Selected Papers from the 14th International Symposium on Marine Natural Products

A special issue of Marine Drugs (ISSN 1660-3397).

Deadline for manuscript submissions: closed (30 November 2013) | Viewed by 180920

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1. School of Chemistry and Physics, University of KwaZulu-Natal, Durban, South Africa
2. Department of Organic Chemistry, University of Barcelona, Barcelona, Spain
Interests: antimicrobial peptides; solid-phase chemistry; combinatorial chemistry; drug delivery systems; peptide drug conjugates; orthogonal chemistry; drug discovery; biomaterials
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Research & Development Area, Pharmamar S.A. Pol. Ind. La Mina Norte, Avda. de los Reyes 1, 28770 Colmenar Viejo, Spain
Interests: marine natural products
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Natural marine compounds have interesting and diverse biological profiles, including bioactive properties, such as anti-tumor, anti-microtubule, anti-proliferative, anti-hypertensive, anti-inflammatory, anti-virus, anti-fungal, cytotoxic, and antibiotic activity.

The efforts channeled into drug development from marine sources have started to bear fruits. Thus, in the last decade, four drugs, Prialt, Eribulin, Adcetris and Yondelis have reached the market, and more importantly, many others are in clinical trials.

The second week of September, the 14th International Symposium on Marine Natural Products and the 8th European Conference on Marine Natural Products will take place in La Toja Island (Galicia, Spain). During these days collages from around the world will present and discuss recent work and ideas covering all areas related to marine natural products.

Marine Drugs is setting up a special issue on "Selected Papers from the 14th International Symposium on Marine Natural Products" which will cover the main highlights presented in the conference.

Carmen Cuevas
Fernando Albericio
Guest Editors

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Published Papers (14 papers)

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Research

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834 KiB  
Article
Maritime Halophyte Species from Southern Portugal as Sources of Bioactive Molecules
by Maria João Rodrigues, Katkam N. Gangadhar, Catarina Vizetto-Duarte, Sileshi G. Wubshet, Nils T. Nyberg, Luísa Barreira, João Varela and Luísa Custódio
Mar. Drugs 2014, 12(4), 2228-2244; https://doi.org/10.3390/md12042228 - 10 Apr 2014
Cited by 79 | Viewed by 9553
Abstract
Extracts of five halophytes from southern Portugal (Arthrocnemum macrostachyum, Mesembryanthemum edule, Juncus acutus, Plantago coronopus and Halimione portulacoides), were studied for antioxidant, anti-inflammatory and in vitro antitumor properties. The most active extracts towards the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical were [...] Read more.
Extracts of five halophytes from southern Portugal (Arthrocnemum macrostachyum, Mesembryanthemum edule, Juncus acutus, Plantago coronopus and Halimione portulacoides), were studied for antioxidant, anti-inflammatory and in vitro antitumor properties. The most active extracts towards the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical were the methanol extracts of M. edule (IC50 = 0.1 mg/mL) and J. acutus (IC50 = 0.4 mg/mL), and the ether extracts of J. acutus (IC50 = 0.2 mg/mL) and A. macrostachyum (IC50 = 0.3 mg/mL). The highest radical scavenging activity (RSA) against the 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) radical was obtained in the ether extract of J. acutus (IC50 = 0.4 mg/mL) and H. portulacoides (IC50 = 0.9 mg/mL). The maximum total phenolic content (TPC) was found in the methanol extract of M. edule (147 mg gallic acid equivalents (GAE)/g) and in the ether extract of J. acutus (94 mg GAE/g). Significant decreases in nitric oxide (NO) production were observed after incubation of macrophages with lipopolysaccharide (LPS) and the chloroform extract of H. portulacoides (IC50 = 109 µg/mL) and the hexane extract of P. coronopus (IC50 = 98.0 µg/mL). High in vitro cytotoxic activity and selectivity was obtained with the ether extract of J. acutus. Juncunol was identified as the active compound and for the first time was shown to display selective in vitro cytotoxicity towards various human cancer cells. Full article
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604 KiB  
Article
Structure Activity Relationship of Brevenal Hydrazide Derivatives
by Allan Goodman, Jennifer R. McCall, Henry M. Jacocks, Alysha Thompson, Daniel Baden, William M. Abraham and Andrea Bourdelais
Mar. Drugs 2014, 12(4), 1839-1858; https://doi.org/10.3390/md12041839 - 28 Mar 2014
Cited by 2 | Viewed by 7775
Abstract
Brevenal is a ladder frame polyether produced by the dinoflagellate Karenia brevis. This organism is also responsible for the production of the neurotoxic compounds known as brevetoxins. Ingestion or inhalation of the brevetoxins leads to adverse effects such as gastrointestinal maladies and [...] Read more.
