Marine pharmacology in 2001--2002: marine compounds with anthelmintic, antibacterial, anticoagulant, antidiabetic, antifungal, anti-inflammatory, antimalarial, antiplatelet, antiprotozoal, antituberculosis, and antiviral activities; affecting the cardiovascular, immune and nervous systems and other miscellaneous mechanisms of action

During 2001--2002, research on the pharmacology of marine chemicals continued to be global in nature involving investigators from Argentina, Australia, Brazil, Canada, China, Denmark, France, Germany, India, Indonesia, Israel, Italy, Japan, Mexico, Netherlands, New Zealand, Pakistan, the Philippines, Russia, Singapore, Slovenia, South Africa, South Korea, Spain, Sweden, Switzerland, Thailand, United Kingdom, and the United States. This current article, a sequel to the authors' 1998, 1999 and 2000 marine pharmacology reviews, classifies 106 marine chemicals derived from a diverse group of marine animals, algae, fungi and bacteria, on the basis of peer-reviewed preclinical pharmacology. Anthelmintic, antibacterial, anticoagulant, antifungal, antimalarial, antiplatelet, antiprotozoal, antituberculosis or antiviral activities were reported for 56 marine chemicals. An additional 19 marine compounds were shown to have significant effects on the cardiovascular, immune and nervous system as well as to possess anti-inflammatory and antidiabetic effects. Finally, 31 marine compounds were reported to act on a variety of molecular targets and thus may potentially contribute to several pharmacological classes. Thus, during 2001--2002 pharmacological research with marine chemicals continued to contribute potentially novel chemical leads for the ongoing global search for therapeutic agents for the treatment of multiple disease categories.     

Marine Pharmacology in 2000: Marine Compounds with Antibacterial,Anticoagulant, Antifungal,Anti-inflammatory,Antimalarial, Antiplatelet,Antituberculosis, and Antiviral Activities; Affecting the Cardiovascular,Immune, and Nervous Systems and Other Miscellaneous Mechanisms of Action

During 2000 research on the pharmacology of marine chemicals involved investigators from Australia, Brazil, Canada, Egypt, France, Germany, India, Indonesia, Israel, Italy, Japan, the Netherlands, New Zealand, Phillipines, Singapore, Slovenia, South Korea, Spain, Sweden, Switzerland, United Kingdom, and the United States. This current review, a sequel to the authors 1998 and 1999 reviews, classifies 68 peer-reviewed articles on the basis of the reported preclinical pharmacologic properties of marine chemicals derived from a diverse group of marine animals, algae, fungi, and bacteria. Antibacterial, anticoagulant, antifungal, antimalarial, antiplatelet, antituberculosis, or antiviral activity was reported for 35 marine chemicals. An additional 20 marine compounds were shown to have significant effects on the cardiovascular and nervous system, and to possess anti-inflammatory or immunosuppressant properties. Finally, 23 marine compounds were reported to act on a variety of molecular targets and thus could potentially contribute to several pharmacologic classes. Thus, as in 1998 and 1999, during 2000 pharmacologic research with marine chemicals continued to contribute potentially novel chemical leads to the ongoing global search for therapeutic agents in the treatment of multiple disease categories.     

Marine pharmacology in 2005–6: Marine compounds with anthelmintic,antibacterial, anticoagulant,antifungal, anti-inflammatory,antimalarial, antiprotozoal,antituberculosis, and antiviral activities; affecting the cardiovascular,immune and nervous systems,and other miscellaneous mechanisms of action

Background

The review presents the 2005–2006 peer-reviewed marine pharmacology literature, and follows a similar format to the authors' 1998–2004 reviews. The preclinical pharmacology of chemically characterized marine compounds isolated from marine animals, algae, fungi and bacteria is systematically presented.

