Marine Pharmacology Research Articles

Marine pharmacology: an ocean to explore novel drugs

The rise in burden of diseases and treatment failure demands discovery of novel compounds. Exploiting natural sources which include territory of land and water in potential manner paves the way for significant future innovations in drug discovery. Marine environment has striking functionalities in its skeleton that has fascinated scientists to show enormous interest in investigation of new compounds. Marine sponges, algae, tunicates, sea whip etc. from the marine pipeline are the important sources for biological active compounds. Recent technology advancements further added to the domain of drug research in isolation and evaluation of marine derived products. To date, significant number of compounds have been isolated. Wide range of antibacterial, anti-inflammatory, antiparasitic, neuroprotective, antiviral, anticancer, analgesic, antimicrobial, antimalarial compounds have been pursued in control and management of diseases. These represent marine ecosystem as a hopeful resource in discovery of novel compounds with ideal starting point in scaffolding additional screening of natural marine products. This is review of abstracting on history, lead development process in identifying and comprehending basic nature of compounds that is promising initial step towards unique pharmacological design, the triumph of approved and ongoing trails, brief depiction on current status and challenges being faced in marine drug discovery field.

The Marine Pharmacology and Pharmaceuticals Pipeline in 2020

The ocean’s organisms continue to deliver a chemical biodiversity that contributes to both the global preclinical and clinical pharmaceutical pipelines. Thus, in November 2019, the clinical marine pharmaceutical pipeline consisted of 9 approved marine‐derived drugs: for Herpes Simplex Virus, vidarabine (Vira‐A®, FDA‐approved 1976); for pain, ziconotide (Prialt®, FDA‐approved 2004); for hypertriglyceridemia, omega‐3‐acid ethyl esters (Lovaza®, FDA‐approved 2004); and for cancer, cytarabine (Cytosar‐U®, Depocyt®, FDA‐approved 1969);, eribulin mesylate (Halaven®, FDA‐approved 2010), brentuximab vedotin (Adcetris®, FDA‐approved 2011), trabectedin (Yondelis®, EU approved 2008, FDA‐approved 2015), plitidepsin (Aplidine®) approved in Australia in 2018 and polatuzumab vedotin (POLIVY®, FDA‐approved 2019). The website www.clinicaltrials.gov was researched for marine‐derived compounds in Phase I, Phase II and Phase III: Our research determined that there were 31 marine‐derived compounds in active clinical trials: 5 marine‐derived compounds were in Phase III, 13 compounds in Phase II, and at least 9 compounds in Phase I, several auristatin‐containing antibody drug conjugates or ADCs. Regular updates on the clinical marine pharmaceutical pipeline are posted on: https://www.midwestern.edu/departments/marinepharmacology.xmlFurthermore, it is important to note that the global preclinical marine pharmacology pipeline continues to generate considerable data on multiple pharmacological classes. We thus conclude that in November 2019, both the marine pharmacology preclinical and clinical pharmaceutical pipelines remained very active.Support or Funding InformationCollege of Pharmacy, Vicki Sears, Pharmacology Department, College of Graduate Studies and Office of Research and Sponsored Programs, Midwestern University

Marine Pharmacology in 2014-2015: Marine Compounds with Antibacterial, Antidiabetic, Antifungal, Anti-Inflammatory, Antiprotozoal, Antituberculosis, Antiviral, and Anthelmintic Activities; Affecting the Immune and Nervous Systems, and Other Miscellaneous Mechanisms of Action.

The systematic review of the marine pharmacology literature from 2014 to 2015 was completed in a manner consistent with the 1998–2013 reviews of this series. Research in marine pharmacology during 2014–2015, which was reported by investigators in 43 countries, described novel findings on the preclinical pharmacology of 301 marine compounds. These observations included antibacterial, antifungal, antiprotozoal, antituberculosis, antiviral, and anthelmintic pharmacological activities for 133 marine natural products, 85 marine compounds with antidiabetic, and anti-inflammatory activities, as well as those that affected the immune and nervous system, and 83 marine compounds that displayed miscellaneous mechanisms of action, and may probably contribute to novel pharmacological classes upon further research. Thus, in 2014–2015, the preclinical marine natural product pharmacology pipeline provided novel pharmacology as well as new lead compounds for the clinical marine pharmaceutical pipeline, and thus continued to contribute to ongoing global research for alternative therapeutic approaches to many disease categories.

