Marine Natural Products Chemistry Research Articles

A Mass Spectrometry Database for Sea Cucumber Triterpene Glycosides.

Sea cucumber triterpene glycosides are a class of secondary metabolites that possess distinctive chemical structures and exhibit a variety of biological and pharmacological activities. The application of MS-based approaches for the study of triterpene glycosides allows rapid evaluation of the structural diversity of metabolites in complex mixtures. However, the identification of the detected triterpene glycosides can be challenging. The objective of this study is to establish the first spectral library containing the mass spectra of sea cucumber triterpene glycosides using ultraperformance liquid chromatography-quadrupole time-of-flight mass spectrometry. The library contains the electrospray ionization tandem mass spectra and retention times of 191 triterpene glycosides previously isolated from 15 sea cucumber species and one starfish at the Laboratory of the Chemistry of Marine Natural Products of the G.B. Elyakov Pacific Institute of Bioorganic Chemistry. In addition, the chromatographic behavior and some structure-related neutral losses in tandem MS are discussed. The obtained data will accelerate the accurate dereplication of known triterpene glycosides and the annotation of novel compounds, as we demonstrated by the processing of LC-MS/MS data of Eupentacta fraudatrix extract.

MULTIDISCIPLINARY APPROACH TO ASSESS COMMERCIALLY IMPORTANT MARINE STOCKS IN THE COASTAL WATERS OF THE YUCATAN PENINSULA – CONTRIBUTION BY CCBA-UADY

<p><strong>Background. </strong>Since the formation of the research group in marine biology at the CCBA, different aspects of this discipline have been developed. One of them is the identification of populations and possible stocks of fish of commercial importance, using different techniques.<strong> </strong>The stock delineation (or population structure) are central considerations for fishery assessment and strategic management of marine natural resources and have to be addressed from a meta-population perspective where complementary technical approaches meet to enable the best picture to delineate complex stock structures. <strong>Objective.</strong> To review the current knowledge on the stock concept and the use of a multidisciplinary approach to properly assess commercially important marine stocks in the coastal waters of the Yucatan peninsula. <strong>Methodology. </strong>We present the research explored so far by the marine biology laboratory (LABIOMA by its acronym in Spanish) of the Autonomous University of Yucatán regarding the marine resources off the coast of the Yucatan peninsula, and the future lines of investigation pursued by our personnel, from fishing gear selectivity, abundances and catchability estimates, traditional morphometrics, parasitological and life history traits as biological tags, to more precise analyses such as fish otolith shape or even stable isotope analysis, genotypic markers, and marine natural products chemistry. <strong>Main findings. </strong>Single technical approaches are insufficient to delineate complex stock structures, especially in wide marine open access ecosystems, and there is a need to harness the full power of complementary and synergistic multidisciplinary approaches to improve fishery assessment and management efficiency in marine natural resources from the coastal areas of the Yucatan peninsula. <strong>Implications. </strong>Most stock assessment models are based on a single unit stock assumption, however the full impact of management actions, including identifying the complexity of the stock of any marine species subject to fishing, could affect the perpetuity of its abundances if the population subunits are not properly located. <strong>Conclusion. </strong>Identification of stocks is necessary for several reasons including allocation of catches, recognition and protection of nursery and spawning areas, and for development of optimal harvest and monitoring strategies. To this end, the LABIOMA are strengthening the assessments of commercially important marine stocks by using multidisciplinary approaches, whose lines of research represent basic aspects to be known and would be of great help to decision makers at the time of establishing more precisely, catch quotas, fishing areas, closed seasons, and therefore make more efficient the management strategies.</p>

Genome Sequence of Streptomyces sp. Strain HB-N217, Isolated from the Marine Sponge Forcepia sp.

The genome sequence of the Forcepia sponge-derived bacterium Streptomyces sp. strain HB-N217 was determined, with approximately 8.25 Mbp and a G+C content of 72.1%. Thirty biosynthetic gene clusters that bear the capability to produce secondary metabolites were predicted. The results will aid marine natural product chemistry and sponge-microbe association studies.

The Chemistry, Biochemistry and Pharmacology of Marine Natural Products from Leptolyngbya, a Chemically Endowed Genus of Cyanobacteria.

