–0.1 mg/kg) and did not cause hyperthermia. Intravenous administration of these polypeptides prolonged hot-plate latency, blocked capsaicin- and formalin-induced behavior, reversed CFA-induced hyperalgesia and produced hypothermia. Notably, APHC3’s ability to inhibit the low pH-induced activation of TRPV1 resulted in a reduced behavioural response in the acetic acid-induced writhing test, whereas APHC1 was much less effective. The polypeptides APHC1 and APHC3 could be referred to as a new class of TRPV1 modulators that produce a significant analgesic effect without hyperthermia. Full article

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Open AccessArticle

Activation of the Nuclear Factor E2-Related Factor 2 Pathway by Novel Natural Products Halomadurones A–D and a Synthetic Analogue

by Thomas P. Wyche, Miranda Standiford, Yanpeng Hou, Doug Braun, Delinda A. Johnson, Jeffrey A. Johnson and Tim S. Bugni

Mar. Drugs 2013, 11(12), 5089-5099; https://doi.org/10.3390/md11125089 - 16 Dec 2013

Cited by 25 | Viewed by 6152

Abstract

Two novel chlorinated pyrones, halomadurones A and B, and two novel brominated analogues, halomadurones C and D, were isolated from a marine Actinomadura sp. cultivated from the ascidian Ecteinascidia turbinata. Additionally, a non-halogenated analogue, 2-methyl-6-((E)-3-methyl-1,3-hexadiene)-γ-pyrone, was synthesized to understand the [...] Read more.

Two novel chlorinated pyrones, halomadurones A and B, and two novel brominated analogues, halomadurones C and D, were isolated from a marine Actinomadura sp. cultivated from the ascidian Ecteinascidia turbinata. Additionally, a non-halogenated analogue, 2-methyl-6-((E)-3-methyl-1,3-hexadiene)-γ-pyrone, was synthesized to understand the role of the halogens for activity. Halomadurones C and D demonstrated potent nuclear factor E2-related factor antioxidant response element (Nrf2-ARE) activation, which is an important therapeutic approach for treatment of neurodegenerative diseases. Full article

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Open AccessCorrection

Correction: Wu, S.-L., et al. Simplexins P–S, Eunicellin-Based Diterpenes from the Soft Coral Klyxum simplex. Mar. Drugs 2012, 10, 1203–1211

by Shwu-Li Wu, Jui-Hsin Su, Chiung-Yao Huang, Chi-Jen Tai, Ping-Jyun Sung, Chih-Chung Liaw and Jyh-Horng Sheu

Mar. Drugs 2013, 11(12), 5087-5088; https://doi.org/10.3390/md11125087 - 13 Dec 2013

Cited by 2 | Viewed by 5220

Abstract

We found some errors in our previous published paper [1]. The structure of simplexin Q was found to be the same as klysimplexin C, previously published in Tetrahedron 2009, 65, 7016–7022 [2]. Also, simplexin S and a known compound cladieunicellin G, [...] Read more.

We found some errors in our previous published paper [1]. The structure of simplexin Q was found to be the same as klysimplexin C, previously published in Tetrahedron 2009, 65, 7016–7022 [2]. Also, simplexin S and a known compound cladieunicellin G, reported in Chem. Pharm. Bull. 2012, 60, 160–163 [3], have the same structure (see Figure 1). We apologize for any inconvenience caused to the readers by these errors. [...] Full article

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Open AccessArticle

Fumigaclavine C from a Marine-Derived Fungus Aspergillus Fumigatus Induces Apoptosis in MCF-7 Breast Cancer Cells

by Yong-Xin Li, S.W.A. Himaya, Pradeep Dewapriya, Chen Zhang and Se-Kwon Kim

Mar. Drugs 2013, 11(12), 5063-5086; https://doi.org/10.3390/md11125063 - 13 Dec 2013

Cited by 69 | Viewed by 10543

Abstract

Recently, much attention has been given to discovering natural compounds as potent anti-cancer candidates. In the present study, the anti-cancer effects of fumigaclavine C, isolated from a marine-derived fungus, Aspergillus fumigatus, was evaluated in vitro. In order to investigate the impact [...] Read more.

Recently, much attention has been given to discovering natural compounds as potent anti-cancer candidates. In the present study, the anti-cancer effects of fumigaclavine C, isolated from a marine-derived fungus, Aspergillus fumigatus, was evaluated in vitro. In order to investigate the impact of fumigaclavine C on inhibition of proliferation and induction of apoptosis in breast cancer, MCF-7 cells were treated with various concentrations of fumigaclavine C, and fumigaclavine C showed significant cytotoxicity towards MCF-7 cells. Anti-proliferation was analyzed via cell mobility and mitogen-activated protein kinase (MAPK) signaling pathway. In addition, fumigaclavine C showed potent inhibition on the protein and gene level expressions of MMP-2, -9 in MCF-7 cells which were manifested in Western blot and reverse transcription polymerase chain reaction (RT-PCR) results. The apoptosis induction abilities of the fumigaclvine C was studied by analyzing the expression of apoptosis related proteins, cell cycle analysis, DNA fragmentation and molecular docking studies. It was found that fumigaclavine C fragmented the MCF-7 cell DNA and arrested the cell cycle by modulating the apoptotic protein expressions. Moreover, fumigaclavine C significantly down-regulated the NF-kappa-B cell survival pathway. Collectively, data suggest that fumigaclavine C has a potential to be developed as a therapeutic candidate for breast cancer. Full article

(This article belongs to the Collection Marine Compounds and Cancer)

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Open AccessArticle

Identification of Four New agr Quorum Sensing-Interfering Cyclodepsipeptides from a Marine Photobacterium

by Louise Kjaerulff, Anita Nielsen, Maria Mansson, Lone Gram, Thomas O. Larsen, Hanne Ingmer and Charlotte H. Gotfredsen

Mar. Drugs 2013, 11(12), 5051-5062; https://doi.org/10.3390/md11125051 - 12 Dec 2013

Cited by 41 | Viewed by 8335

Abstract

During our search for new natural products from the marine environment, we discovered a wide range of cyclic peptides from a marine Photobacterium, closely related to P. halotolerans. The chemical fingerprint of the bacterium showed primarily non-ribosomal peptide synthetase (NRPS)-like compounds, [...] Read more.

