Open AccessArticle
Lipid Composition of Oil Extracted from Wasted Norway Lobster (Nephrops norvegicus) Heads and Comparison with Oil Extracted from Antarctic Krill (Euphasia superba)
Mar. Drugs 2016, 14(12), 219; doi:10.3390/md14120219 (registering DOI) -
Abstract
In the UK, the Norway lobster (Nephrops norvegicus) supports its most important shellfish fishery. Nephrops are sold either whole, or as “tails-only” for the scampi trade. In the “tailing” process, the “head” (cephalothorax) is discarded as waste. A smaller crustacean species,
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In the UK, the Norway lobster (Nephrops norvegicus) supports its most important shellfish fishery. Nephrops are sold either whole, or as “tails-only” for the scampi trade. In the “tailing” process, the “head” (cephalothorax) is discarded as waste. A smaller crustacean species, the Antarctic krill Euphasia superba, represents an economically valuable industry, as its extractable oil is sold as a human dietary supplement. The aim of this study was to determine the amount and composition of the oil contained in discarded Nephrops heads and to compare its composition to the oil extracted from krill. Differences due to Geographical variation and seasonal patterns in the amount and composition of lipid were also noted. Results indicated that Nephrops head waste samples collected from more southern locations in Scotland (Clyde Sea area) contained higher levels of oil when compared to samples collected from northern locations in Iceland. Moreover, seasonal differences within the Clyde Sea area in Scotland were also observed, with oil extracted from Nephrops head waste peaking at around 11.5% during the summer months when larger and more mature females were caught by trawl. At this time of the year, the valuable fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) accounted for around 23% of the total fatty acid content in oil extracted from Nephrops head waste. A seasonal effect on EPA content was found, with higher levels obtained in the summer, while no trend was found in DHA percentages. Finally, oil from Nephrops head waste contained a higher proportion of EPA and DHA than krill oil but these fatty acids were more abundantly linked to the neutral lipids rather to than polar lipids. The characterization of lipid that could be extracted from Nephrops head waste should be seen as a first step for the commercial use of a valuable resource currently wasted. This approach is extremely relevant given the current limited supply of EPA and DHA and changes in the Common Fisheries Policy. Full article
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Open AccessReview
Marine Organisms with Anti-Diabetes Properties
Mar. Drugs 2016, 14(12), 220; doi:10.3390/md14120220 (registering DOI) -
Abstract
Diabetes is a chronic degenerative metabolic disease with high morbidity and mortality rates caused by its complications. In recent years, there has been a growing interest in looking for new bioactive compounds to treat this disease, including metabolites of marine origin. Several aquatic
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Diabetes is a chronic degenerative metabolic disease with high morbidity and mortality rates caused by its complications. In recent years, there has been a growing interest in looking for new bioactive compounds to treat this disease, including metabolites of marine origin. Several aquatic organisms have been screened to evaluate their possible anti-diabetes activities, such as bacteria, microalgae, macroalgae, seagrasses, sponges, corals, sea anemones, fish, salmon skin, a shark fusion protein as well as fish and shellfish wastes. Both in vitro and in vivo screenings have been used to test anti-hyperglycemic and anti-diabetic activities of marine organisms. This review summarizes recent discoveries in anti-diabetes properties of several marine organisms as well as marine wastes, existing patents and possible future research directions in this field. Full article
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Open AccessArticle
New Anti-Inflammatory 9,11-Secosterols with a Rare Tricyclo[5,2,1,1]decane Ring from a Formosan Gorgonian Pinnigorgia sp.