Leptolyngbya, a well-known genus of cyanobacteria, is found in various ecological habitats including marine, fresh water, swamps, and rice fields. Species of this genus are associated with many ecological phenomena such as nitrogen fixation, primary productivity through photosynthesis and algal blooms. As a result, there have been a number of investigations of the ecology, natural product chemistry, and biological characteristics of members of this genus. In general, the secondary metabolites of cyanobacteria are considered to be rich sources for drug discovery and development. In this review, the secondary metabolites reported in marine Leptolyngbya with their associated biological activities or interesting biosynthetic pathways are reviewed, and new insights and perspectives on their metabolic capacities are gained.

CMNPD: a comprehensive marine natural products database towards facilitating drug discovery from the ocean

Marine organisms are expected to be an important source of inspiration for drug discovery after terrestrial plants and microorganisms. Despite the remarkable progress in the field of marine natural products (MNPs) chemistry, there are only a few open access databases dedicated to MNPs research. To meet the growing demand for mining and sharing for MNPs-related data resources, we developed CMNPD, a comprehensive marine natural products database based on manually curated data. CMNPD currently contains more than 31 000 chemical entities with various physicochemical and pharmacokinetic properties, standardized biological activity data, systematic taxonomy and geographical distribution of source organisms, and detailed literature citations. It is an integrated platform for structure dereplication (assessment of novelty) of (marine) natural products, discovery of lead compounds, data mining of structure-activity relationships and investigation of chemical ecology. Access is available through a user-friendly web interface at https://www.cmnpd.org. We are committed to providing a free data sharing platform for not only professional MNPs researchers but also the broader scientific community to facilitate drug discovery from the ocean.

How can we develop marine natural products chemistry in Indonesia?

In this article, a brief overview of marine natural products (MNPs) is given along with some useful references. The minimum required instruments and information for conducting the related research are reviewed, and the benefits of searching for MNPs in Indonesia are discussed. Several MNPs that are known from Indonesia are then mentioned. In addition to knowing the existing resources, we should place emphasis on the discovery by Indonesian researchers of new molecules having a chemical or biological interest. Finally, some additional information related to natural products is presented.

Search for Protein Tyrosine Phosphatase 1B Inhibitors from Marine Organisms and Induced Production of New Fungal Metabolites by Modulating Culture Methods

Marine environments offer a rich source of natural products with potential therapeutic applications because the ocean covers 70% of the earth's surface and approximately 80% of all living organisms live in the sea. Therefore we have investigated bioactive compounds from marine organisms such as marine sponges, ascidians, and marine-derived microorganisms. This review consists of two topics based on marine natural product chemistry. (1) Protein tyrosine phosphatase (PTP) 1B plays a key role as a negative regulator in the insulin and leptin signaling pathways. Accordingly, the development of PTP1B inhibitors is expected to provide new drugs for type 2 diabetes and obesity. We have been searching for new types of PTP1B inhibitors among marine organisms and identified various PTP1B inhibitors from marine sponges and fungi. This review presents their structural diversities and unique biological properties. (2) In the course of our studies on the induced production of new fungal metabolites, the Palauan marine-derived fungus, Trichoderma cf. brevicompactum TPU199, was found to produce the unusual epipolythiodiketopiperazines, gliovirin and pretrichodermamide A. Long-term static fermentation of the strain induced production of a new dipeptide, dithioaspergillazine A, whereas fermentation of the strain with NaCl, NaBr, and NaI produced the Cl and Br derivatives of pretrichodermamide A and a new iodinated derivative, iododithiobrevamide, respectively. Moreover, DMSO-added seawater medium induced the production of diketopiperazine with the unprecedented trithio-bridge, chlorotrithiobrevamide. This fermentation study on the strain as well as the structures of the metabolites obtained are described in this review.

Natural Products from Marine Invertebrates and Microorganisms in Brazil between 2004 and 2017: Still the Challenges, More Rewards

The Brazilian marine biodiversity represents a unique, yet underexplored resource of biologically active compounds. This review provides an analysis of the development of marine natural products chemistry in Brazil within the period comprised between 2004 and 2017. Emphasis is directed towards marine invertebrate and marine microorganisms metabolites, including isolation, structure analysis, biosynthesis, bioactivities and total synthesis. An overview of the research on marine natural products by Brazilian researchers is also discussed, as well as perspectives for the development of the chemistry of marine natural products in Brazil.