Marine biomaterials: Biomimetic and pharmacological potential of cultivated Aplysina aerophoba marine demosponge.

Marine demosponges of the Verongiida order are considered a gold-mine for bioinspired materials science and marine pharmacology. The aim of this work was to simultaneously isolate selected bromotyrosines and unique chitinous structures from A. aerophoba and to propose these molecules and biomaterials for possible application as antibacterial and antitumor compounds and as ready-to-use scaffolds for cultivation of cardiomyocytes, respectively. Among the extracted bromotyrosines, the attention has been focused on aeroplysinin-1 that showed interesting unexpected growth inhibition properties for some Gram-negative clinical multi-resistant bacterial strains, such as A. baumannii and K. pneumoniae, and on aeroplysinin-1 and on isofistularin-3 for their anti-tumorigenic activity. For both compounds, the effects are cell line dependent, with significant growth inhibition activity on the neuroblastoma cell line SH-SY5Y by aeroplysinin-1 and on breast cancer cell line MCF-7 by isofistularin-3. In this study, we also compared the cultivation of human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) on the A. aerophoba chitinous scaffolds, in comparison to chitin structures that were pre-coated with Geltrex™, an extracellular matrix mimetic which is used to enhance iPSC-CM adhesion. The iPSC-CMs on uncoated and pure chitin structures started contracting 24h after seeding, with comparable behaviour observed on Geltrex-coated cell culture plates, confirming the biocompatibility of the sponge biomaterial with this cell type. The advantage of A. aerophoba is that this source organism does not need to be collected in large quantities to supply the necessary amount for further pre-clinical studies before chemical synthesis of the active compounds will be available. A preliminary analysis of marine sponge bioeconomy as a perspective direction for application of biomaterials and secondary bioactive metabolites has been finally performed for the first time.

ANALISIS ARTIKEL ILMIAH BIDANG ILMU MARITIM DALAM MENDUKUNG REPOSITORI NASIONAL

The aim of this research are to find out: (1) data proceed from database with the topic maritime and marine that can access by the user through the OPAC: (2) precision of the data in database: (3) the precision between data proceed by the standard tabulation of literature (keyword) and title in database; (4) the precision between data was inputed with content and metadata field. Result of the extract data from ISJD is descriptor (keyword) Maritime Field (25 pieces keyword from 609 article title) tabulated and made the matrix by excel office. Data that have been collected will be validated base on the recall result, and the precision it will be analyzed descriptively. It found that in Maritime field the descriptor used as keyword was 25 pieces. The keywords were: marine alga as food, ocean mining, marine park and reserves, marine chemical ecology, marine biodiversity, marine law, maritime policy, maritime industry, marine mineral resources, maritime safety, marine biological diversity, loading and unloading, marine ecosystem, marine resources, marine pharmacology, marine resources conservation, marine ecology, marine tourism, marine fisheries, marine environmental, ports, marine shipping, marine pollution, maritime law, and marine transportation. The number of article is found based on keywords.