Brevenal is a ladder frame polyether produced by the dinoflagellate Karenia brevis. This organism is also responsible for the production of the neurotoxic compounds known as brevetoxins. Ingestion or inhalation of the brevetoxins leads to adverse effects such as gastrointestinal maladies and bronchoconstriction. Brevenal shows antagonistic behavior to the brevetoxins and shows beneficial attributes when administered alone. For example, in an asthmatic sheep model, brevenal has been shown to increase tracheal mucosal velocity, an attribute which has led to its development as a potential treatment for Cystic Fibrosis. The mechanism of action of brevenal is poorly understood and the exact binding site has not been elucidated. In an attempt to further understand the mechanism of action of brevenal and potentially develop a second generation drug candidate, a series of brevenal derivatives were prepared through modification of the aldehyde moiety. These derivatives include aliphatic, aromatic and heteroaromatic hydrazide derivatives. The brevenal derivatives were tested using in vitro synaptosome binding assays to determine the ability of the compounds to displace brevetoxin and brevenal from their native receptors. A sheep inhalation model was used to determine if instillation of the brevenal derivatives resulted in bronchoconstriction. Only small modifications were tolerated, with larger moieties leading to loss of affinity for the brevenal receptor and bronchoconstriction in the sheep model. Full article
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764 KiB  
Article
Antioxidant and Antimicrobial Potential of the Bifurcaria bifurcata Epiphytic Bacteria
by André Horta, Susete Pinteus, Celso Alves, Nádia Fino, Joana Silva, Sara Fernandez, Américo Rodrigues and Rui Pedrosa
Mar. Drugs 2014, 12(3), 1676-1689; https://doi.org/10.3390/md12031676 - 24 Mar 2014
Cited by 53 | Viewed by 10795
Abstract
Surface-associated marine bacteria are an interesting source of new secondary metabolites. The aim of this study was the isolation and identification of epiphytic bacteria from the marine brown alga, Bifurcaria bifurcata, and the evaluation of the antioxidant and antimicrobial activity of bacteria [...] Read more.