Mar. Drugs 2016, 14(12), 218; doi:10.3390/md14120218 -
Abstract
Pinnigorgiols D (1) and E (2), two new 9,11-secosterols with a rearranged carbon skeleton, were isolated from a Taiwan gorgonian Pinnigorgia sp. The structures of these two compounds were elucidated on the basis of spectroscopic methods and were proven
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Pinnigorgiols D (1) and E (2), two new 9,11-secosterols with a rearranged carbon skeleton, were isolated from a Taiwan gorgonian Pinnigorgia sp. The structures of these two compounds were elucidated on the basis of spectroscopic methods and were proven to possess a tricyclo[5,2,1,1]decane ring. The new secosterols 1 and 2 displayed significant inhibitory effects on the generation of superoxide anions and the release of elastase by human neutrophils. Full article
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Open AccessArticle
Polyketides with Immunosuppressive Activities from Mangrove Endophytic Fungus Penicillium sp. ZJ-SY2
Mar. Drugs 2016, 14(12), 217; doi:10.3390/md14120217 -
Abstract
Nine polyketides, including two new benzophenone derivatives, peniphenone (1) and methyl peniphenone (2), along with seven known xanthones (39) were obtained from mangrove endophytic fungus Penicillium sp. ZJ-SY2 isolated from the leaves of Sonneratia
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Nine polyketides, including two new benzophenone derivatives, peniphenone (1) and methyl peniphenone (2), along with seven known xanthones (39) were obtained from mangrove endophytic fungus Penicillium sp. ZJ-SY2 isolated from the leaves of Sonneratia apetala. Their structures were elucidated on the basis of MS, 1D, and 2D NMR data. Compounds 1, 3, 5, and 7 showed potent immunosuppressive activity with IC50 values ranging from 5.9 to 9.3 μg/mL. Full article
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Open AccessReview
Alkynyl-Containing Peptides of Marine Origin: A Review
Mar. Drugs 2016, 14(11), 216; doi:10.3390/md14110216 -
Abstract
Since the 1990s, a number of terminal alkynyl residue-containing cyclic/acyclic peptides have been identified from marine organisms, especially cyanobacteria and marine mollusks. This review has presented 66 peptides, which covers over 90% marine peptides with terminal alkynyl fatty acyl units. In fact, more
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Since the 1990s, a number of terminal alkynyl residue-containing cyclic/acyclic peptides have been identified from marine organisms, especially cyanobacteria and marine mollusks. This review has presented 66 peptides, which covers over 90% marine peptides with terminal alkynyl fatty acyl units. In fact, more than 90% of these peptides described in the literature are of cyanobacterial origin. Interestingly, all the linear peptides featured with terminal alkyne were solely discovered from marine cyanobacteria. The objective of this article is to provide an overview on the types, structural characterization of these unusual terminal alkynyl fatty acyl units, as well as the sources and biological functions of their composed peptides. Many of these peptides have a variety of biological activities, including antitumor, antibacterial, antimalarial, etc. Further, we have also discussed the evident biosynthetic origin responsible for formation of terminal alkynes of natural PKS (polyketide synthase)/NRPS (nonribosome peptide synthetase) hybrids. Full article
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Open AccessArticle
Phomopsichin A–D; Four New Chromone Derivatives from Mangrove Endophytic Fungus Phomopsis sp. 33#
Mar. Drugs 2016, 14(11), 215; doi:10.3390/md14110215 -
Abstract
Four new chromone derivatives, phomopsichins A–D (14), along with a known compound, phomoxanthone A (5), were isolated from the fermentation products of mangrove endophytic fungus Phomopsis sp. 33#. Their structures were elucidated based on comprehensive spectroscopic analysis