The Marine Pharmacology and Pharmaceuticals Pipeline in 2018

The ocean's organisms continue to deliver a chemical biodiversity that contributes to both the global preclinical and clinical pharmaceutical pipelines. Thus, in November 2018, the clinical marine pharmaceutical pipeline consisted of seven marine‐derived drugs approved by the United States Food and Drug Administration (FDA): for cancer, cytarabine (Cytosar‐U®, Depocyt®, FDA‐approved 1969); for Herpes Simplex Virus, vidarabine (Vira‐A®, FDA‐approved 1976); for pain, ziconotide (Prialt®, FDA‐approved 2004); for hypertriglyceridemia, omega‐3‐acid ethyl esters (Lovaza®, FDA‐approved 2004); for cancer, eribulin mesylate (Halaven®, FDA‐approved 2010), brentuximab vedotin (Adcetris®, FDA‐approved 2011), and trabectedin (Yondelis®, FDA‐approved 2015). The website www.clinicaltrials.gov was searched to determine marine‐derived pharmaceuticals that were in Phase I, Phase II and Phase III of clinical development in November 2018. Confirmation of our findings in the www.clinicaltrials.gov website was conducted by visiting the websites of all pharmaceutical companies supporting the development of compounds currently in Phase I, Phase II and Phase III of clinical development. Our clinical research determined that there were 25 marine‐derived compounds in active clinical trials in November 2018: 6 marine‐derived compounds were in Phase III, 10 compounds in Phase II, and at least 9 compounds in Phase I, many of them auristatin‐containing antibody drug conjugates or ADCs. Regular updates on the clinical marine pharmaceutical pipeline will be posted on the dedicated website: http://marinepharmacology.midwestern.edu/clinical_pipeline.html. Furthermore, it is important to note that the global preclinical marine pharmacology pipeline continues to generate considerable data on multiple pharmacological classes, as highlighted in a recent review: A. M. S. Mayer, A. D. Rodríguez, O. Taglialatela‐Scafati and N. Fusetani. Marine Pharmacology in 2012–2013: Marine Compounds with Antibacterial, Antidiabetic, Antifungal, Anti‐Inflammatory, Antiprotozoal, Antituberculosis, and Antiviral Activities; Affecting the Immune and Nervous Systems, and other Miscellaneous Mechanisms of Action. Marine Drugs 15 (9): 273, 2017. We thus conclude that in November 2018, both the marine pharmacology preclinical and clinical pharmaceutical pipelines continued to remain very active.Support or Funding InformationSupport by the College of Pharmacy, Vicki Sears, Pharmacology Department, College of Graduate Studies and Elizabeth Tallman, Information Technology Services, Midwestern University are gratefully acknowledged.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

The Marine Pharmacology and Pharmaceuticals Pipeline in 2017

The ocean's organisms continue to deliver a chemical biodiversity that contributes to both the global preclinical and clinical pharmaceutical pipelines. Thus, in November 2017, the clinical marine pharmaceutical pipeline consisted of six marine‐derived drugs approved by the United States Food and Drug Administration (FDA): for cancer, cytarabine (Cytosar‐U®, Depocyt®, FDA‐approved 1969); for pain, ziconotide (Prialt®, FDA‐approved 2004); for hypertriglyceridemia, omega‐3‐acid ethyl esters (Lovaza®, FDA‐approved 2004); for cancer, eribulin mesylate (Halaven®, FDA‐approved 2010), brentuximab vedotin (Adcetris®, FDA‐approved 2011), and trabectedin (Yondelis®, FDA‐approved 2015). Furthermore, there were 23 marine‐derived compounds in clinical trials: 6 marine‐derived compounds in Phase III, 8 compounds in Phase II, and at least 9 compounds in Phase I, many of them auristatin‐containing antibody drug conjugates. Regular updates on the clinical marine pharmaceutical pipeline are posted at http://marinepharmacology.midwestern.edu/clinPipeline.htm. Furthermore, the global preclinical marine pharmacology pipeline continues to generate considerable data on multiple pharmacological classes, as highlighted in a recent review: A. M. S. Mayer, A. D. Rodríguez, O. Taglialatela‐Scafati and N. Fusetani. Marine Pharmacology in 2012–2013: Marine Compounds with Antibacterial, Antidiabetic, Antifungal, Anti‐Inflammatory, Antiprotozoal, Antituberculosis, and Antiviral Activities; Affecting the Immune and Nervous Systems, and other Miscellaneous Mechanisms of Action. Marine Drugs 15 (9): 273, 2017. We thus conclude that in November 2017, both the marine pharmacology preclinical and clinical pharmaceutical pipelines continued to remain very active.Support or Funding InformationSupported by Midwestern University.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Marine pharmacology: Potential, challenges, and future in India

More than 50% of the marketed drugs today are derived from natural sources. There are various cancers and diseases which cannot be managed well with the current available drugs. It is, therefore, important to identify new sources of drugs for the future. The biological diversity offered by the oceans shows promise in expressing some lead compounds for diseases which show a dearth of drug options for management. A handful of marine products have been approved by the United States – Food and Drug Administration (US-FDA) because of the involvement of academia and the pharmaceutical industry. However, there are many challenges involved which deter a better and faster process for drug development from marine sources. The current scenario in India is in a nascent phase, but steps are being taken in the right direction to develop a potential source of new drugs. In this review article, we try to give an overview over the history and impending potential of marine pharmacology, with an overlook on the current approved marine-sourced drugs by the US-FDA. We also take a brief look over the challenges involved in the field of marine pharmacology, its current progress in India and possible future scope.