Results

Anthelmintic, antibacterial, anticoagulant, antifungal, antimalarial, antiprotozoal, antituberculosis and antiviral activities were reported for 78 marine chemicals. Additionally 47 marine compounds were reported to affect the cardiovascular, immune and nervous system as well as possess anti-inflammatory effects. Finally, 58 marine compounds were shown to bind to a variety of molecular targets, and thus could potentially contribute to several pharmacological classes.

Conclusions

Marine pharmacology research during 2005–2006 was truly global in nature, involving investigators from 32 countries, and the United States, and contributed 183 marine chemical leads to the research pipeline aimed at the discovery of novel therapeutic agents.

General significance

Continued preclinical and clinical research with marine natural products demonstrating a broad spectrum of pharmacological activity will probably result in novel therapeutic agents for the treatment of multiple disease categories.     

Marine pharmacology in 2007–8: Marine compounds with antibacterial,anticoagulant, antifungal,anti-inflammatory,antimalarial, antiprotozoal,antituberculosis, and antiviral activities; affecting the immune and nervous system,and other miscellaneous mechanisms of action

The peer-reviewed marine pharmacology literature in 2007–8 is covered in this review, which follows a similar format to the previous 1998–2006 reviews of this series. The preclinical pharmacology of structurally characterized marine compounds isolated from marine animals, algae, fungi and bacteria is discussed in a comprehensive manner. Antibacterial, anticoagulant, antifungal, antimalarial, antiprotozoal, antituberculosis and antiviral activities were reported for 74 marine natural products. Additionally, 59 marine compounds were reported to affect the cardiovascular, immune and nervous systems as well as to possess anti-inflammatory effects. Finally, 65 marine metabolites were shown to bind to a variety of receptors and miscellaneous molecular targets, and thus upon further completion of mechanism of action studies, will contribute to several pharmacological classes. Marine pharmacology research during 2007–8 remained a global enterprise, with researchers from 26 countries, and the United States, contributing to the preclinical pharmacology of 197 marine compounds which are part of the preclinical marine pharmaceuticals pipeline. Sustained preclinical research with marine natural products demonstrating novel pharmacological activities, will probably result in the expansion of the current marine pharmaceutical clinical pipeline, which currently consists of 13 marine natural products, analogs or derivatives targeting a limited number of disease categories.     

Marine pharmacology in 1999: compounds with antibacterial,anticoagulant, antifungal,anthelmintic, anti-inflammatory,antiplatelet, antiprotozoal and antiviral activities affecting the cardiovascular,endocrine, immune and nervous systems,and other miscellaneous mechanisms of action

This review, a sequel to the 1998 review, classifies 63 peer-reviewed articles on the basis of the reported preclinical pharmacological properties of marine chemicals derived from a diverse group of marine animals, algae, fungi and bacteria. In all, 21 marine chemicals demonstrated anthelmintic, antibacterial, anticoagulant, antifungal, antimalarial, antiplatelet, antituberculosis or antiviral activities. An additional 23 compounds had significant effects on the cardiovascular, sympathomimetic or the nervous system, as well as possessed anti-inflammatory, immunosuppressant or fibrinolytic effects. Finally, 22 marine compounds were reported to act on a variety of molecular targets, and thus could potentially contribute to several pharmacological classes. Thus, during 1999 pharmacological research with marine chemicals continued to contribute potentially novel chemical leads in the ongoing global search for therapeutic agents for the treatment of multiple disease categories.     