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Four new chromone derivatives, phomopsichins A–D (14), along with a known compound, phomoxanthone A (5), were isolated from the fermentation products of mangrove endophytic fungus Phomopsis sp. 33#. Their structures were elucidated based on comprehensive spectroscopic analysis coupled with single-crystal X-ray diffraction or theoretical calculations of electronic circular dichroism (ECD). They feature a tricyclic framework, in which a dihydropyran ring is fused with the chromone ring. Compounds 15 showed weak inhibitory activities on acetylcholinesterase as well as α-glucosidase, weak radical scavenging effects on 1,1-diphenyl-2-picrylhydrazyl (DPPH) as well as OH, and weak antimicrobial activities. Compounds 14 showed no cytotoxic activity against MDA-MB-435 breast cancer cells. Their other bioactivities are worthy of further study, considering their unique molecular structures. Full article
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Open AccessReview
Innovative Alternative Technologies to Extract Carotenoids from Microalgae and Seaweeds
Mar. Drugs 2016, 14(11), 214; doi:10.3390/md14110214 -
Abstract
Marine microalgae and seaweeds (microalgae) represent a sustainable source of various bioactive natural carotenoids, including β-carotene, lutein, astaxanthin, zeaxanthin, violaxanthin and fucoxanthin. Recently, the large-scale production of carotenoids from algal sources has gained significant interest with respect to commercial and industrial applications for
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Marine microalgae and seaweeds (microalgae) represent a sustainable source of various bioactive natural carotenoids, including β-carotene, lutein, astaxanthin, zeaxanthin, violaxanthin and fucoxanthin. Recently, the large-scale production of carotenoids from algal sources has gained significant interest with respect to commercial and industrial applications for health, nutrition, and cosmetic applications. Although conventional processing technologies, based on solvent extraction, offer a simple approach to isolating carotenoids, they suffer several, inherent limitations, including low efficiency (extraction yield), selectivity (purity), high solvent consumption, and long treatment times, which have led to advancements in the search for innovative extraction technologies. This comprehensive review summarizes the recent trends in the extraction of carotenoids from microalgae and seaweeds through the assistance of different innovative techniques, such as pulsed electric fields, liquid pressurization, supercritical fluids, subcritical fluids, microwaves, ultrasounds, and high-pressure homogenization. In particular, the review critically analyzes technologies, characteristics, advantages, and shortcomings of the different innovative processes, highlighting the differences in terms of yield, selectivity, and economic and environmental sustainability. Full article
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Open AccessReview
Preclinical and Clinical Studies on Antioxidative, Antihypertensive and Cardioprotective Effect of Marine Proteins and Peptides—A Review
Mar. Drugs 2016, 14(11), 211; doi:10.3390/md14110211 -
Abstract
High seafood consumption has traditionally been linked to a reduced risk of cardiovascular diseases, mainly due to the lipid lowering effects of the long chained omega 3 fatty acids. However, fish and seafood are also excellent sources of good quality proteins and emerging
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High seafood consumption has traditionally been linked to a reduced risk of cardiovascular diseases, mainly due to the lipid lowering effects of the long chained omega 3 fatty acids. However, fish and seafood are also excellent sources of good quality proteins and emerging documentation show that, upon digestion, these proteins are sources for bioactive peptides with documented favorable physiological effects such as antioxidative, antihypertensive and other cardioprotective effects. This documentation is mainly from in vitro studies, but also animal studies are arising. Evidence from human studies evaluating the positive health effects of marine proteins and peptides are scarce. In one study, a reduction in oxidative stress after intake of cod has been documented and a few human clinical trials have been performed evaluating the effect on blood pressure. The results are, however, inconclusive. The majority of the human clinical trials performed to investigate positive health effects of marine protein and lean fish intake, has focused on blood lipids. While some studies have documented a reduction in triglycerides after intake of lean fish, others have documented no effects. Full article