Marine Pharmacology in 2012-2013: Marine Compounds with Antibacterial, Antidiabetic, Antifungal, Anti-Inflammatory, Antiprotozoal, Antituberculosis, and Antiviral Activities; Affecting the Immune and Nervous Systems, and Other Miscellaneous Mechanisms of Action.

The peer-reviewed marine pharmacology literature from 2012 to 2013 was systematically reviewed, consistent with the 1998–2011 reviews of this series. Marine pharmacology research from 2012 to 2013, conducted by scientists from 42 countries in addition to the United States, reported findings on the preclinical pharmacology of 257 marine compounds. The preclinical pharmacology of compounds isolated from marine organisms revealed antibacterial, antifungal, antiprotozoal, antituberculosis, antiviral and anthelmitic pharmacological activities for 113 marine natural products. In addition, 75 marine compounds were reported to have antidiabetic and anti-inflammatory activities and affect the immune and nervous system. Finally, 69 marine compounds were shown to display miscellaneous mechanisms of action which could contribute to novel pharmacological classes. Thus, in 2012–2013, the preclinical marine natural product pharmacology pipeline provided novel pharmacology and lead compounds to the clinical marine pharmaceutical pipeline, and contributed significantly to potentially novel therapeutic approaches to several global disease categories.

HIV-1 Protease Inhibitors From Marine Brown Alga: A Literature Review

The human immunodeficiency virus type 1 (HIV-1) causes an infectious disease that if left untreated can progress to acquired immunodeficiency syndrome (AIDS) and be fatal. Finding a cure and more treatments for HIV has become a top priority in medical research, and due to the cost of synthetic HIV medication, finding a low-cost alternative is essential. Marine pharmacology has provided a possible solution to costly HIV medication through compounds derived from marine brown algae that inhibit the HIV-1 protease (PR). The objective of this study is to emphasize the necessity for further research in HIV-1 protease inhibition using marine wildlife-derived compounds. In order to better understand the process of protease inhibitors, I will investigate the process of producing and purifying HIV-1 PR, extracting and isolating brown algal compounds, and the assays used to test the inhibition effects of the brown alga compounds. This study demonstrates the potential of marine pharmacology as an inexpensive alternative to synthetic pharmaceuticals for HIV-1 PR inhibition.

The Marine Pharmacology and Pharmaceuticals Pipeline in 2016

The pharmaceutical potential of the enormousbiodiversity of organisms present in the world's oceans continues to be the focus of intense global preclinical and clinical research. In October 2016 there were six marine‐derived drugs approved by the FDA: for cancer, cytarabine (Cytosar‐U®, Depocyt®, FDA‐approved 1969), eribulin mesylate (Halaven®, FDA‐approved 2010), brentuximabvedotin (Adcetris®, FDA‐approved 2011, and, trabectedin (Yondelis®, FDA‐approved2015); for pain, ziconotide (Prialt®, FDA‐approved 2004); forhypertriglyceridemia, omega‐3‐acid ethyl esters (Lovaza®, FDA‐approved 2004). The clinical marine pharmaceuticalpipeline in 2016 consisted of multiple compounds in clinical trials: 5 marine‐derived compounds in Phase III, 8 compounds in Phase II, and 14 compounds in Phase I, many of them auristatin‐containing antibody drug conjugates. Regular updates on the clinical marine pharmaceutical pipeline are posted at http://marinepharmacology.midwestern.edu/clinPipeline.htm. Furthermore, the preclinical marine pharmacology pipeline continued to be very productive as highlighted by the over 500 manuscripts published during the past 21 months by MARINE DRUGS, a journal that publishes original research on the pharmacology of drugs from the sea: http://www.mdpi.com/journal/marinedrugs. We conclude that in late 2016, both the marine pharmacology preclinical and clinical pharmaceuticalpipelines remained very active.Support or Funding InformationSupported by Midwestern University.