During our search for new natural products from the marine environment, we discovered a wide range of cyclic peptides from a marine Photobacterium, closely related to P. halotolerans. The chemical fingerprint of the bacterium showed primarily non-ribosomal peptide synthetase (NRPS)-like compounds, including the known pyrrothine antibiotic holomycin and a wide range of peptides, from diketopiperazines to cyclodepsipeptides of 500–900 Da. Purification of components from the pellet fraction led to the isolation and structure elucidation of four new cyclodepsipeptides, ngercheumicin F, G, H, and I. The ngercheumicins interfered with expression of virulence genes known to be controlled by the agr quorum sensing system of Staphylococcus aureus, although to a lesser extent than the previously described solonamides from the same strain of Photobacterium. Full article

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Open AccessArticle

Screening Mangrove Endophytic Fungi for Antimalarial Natural Products

by Laurent Calcul, Carrie Waterman, Wai Sheung Ma, Matthew D. Lebar, Charles Harter, Tina Mutka, Lindsay Morton, Patrick Maignan, Alberto Van Olphen, Dennis E. Kyle, Lilian Vrijmoed, Ka-Lai Pang, Cedric Pearce and Bill J. Baker

Mar. Drugs 2013, 11(12), 5036-5050; https://doi.org/10.3390/md11125036 - 12 Dec 2013

Cited by 56 | Viewed by 10232

Abstract

We conducted a screening campaign to investigate fungi as a source for new antimalarial compounds. A subset of our fungal collection comprising Chinese mangrove endophytes provided over 5000 lipophilic extracts. We developed an accelerated discovery program based on small-scale cultivation for crude extract [...] Read more.

We conducted a screening campaign to investigate fungi as a source for new antimalarial compounds. A subset of our fungal collection comprising Chinese mangrove endophytes provided over 5000 lipophilic extracts. We developed an accelerated discovery program based on small-scale cultivation for crude extract screening and a high-throughput malaria assay. Criteria for hits were developed and high priority hits were subjected to scale-up cultivation. Extracts from large scale cultivation were fractionated and these fractions subjected to both in vitro malaria and cytotoxicity screening. Criteria for advancing fractions to purification were developed, including the introduction of a selectivity index and by dereplication of known metabolites. From the Chinese mangrove endophytes, four new compounds (14–16, 18) were isolated including a new dimeric tetrahydroxanthone, dicerandrol D (14), which was found to display the most favorable bioactivity profile. Full article

(This article belongs to the Special Issue Antiprotozoal Marine Natural Products)

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Open AccessArticle

Diamond Squid (Thysanoteuthis rhombus)-Derived Chondroitin Sulfate Stimulates Bone Healing within a Rat Calvarial Defect

by Yoshinao Z. Hosaka, Yuji Iwai, Jun-ichi Tamura and Masato Uehara

Mar. Drugs 2013, 11(12), 5024-5035; https://doi.org/10.3390/md11125024 - 11 Dec 2013

Cited by 8 | Viewed by 8979

Abstract

Chondroitin sulfate (CS) has been suggested to be involved in bone formation and mineralization processes. A previous study showed that squid-derived CS (sqCS) has osteoblastogenesis ability in cooperation with bone morphogenetic protein (BMP)-4 in vitro. However, in vivo, osteogenic potential has [...] Read more.

Chondroitin sulfate (CS) has been suggested to be involved in bone formation and mineralization processes. A previous study showed that squid-derived CS (sqCS) has osteoblastogenesis ability in cooperation with bone morphogenetic protein (BMP)-4 in vitro. However, in vivo, osteogenic potential has not been verified. In this study, we created a critical-sized bone defect in the rat calvaria and implanted sqCS-loaded gelatin hydrogel sponges (Gel) into the defect with or without BMP-4 (CS/BMP/Gel and CS/Gel, respectively). At 15 weeks, bone repair rate of CS/Gel-treated defects and CS/BMP/Gel-treated defects were 47.2% and 51.1%, respectively, whereas empty defects and defects with untreated sponges showed significantly less bone ingrowth. The intensity of von Kossa staining of the regenerated bone was less than that of the original one. Mineral apposition rates at 9 to 10 weeks were not significantly different between all treatment groups. Although bone repair was not completed, sqCS stimulated bone regeneration without BMP-4 and without external mesenchymal cells or preosteoblasts. Therefore, sqCS is a promising substance for promotion of osteogenesis. Full article

(This article belongs to the Collection Bioactive Compounds from Marine Invertebrates)

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Open AccessArticle

Biosynthesis of Polyunsaturated Fatty Acids in the Oleaginous Marine Diatom Fistulifera sp. Strain JPCC DA0580

by Yue Liang, Yoshiaki Maeda, Yoshihiko Sunaga, Masaki Muto, Mitsufumi Matsumoto, Tomoko Yoshino and Tsuyoshi Tanaka

Mar. Drugs 2013, 11(12), 5008-5023; https://doi.org/10.3390/md11125008 - 11 Dec 2013

Cited by 29 | Viewed by 7524

Abstract

Studies of polyunsaturated fatty acid (PUFA) biosynthesis in microalgae are of great importance for many reasons, including the production of biofuel and variable omega 3-long chain PUFAs. The elucidation of the PUFA biosynthesis pathway is necessary for bioengineering to increase or decrease PUFA [...] Read more.