An Assessment of Toxic Substances Pollution in the Hong Kong Marine Environment

The Environmental Protection Department (EPD) of the Hong Kong Special Administrative Region Government (HKSARG) commissioned a consultancy study in 1999 to better understand the potential sources, fates, and existing pollution state of toxic substances in Hong Kong's marine environment. A desk-top survey and assessment was first performed on a comprehensive initial list of 556 toxic substances. A Preliminary Priority Toxic Substances List (PPTSL) of 135 chemicals was established, consisting of heavy metals, inorganic compounds, organo-metallic compounds, and trace organics. A territory-wide baseline field sampling and laboratory analysis exercise was then undertaken during 2001–2002 to determine the level of these PPTSL chemicals in the potential pollution sources (effluent discharges, stormwater discharges, air deposition) and the receiving marine environment (water, sediment, biota). A draft Priority Toxic Substances List (PTSL) was developed, taking into account chemicals detected in the local marine environment and those listed under the Stockholm Convention, the Rotterdam Convention, and the International Maritime Organization's Harmful Antifouling System Convention. The draft PTSL chemicals were subject to ecological and incremental human health risk assessments. Based on the risk assessment results, 17 Chemicals of Potential Concern (COPC) for Hong Kong's marine environment were identified, most of which were heavy metals in the sediment. The study findings suggest that Hong Kong's marine environment is not widely polluted with chemicals present at concentrations of toxicological concern. Although a number of potentially problematic pollutants (COPC) were identified, they are confined to a few “hot spots” and are unlikely to pose a territory-wide risk. Based on the study recommendations, the EPD initiated in 2004 a toxic substances monitoring program to keep the COPC in the marine environment under close surveillance.     

Achievements in the Study of Marine Low‐Molecular Weight Biologically Active Metabolites from the Vietnamese Territorial Waters as a Result of Expeditions aboard the Research Vessel ‘Akademik Oparin’ (2004–2017)

Until 2004, the secondary metabolites of marine organisms of the Vietnamese territorial waters had been studied very poorly. Only four new compounds were isolated from 1977 to 2003. Joint Russian‐Vietnamese expeditions aboard the research vessel ‘Akademik Oparin’ made it possible to study in detail the chemical diversity of marine micro‐ and macroorganisms. As a result of five expeditions, more than 250 low‐molecular weight natural compounds, including 117 new metabolites, were isolated from marine invertebrates and microfilamentous fungi. Their biological activities, such as cytotoxic, cytoprotective, and antioxidant activities, were investigated. Information about the structure and biological activity of the compounds, the source for their isolation and the geographical location of the objects is summarized in this review.     

Population dynamics of Aphis glycines (Homoptera: Aphididae) and impact of natural enemies in northern China

Field surveys of soybean aphid, Aphis glycines Matsumura, and its natural enemies, as well as natural enemy exclosure experiments, were conducted during 2003 and 2004 in soybean fields near Langfang, China. In 2003, aphid density increased six-fold during 12 d in July from 66+/-12 per 10 plants to a seasonal peak of 401+/-79 per 10 plants. Aphid density remained high for another 10 d and declined during late July and early August. In 2004, aphid density increased 29-fold during 13 d in July from 14+/-2 per 10 plants to a seasonal peak of 375+/-30 per 10 plants. Unlike 2003, aphid density remained relatively high during late July and August, peaking again at 296+/-31 per 10 plants on 24 August. In both years, aphid density remained below economic injury level and seemed to be limited by natural enemies. Exclosure of natural enemies led to increases in A. glycines density in 2003 and 2004. In 2003, peak aphid densities in large- and medium-mesh cages were three- and seven-fold higher, respectively, than densities on uncaged plants. In 2004, peak aphid densities in large- and medium-mesh cages were 2-fold and 30-fold higher, respectively, than densities on uncaged plants in one experiment. In another experiment, peak aphid densities in large-, medium-, and small-mesh cages were 8-fold, 28-fold, and 68-fold higher, respectively, than densities on uncaged plants. Both predators and parasitoids were important in limiting aphid density. We compare our results with those from North America and discuss implications for biological control.     