The Marine Pharmacology and Pharmaceuticals Pipeline in 2015

In October 2015 there were six FDA‐approved marine‐derived drugs: for cancer, cytarabine (Cytosar‐U®, Depocyt®, FDA‐approved 1969), eribulin mesylate (Halaven®, FDA‐approved 2010), trabectedin (Yondelis®, FDA‐orphan drug approval 2005) being EU‐registered, and brentuximab vedotin (Adcetris®, FDA‐approved 2011); for pain, ziconotide (Prialt®, FDA‐approved 2004); for hypertriglyceridemia, omega‐3‐acid ethyl esters (Lovaza®, FDA‐approved 2004). The clinical marine pharmaceutical pipeline (Mayer et al. TIPS 31:255–265, 2010) consisted of 10 marine‐derived compounds in clinical development in 2010, including three monoclonal antibodies conjugated to monomethyl auristatin E, a synthetic analog of the marine compound dolastatin, in either Phase I, Phase II or Phase III clinical trials. The current clinical marine pharmaceutical pipeline consists of 9 marine‐derived compounds, and at least 16 other auristatin‐containing antibody drug conjugates in clinical development. Updated information on the clinical marine pharmaceutical pipeline is available at http://marinepharmacology.midwestern.edu/clinPipeline.htm. Finally, the global preclinical marine pharmacology pipeline was reviewed in Mayer et al. MARINE DRUGS 11:2510–2573, 2013). In late 2015, both the marine pharmacology preclinical and clinical pharmaceutical pipelines remained very active.Support or Funding InformationSupported by Midwestern University

Exploring the ocean for new drug developments: Marine pharmacology.

Disease ailments are changing the patterns, and the new diseases are emerging due to changing environments. The enormous growth of world population has overburdened the existing resources for the drugs. And hence, the drug manufacturers are always on the lookout for new resources to develop effective and safe drugs for the increasing demands of the world population. Seventy-five percentage of earth's surface is covered by water but research into the pharmacology of marine organisms is limited, and most of it still remains unexplored. Marine environment represents countless and diverse resource for new drugs to combat major diseases such as cancer or malaria. It also offers an ecological resource comprising a variety of aquatic plants and animals. These aquatic organisms are screened for antibacterial, immunomodulator, anti-fungal, anti-inflammatory, anticancer, antimicrobial, neuroprotective, analgesic, and antimalarial properties. They are used for new drug developments extensively across the world. Marine pharmacology offers the scope for research on these drugs of marine origin. Few institutes in India offer such opportunities which can help us in the quest for new drugs. This is an extensive review of the drugs developed and the potential new drug candidates from marine origin along with the opportunities for research on marine derived products. It also gives the information about the institutes in India which offer marine pharmacology related courses.

A perspective on toxicology of Conus venom peptides.

The evolutionarily unique and ecologically diverse family Conidae presents fundamental opportunities for marine pharmacology research and drug discovery. The focus of this investigation is to summarize the worldwide distribution of Conus and their species diversity with special reference to the Indian coast. In addition, this study will contribute to understanding the structural properties of conotoxin and therapeutic application of Conus venom peptides. Cone snails can inject a mix of various conotoxins and these venoms are their major weapon for prey capture, and may also have other biological purposes, and some of these conotoxins fatal to humans. Conus venoms contain a remarkable diversity of pharmacologically active small peptides; their targets are an iron channel and receptors in the neuromuscular system. Interspecific divergence is pronounced in venom peptide genes, which is generally attributed to their species specific biotic interactions. There is a notable interspecific divergence observed in venom peptide genes, which can be justified as of biotic interactions that stipulate species peculiar habitat and ecology of cone snails. There are several conopeptides used in clinical trials and one peptide (Ziconotide) has received FDA approval for treatment of pain. This perspective provides a comprehensive overview of the distribution of cone shells and focus on the molecular approach in documenting their taxonomy and diversity with special reference to geographic distribution of Indian cone snails, structure and properties of conopeptide and their pharmacological targets and future directions.