Natural products from Eastern Australian marine invertebrates; A source of drug-like molecules with Staphylococcus aureus inhibitory

Bacteria that cause diseases in humans can rapidly acquire resistance to the antibiotics that are used to eradicate them. As a result of the use and misuse of antibiotics, the number of multidrug resistant (MDR) bacterial strains is on the rise. Over the last thirty years the number of new antibiotics introduced to treat human infections has declined, this observation in combination with rising incidence of MDR bacterial strains have resulted in an urgent need to discover new antibiotics. Of the antibiotics that we currently use, the majority were originally isolated from, or derived from natural sources. The primary focus of this study is the identification of novel natural products, which are bioactive against Staphylococcus aureus. To achieve this, a collection of 500 marine invertebrates, consisting predominantly of sponges, ascidians and bryozoans, were screened against S. aureus. The marine invertebrates were collected from the northern New South Wales region of Australia. The marine invertebrate biodiversity of this region is poorly understood, and thus knowledge relating to their chemistry is virtually non-existent. As a result of this lack of knowledge it was expected the majority of isolated bioactive compounds would be novel. Purified compounds were screened against a suite of S. aureus strains to assess inter-strain resistance/inhibition variations. This presentation will report on the bioactivity, chemistry and selectivity of marine natural products isolated as part of this study.

Marine Drugs Best Paper Award 2014

Marine Drugs initiated a “Best Paper Award” in 2013 [1] to recognize outstanding papers published in our journal in the area of research, development and production of drugs from the sea, including marine natural product chemistry. We are pleased to announce the second “Marine Drugs Best Paper Award” for 2014. Nominations were selected by the Editor-in-Chief, Associate Editors and Editorial Board Members of Marine Drugs from all papers published in 2010; reviews and articles being evaluated separately. [...]

Marine Drugs Best Paper Award 2013

To recognize the most outstanding papers in the area of research, development and production of drugs from the sea, including marine natural product chemistry, that have been published in Marine Drugs, we would like to start an annual “Best Paper Award”. [...]

Investigations of the marine flora and fauna of the Fiji Islands

Over the past 30 years, approximately 140 papers have been published on marine natural products chemistry and related research from the Fiji Islands. These came about from studies starting in the early 1980s by the research groups of Crews at the University of California Santa Cruz, Ireland at the University of Utah, Gerwick from the Scripps Institution of Oceanography, the University of California at San Diego and the more recent groups of Hay at the Georgia Institute of Technology (GIT) and Jaspars from the University of Aberdeen. This review covers both known and novel marine-derived natural products and their biological activities. The marine organisms reviewed include invertebrates, plants and microorganisms, highlighting the vast structural diversity of compounds isolated from these organisms. Increasingly during this period, natural products chemists at the University of the South Pacific have been partners in this research, leading in 2006 to the development of a Centre for Drug Discovery and Conservation (CDDC).

Survey of marine natural product structure revisions: A synergy of spectroscopy and chemical synthesis

The structural assignment of new natural product molecules supports research in a multitude of disciplines that may lead to new therapeutic agents and or new understanding of disease biology. However, reports of numerous structural revisions, even of recently elucidated natural products, inspired the present survey of techniques used in structural misassignments and subsequent revisions in the context of constitutional or configurational errors. Given the comparatively recent development of marine natural products chemistry, coincident with modern spectroscopy, it is of interest to consider the relative roles of spectroscopy and chemical synthesis in the structure elucidation and revision of those marine natural products that were initially misassigned. Thus, a tabulated review of all marine natural product structural revisions from 2005 to 2010 is organized according to structural motif revised. Misassignments of constitution are more frequent than perhaps anticipated by reliance on HMBC and other advanced NMR experiments, especially when considering the full complement of all natural products. However, these techniques also feature prominently in structural revisions, specifically of marine natural products. Nevertheless, as is the case for revision of relative and absolute configuration, total synthesis is a proven partner for marine, as well as terrestrial, natural products structure elucidation. It also becomes apparent that considerable ‘detective work’ remains in structure elucidation, in spite of the spectacular advances in spectroscopic techniques.