Trends in the postfortification prevalence of spina bifida and anencephaly in the United States

BACKGROUND: The prevalence of NTDs in the US declined significantly after mandatory folic acid fortification; however, it is not known if the prevalence of NTDs has continued to decrease in recent years relative to the period immediately following the fortification mandate. METHODS: Population‐based data from 21 birth defects surveillance systems were used to examine trends in the birth prevalence of spina bifida and anencephaly during 1999–2000, 2001–2002, and 2003–2004. Prevalence data were stratified by non‐Hispanic White, non‐Hispanic Black, and Hispanic race or ethnicity. Prevalence ratios were calculated by dividing the birth prevalences during the later time periods (2001–2002 and 2003–2004) by the birth prevalences during 1999–2000. RESULTS: During 1999–2004, 3,311 cases of spina bifida and 2,116 cases of anencephaly were reported. Hispanic infants had the highest prevalences of NTDs for all years. For all infants, the combined birth prevalences of spina bifida and anencephaly decreased 10% from the 1999–2000 period to the 2003–2004 period. The decline in spina bifida (3%) was not significant; however the decline in anencephaly (20%) was statistically significant. CONCLUSIONS: While the prevalences of spina bifida and anencephaly in the United States have declined since folic acid fortification in the food supply began, these data suggest that reductions in the prevalence of anencephaly continued during 2001–2004 and that racial and ethnic and other disparities remain. Birth Defects Research (Part A), 2008. © 2008 Wiley‐Liss, Inc.     

Glutamate receptor ligands: synthesis, stereochemistry, and enantiopharmacology of methylated 2-aminoadipic acid analogs

Homologation and substitution on the carbon backbone of (S)-glutamic acid [(S)-Glu, 1], as well as absolute stereochemistry, are structural parameters of key importance for the pharmacological profile of (S)-Glu receptor ligands. We describe a series of methyl-substituted 2-aminoadipic acid (AA) analogs, and the synthesis, stereochemistry, and enantiopharmacology of 3-methyl-AA (4a-d), 4-methyl-AA (5a-d), 5-methyl-AA (6a-d), and (E)-Delta(4)-5-methyl-AA (7a and 7b) are reported. The compounds were resolved using chiral HPLC and the configurational assignments of the enantiomers were based on X-ray crystallographic analyses, chemical correlation, and CD spectral analyses. The effects of the individual stereoisomers at ionotropic and metabotropic (S)-Glu receptors (iGluRs and mGluRs) were characterized. Compounds with S-configuration at the alpha-carbon generally showed mGluR2 agonist activity of similar or slightly lower potencies than (S)-AA [e.g., EC(50) = 76 microM for (2S,4S)-4-methyl-AA (5a) as compared to EC(50) = 35 microM for (S)-AA]. The position of the methyl substituent had a profound effect on the observed pharmacology, whereas the absolute stereochemistry at the methylated carbon atom had a very limited effect on pharmacology. Structure-activity relationships at iGluRs in the rat cortical wedge preparation showed a complex pattern, some compounds being NMDA receptor agonists [e.g., EC(50) =110 microM for (2S,5RS)-5-methyl-AA (6a,b)] and some compounds showing NMDA receptor antagonist effects [e.g., IC(50) = 300 microM for (2R,4S)-4-methyl-AA (5d)]. The two unsaturated analogs (S)- (7a) and (R)-(E)-Delta(4)-5-methyl-AA (7b) turned out to be a weak AMPA receptor agonist and a weak mixed NMDA/AMPA receptor antagonist, respectively.     

Monitoring of diamondback moth (Lepidoptera: Plutellidae) resistance to spinosad, indoxacarb, and emamectin benzoate

Six to nine populations of the diamondback moth, Plutella xylostella (L.), were collected annually from fields of crucifer vegetables in the United States and Mexico from 2001 to 2004 for baseline susceptibility tests and resistance monitoring to spinosad, indoxacarb, and emamectin benzoate. A discriminating concentration for resistance monitoring to indoxacarb and emamectin benzoate was determined based on baseline data in 2001 and was used in the diagnostic assay for each population in 2002-2004 together with a discriminating concentration for spinosad determined previously. Most populations were susceptible to all three insecticides, but a population from Hawaii in 2003 showed high levels of resistance to indoxacarb. Instances of resistance to spinosad occurred in Hawaii (2000), Georgia (2001), and California (2002) as a consequence of a few years of extensive applications in each region. The collaborative monitoring program between university and industry scientists we discuss in this article has provided useful information to both parties as well as growers who use the products. These studies provide a baseline for developing a more effective resistance management program for diamondback moth.     