The Marine Pharmacology and Pharmaceuticals Pipeline in 2014

In October 2014 there were six FDA‐approved marine‐derived drugs: for cancer, cytarabine (Cytosar‐U®, Depocyt®, FDA‐approved 1969), eribulin mesylate (Halaven®, FDA‐approved 2010), trabectedin (Yondelis®, FDA‐orphan drug approval 2005) being EU‐registered, and brentuximab vedotin (Adcetris®, FDA‐approved 2011); for pain, ziconotide (Prialt®, FDA‐approved 2004); for hypertriglyceridemia omega‐3‐acid ethyl esters (Lovaza®, FDAapproved2004). The clinical marine pharmaceutical pipeline (Mayer et al. TIPS 31:255‐265, 2010) consisted of 10 marine‐derived compounds in clinical development in 2010, including three monoclonal antibodies conjugated to monomethyl auristatin E, a synthetic analog of the marine compound dolastatin, in either Phase I, Phase II or Phase III clinical trials. The current clinical marine pharmaceutical pipeline consists of 9 marine‐derived compounds, and greater than 14 other auristatin‐containing antibody drug conjugates in clinical development. Updated information on the clinical marine pharmaceutical pipeline is available at <a href=“http://marinepharmacology.midwestern.edu/clinPipeline.htm” >http://marinepharmacology.midwestern.edu/clinPipeline.htm</a>. Finally, the global preclinical marine pharmacology pipeline was reviewed in Mayer et al. MARINE DRUGS 11:2510‐2573, 2013). In late 2014, both the marine pharmacology preclinical and clinical pharmaceutical pipelines remained very active. Supported by Midwestern University.

The marine pharmacology and pharmaceuticals pipeline in 2013 (657.17)

In October 2013 there were six FDA‐approved marine‐derived drugs: for cancer, cytarabine (Cytosar‐U®, Depocyt®, FDA‐approved 1969), eribulin mesylate (Halaven®, FDA‐approved 2010), trabectedin (Yondelis®, FDA‐orphan drug approval 2005) being EU‐registered, and brentuximab vedotin (Adcetris®, FDA‐approved 2011); for pain, ziconotide (Prialt®, FDA‐approved 2004); for hypertriglyceridemia omega‐3‐acid ethyl esters (Lovaza®, FDA‐approved 2004). The clinical marine pharmaceutical pipeline (Mayer et al. TIPS 31:255‐265, 2010) consisted of 10 marine‐derived compounds in clinical development, including three new monoclonal antibodies conjugated to monomethyl auristatin E, a synthetic analog of the marine compound dolastatin, currently in either Phase I, Phase II or Phase III clinical trials. There are currently at least 14 other auristatin‐containing antibody drug conjugates in clinical development. Updated information on the clinical marine pharmaceutical pipeline is available at http://marinepharmacology.midwestern.edu/clinPipeline.htm. Finally, the global preclinical marine pharmacology pipeline was reviewed in Mayer et al. MARINE DRUGS 11:2510‐2573, 2013). In late 2013, both the marine pharmacology preclinical and clinical pharmaceutical pipelines remained very active. Supported by Midwestern University.

Marine Pharmacology in 2009–2011: Marine Compounds with Antibacterial, Antidiabetic, Antifungal, Anti-Inflammatory, Antiprotozoal, Antituberculosis, and Antiviral Activities; Affecting the Immune and Nervous Systems, and other Miscellaneous Mechanisms of Action

The peer-reviewed marine pharmacology literature from 2009 to 2011 is presented in this review, following the format used in the 1998–2008 reviews of this series. The pharmacology of structurally-characterized compounds isolated from marine animals, algae, fungi and bacteria is discussed in a comprehensive manner. Antibacterial, antifungal, antiprotozoal, antituberculosis, and antiviral pharmacological activities were reported for 102 marine natural products. Additionally, 60 marine compounds were observed to affect the immune and nervous system as well as possess antidiabetic and anti-inflammatory effects. Finally, 68 marine metabolites were shown to interact with a variety of receptors and molecular targets, and thus will probably contribute to multiple pharmacological classes upon further mechanism of action studies. Marine pharmacology during 2009–2011 remained a global enterprise, with researchers from 35 countries, and the United States, contributing to the preclinical pharmacology of 262 marine compounds which are part of the preclinical pharmaceutical pipeline. Continued pharmacological research with marine natural products will contribute to enhance the marine pharmaceutical clinical pipeline, which in 2013 consisted of 17 marine natural products, analogs or derivatives targeting a limited number of disease categories.