Chemistry and Biology of Kahalalides

With drug discovery from marine natural products hailing a renaissance over the past 5 years, the use of marine extracts in the search for biologically active natural products continues to be a powerful approach for the identification of lead compounds for chemistry programs involved in drug discovery.1 Natural products continue to serve as valuable starting points in developing druglike candidates, and the first step in the development of therapeutic agents is the identification of lead compounds that bind to a specific target or receptor of interest.2 Structure-activity relationships (SARs) of lead compounds are then studied by synthesis or semisynthesis of a number of analogues to define the key recognition elements for maximal activity.3 However, the role of natural products in drug discovery became a lower priority in terms of participation by the major pharmaceutical companies by the mid-1990s.4 Reasons for this decline include the perceived disadvantages of natural products, including difficulties in access and supply, structure elucidation and synthesis because of the complexity of natural products, and concerns about intellectual property rights associated with published structures and international collections. In addition, the availability of large collections of compounds prepared by combinatorial chemistry methods provides inexpensive access to large numbers of molecules for random screening and starting materials for rational design.5,6 Nevertheless, the natural products chemistry field has welcomed a renaissance over the past 5 years because of new developments in analytical chemistry, spectroscopy highthroughput screening, and a disappointing number of leads generated through combinatorial chemistry.1,7-9 Currently, basic scientific research in chemistry and biology of marine natural products that started in the 1970s has finally borne fruit for marine-derived drug discovery. Ziconotide (Prialt; Elan Pharmaceuticals), a peptide originally discovered from a tropical cone snail, was the first marine-derived compound approved in the United States in December 2004 for the treatment of pain. Then, in October 2007, trabectedin (Yondelis; PharmaMar) was approved and became the first marine anticancer drug in the European Union. Collaborations between industrial and academic scientists continue to meet the challenges involved in discovering, understanding, and developing new anticancer drugs.10 Several other candidate compounds from marine origins are in the pipeline and are being evaluated in phase I-III clinical trials for the treatment of various cancers in the United States and in Europe.11-13 Here, we review the kahalalides, a family of structurally unrelated depsipeptides isolated from the herbivorous marine mollusk Elysia rufescens, Elysia ornata, or Elysia grandifolia and their algal diet of Bryopsis pennata.14-27 Two of the most active compounds of this family, kahalalide F (KF) (6) and isoKF (22), have been evaluated in phase II clinical trials in hepatocellular carcinoma, non-small-cell lung cancer (NSCLC), and melanoma. Moreover, KF (6) is being evaluated in phase II clinical trials in patients with severe psoriasis.83-93 Of greatest significance is the fact that KF (6) can effectively inhibit receptor tyrosine kinase ErbB3 (HER3) and the phosphatidylinositol 3-kinase-Akt signaling pathways in sensitive cell lines, which suggests that KF (6) and isoKF (22) are involved in an unknown oncosis signaling pathway, though the mechanism of action has not yet been completely characterized.103-107 The kahalalides would represent the first anticancer drugs that can inhibit HER3 receptors.

ChemInform Abstract: Highlights of Marine Natural Products Chemistry (1972-1999)

Marine Natural Products Chemistry is essentially a child of the 1970's that developed rapidly during the 1980's and matured in the last decade. With a few notable exceptions, it is difficult to select individual papers that significantly impacted the field. However, marine natural products chemistry has often influenced other fields and that aspect is the focus of this review. It is clear that the early directions taken by marine natural products chemists drew as much from the examples provided by insect chemical ecology as from the longer history of phytochemistry. By 1975 there were already three parallel tracks in marine natural products chemistry: marine toxins, marine biomedicinals and marine chemical ecology. It is the integration of the three fields of study that has given marine natural products chemistry its unique character and vigour.

Marine Natural Products Chemistry: Past, Present, and Future

Marine metabolites represent an extraordinary pre-assembled pool of biologically active molecular diversity, programmed by evolution to be potent and selective modulators of key biopolymers, cells, tissues, organs, and animals. Over the past half-century the study of these metabolites (Marine Natural Products Chemistry) has evolved into a multidisciplinary endeavour, rich in complementary technologies and methodologies, and embracing diverse objectives and outcomes.