Open AccessArticle
The Role of Individual Disulfide Bonds of μ-Conotoxin GIIIA in the Inhibition of NaV1.4
Mar. Drugs 2016, 14(11), 213; doi:10.3390/md14110213 -
Abstract
μ-Conotoxin GIIIA, a peptide toxin isolated from Conus geographus, preferentially blocks the skeletal muscle sodium channel NaV1.4. GIIIA folds compactly to a pyramidal structure stabilized by three disulfide bonds. To assess the contributions of individual disulfide bonds of GIIIA to
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μ-Conotoxin GIIIA, a peptide toxin isolated from Conus geographus, preferentially blocks the skeletal muscle sodium channel NaV1.4. GIIIA folds compactly to a pyramidal structure stabilized by three disulfide bonds. To assess the contributions of individual disulfide bonds of GIIIA to the blockade of NaV1.4, seven disulfide-deficient analogues were prepared and characterized, each with one, two, or three pairs of disulfide-bonded Cys residues replaced with Ala. The inhibitory potency of the analogues against NaV1.4 was assayed by whole cell patch-clamp on rNaV1.4, heterologously expressed in HEK293 cells. The corresponding IC50 values were 0.069 ± 0.005 μM for GIIIA, 2.1 ± 0.3 μM for GIIIA-1, 3.3 ± 0.2 μM for GIIIA-2, and 15.8 ± 0.8 μM for GIIIA-3 (-1, -2 and -3 represent the removal of disulfide bridges Cys3–Cys15, Cys4–Cys20 and Cys10–Cys21, respectively). Other analogues were not active enough for IC50 measurement. Our results indicate that all three disulfide bonds of GIIIA are required to produce effective inhibition of NaV1.4, and the removal of any one significantly lowers its sodium channel binding affinity. Cys10–Cys21 is the most important for the NaV1.4 potency. Full article
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Open AccessArticle
Anti-Melanogenic Activity of Gagunin D, a Highly Oxygenated Diterpenoid from the Marine Sponge Phorbas sp., via Modulating Tyrosinase Expression and Degradation
Mar. Drugs 2016, 14(11), 212; doi:10.3390/md14110212 -
Abstract
Tyrosinase is the rate-limiting enzyme critical for melanin synthesis and controls pigmentation in the skin. The inhibition of tyrosinase is currently the most common approach for the development of skin-whitening cosmetics. Gagunin D (GD), a highly oxygenated diterpenoid isolated from the marine sponge
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Tyrosinase is the rate-limiting enzyme critical for melanin synthesis and controls pigmentation in the skin. The inhibition of tyrosinase is currently the most common approach for the development of skin-whitening cosmetics. Gagunin D (GD), a highly oxygenated diterpenoid isolated from the marine sponge Phorbas sp., has exhibited cytotoxicity toward human leukemia cells. However, the effect of GD on normal cells and the molecular mechanisms remain to be elucidated. In the present study, we identified for the first time the anti-melanogenic activity of GD and its precise underlying mechanisms in mouse melan-a cells. GD significantly inhibited melanin synthesis in the melan-a cells and a reconstructed human skin model. Further analysis revealed that GD suppressed the expression of tyrosinase and increased the rate of tyrosinase degradation. GD also inhibited tyrosinase enzymatic activity. In addition, GD effectively suppressed the expression of proteins associated with melanosome transfer. These findings suggest that GD is a potential candidate for cosmetic formulations due to its multi-functional properties. Full article
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Open AccessArticle
The Potential Exploitation of the Mediterranean Invasive Alga Caulerpa cylindracea: Can the Invasion Be Transformed into a Gain?