Studies of polyunsaturated fatty acid (PUFA) biosynthesis in microalgae are of great importance for many reasons, including the production of biofuel and variable omega 3-long chain PUFAs. The elucidation of the PUFA biosynthesis pathway is necessary for bioengineering to increase or decrease PUFA content in certain microalgae. In this study, we identified the PUFA synthesis pathway in the oleaginous marine diatom, Fistulifera sp. strain JPCC DA0580, a promising candidate for biodiesel production. The data revealed not only the presence of the desaturases and elongases involved in eicosapentaenoic acid (EPA) synthesis, but also the unexpected localization of ω3-desaturase expression in the chloroplast. This suggests that this microalga might perform the final step of EPA synthesis in the chloroplast and not in the endoplasmic reticulum (ER) like other diatoms. The detailed fatty acid profile suggests that the EPA was synthesized only through the ω6-pathway in this strain, which was also different from other diatoms. Finally, the transcriptome analysis demonstrated an overall down-regulation of desaturases and elongases over incubation time. These genetic features might explain the decrease of PUFA percentage over incubation time in this strain. The important insights into metabolite synthesis acquired here will be useful for future metabolic engineering to control PUFA content in this diatom. Full article

(This article belongs to the Special Issue Metabolites in Diatoms)

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Open AccessArticle

The Effect of Eating Sea Cucumber Jelly on Candida Load in the Oral Cavity of Elderly Individuals in a Nursing Home

by Akira Yano, Akiko Abe, Fumie Aizawa, Hidetoshi Yamada, Kentaro Minami, Miki Matsui and Mitsuo Kishi

Mar. Drugs 2013, 11(12), 4993-5007; https://doi.org/10.3390/md11124993 - 11 Dec 2013

Cited by 13 | Viewed by 11453

Abstract

We conducted a double-blind randomized controlled study of elderly individuals in a nursing home to investigate the effect of the consumption of jelly containing sea cucumber on their oral Candida load. The jelly contained a hydrolysate of the sea cucumber Stichopus japonicus, [...] Read more.

We conducted a double-blind randomized controlled study of elderly individuals in a nursing home to investigate the effect of the consumption of jelly containing sea cucumber on their oral Candida load. The jelly contained a hydrolysate of the sea cucumber Stichopus japonicus, which contained triterpene glycosides called holotoxins. The holotoxins worked as a fungicide, and their minimum inhibitory concentrations for Candida albicans were 7 µg/mL. Eight individuals in the nursing home took the sea cucumber jelly for a week and their oral Candida were counted before and after the intervention. Nine individuals took a control jelly without S. japonicus. The sea cucumber jelly showed inhibitory effects on the oral Candida. Thus, daily consumption of the S. japonicus jelly has the potential to reduce the oral Candida load in the elderly in nursing homes. Full article

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Open AccessArticle

The Effect of 17α-Ethynylestradiol on Steroidogenesis and Gonadal Cytokine Gene Expression Is Related to the Reproductive Stage in Marine Hermaphrodite Fish

by Isabel Cabas, Elena Chaves-Pozo, Alicia García-Alcázar, José Meseguer, Victoriano Mulero and Alfonsa García-Ayala

Mar. Drugs 2013, 11(12), 4973-4992; https://doi.org/10.3390/md11124973 - 11 Dec 2013

Cited by 23 | Viewed by 7415

Abstract

Pollutants have been reported to disrupt the endocrine system of marine animals, which may be exposed through contaminated seawater or through the food chain. Although 17α-ethynylestradiol (EE₂), a drug used in hormone therapies, is widely present in the aquatic environment, current [...] Read more.

Pollutants have been reported to disrupt the endocrine system of marine animals, which may be exposed through contaminated seawater or through the food chain. Although 17α-ethynylestradiol (EE₂), a drug used in hormone therapies, is widely present in the aquatic environment, current knowledge on the sensitivity of marine fish to estrogenic pollutants is limited. We report the effect of the dietary intake of 5 µg EE₂/g foodon different processes of testicular physiology, ranging from steroidogenesis to pathogen recognition, at both pre-spermatogenesis (pre-SG) and spermatogenesis (SG) reproductive stages, of gilthead seabream (Sparus aurata L.), a marine hermaphrodite teleost. A differential effect between pre-SG and SG specimens was detected in the sex steroid serum levels and in the expression profile of some steroidogenic-relevant molecules, vitellogenin, double sex- and mab3-related transcription factor 1 and some hormone receptors. Interestingly, EE₂ modified the expression pattern of some immune molecules involved in testicular physiology. These differences probably reflect a developmental adjustment of the sensitivity to EE₂ in the gilthead seabream gonad. Full article

(This article belongs to the Special Issue Marine Fish Endocrine Disruption)

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Open AccessArticle

New Dimeric Members of the Phomoxanthone Family: Phomolactonexanthones A, B and Deacetylphomoxanthone C Isolated from the Fungus Phomopsis sp.

by Bo Ding, Jie Yuan, Xishan Huang, Weitao Wen, Xu Zhu, Yayue Liu, Hanxiang Li, Yongjun Lu, Lei He, Hongmei Tan and Zhigang She

Mar. Drugs 2013, 11(12), 4961-4972; https://doi.org/10.3390/md11124961 - 11 Dec 2013

Cited by 43 | Viewed by 6688

Abstract

Three new phomoxanthone compounds, phomolactonexanthones A (1), B (2) and deacetylphomoxanthone C (3), along with five known phomoxanthones, including dicerandrol A (4), dicerandrol B (5), dicerandrol (6), deacetylphomoxanthone B (7 [...] Read more.