Surface-associated marine bacteria are an interesting source of new secondary metabolites. The aim of this study was the isolation and identification of epiphytic bacteria from the marine brown alga, Bifurcaria bifurcata, and the evaluation of the antioxidant and antimicrobial activity of bacteria extracts. The identification of epiphytic bacteria was determined by 16S rRNA gene sequencing. Bacteria extracts were obtained with methanol and dichloromethane (1:1) extraction. The antioxidant activity of extracts was performed by quantification of total phenolic content (TPC), 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity and oxygen radical absorbance capacity (ORAC). Antimicrobial activities were evaluated against Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis, Salmonella enteritidis, Staphylococcus aureus, Saccharomyces cerevisiae and Candida albicans. A total of 39 Bifurcaria bifurcata-associated bacteria were isolated and 33 were identified as Vibrio sp. (48.72%), Alteromonas sp. (12.82%), Shewanella sp. (12.26%), Serratia sp. (2.56%), Citricoccus sp. (2.56%), Cellulophaga sp. (2.56%), Ruegeria sp. (2.56%) and Staphylococcus sp. (2.56%). Six (15.38%) of the 39 bacteria Bifurcaria bifurcata-associated bacteria presented less than a 90% Basic Local Alignment Search Tool (BLAST) match, and some of those could be new. The highest antioxidant activity and antimicrobial activity (against B. subtilis) was exhibited by strain 16 (Shewanella sp.). Several strains also presented high antimicrobial activity against S. aureus, mainly belonging to Alteromonas sp. and Vibrio sp. There were no positive results against fungi and Gram-negative bacteria. Bifurcaria bifurcata epiphytic bacteria were revealed to be excellent sources of natural antioxidant and antimicrobial compounds. Full article
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Article
Tanjungides A and B: New Antitumoral Bromoindole Derived Compounds from Diazona cf formosa. Isolation and Total Synthesis
by Carmen Murcia, Laura Coello, Rogelio Fernández, María Jesús Martín, Fernando Reyes, Andrés Francesch, Simon Munt and Carmen Cuevas
Mar. Drugs 2014, 12(2), 1116-1130; https://doi.org/10.3390/md12021116 - 21 Feb 2014
Cited by 14 | Viewed by 8708
Abstract
Tanjungides A (1) (Z isomer) and B (2) (E isomer), two novel dibrominated indole enamides, have been isolated from the tunicate Diazona cf formosa. Their structures were determined by spectroscopic methods including HRMS, and extensive 1D [...] Read more.
Tanjungides A (1) (Z isomer) and B (2) (E isomer), two novel dibrominated indole enamides, have been isolated from the tunicate Diazona cf formosa. Their structures were determined by spectroscopic methods including HRMS, and extensive 1D and 2D NMR. The stereochemistry of the cyclised cystine present in both compounds was determined by Marfey’s analysis after chemical degradation and hydrolysis. We also report the first total synthesis of these compounds using methyl 1H-indole-3-carboxylate as starting material and a linear sequence of 11 chemical steps. Tanjungides A and B exhibit significant cytotoxicity against human tumor cell lines. Full article
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403 KiB  
Article
Gageostatins A–C, Antimicrobial Linear Lipopeptides from a Marine Bacillus subtilis
by Fakir Shahidullah Tareq, Min Ah Lee, Hyi-Seung Lee, Jong-Seok Lee, Yeon-Ju Lee and Hee Jae Shin
Mar. Drugs 2014, 12(2), 871-885; https://doi.org/10.3390/md12020871 - 31 Jan 2014
Cited by 59 | Viewed by 9388
Abstract
Concerning the requirements of effective drug candidates to combat against high rising multidrug resistant pathogens, we isolated three new linear lipopeptides, gageostatins A–C (13), consisting of hepta-peptides and new 3-β-hydroxy fatty acids from the fermentation broth of a marine-derived [...] Read more.