Mar. Drugs 2016, 14(11), 210; doi:10.3390/md14110210 -
Abstract
Recently, there is a growing interest towards the development of strategies for invasive seaweed control and exploitation as source of secondary metabolites. Here, we investigated the potential of exploitation in biotechnology and recycling options in eradication programs of the lipidic extract of the
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Recently, there is a growing interest towards the development of strategies for invasive seaweed control and exploitation as source of secondary metabolites. Here, we investigated the potential of exploitation in biotechnology and recycling options in eradication programs of the lipidic extract of the Mediterranean invasive seaweed Caulerpa cylindracea (Chlorophyta). The chemical characterization was carried out by means of multinuclear and multidimensional NMR spectroscopy. The fatty acid profile of C. cylindracea assessed the presence of several types of molecules known for antioxidant activity such as carotenoids, chlorophylls, pheophytins, and sterols. The NMR spectroscopy showed also the characteristic signals of saturated, unsaturated, and free fatty acids as well as other metabolites including the biopolymer polyhydroxybutyrate. The lipidic extract exerted an antioxidant activity corresponding to 552.14 ± 69.13 mmol Trolox equivalent/g (ORAC) and to 70.3 ± 2.67 mmol Trolox equivalent/g (TEAC). The extract showed an antibacterial activity against several Vibrio species, suggesting its potential use in the control of diseases in mariculture. Our results show that C. cylindracea, representing a critical hazard in coastal areas, could be transformed into a gain supporting specific management actions to reduce the effects of human pressures. Full article
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Open AccessArticle
Chemical and Genetic Diversity of Nodularia spumigena from the Baltic Sea
Mar. Drugs 2016, 14(11), 209; doi:10.3390/md14110209 -
Abstract
Nodularia spumigena is a toxic, filamentous cyanobacterium occurring in brackish waters worldwide, yet forms extensive recurrent blooms in the Baltic Sea. N. spumigena produces several classes of non-ribosomal peptides (NRPs) that are active against several key metabolic enzymes. Previously, strains from geographically distant
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Nodularia spumigena is a toxic, filamentous cyanobacterium occurring in brackish waters worldwide, yet forms extensive recurrent blooms in the Baltic Sea. N. spumigena produces several classes of non-ribosomal peptides (NRPs) that are active against several key metabolic enzymes. Previously, strains from geographically distant regions showed distinct NRP metabolic profiles. In this work, conspecific diversity in N. spumigena was studied using chemical and genetic approaches. NRP profiles were determined in 25 N. spumigena strains isolated in different years and from different locations in the Baltic Sea using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Genetic diversity was assessed by targeting the phycocyanin intergenic spacer and flanking regions (cpcBA-IGS). Overall, 14 spumigins, 5 aeruginosins, 2 pseudaeruginosins, 2 nodularins, 36 anabaenopeptins, and one new cyanopeptolin-like peptide were identified among the strains. Seven anabaenopeptins were new structures; one cyanopeptolin-like peptide was discovered in N. spumigena for the first time. Based on NRP profiles and cpcBA-IGS sequences, the strains were grouped into two main clusters without apparent influence of year and location, indicating persistent presence of these two subpopulations in the Baltic Sea. This study is a major step in using chemical profiling to explore conspecific diversity with a higher resolution than with a sole genetic approach. Full article
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Open AccessArticle
Astaxanthin and Docosahexaenoic Acid Reverse the Toxicity of the Maxi-K (BK) Channel Antagonist Mycotoxin Penitrem A
Mar. Drugs 2016, 14(11), 208; doi:10.3390/md14110208 -
Abstract
Penitrem A (PA) is a food mycotoxin produced by several terrestrial and few marine Penicillium species. PA is a potent tremorgen through selective antagonism of the calcium-dependent potassium BK (Maxi-K) channels. Discovery of natural products that can prevent the toxic effects of PA