Chemistry and biology of Okinawan marine natural products

Abstract Marine macro- and micro-organisms collected in Okinawa are good sources of compounds with intriguing structures and interesting biological activities. Synthetic hybrid molecules of caffeine and eudistomin D from tunicates Eudistoma sp. were found to show better potency as adenosine receptor ligands than caffeine, and one of them exhibits potent activity for adenosine receptors tested, especially for A3 subtype. Potent cytotoxic polyene macrolides from a tunicate Cystodytes sp. were found to be potent osteoclast inhibitors and to inhibit vacuolar type H+-ATPase (V-ATPase) of both mammalian and yeast cells. Amphidinolactones A and B are new macrolides from a dinoflagellate Amphidinium sp., and a potent cytotoxic macrolide from another strain was found to target actin cytoskeleton. Theonezolide A, a long-chain polyketide from a sponge Theonella sp., induces a drastic shape change in platelets by reorganization of microtubules. The stereochemistry of many chiral centers in theonezolide A was elucidated by spectral data and chemical means. Metachromins L-Q are new sesquiterpenoid quinones with an amino acid residue, while nakijiquinones E and F were the first dimeric sesquiterpenoid quinones possessing a 3-aminobenzoate moiety. Halichonadin E is the first hetero-dimeric sesquiterpenoid with eudesmane and aromadendrane skeletons linked through a urea fragment isolated from a sponge Halichondria sp. Pyrinadine A and nakinadine A are novel bis-pyridine alkaloids from sponges, while nagelamides are new bromopyrrole alkaloids from a sponge Agelas sp. Here, the structures and bioactivities of these interesting marine natural products will be described.

A renaissance in marine pharmacology: From preclinical curiosity to clinical reality

Marine pharmacology, the pharmacology of marine natural products, has been for some time more associated with marine natural products chemistry rather than mainstay pharmacology. However, in recent years a renaissance has occurred in this area of research, and has seen the US Food & Drug Administration (FDA) approval in 2004 of Prialt® (ziconotide, ω-conotoxin MVIIA) the synthetic equivalent of a conopeptide found in marine snails, used for the management of severe chronic pain. Furthermore Yondelis® (trabectedin, ET-743) an antitumor agent discovered in a marine colonial tunicate, and now produced synthetically, receiving Orphan Drug designation from the European Commission (EC) and FDA for soft tissue sarcomas and ovarian cancer and its registration in 2007 in the EU for the treatment of soft tissue sarcoma. The approval/marketing of so few marine natural products has come after many years of research primarily by the academic community and the sporadic involvement of major pharmaceutical companies. This commentary, through the opinions provided by several leaders in the marine natural products field, will examine the potential reasons and perceptions from both the academic and pharmaceutical communities regarding the development of marine natural products as viable therapeutic entities.

Bis and Tris Indole Alkaloids from Marine Organisms: New Leads for Drug Discovery

The marine organisms are a rich source of varied natural products with unique functionality. Marine natural products chemistry has undergone an explosive growth during the past three decades. A variety of natural products of new molecular structures with diverse biological activities have been reported from marine flora and fauna, thus ensuring motivation in the search of newer natural products. The bis and trisindole alkaloids are a class of marine natural products that show unique promise in the development of new drug leads. 3-hydroxy staurosporine 51, an indolo carbazole having powerful antiproliferative activity. Hamacanthin A 1 and B 2, pyrazinone alkaloids have significant antimicrobial activity. Coscinamides 60-62 and Chondriamides 63-65 an indolic enamides which have anti-HIV and cytotoxic activity respectively. Gelluisine A 66 and B 67, trisindole alkaloids have strong anti-serotonin activity and strong affinity with somatostatin and neuropeptide Y receptors in receptor-binding assays. This report reviews the literature on these alkaloids of marine origin and highlights the isolation, structure, latest synthesis and specific biological activities including cytotoxicity, antiviral, antiparasitic, serotonin antagonism and other pharmacological activities of sixty-nine bis and trisindole alkaloids.

The Dawn of Marine Natural Product Chemistry – the Brazilian Origin

The structure of a purple water-soluble pigment from the marine bryozoan, Bugula neritina, has been studied for more than 100 years, but is still entirely unknown. The compound is presumably the first marine natural product to be studied in detail and the first papers to be registered in the literature originate from Brazil.