Concerning the requirements of effective drug candidates to combat against high rising multidrug resistant pathogens, we isolated three new linear lipopeptides, gageostatins A–C (13), consisting of hepta-peptides and new 3-β-hydroxy fatty acids from the fermentation broth of a marine-derived bacterium Bacillus subtilis. Their structures were elucidated by analyzing a combination of extensive 1D, 2D NMR spectroscopic data and high resolution ESIMS data. Fatty acids, namely 3-β-hydroxy-11-methyltridecanoic and 3-β-hydroxy-9,11-dimethyltridecanoic acids were characterized in lipopeptides 1 and 2, respectively, whereas an unsaturated fatty acid (E)-7,9-dimethylundec-2-enoic acid was assigned in 3. The 3R configuration of the stereocenter of 3-β-hydroxy fatty acids in 1 and 2 was established by Mosher’s MTPA method. The absolute stereochemistry of amino acid residues in 13 was ascertained by acid hydrolysis followed by Marfey’s derivatization studies. Gageostatins 13 exhibited good antifungal activities with MICs values of 4–32 µg/mL when tested against pathogenic fungi (R. solani, B. cinerea and C. acutatum) and moderate antibacterial activity against bacteria (B. subtilis, S. aeureus, S. typhi and P. aeruginosa) with MICs values of 8–64 µg/mL. Futhermore, gageostatins 13 displayed cytotoxicity against six human cancer cell lines with GI50 values of 4.6–19.6 µg/mL. It is also noteworthy that mixed compounds 1+2 displayed better antifungal and cytotoxic activities than individuals. Full article
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2915 KiB  
Article
Analysis of the Toxicity and Histopathology Induced by the Oral Administration of Pseudanabaena galeata and Geitlerinema splendidum (Cyanobacteria) Extracts to Mice
by Marisa Rangel, Joyce C. G. Martins, Angélica Nunes Garcia, Geanne A. A. Conserva, Adriana Costa-Neves, Célia Leite Sant'Anna and Luciana Retz De Carvalho
Mar. Drugs 2014, 12(1), 508-524; https://doi.org/10.3390/md12010508 - 22 Jan 2014
Cited by 21 | Viewed by 10453
Abstract
Cyanobacteria are common members of the freshwater microbiota in lakes and drinking water reservoirs, and are responsible for several cases of human intoxications in Brazil. Pseudanabaena galeata and Geitlerinema splendidum are examples of the toxic species that are very frequently found in reservoirs [...] Read more.
Cyanobacteria are common members of the freshwater microbiota in lakes and drinking water reservoirs, and are responsible for several cases of human intoxications in Brazil. Pseudanabaena galeata and Geitlerinema splendidum are examples of the toxic species that are very frequently found in reservoirs in Sao Paulo, which is the most densely populated area in Brazil. In the search for toxic strains collected from water reservoirs and maintained in the Cyanobacterial Culture Collection (CCIBt) of the Institute of Botany of Brazil, the acetic acid extracts (AE) of P. galeata CCIBt 3082 and G. splendidum CCIBt 3223 were analyzed by planar chromatography, which indicated the absence of cyanotoxins. Animal tests were then carried out, and both extracts were found to induce toxic effects in mice when administered intraperitoneally. The present study aimed to investigate whether the oral ingestion of the above mentioned cyanobacteria extracts would also induce toxic effects in mice. Necropsy and histopathological studies were conducted using tissue samples from the animals, which were euthanized one week after the administration of the extracts. The AE of P. galeata did not cause death but did induce transient symptoms, including eyebrow ptosis, straub tail, and pain. The euthanized animals presented hemorrhage in the liver, whereas the histological analysis showed disorganization of the hepatic parenchyma, necrosis, hyperemia, and proximity of the centrilobular vein in the liver. In addition, alterations in the convoluted tubules of the kidneys were observed, and the lungs were unaffected. The AE of G. splendidum caused only one death, and induced transient symptoms, such as dyspnea, paralysis, and pain, in the other mice. The necropsy of the euthanized mice showed hemorrhage in the lungs and liver. The lungs presented hemorrhagic focuses, alveolar collapse, and granulomatous foci. The liver presented hemorrhagic and enlarged sinusoids, hyperemia, proximity of the centrilobular vein, and disorganization of the hepatic parenchyma. Some areas also exhibited an inflammatory infiltrate and calcified tissue inside blood vessels. Necrosis and rupture of the convoluted tubule cells were observed in the kidneys. Further analysis of the both extracts indicated the lack of hemolytic activity, and the presence of two unknown anti-AChE substances in the AE of G. splendidum. Thus, P. galeata and G. splendidum are producers of novel toxins that affect mammals when administered orally. Full article
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1386 KiB  
Article
Stereochemistry of Complex Marine Natural Products by Quantum Mechanical Calculations of NMR Chemical Shifts: Solvent and Conformational Effects on Okadaic Acid
by Humberto J. Domínguez, Guillermo D. Crespín, Adrián J. Santiago-Benítez, José A. Gavín, Manuel Norte, José J. Fernández and Antonio Hernández Daranas
Mar. Drugs 2014, 12(1), 176-192; https://doi.org/10.3390/md12010176 - 7 Jan 2014
Cited by 22 | Viewed by 8627
Abstract
Marine organisms are an increasingly important source of novel metabolites, some of which have already inspired or become new drugs. In addition, many of these molecules show a high degree of novelty from a structural and/or pharmacological point of view. Structure determination is [...] Read more.