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Penitrem A (PA) is a food mycotoxin produced by several terrestrial and few marine Penicillium species. PA is a potent tremorgen through selective antagonism of the calcium-dependent potassium BK (Maxi-K) channels. Discovery of natural products that can prevent the toxic effects of PA is important for food safety. Astaxanthin (AST) is a marine natural xanthophyll carotenoid with documented antioxidant activity. Unlike other common antioxidants, AST can cross blood brain barriers (BBBs), inducing neuroprotective effects. Docosahexaenoic acid (DHA) is polyunsaturated ω-3 fatty acid naturally occurring in fish and algae. DHA is essential for normal neurological and cellular development. This study evaluated the protective activity of AST and DHA against PA-induced toxicity, in vitro on Schwann cells CRL-2765 and in vivo in the worm Caenorhbitidis elegans and Sprague Dawley rat models. PA inhibited the viability of Schwann cells, with an IC50 of 22.6 μM. Dose-dependent treatments with 10–100 μM DHA significantly reversed the PA toxicity at its IC50 dose, and improved the survival of Schwann cells to 70.5%–98.8%. Similarly, dose-dependent treatments with 10–20 μM AST reversed the PA toxicity at its IC50 dose and raised these cells’ survival to 61.7%–70.5%. BK channel inhibition in the nematode C. elegans is associated with abnormal reversal locomotion. DHA and AST counteracted the in vivo PA BK channel antagonistic activity in the C. elegans model. Rats fed a PA-contaminated diet showed high levels of glutamate (GLU), aspartate (ASP), and gamma amino butyric acid (GABA), with observed necrosis or absence of Purkinjie neurons, typical of PA-induced neurotoxicity. Dopamine (DA), serotonin (5-HT), and norepinephrine (NE) levels were abnormal, Nitric Oxide (NO) and Malondialdehyde (MDA) levels were significantly increased, and total antioxidant capacity (TAC) level in serum and brain homogenates was significantly decreased in PA-treated rats. DHA and AST treatments effectively counteracted the toxic effects of PA and normalized most biochemical parameters in rats. DHA and AST can be useful food additives to prevent and reverse PA food-induced toxicity. Full article
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Open AccessArticle
Structure–Activity Relationship Studies Using Natural and Synthetic Okadaic Acid/Dinophysistoxin Toxins
Mar. Drugs 2016, 14(11), 207; doi:10.3390/md14110207 -
Abstract
Okadaic acid (OA) and the closely related dinophysistoxins (DTXs) are algal toxins that accumulate in shellfish and are known serine/threonine protein phosphatase (ser/thr PP) inhibitors. Phosphatases are important modulators of enzyme activity and cell signaling pathways. However, the interactions between the OA/DTX toxins
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Okadaic acid (OA) and the closely related dinophysistoxins (DTXs) are algal toxins that accumulate in shellfish and are known serine/threonine protein phosphatase (ser/thr PP) inhibitors. Phosphatases are important modulators of enzyme activity and cell signaling pathways. However, the interactions between the OA/DTX toxins and phosphatases are not fully understood. This study sought to identify phosphatase targets and characterize their structure–activity relationships (SAR) with these algal toxins using a combination of phosphatase activity and cytotoxicity assays. Preliminary screening of 21 human and yeast phosphatases indicated that only three ser/thr PPs (PP2a, PP1, PP5) were inhibited by physiologically saturating concentrations of DTX2 (200 nM). SAR studies employed naturally-isolated OA, DTX1, and DTX2, which vary in degree and/or position of methylation, in addition to synthetic 2-epi-DTX2. OA/DTX analogs induced cytotoxicity and inhibited PP activity with a relatively conserved order of potency: OA = DTX1 ≥ DTX2 >> 2-epi-DTX. The PPs were also differentially inhibited with sensitivities of PP2a > PP5 > PP1. These findings demonstrate that small variations in OA/DTX toxin structures, particularly at the head region (i.e., C1/C2), result in significant changes in toxicological potency, whereas changes in methylation at C31 and C35 (tail region) only mildly affect potency. In addition to this being the first study to extensively test OA/DTX analogs’ activities towards PP5, these data will be helpful for accurately determining toxic equivalence factors (TEFs), facilitating molecular modeling efforts, and developing highly selective phosphatase inhibitors. Full article
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Open AccessReview
Chiral Alkyl Halides: Underexplored Motifs in Medicine
Mar. Drugs 2016, 14(11), 206; doi:10.3390/md14110206 -
Abstract
While alkyl halides are valuable intermediates in synthetic organic chemistry, their use as bioactive motifs in drug discovery and medicinal chemistry is rare in comparison. This is likely attributable to the common misconception that these compounds are merely non-specific alkylators in biological systems.