Polyketides from dinoflagellates: origins, pharmacology and biosynthesis

Dinoflagellates, unicellular marine protists, produce some of the largest and most complex polyketides identified to date. The biological activities of these compounds are quite diverse. Compounds having potential therapeutic value as anti-cancer agents as well as deadly neurotoxins, whose production has resulted in severe public health hazards and economic hardships, are represented in this group of secondary metabolites. Stable isotope feeding experiments have firmly established the polyketide origins of representative compounds from each of the three structural classes, the polyether ladders, the macrocycles and the linear polyethers. Yet some unusual labeling patterns have been observed in each class. Pendant methyl groups are most often derived from C-2 of acetate and deletions of C-1 of acetate are common. Studies on the biosynthesis of dinoflagellate derived polyketides at the genomic level have not been reported, in part due to the peculiarities of the dinoflagellate nucleus and the lack of a dinoflagellate transformation system. Nevertheless, a fundamental understanding of the genetics of polyketide biosynthesis by dinoflagellates could be the catalyst for developing several fruitful avenues of research. Dinoflagellate derived polyketides are reviewed with special emphasis on pharmacology and biosynthesis.     

Response to oxygen deficiency (depletion): Bivalve assemblages as an indicator of ecosystem instability in the northern Adriatic Sea

Benthic communities represent a powerful tool for the detection of natural and anthropogenic disturbances, as well as for the assessment of marine ecosystem stability. This paper shows that bivalve assemblages could serve as excellent indicators of disturbance and ecosystem instability. The goal of this study was to compare two sets of data in order to determine the differences between two different periods belonging to bivalve assemblage in the muddy detritic bottom of the northern Adriatic Sea in the post-anoxic period during December 1989, 1990, 1991 and quite a while later, during 2003, 2004 and 2005. Abundances of some indicator species such as Corbula gibba, Modiolarca subpicta and Timoclea ovata were detected during the post-anoxic period. Recruitment in the quality of bivalve assemblages was proved by the ecologic and biotic indexes during 2003, 2004 and 2005, during a period of relatively stable ecological conditions. Fluctuation in bivalve diversity due to the ecological quality of the marine ecosystem in the eastern part of the northern Adriatic Sea is also discussed.     

Chemical induction of settlement and metamorphosis of Capitella capitata Sp. I (Polychaeta) larvae by juvenile hormone-active compounds

Summary

The influence of juvenile hormone (JH)-active chemicals on the settlement and metamorphosis of metatrochophore larvae of the polychaete annelid Capitella sp. I of the Capitella complex has been investigated. These studies demonstrate that JH-active chemicals are able to induce settlement and metamorphosis of Capitella larvae, and that these effects may possibly be mediated by protein kinase C induction. Evidence for the presence of JH-active compounds in marine sediments is also presented, suggesting that these chemicals may serve a natural role as chemical cues for settlement and metamorphosis for Capitella larvae in the marine environment.     

三种前鳃亚纲海产腹足类性畸变现象的组织学研究

有机锡污染可以导致海产腹足类雌性个体产生性畸变现象。本文报道了阿文绶贝(Mauritia arabica)、褐棘螺(Chicoreus brunneus)和桶形芋螺(Conus betulinus)三种前鳃亚纲腹足类正常雄性个体和性畸变个体雄性生殖器官的组织学结构。结果表明,不同种间雄性个体的输精管和阴茎的结构存在开放和封闭两种类型,封闭型是由开放型进化而来。虽然性畸变个体的雄性生殖器官与正常雄性个体的在组织结构上无明显差异,但性畸变个体的雄性生殖器官并不完整,无法行使生殖功能。由于内分泌扰乱物质对人和动物影响的相似性,使得海产腹足类性畸变现象应受到人们的重视。     