Marine organisms are an increasingly important source of novel metabolites, some of which have already inspired or become new drugs. In addition, many of these molecules show a high degree of novelty from a structural and/or pharmacological point of view. Structure determination is generally achieved by the use of a variety of spectroscopic methods, among which NMR (nuclear magnetic resonance) plays a major role and determination of the stereochemical relationships within every new molecule is generally the most challenging part in structural determination. In this communication, we have chosen okadaic acid as a model compound to perform a computational chemistry study to predict 1H and 13C NMR chemical shifts. The effect of two different solvents and conformation on the ability of DFT (density functional theory) calculations to predict the correct stereoisomer has been studied. Full article
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620 KiB  
Article
Exploring Bioactive Properties of Marine Cyanobacteria Isolated from the Portuguese Coast: High Potential as a Source of Anticancer Compounds
by Margarida Costa, Mónica Garcia, João Costa-Rodrigues, Maria Sofia Costa, Maria João Ribeiro, Maria Helena Fernandes, Piedade Barros, Aldo Barreiro, Vitor Vasconcelos and Rosário Martins
Mar. Drugs 2014, 12(1), 98-114; https://doi.org/10.3390/md12010098 - 31 Dec 2013
Cited by 64 | Viewed by 14078
Abstract
The oceans remain a major source of natural compounds with potential in pharmacology. In particular, during the last few decades, marine cyanobacteria have been in focus as producers of interesting bioactive compounds, especially for the treatment of cancer. In this study, the anticancer [...] Read more.
The oceans remain a major source of natural compounds with potential in pharmacology. In particular, during the last few decades, marine cyanobacteria have been in focus as producers of interesting bioactive compounds, especially for the treatment of cancer. In this study, the anticancer potential of extracts from twenty eight marine cyanobacteria strains, belonging to the underexplored picoplanktonic genera, Cyanobium, Synechocystis and Synechococcus, and the filamentous genera, Nodosilinea, Leptolyngbya, Pseudanabaena and Romeria, were assessed in eight human tumor cell lines. First, a crude extract was obtained by dichloromethane:methanol extraction, and from it, three fractions were separated in a Si column chromatography. The crude extract and fractions were tested in eight human cancer cell lines for cell viability/toxicity, accessed with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and lactic dehydrogenase release (LDH) assays. Eight point nine percent of the strains revealed strong cytotoxicity; 17.8% showed moderate cytotoxicity, and 14.3% assays showed low toxicity. The results obtained revealed that the studied genera of marine cyanobacteria are a promising source of novel compounds with potential anticancer activity and highlight the interest in also exploring the smaller filamentous and picoplanktonic genera of cyanobacteria. Full article
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1016 KiB  
Article
Derivatives of Salarin A, Salarin C and Tulearin A—Fascaplysinopsis sp. Metabolites
by Lee Goren Zur, Ashgan Bishara, Maurice Aknin, Drorit Neumann, Nathalie Ben-Califa and Yoel Kashman
Mar. Drugs 2013, 11(11), 4487-4509; https://doi.org/10.3390/md11114487 - 11 Nov 2013
Cited by 7 | Viewed by 7885
Abstract
Derivatives of salarin A, salarin C and tulearin A, three new cytotoxic sponge derived nitrogenous macrolides, were prepared and bio-evaluated as inhibitors of K562 leukemia cells. Interesting preliminary SAR (structure activity relationship) information was obtained from the products. The most sensitive functionalities were [...] Read more.