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While alkyl halides are valuable intermediates in synthetic organic chemistry, their use as bioactive motifs in drug discovery and medicinal chemistry is rare in comparison. This is likely attributable to the common misconception that these compounds are merely non-specific alkylators in biological systems. A number of chlorinated compounds in the pharmaceutical and food industries, as well as a growing number of halogenated marine natural products showing unique bioactivity, illustrate the role that chiral alkyl halides can play in drug discovery. Through a series of case studies, we demonstrate in this review that these motifs can indeed be stable under physiological conditions, and that halogenation can enhance bioactivity through both steric and electronic effects. Our hope is that, by placing such compounds in the minds of the chemical community, they may gain more traction in drug discovery and inspire more synthetic chemists to develop methods for selective halogenation. Full article
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Open AccessArticle
New Typical Vector of Neurotoxin β-N-Methylamino-l-Alanine (BMAA) in the Marine Benthic Ecosystem
Mar. Drugs 2016, 14(11), 202; doi:10.3390/md14110202 -
Abstract
The neurotoxin β-N-methylamino-l-alanine (BMAA) has been identified as an environmental factor triggering neurodegenerative diseases such as Amyotrophic Lateral Sclerosis (ALS) and Alzheimer’s disease (AD). We investigated the possible vectors of BMAA and its isomers 2,4-diaminobutyric acid (DAB) and N
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The neurotoxin β-N-methylamino-l-alanine (BMAA) has been identified as an environmental factor triggering neurodegenerative diseases such as Amyotrophic Lateral Sclerosis (ALS) and Alzheimer’s disease (AD). We investigated the possible vectors of BMAA and its isomers 2,4-diaminobutyric acid (DAB) and N-2(aminoethyl)glycine (AEG) in marine mollusks collected from the Chinese coast. Sixty-eight samples of marine mollusks were collected along the Chinese coast in 2016, and were analyzed by an HILIC-MS/MS (hydrophilic interaction liquid chromatography with tandem quadrupole mass spectrometer) method without derivatization. BMAA was detected in a total of five samples from three species: Neverita didyma, Solen strictus, and Mytilus coruscus. The top three concentrations of free-form BMAA (0.99~3.97 μg·g−1 wet weight) were detected in N. didyma. DAB was universally detected in most of the mollusk samples (53/68) with no species-specific or regional differences (0.051~2.65 μg·g−1 wet weight). No AEG was detected in any mollusk samples tested here. The results indicate that the gastropod N. didyma might be an important vector of the neurotoxin BMAA in the Chinese marine ecosystem. The neurotoxin DAB was universally present in marine bivalve and gastropod mollusks. Since N. didyma is consumed by humans, we suggest that the origin and risk of BMAA and DAB toxins in the marine ecosystem should be further investigated in the future. Full article
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Open AccessReview
Ceramide as a Target of Marine Triterpene Glycosides for Treatment of Human Myeloid Leukemia
Mar. Drugs 2016, 14(11), 205; doi:10.3390/md14110205 -
Abstract
Acute myeloid leukemia (AML) is a heterogeneous myeloid clonal disorder exhibiting the accumulation of immature myeloid progenitors in the bone marrow and peripheral blood. Standard AML therapy requires intensive combination chemotherapy, which leads to significant treatment-related toxicity. The search for new, low toxic
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Acute myeloid leukemia (AML) is a heterogeneous myeloid clonal disorder exhibiting the accumulation of immature myeloid progenitors in the bone marrow and peripheral blood. Standard AML therapy requires intensive combination chemotherapy, which leads to significant treatment-related toxicity. The search for new, low toxic marine agents, inducing the generation of ceramide in leukemic cells is a new approach to improve the therapy of leukemia. This review focuses on the metabolism of sphingolipids, the role of ceramide in treating leukemia, and the antitumor activity, related to ceramide metabolism, of some marine metabolites, particularly stichoposides, triterpene glycosides extracted from sea cucumbers of the family Stichopodiidae. Full article