Three new phomoxanthone compounds, phomolactonexanthones A (1), B (2) and deacetylphomoxanthone C (3), along with five known phomoxanthones, including dicerandrol A (4), dicerandrol B (5), dicerandrol (6), deacetylphomoxanthone B (7) and penexanthone A (8), were isolated in the metabolites of the fungus Phomopsis sp. HNY29-2B, which was isolated from the mangrove plants. The structures of compounds 1–3 were established on the basis of spectroscopic analysis. All compounds were evaluated against four human cancer cell lines including human breast MDA-MB-435, human colon HCT-116, human lung Calu-3 and human liver Huh7 by MTT assay. The compounds 4, 5, 7 and 8 showed cyctotoxic activities against tested cancer cell lines (IC₅₀ < 10 μM). Full article

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Open AccessArticle

Eight New Peptaibols from Sponge-Associated Trichoderma atroviride

by Irina Panizel, Oded Yarden, Micha Ilan and Shmuel Carmeli

Mar. Drugs 2013, 11(12), 4937-4960; https://doi.org/10.3390/md11124937 - 11 Dec 2013

Cited by 35 | Viewed by 7963

Abstract

Eight new and four known peptaibols were isolated from a strain of the fungus, Trichoderma atroviride (NF16), which was cultured from an Axinellid sponge collected from the East Mediterranean coast of Israel. The structures of the pure compounds were determined using HRMS, MS/MS [...] Read more.

Eight new and four known peptaibols were isolated from a strain of the fungus, Trichoderma atroviride (NF16), which was cultured from an Axinellid sponge collected from the East Mediterranean coast of Israel. The structures of the pure compounds were determined using HRMS, MS/MS and one- and two-dimensional NMR measurements. The isolated compounds belong to the trichorzianines, a family of 19-residue linear hydrophobic peptides containing a high proportion of α-aminoisobutyric acid (Aib), an acetylated N-terminus and a C-terminal amino alcohol. These new peptaibols exhibited antimicrobial activity against environmental bacteria isolated from the Mediterranean coast of Israel. Full article

(This article belongs to the Special Issue Advances and New Perspectives in Marine Biotechnology)

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Open AccessArticle

Cytotoxic, Cytostatic and HIV-1 PR Inhibitory Activities of the Soft Coral Litophyton arboreum

by Mona S. Ellithey, Namrita Lall, Ahmed A. Hussein and Debra Meyer

Mar. Drugs 2013, 11(12), 4917-4936; https://doi.org/10.3390/md11124917 - 10 Dec 2013

Cited by 40 | Viewed by 7815

Abstract

Bioassay-guided fractionation using different chromatographic and spectroscopic techniques in the analysis of the Red Sea soft coral Litophyton arboreum led to the isolation of nine compounds; sarcophytol M (1), alismol (2), 24-methylcholesta-5,24(28)-diene-3β-ol (3), 10-O-methyl alismoxide [...] Read more.

Bioassay-guided fractionation using different chromatographic and spectroscopic techniques in the analysis of the Red Sea soft coral Litophyton arboreum led to the isolation of nine compounds; sarcophytol M (1), alismol (2), 24-methylcholesta-5,24(28)-diene-3β-ol (3), 10-O-methyl alismoxide (4), alismoxide (5), (S)-chimyl alcohol (6), 7β-acetoxy-24-methylcholesta-5-24(28)-diene-3,19-diol (7), erythro-N-dodecanoyl-docosasphinga-(4E,8E)-dienine (8), and 24-methylcholesta-5,24 (28)-diene-3β,7β,19-triol (9). Some of the isolated compounds demonstrated potent cytotoxic- and/or cytostatic activity against HeLa and U937 cancer cell lines and inhibitory activity against HIV-1 protease (PR). Compound 7 was strongly cytotoxic against HeLa cells (CC₅₀ 4.3 ± 0.75 µM), with selectivity index of SI 8.1, which was confirmed by real time cell electronic sensing (RT-CES). Compounds 2, 7, and 8 showed strong inhibitory activity against HIV-1 PR at IC₅₀s of 7.20 ± 0.7, 4.85 ± 0.18, and 4.80 ± 0.92 µM respectively. In silico docking of most compounds presented comparable scores to that of acetyl pepstatin, a known HIV-1 PR inhibitor. Interestingly, compound 8 showed potent HIV-1 PR inhibitory activity in the absence of cytotoxicity against the cell lines used. In addition, compounds 2 and 5 demonstrated cytostatic action in HeLa cells, revealing potential use in virostatic cocktails. Taken together, data presented here suggest Litophyton arboreum to contain promising compounds for further investigation against the diseases mentioned. Full article

(This article belongs to the Collection Bioactive Compounds from Marine Invertebrates)

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Open AccessArticle

N-Terminal Protease Gene Phylogeny Reveals the Potential for Novel Cyanobactin Diversity in Cyanobacteria

by Joana Martins, Pedro N. Leão, Vitor Ramos and Vitor Vasconcelos

Mar. Drugs 2013, 11(12), 4902-4916; https://doi.org/10.3390/md11124902 - 9 Dec 2013

Cited by 13 | Viewed by 8089

Abstract

Cyanobactins are a recently recognized group of ribosomal cyclic peptides produced by cyanobacteria, which have been studied because of their interesting biological activities. Here, we have used a PCR-based approach to detect the N-terminal protease (A) gene from cyanobactin synthetase gene clusters, [...] Read more.