Derivatives of salarin A, salarin C and tulearin A, three new cytotoxic sponge derived nitrogenous macrolides, were prepared and bio-evaluated as inhibitors of K562 leukemia cells. Interesting preliminary SAR (structure activity relationship) information was obtained from the products. The most sensitive functionalities were the 16,17-vinyl epoxide in both salarins, the triacylamino group in salarin A and the oxazole in salarin C (less sensitive). Regioselectivity of reactions was also found for tulearin A. Full article
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Review

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949 KiB  
Review
Biosynthetic Modularity Rules in the Bisintercalator Family of Antitumor Compounds
by Javier Fernández, Laura Marín, Raquel Álvarez-Alonso, Saúl Redondo, Juan Carvajal, Germán Villamizar, Claudio J. Villar and Felipe Lombó
Mar. Drugs 2014, 12(5), 2668-2699; https://doi.org/10.3390/md12052668 - 9 May 2014
Cited by 18 | Viewed by 11640
Abstract
Diverse actinomycetes produce a family of structurally and biosynthetically related non-ribosomal peptide compounds which belong to the chromodepsipeptide family. These compounds act as bisintercalators into the DNA helix. They give rise to antitumor, antiparasitic, antibacterial and antiviral bioactivities. These compounds show a high [...] Read more.
Diverse actinomycetes produce a family of structurally and biosynthetically related non-ribosomal peptide compounds which belong to the chromodepsipeptide family. These compounds act as bisintercalators into the DNA helix. They give rise to antitumor, antiparasitic, antibacterial and antiviral bioactivities. These compounds show a high degree of conserved modularity (chromophores, number and type of amino acids). This modularity and their high sequence similarities at the genetic level imply a common biosynthetic origin for these pathways. Here, we describe insights about rules governing this modular biosynthesis, taking advantage of the fact that nowadays five of these gene clusters have been made public (thiocoraline, triostin, SW-163 and echinomycin/quinomycin). This modularity has potential application for designing and producing novel genetic engineered derivatives, as well as for developing new chemical synthesis strategies. These would facilitate their clinical development. Full article
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498 KiB  
Review
Natural Products from Mangrove Actinomycetes
by Dong-Bo Xu, Wan-Wan Ye, Ying Han, Zi-Xin Deng and Kui Hong
Mar. Drugs 2014, 12(5), 2590-2613; https://doi.org/10.3390/md12052590 - 2 May 2014
Cited by 128 | Viewed by 16184
Abstract
Mangroves are woody plants located in tropical and subtropical intertidal coastal regions. The mangrove ecosystem is becoming a hot spot for natural product discovery and bioactivity survey. Diverse mangrove actinomycetes as promising and productive sources are worth being explored and uncovered. At the [...] Read more.
Mangroves are woody plants located in tropical and subtropical intertidal coastal regions. The mangrove ecosystem is becoming a hot spot for natural product discovery and bioactivity survey. Diverse mangrove actinomycetes as promising and productive sources are worth being explored and uncovered. At the time of writing, we report 73 novel compounds and 49 known compounds isolated from mangrove actinomycetes including alkaloids, benzene derivatives, cyclopentenone derivatives, dilactones, macrolides, 2-pyranones and sesquiterpenes. Attractive structures such as salinosporamides, xiamycins and novel indolocarbazoles are highlighted. Many exciting compounds have been proven as potential new antibiotics, antitumor and antiviral agents, anti-fibrotic agents and antioxidants. Furthermore, some of their biosynthetic pathways have also been revealed. This review is an attempt to consolidate and summarize the past and the latest studies on mangrove actinomycetes natural product discovery and to draw attention to their immense potential as novel and bioactive compounds for marine drugs discovery. Full article
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3171 KiB  
Review
Chemistry and Biology of Bengamides and Bengazoles, Bioactive Natural Products from Jaspis Sponges
by Cristina García-Ruiz and Francisco Sarabia
Mar. Drugs 2014, 12(3), 1580-1622; https://doi.org/10.3390/md12031580 - 18 Mar 2014
Cited by 35 | Viewed by 10749
Abstract
Sponges corresponding to the Jaspidae family have proved to be a prolific source of bioactive natural products. Among these, the bengamides and the bengazoles stand out by virtue of their unprecedented molecular architectures and impressive biological profiles, including antitumor, antibiotic and anthelmintic properties. [...] Read more.