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Open AccessArticle
Natural Products from Microalgae with Potential against Alzheimer’s Disease: Sulfolipids Are Potent Glutaminyl Cyclase Inhibitors
Mar. Drugs 2016, 14(11), 203; doi:10.3390/md14110203 -
Abstract
In recent years, many new enzymes, like glutaminyl cyclase (QC), could be associated with pathophysiological processes and represent targets for many diseases, so that enzyme-inhibiting properties of natural substances are becoming increasingly important. In different studies, the pathophysiology connection of QC to various
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In recent years, many new enzymes, like glutaminyl cyclase (QC), could be associated with pathophysiological processes and represent targets for many diseases, so that enzyme-inhibiting properties of natural substances are becoming increasingly important. In different studies, the pathophysiology connection of QC to various diseases including Alzheimer’s disease (AD) was described. Algae are known for the ability to synthesize complex and highly-diverse compounds with specific enzyme inhibition properties. Therefore, we screened different algae species for the presence of QC inhibiting metabolites using a new “Reverse Metabolomics” technique including an Activity-correlation Analysis (AcorA), which is based on the correlation of bioactivities to mass spectral data with the aid of mathematic informatics deconvolution. Thus, three QC inhibiting compounds from microalgae belonging to the family of sulfolipids were identified. The compounds showed a QC inhibition of 81% and 76% at concentrations of 0.25 mg/mL and 0.025 mg/mL, respectively. Thus, for the first time, sulfolipids are identified as QC inhibiting compounds and possess substructures with the required pharmacophore qualities. They represent a new lead structure for QC inhibitors. Full article
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Open AccessArticle
Biscogniauxone, a New Isopyrrolonaphthoquinone Compound from the Fungus Biscogniauxia mediterranea Isolated from Deep-Sea Sediments
Mar. Drugs 2016, 14(11), 204; doi:10.3390/md14110204 -
Abstract
The properties and the production of new metabolites from the fungal strain LF657 isolated from the Herodotes Deep (2800 m depth) in the Mediterranean Sea are reported in this study. The new isolate was identified as Biscogniauxia mediterranea based on ITS1-5.8S-ITS2 and 28S
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The properties and the production of new metabolites from the fungal strain LF657 isolated from the Herodotes Deep (2800 m depth) in the Mediterranean Sea are reported in this study. The new isolate was identified as Biscogniauxia mediterranea based on ITS1-5.8S-ITS2 and 28S rRNA gene sequences. A new isopyrrolonaphthoquinone with inhibitory activity against glycogen synthase kinase (GSK-3β) was isolated from this fungus. This is the first report of this class of compounds from a fungus isolated from a deep-sea sediment, as well as from a Biscogniauxia species. Full article
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Open AccessArticle
Marine Fungi as Producers of Benzocoumarins, a New Class of Inhibitors of Glycogen-Synthase-Kinase 3β
Mar. Drugs 2016, 14(11), 200; doi:10.3390/md14110200 -
Abstract
The glycogen-synthase-kinase 3 (GSK-3) is an important target in drug discovery. This enzyme is involved in the signaling pathways of type 2 diabetes, neurological disorders, cancer, and other diseases. Therefore, inhibitors of GSK-3 are promising drug candidates for the treatment of a broad
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The glycogen-synthase-kinase 3 (GSK-3) is an important target in drug discovery. This enzyme is involved in the signaling pathways of type 2 diabetes, neurological disorders, cancer, and other diseases. Therefore, inhibitors of GSK-3 are promising drug candidates for the treatment of a broad range of diseases. Here we report pannorin (1), alternariol (2), and alternariol-9-methylether (3) to be promising inhibitors of the isoform GSK-3β showing sub-μM IC50 values. The in vitro inhibition is in the range of the known highly active GSK-3β inhibitor TDZD-8. Compounds 13 have a highly oxygenated benzocoumarin core structure in common, which suggests that this may be a new structural feature for efficient GSK-3β inhibition. Full article
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