Marine Pharmacology and the Marine Pharmaceuticals Pipeline

As the renaissance in the pharmacology of marine natural products continues (Glaser and Mayer, Biochemical Pharmacology 78:440–448, 2009), the purpose of this project was to assess the status of the clinical marine pharmaceuticals pipeline. Results were the following: there were five FDA‐approved marine‐derived drugs in the US market, namely cytarabine for cancer (Cytosar‐U®, Depocyt®, FDA‐approved 1969), ziconotide for pain (Prialt®, FDA‐approved 2004), omega‐3‐acid ethyl esters for hypertriglyceridemia (Lovaza®, FDA‐approved 2004), eribulin mesylate for cancer (Halaven®, FDA‐approved 2010), brentuximab vedotin for cancer (Adcertis®, FDA‐approved 2011), while vidarabine as an antiviral (Vira‐A®, FDA‐approved 1976) was no longer available, and trabectedin for cancer (Yondelis®, FDA‐orphan drug approval 2005) being EU‐registered. The clinical marine pharmaceutical pipeline, recently reviewed (Mayer et al. TIPS 31:255–265, 2010), as of October 2012 consisted of 11 marine‐derived compounds in clinical development. These included three new monoclonal antibodies conjugated to synthetic dolastatin derivatives, that were in either Phase I, Phase II or Phase III clinical trials. Finally, the preclinical marine pharmacology pipeline remained a global enterprise with researchers from several countries reporting novel mechanisms of action for multiple marine chemicals (Mayer et al. Comparative Biochemistry and Physiology C 153: 191–222, 2011). We conclude that both marine pharmacology preclinical research as well as the clinical pharmaceutical pipeline remained very active in 2012. Supported by Midwestern University.

Pyrosequencing of Bacterial Symbionts within Axinella corrugata Sponges: Diversity and Seasonal Variability

BackgroundMarine sponge species are of significant interest to many scientific fields including marine ecology, conservation biology, genetics, host-microbe symbiosis and pharmacology. One of the most intriguing aspects of the sponge “holobiont” system is the unique physiology, interaction with microbes from the marine environment and the development of a complex commensal microbial community. However, intraspecific variability and temporal stability of sponge-associated bacterial symbionts remain relatively unknown.Methodology/Principal FindingsWe have characterized the bacterial symbiont community biodiversity of seven different individuals of the Caribbean reef sponge Axinella corrugata, from two different Florida reef locations during variable seasons using multiplex 454 pyrosequencing of 16 S rRNA amplicons. Over 265,512 high-quality 16 S rRNA sequences were generated and analyzed. Utilizing versatile bioinformatics methods and analytical software such as the QIIME and CloVR packages, we have identified 9,444 distinct bacterial operational taxonomic units (OTUs). Approximately 65,550 rRNA sequences (24%) could not be matched to bacteria at the class level, and may therefore represent novel taxa. Differentially abundant classes between seasonal Axinella communities included Gammaproteobacteria, Flavobacteria, Alphaproteobacteria, Cyanobacteria, Acidobacter and Nitrospira. Comparisons with a proximal outgroup sponge species (Amphimedon compressa), and the growing sponge symbiont literature, indicate that this study has identified approximately 330 A. corrugata-specific symbiotic OTUs, many of which are related to the sulfur-oxidizing Ectothiorhodospiraceae. This family appeared exclusively within A. corrugata, comprising >34.5% of all sequenced amplicons. Other A. corrugata symbionts such as Deltaproteobacteria, Bdellovibrio, and Thiocystis among many others are described.Conclusions/SignificanceSlight shifts in several bacterial taxa were observed between communities sampled during spring and fall seasons. New 16 S rDNA sequences and concomitant identifications greatly expand the microbial community profile for this model reef sponge, and will likely be useful as a baseline for any future comparisons regarding sponge microbial community dynamics.

16. Marine Pharmacology and the Late 2011 Marine Pharmaceuticals Pipeline

16. Marine Pharmacology and the Late 2011 Marine Pharmaceuticals Pipeline