Cyanobactins are a recently recognized group of ribosomal cyclic peptides produced by cyanobacteria, which have been studied because of their interesting biological activities. Here, we have used a PCR-based approach to detect the N-terminal protease (A) gene from cyanobactin synthetase gene clusters, in a set of diverse cyanobacteria from our culture collection (Laboratory of Ecotoxicology, Genomics and Evolution (LEGE) CC). Homologues of this gene were found in Microcystis and Rivularia strains, and for the first time in Cuspidothrix, Phormidium and Sphaerospermopsis strains. Phylogenetic relationships inferred from available A-gene sequences, including those obtained in this work, revealed two new groups of phylotypes, harboring Phormidium, Sphaerospermopsis and Rivularia LEGE isolates. Thus, this study shows that, using underexplored cyanobacterial strains, it is still possible to expand the known genetic diversity of genes involved in cyanobactin biosynthesis. Full article

(This article belongs to the Special Issue Compounds from Cyanobacteria)

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Open AccessReview

Anticancer and Cancer Preventive Properties of Marine Polysaccharides: Some Results and Prospects

by Sergey N. Fedorov, Svetlana P. Ermakova, Tatyana N. Zvyagintseva and Valentin A. Stonik

Mar. Drugs 2013, 11(12), 4876-4901; https://doi.org/10.3390/md11124876 - 2 Dec 2013

Cited by 150 | Viewed by 11452

Abstract

Many marine-derived polysaccharides and their analogues have been reported as showing anticancer and cancer preventive properties. These compounds demonstrate interesting activities and special modes of action, differing from each other in both structure and toxicity profile. Herein, literature data concerning anticancer and cancer [...] Read more.

Many marine-derived polysaccharides and their analogues have been reported as showing anticancer and cancer preventive properties. These compounds demonstrate interesting activities and special modes of action, differing from each other in both structure and toxicity profile. Herein, literature data concerning anticancer and cancer preventive marine polysaccharides are reviewed. The structural diversity, the biological activities, and the molecular mechanisms of their action are discussed. Full article

(This article belongs to the Collection Marine Compounds and Cancer)

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Open AccessArticle

Hypoxia Reduces the Efficiency of Elisidepsin by Inhibiting Hydroxylation and Altering the Structure of Lipid Rafts

by Anna Király, Tímea Váradi, Tímea Hajdu, Ralph Rühl, Carlos M. Galmarini, János Szöllősi and Peter Nagy

Mar. Drugs 2013, 11(12), 4858-4875; https://doi.org/10.3390/md11124858 - 2 Dec 2013

Cited by 11 | Viewed by 6644

Abstract

The mechanism of action of elisidepsin (PM02734, Irvalec^®) is assumed to involve membrane permeabilization via attacking lipid rafts and hydroxylated lipids. Here we investigate the role of hypoxia in the mechanism of action of elisidepsin. Culturing under hypoxic conditions increased the [...] Read more.

The mechanism of action of elisidepsin (PM02734, Irvalec^®) is assumed to involve membrane permeabilization via attacking lipid rafts and hydroxylated lipids. Here we investigate the role of hypoxia in the mechanism of action of elisidepsin. Culturing under hypoxic conditions increased the half-maximal inhibitory concentration and decreased the drug’s binding to almost all cell lines which was reversed by incubation of cells with 2-hydroxy palmitic acid. The expression of fatty acid 2-hydroxylase was strongly correlated with the efficiency of the drug and inversely correlated with the effect of hypoxia. Number and brightness analysis and fluorescence anisotropy experiments showed that hypoxia decreased the clustering of lipid rafts and altered the structure of the plasma membrane. Although the binding of elisidepsin to the membrane is non-cooperative, its membrane permeabilizing effect is characterized by a Hill coefficient of ~3.3. The latter finding is in agreement with elisidepsin-induced clusters of lipid raft-anchored GFP visualized by confocal microscopy. We propose that the concentration of elisidepsin needs to reach a critical level in the membrane above which elisidepsin induces the disruption of the cell membrane. Testing for tumor hypoxia or the density of hydroxylated lipids could be an interesting strategy to increase the efficiency of elisidepsin. Full article

(This article belongs to the Collection Marine Compounds and Cancer)

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831 KiB

Open AccessArticle

Champacyclin, a New Cyclic Octapeptide from Streptomyces Strain C42 Isolated from the Baltic Sea

by Alexander Pesic, Heike I. Baumann, Katrin Kleinschmidt, Paul Ensle, Jutta Wiese, Roderich D. Süssmuth and Johannes F. Imhoff

Mar. Drugs 2013, 11(12), 4834-4857; https://doi.org/10.3390/md11124834 - 2 Dec 2013

Cited by 36 | Viewed by 11254

Abstract

New isolates of Streptomyces champavatii were isolated from marine sediments of the Gotland Deep (Baltic Sea), from the Urania Basin (Eastern Mediterranean), and from the Kiel Bight (Baltic Sea). The isolates produced several oligopeptidic secondary metabolites, including the new octapeptide champacyclin (1a [...] Read more.

New isolates of Streptomyces champavatii were isolated from marine sediments of the Gotland Deep (Baltic Sea), from the Urania Basin (Eastern Mediterranean), and from the Kiel Bight (Baltic Sea). The isolates produced several oligopeptidic secondary metabolites, including the new octapeptide champacyclin (1a) present in all three strains. Herein, we report on the isolation, structure elucidation and determination of the absolute stereochemistry of this isoleucine/leucine (Ile/Leu = Xle) rich cyclic octapeptide champacyclin (1a). As 2D nuclear magnetic resonance (NMR) spectroscopy could not fully resolve the structure of (1a), additional information on sequence and configuration of stereocenters were obtained by a combination of multi stage mass spectrometry (MSⁿ) studies, amino acid analysis, partial hydrolysis and subsequent enantiomer analytics with gas chromatography positive chmical ionization/electron impact mass spectrometry (GC-PCI/EI-MS) supported by comparison to reference dipeptides. Proof of the head-to-tail cyclization of (1a) was accomplished by solid phase peptide synthesis (SPPS) compared to an alternatively side chain cyclized derivative (2). Champacyclin (1a) is likely synthesized by a non-ribosomal peptide synthetase (NRPS), because of its high content of (d)-amino acids. The compound (1a) showed antimicrobial activity against the phytopathogen Erwinia amylovora causing the fire blight disease of certain plants. Full article