Sponges corresponding to the Jaspidae family have proved to be a prolific source of bioactive natural products. Among these, the bengamides and the bengazoles stand out by virtue of their unprecedented molecular architectures and impressive biological profiles, including antitumor, antibiotic and anthelmintic properties. As a consequence, intense research activity has been devoted to these compounds from both chemical and biological standpoints. This review describes in detail the research into these classes of natural products and the benefits they offer in chemistry and biology. Full article
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723 KiB  
Review
Marketed Marine Natural Products in the Pharmaceutical and Cosmeceutical Industries: Tips for Success
by Ana Martins, Helena Vieira, Helena Gaspar and Susana Santos
Mar. Drugs 2014, 12(2), 1066-1101; https://doi.org/10.3390/md12021066 - 17 Feb 2014
Cited by 421 | Viewed by 34524
Abstract
The marine environment harbors a number of macro and micro organisms that have developed unique metabolic abilities to ensure their survival in diverse and hostile habitats, resulting in the biosynthesis of an array of secondary metabolites with specific activities. Several of these metabolites [...] Read more.
The marine environment harbors a number of macro and micro organisms that have developed unique metabolic abilities to ensure their survival in diverse and hostile habitats, resulting in the biosynthesis of an array of secondary metabolites with specific activities. Several of these metabolites are high-value commercial products for the pharmaceutical and cosmeceutical industries. The aim of this review is to outline the paths of marine natural products discovery and development, with a special focus on the compounds that successfully reached the market and particularly looking at the approaches tackled by the pharmaceutical and cosmetic companies that succeeded in marketing those products. The main challenges faced during marine bioactives discovery and development programs were analyzed and grouped in three categories: biodiversity (accessibility to marine resources and efficient screening), supply and technical (sustainable production of the bioactives and knowledge of the mechanism of action) and market (processes, costs, partnerships and marketing). Tips to surpass these challenges are given in order to improve the market entry success rates of highly promising marine bioactives in the current pipelines, highlighting what can be learned from the successful and unsuccessful stories that can be applied to novel and/or ongoing marine natural products discovery and development programs. Full article
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2638 KiB  
Review
Thiopeptide Antibiotics: Retrospective and Recent Advances
by Xavier Just-Baringo, Fernando Albericio and Mercedes Álvarez
Mar. Drugs 2014, 12(1), 317-351; https://doi.org/10.3390/md12010317 - 17 Jan 2014
Cited by 144 | Viewed by 18721
Abstract
Thiopeptides, or thiazolyl peptides, are a relatively new family of antibiotics that already counts with more than one hundred different entities. Although they are mainly isolated from soil bacteria, during the last decade, new members have been isolated from marine samples. Far from [...] Read more.
Thiopeptides, or thiazolyl peptides, are a relatively new family of antibiotics that already counts with more than one hundred different entities. Although they are mainly isolated from soil bacteria, during the last decade, new members have been isolated from marine samples. Far from being limited to their innate antibacterial activity, thiopeptides have been found to possess a wide range of biological properties, including anticancer, antiplasmodial, immunosuppressive, etc. In spite of their ribosomal origin, these highly posttranslationally processed peptides have posed a fascinating synthetic challenge, prompting the development of various methodologies and strategies. Regardless of their limited solubility, intensive investigations are bringing thiopeptide derivatives closer to the clinic, where they are likely to show their veritable therapeutic potential. Full article
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