What Hydra can teach us about chemical ecology -how a simple, soft organism survives in a hostile aqueous environment

Hydra and its fellow cnidarians - sea anemones, corals and jellyfish - are simple, mostly sessile animals that depend on bioactive chemicals for survival. In this review, we briefly describe what is known about the chemical armament of Hydra, and detail future research directions where Hydra can help illuminate major questions in chemical ecology, pharmacology, developmental biology and evolution. Focusing on two groups of putative toxins from Hydra - phospholipase A2s and proteins containing ShK and zinc metalloprotease domains, we ask: how do different venom components act together during prey paralysis? How is a venom arsenal created and how does it evolve? How is the chemical arsenal delivered to its target? To what extent does a chemical and biotic coupling exist between an organism and its environment? We propose a model whereby in Hydra and other cnidarians, bioactive compounds are secreted both as localized point sources (nematocyte discharges) and across extensive body surfaces, likely combining to create complex "chemical landscapes". We speculate that these cnidarian-derived chemical landscapes may affect the surrounding community on scales from microns to, in the case of coral reefs, hundreds of kilometers.     

Anaemia, hypothyroidism and immune suppression associated with polychlorinated biphenyl exposure in bottlenose dolphins (Tursiops truncatus)

Polychlorinated biphenyls (PCBs), persistent chemicals widely used for industrial purposes, have been banned in most parts of the world for decades. Owing to their bioaccumulative nature, PCBs are still found in high concentrations in marine mammals, particularly those that occupy upper trophic positions. While PCB-related health effects have been well-documented in some mammals, studies among dolphins and whales are limited. We conducted health evaluations of bottlenose dolphins (Tursiops truncatus) near a site on the Georgia, United States coast heavily contaminated by Aroclor 1268, an uncommon PCB mixture primarily comprised of octa- through deca-chlorobiphenyl congeners. A high proportion (26%) of sampled dolphins suffered anaemia, a finding previously reported from primate laboratory studies using high doses of a more common PCB mixture, Aroclor 1254. In addition, the dolphins showed reduced thyroid hormone levels and total thyroxine, free thyroxine and triiodothyronine negatively correlated with PCB concentration measured in blubber (p = 0.039, < 0.001, 0.009, respectively). Similarly, T-lymphocyte proliferation and indices of innate immunity decreased with blubber PCB concentration, suggesting an increased susceptibility to infectious disease. Other persistent contaminants such as DDT which could potentially confound results were similar in the Georgia dolphins when compared with previously sampled reference sites, and therefore probably did not contribute to the observed correlations. Our results clearly demonstrate that dolphins are vulnerable to PCB-related toxic effects, at least partially mediated through the endocrine system. The severity of the effects suggests that the PCB mixture to which the Georgia dolphins were exposed has substantial toxic potential and further studies are warranted to elucidate mechanisms and potential impacts on other top-level predators, including humans, who regularly consume fish from the same marine waters.     

Mini-review: Marine natural products and their synthetic analogs as antifouling compounds: 2009–2014

This review covers 214 marine natural compounds and 23 of their synthetic analogs, which were discovered and/or synthesized from mid-2009 to August 2014. The antifouling (AF) compounds reported have medium to high bioactivity (with a threshold of EC₅₀ < 15.0 mg ml^?1). Among these compounds, 82 natural compounds were identified as new structures. All the compounds are marine-derived, demonstrating that marine organisms are prolific and promising sources of natural products that may be developed as environmentally friendly antifoulants. However, this mini-review excludes more than 200 compounds that were also reported as AF compounds but with rather weak bioactivity during the same period. Also excluded are terrestrial-derived AF compounds reported during the last five years. A brief discussion on current challenges in AF compound research is also provided to reflect the authors’ own views in terms of future research directions.