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Open AccessArticle

HPLC-ESI-IT-MS/MS Analysis and Biological Activity of Triterpene Glycosides from the Colombian Marine Sponge Ectyoplasia ferox

by Jhonny Colorado-Ríos, Diana Muñoz, Guillermo Montoya, Diana Márquez, Maria-Elena Márquez, Juan López and Alejandro Martínez

Mar. Drugs 2013, 11(12), 4815-4833; https://doi.org/10.3390/md11124815 - 2 Dec 2013

Cited by 7 | Viewed by 8840

Abstract

The marine sponge Ectyoplasia ferox produces antipredatory and allelopathic triterpenoid glycosides as part of its chemical defense repertoire against predators, competitors, and fouling organisms. These molecules are responsible for the pharmacological potential found in the glycosides present in this species. In order to [...] Read more.

The marine sponge Ectyoplasia ferox produces antipredatory and allelopathic triterpenoid glycosides as part of its chemical defense repertoire against predators, competitors, and fouling organisms. These molecules are responsible for the pharmacological potential found in the glycosides present in this species. In order to observe the glycochemical diversity present in E. ferox, a liquid chromatography coupled to a tandem mass spectrometry approach to analyse a complex polar fraction of this marine sponge was performed. This gave valuable information for about twenty-five compounds three of which have been previously reported and another three which were found to be composed of known aglycones. Furthermore, a group of four urabosides, sharing two uncommon substitutions with carboxyl groups at C-4 on the terpenoid core, were identified by a characteristic fragmentation pattern. The oxidized aglycones present in this group of saponins can promote instability, making the purification process difficult. Cytotoxicity, cell cycle modulation, a cell cloning efficiency assay, as well as its hemolytic activity were evaluated. The cytotoxic activity was about IC₅₀ 40 µg/mL on Jurkat and CHO-k₁ cell lines without exhibiting hemolysis. Discussion on this bioactivity suggests the scanning of other biological models would be worthwhile. Full article

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Open AccessArticle

Exposure to the Neurotoxic Dinoflagellate, Alexandrium catenella, Induces Apoptosis of the Hemocytes of the Oyster, Crassostrea gigas

by Walid Medhioub, Simon Ramondenc, Audrey Sophie Vanhove, Agnes Vergnes, Estelle Masseret, Veronique Savar, Zouher Amzil, Mohamed Laabir and Jean Luc Rolland

Mar. Drugs 2013, 11(12), 4799-4814; https://doi.org/10.3390/md11124799 - 2 Dec 2013

Cited by 31 | Viewed by 7948

Abstract

This study assessed the apoptotic process occurring in the hemocytes of the Pacific oyster, Crassostrea gigas, exposed to Alexandrium catenella, a paralytic shellfish toxins (PSTs) producer. Oysters were experimentally exposed during 48 h to the toxic algae. PSTs accumulation, the expression [...] Read more.

This study assessed the apoptotic process occurring in the hemocytes of the Pacific oyster, Crassostrea gigas, exposed to Alexandrium catenella, a paralytic shellfish toxins (PSTs) producer. Oysters were experimentally exposed during 48 h to the toxic algae. PSTs accumulation, the expression of 12 key apoptotic-related genes, as well as the variation of the number of hemocytes in apoptosis was measured at time intervals during the experiment. Results show a significant increase of the number of hemocytes in apoptosis after 29 h of exposure. Two pro-apoptotic genes (Bax and Bax-like) implicated in the mitochondrial pathway were significantly upregulated at 21 h followed by the overexpression of two caspase executor genes (caspase-3 and caspase-7) at 29 h, suggesting that the intrinsic pathway was activated. No modulation of the expression of genes implicated in the cell signaling Fas-Associated protein with Death Domain (FADD) and initiation-phase (caspase-2) was observed, suggesting that only the extrinsic pathway was not activated. Moreover, the clear time-dependent upregulation of five (Bcl2, BI-1, IAP1, IAP7B and Hsp70) inhibitors of apoptosis-related genes associated with the return to the initial number of hemocytes in apoptosis at 48 h of exposure suggests the involvement of strong regulatory mechanisms of apoptosis occurring in the hemocytes of the Pacific oyster. Full article

(This article belongs to the Special Issue Marine Shellfish Toxins)

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Open AccessArticle

Polyhydroxylated Steroids from the South China Sea Soft Coral Sarcophyton sp. and Their Cytotoxic and Antiviral Activities

by Kai-Kai Gong, Xu-Li Tang, Gang Zhang, Can-Ling Cheng, Xing-Wang Zhang, Ping-Lin Li and Guo-Qiang Li

Mar. Drugs 2013, 11(12), 4788-4798; https://doi.org/10.3390/md11124788 - 2 Dec 2013

Cited by 31 | Viewed by 6945

Abstract

Chemical investigation on the soft coral Sarcophyton sp. collected from the South China Sea yielded three new polyhydroxylated steroids, compounds (1–3), together with seven known ones (4–10). Their structures were established by extensive spectroscopic methods [...] Read more.

Chemical investigation on the soft coral Sarcophyton sp. collected from the South China Sea yielded three new polyhydroxylated steroids, compounds (1–3), together with seven known ones (4–10). Their structures were established by extensive spectroscopic methods and comparison of their data with those of the related known compounds. All the isolates possessed the 3β,5α,6β-trihydroxylated steroidal nucleus. The cytotoxicities against selected HL-60, HeLa and K562 tumor cell lines and anti-H1N1 (Influenza A virus (IAV)) activities for the isolates were evaluated. Compounds 2, 3 and 5–8 exhibited potent activities against K562 cell lines with IC₅₀values ranging from 6.4 to 10.3 μM. Compounds 1, 6–8 potently inhibited the growth of HL-60 tumor cell lines, and 6 also showed cytotoxicity towards HeLa cell lines. In addition, preliminary structure-activity relationships for the isolates are discussed. The OAc group at C-11 is proposed to be an important pharmacophore for their cytotoxicities in the 3β,5α,6β-triol steroids. Compounds 4 and 9 exhibited significant anti-H1N1 IAV activity with IC₅₀ values of 19.6 and 36.7 μg/mL, respectively. Full article

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A New in Vitro Anti-Tumor Polypeptide Isolated from Arca inflata

by Jian Xu, Zhiyan Chen, Liyan Song, Lili Chen, Jianhua Zhu, Shuangshuang Lv and Rongmin Yu

Mar. Drugs 2013, 11(12), 4773-4787; https://doi.org/10.3390/md11124773 - 2 Dec 2013

Cited by 15 | Viewed by 8153

Abstract

A new in vitro anti-tumor polypeptide, coded as J2-C3, was isolated from Arca inflata Reeve and purified by diethyl-aminoethanol (DEAE)-sepharose Fast Flow anion exchange and phenyl sepharose CL-4B hydrophobic chromatography. J2-C3 was identified to be a homogeneous compound by native polyacrylamide gel electrophoresis [...] Read more.

A new in vitro anti-tumor polypeptide, coded as J2-C3, was isolated from Arca inflata Reeve and purified by diethyl-aminoethanol (DEAE)-sepharose Fast Flow anion exchange and phenyl sepharose CL-4B hydrophobic chromatography. J2-C3 was identified to be a homogeneous compound by native polyacrylamide gel electrophoresis (Native-PAGE). The purity of J2-C3 was over 99% in reversed phase-high performance liquid chromatography (RP-HPLC). The molecular weight was determined as 20,538.0 Da by electrospray-ionization mass spectrometry (ESI-MS/MS). J2-C3 was rich in Glx (Gln + Glu), Lys, and Asx (Asp + Asn) according to amino acid analysis. Four partial amino acid sequences of this peptide were determined as L/ISMEDVEESR, KNGMHSI/LDVNHDGR, AMKI/LI/LNPKKGI/LVPR and AMGAHKPPKGNEL/IGHR via MALDI-TOF/TOF-MS and de novo sequencing. Secondary structural analysis by CD spectroscopy revealed that J2-C3 had the α-helix (45.2%), β-sheet (2.9%), β-turn (26.0%) and random coil (25.9%). The anti-tumor effect of J2-C3 against human tumor cells was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and the IC₅₀ values of J2-C3 were 65.57, 93.33 and 122.95 µg/mL against A549, HT-29 and HepG2 cell lines, respectively. Therefore, J2-C3 might be developed as a potential anti-tumor agent. Full article

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Open AccessArticle

Two Novel Hepatocellular Carcinoma Cycle Inhibitory Cyclodepsipeptides from a Hydrothermal Vent Crab-Associated Fungus Aspergillus clavatus C2WU

by Wei Jiang, Panpan Ye, Chen-Tung Arthur Chen, Kuiwu Wang, Pengyuan Liu, Shan He, Xiaodan Wu, Lishe Gan, Ying Ye and Bin Wu

Mar. Drugs 2013, 11(12), 4761-4772; https://doi.org/10.3390/md11124761 - 2 Dec 2013

Cited by 57 | Viewed by 7790

Abstract

Two novel cyclodepsipeptides containing an unusual anthranilic acid dimer and a d-phenyllactic acid residues, clavatustides A (1) and B (2), were identified from cultured mycelia and broth of Aspergillus clavatus C2WU isolated from Xenograpsus testudinatus, which lives at [...] Read more.

Two novel cyclodepsipeptides containing an unusual anthranilic acid dimer and a d-phenyllactic acid residues, clavatustides A (1) and B (2), were identified from cultured mycelia and broth of Aspergillus clavatus C2WU isolated from Xenograpsus testudinatus, which lives at extreme, toxic habitat around the sulphur-rich hydrothermal vents in Taiwan Kueishantao. This is the first example of cyclopeptides containing an anthranilic acid dimer in natural products, and the first report of microbial secondary metabolites from the hydrothermal vent crab. Clavatustides A (1) and B (2) suppressed the proliferation of hepatocellular carcinoma (HCC) cell lines (HepG2, SMMC-7721 and Bel-7402) in a dose-dependent manner, and induced an accumulation of HepG2 cells in G1 phase and reduction of cells in S phase. Full article

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Okadaic Acid Toxin at Sublethal Dose Produced Cell Proliferation in Gastric and Colon Epithelial Cell Lines

by Miguel Del Campo, Héctor Toledo and Néstor Lagos

Mar. Drugs 2013, 11(12), 4751-4760; https://doi.org/10.3390/md11124751 - 2 Dec 2013

Cited by 16 | Viewed by 5231

Abstract

The aim of this study was to analyze the effect of Okadaic Acid (OA) on the proliferation of gastric and colon epithelial cells, the main target tissues of the toxin. We hypothesized that OA, at sublethal doses, activates multiple signaling pathways, such as [...] Read more.

The aim of this study was to analyze the effect of Okadaic Acid (OA) on the proliferation of gastric and colon epithelial cells, the main target tissues of the toxin. We hypothesized that OA, at sublethal doses, activates multiple signaling pathways, such as Erk and Akt, through the inhibition of PP2A. To demonstrate this, we carried out curves of doses and time response against OA in AGS, MKN-45 and Caco 2 cell lines, and found an increase in the cell proliferation at sublethal doses, at 24 h or 48 h exposure. Indeed, cells can withstand high concentrations of the toxin at 4 h exposure, the time chosen considering the maximum time before total gastric emptying. We have proved that this increased proliferation is due to an overexpression of Cyclin B, a cyclin that promotes the passage from G2 to mitosis. In addition, we have demonstrated that OA induces activation of Akt and Erk in the three cells lines, showing that OA can activate pathways involved in oncogenesis. In conclusion, this study contributes to the knowledge about the possible effects of chronic OA consumption. Full article

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Open AccessArticle

New Sinularianin Sesquiterpenes from Soft Coral Sinularia sp.

by Bin Yang, Shengrong Liao, Xiuping Lin, Junfeng Wang, Juan Liu, Xuefeng Zhou, Xianwen Yang and Yonghong Liu

Mar. Drugs 2013, 11(12), 4741-4750; https://doi.org/10.3390/md11124741 - 2 Dec 2013

Cited by 22 | Viewed by 5920

Abstract

Four new sesquiterpenes, sinularianins C–F (3–6), together with known sinularianins A (1) and B (2) were identified from a South China Sea soft coral Sinularia sp. Compounds 1–6 were evaluated for inhibition of [...] Read more.

Four new sesquiterpenes, sinularianins C–F (3–6), together with known sinularianins A (1) and B (2) were identified from a South China Sea soft coral Sinularia sp. Compounds 1–6 were evaluated for inhibition of NF-κB activation using the cell-based HEK293 NF-κB luciferase reporter gene assay. Compounds 1 and 4 were exhibited a potent effect with inhibitory rates of 41.3% and 43.0% at the concentration of 10 µg/mL, respectively. Full article

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Open AccessArticle

Toxic C17-Sphinganine Analogue Mycotoxin, Contaminating Tunisian Mussels, Causes Flaccid Paralysis in Rodents

by Riadh Marrouchi, Evelyne Benoit, Jean-Pierre Le Caer, Nawel Belayouni, Hafedh Belghith, Jordi Molgó and Riadh Kharrat

Mar. Drugs 2013, 11(12), 4724-4740; https://doi.org/10.3390/md11124724 - 28 Nov 2013

Cited by 11 | Viewed by 7655

Abstract

Severe toxicity was detected in mussels from Bizerte Lagoon (Northern Tunisia) using routine mouse bioassays for detecting diarrheic and paralytic toxins not associated to classical phytoplankton blooming. The atypical toxicity was characterized by rapid mouse death. The aim of the present work was [...] Read more.

Severe toxicity was detected in mussels from Bizerte Lagoon (Northern Tunisia) using routine mouse bioassays for detecting diarrheic and paralytic toxins not associated to classical phytoplankton blooming. The atypical toxicity was characterized by rapid mouse death. The aim of the present work was to understand the basis of such toxicity. Bioassay-guided chromatographic separation and mass spectrometry were used to detect and characterize the fraction responsible for mussels’ toxicity. Only a C17-sphinganine analog mycotoxin (C17-SAMT), with a molecular mass of 287.289 Da, was found in contaminated shellfish. The doses of C17-SAMT that were lethal to 50% of mice were 750 and 150 μg/kg following intraperitoneal and intracerebroventricular injections, respectively, and 900 μg/kg following oral administration. The macroscopic general aspect of cultures and the morphological characteristics of the strains isolated from mussels revealed that the toxicity episodes were associated to the presence of marine microfungi (Fusarium sp., Aspergillus sp. and Trichoderma sp.) in contaminated samples. The major in vivo effect of C17-SAMT on the mouse neuromuscular system was a dose- and time-dependent decrease of compound muscle action potential amplitude and an increased excitability threshold. In vitro, C17-SAMT caused a dose- and time-dependent block of directly- and indirectly-elicited isometric contraction of isolated mouse hemidiaphragms. Full article

(This article belongs to the Special Issue Marine Shellfish Toxins)

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Open AccessReview

Shellfish Toxins Targeting Voltage-Gated Sodium Channels

by Fan Zhang, Xunxun Xu, Tingting Li and Zhonghua Liu

Mar. Drugs 2013, 11(12), 4698-4723; https://doi.org/10.3390/md11124698 - 28 Nov 2013

Cited by 57 | Viewed by 16701

Abstract

Voltage-gated sodium channels (VGSCs) play a central role in the generation and propagation of action potentials in excitable neurons and other cells and are targeted by commonly used local anesthetics, antiarrhythmics, and anticonvulsants. They are also common targets of neurotoxins including shellfish toxins. [...] Read more.

Voltage-gated sodium channels (VGSCs) play a central role in the generation and propagation of action potentials in excitable neurons and other cells and are targeted by commonly used local anesthetics, antiarrhythmics, and anticonvulsants. They are also common targets of neurotoxins including shellfish toxins. Shellfish toxins are a variety of toxic secondary metabolites produced by prokaryotic cyanobacteria and eukaryotic dinoflagellates in both marine and fresh water systems, which can accumulate in marine animals via the food chain. Consumption of shellfish toxin-contaminated seafood may result in potentially fatal human shellfish poisoning. This article provides an overview of the structure, bioactivity, and pharmacology of shellfish toxins that act on VGSCs, along with a brief discussion on their pharmaceutical potential for pain management. Full article

(This article belongs to the Special Issue Marine Shellfish Toxins)

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Mar. Drugs, Volume 11, Issue 12 (December 2013) – 30 articles , Pages 4698-5189

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