Marine Drugs

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Open AccessReview

Marine Invertebrate Metabolites with Anticancer Activities: Solutions to the “Supply Problem”

by Nelson G. M. Gomes, Ramesh Dasari, Sunena Chandra, Robert Kiss and Alexander Kornienko

Mar. Drugs 2016, 14(5), 98; https://doi.org/10.3390/md14050098 - 21 May 2016

Cited by 73 | Viewed by 15020

Marine invertebrates provide a rich source of metabolites with anticancer activities and several marine-derived agents have been approved for the treatment of cancer. However, the limited supply of promising anticancer metabolites from their natural sources is a major hurdle to their preclinical and [...] Read more.

Marine invertebrates provide a rich source of metabolites with anticancer activities and several marine-derived agents have been approved for the treatment of cancer. However, the limited supply of promising anticancer metabolites from their natural sources is a major hurdle to their preclinical and clinical development. Thus, the lack of a sustainable large-scale supply has been an important challenge facing chemists and biologists involved in marine-based drug discovery. In the current review we describe the main strategies aimed to overcome the supply problem. These include: marine invertebrate aquaculture, invertebrate and symbiont cell culture, culture-independent strategies, total chemical synthesis, semi-synthesis, and a number of hybrid strategies. We provide examples illustrating the application of these strategies for the supply of marine invertebrate-derived anticancer agents. Finally, we encourage the scientific community to develop scalable methods to obtain selected metabolites, which in the authors’ opinion should be pursued due to their most promising anticancer activities. Full article

(This article belongs to the Collection Bioactive Compounds from Marine Invertebrates)

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Open AccessArticle

Time Dependency of Chemodiversity and Biosynthetic Pathways: An LC-MS Metabolomic Study of Marine-Sourced Penicillium

by Catherine Roullier, Samuel Bertrand, Elodie Blanchet, Mathilde Peigné, Thibaut Robiou du Pont, Yann Guitton, Yves François Pouchus and Olivier Grovel

Mar. Drugs 2016, 14(5), 103; https://doi.org/10.3390/md14050103 - 21 May 2016

Cited by 24 | Viewed by 7529

Abstract

This work aimed at studying metabolome variations of marine fungal strains along their growth to highlight the importance of the parameter “time” for new natural products discovery. An untargeted time-scale metabolomic study has been performed on two different marine-derived Penicillium strains. They were [...] Read more.

This work aimed at studying metabolome variations of marine fungal strains along their growth to highlight the importance of the parameter “time” for new natural products discovery. An untargeted time-scale metabolomic study has been performed on two different marine-derived Penicillium strains. They were cultivated for 18 days and their crude extracts were analyzed by HPLC-DAD-HRMS (High Performance Liquid Chromatography-Diode Array Detector-High Resolution Mass Spectrometry) each day. With the example of griseofulvin biosynthesis, a pathway shared by both strains, this work provides a new approach to study biosynthetic pathway regulations, which could be applied to other metabolites and more particularly new ones. Moreover, the results of this study emphasize the interest of such an approach for the discovery of new chemical entities. In particular, at every harvesting time, previously undetected features were observed in the LC-MS (Liquid Chromatography-Mass Spectrometry) data. Therefore, harvesting times for metabolite extraction should be performed at different time points to access the hidden metabolome. Full article

(This article belongs to the Special Issue Selected Papers from the 1st Congress of Marine Fungal Natural Products Consortium)

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Open AccessArticle

Structure and Bioactivity of a Modified Peptide Derived from the LPS-Binding Domain of an Anti-Lipopolysaccharide Factor (ALF) of Shrimp

by Hui Yang, Shihao Li, Fuhua Li and Jianhai Xiang

Mar. Drugs 2016, 14(5), 96; https://doi.org/10.3390/md14050096 - 19 May 2016

Cited by 30 | Viewed by 6025

Abstract

The lipopolysaccharide binding domain (LBD) in anti-lipopolysaccharide factor (ALF) is the main functional element of ALF, which exhibits antimicrobial activities. Our previous studies show that the peptide LBDv, synthesized based on the modified sequence of LBD (named LBD2) from FcALF2, exhibited an apparently [...] Read more.

The lipopolysaccharide binding domain (LBD) in anti-lipopolysaccharide factor (ALF) is the main functional element of ALF, which exhibits antimicrobial activities. Our previous studies show that the peptide LBDv, synthesized based on the modified sequence of LBD (named LBD2) from FcALF2, exhibited an apparently enhanced antimicrobial activity. To learn the prospect of LBDv application, the characteristics of LBDv were analyzed in the present study. The LBDv peptide showed higher antimicrobial and bactericidal activities compared with LBD2. These activities of the LBDv peptide were stable after heat treatment. LBDv could also exhibit in vivo antimicrobial activity to Vibrio harveyi. The LBDv peptide was found to bind bacteria, quickly cause bacterial agglutination, and kill bacteria by damaging their membrane integrity. Structure analysis showed that both LBDv and LBD2 held the β-sheet structure, and the positive net charge and amphipathicity characteristic were speculated as two important components for their antimicrobial activity. The cytotoxicity of LBDv was evaluated in cultured Spodoptera frugiperda (Sf9) cells and Cherax quadricarinatus hemocytes. More than 80% cells could survive with the LBDv concentration up to 16 μM. Collectively, these findings highlighted the potential antimicrobial mechanism of LBD peptides, and provided important information for the commercial use of LBDv in the future. Full article

(This article belongs to the Collection Bioactive Compounds from Marine Invertebrates)

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Open AccessReview

Axonal Transport and Neurodegeneration: How Marine Drugs Can Be Used for the Development of Therapeutics

by Joseph A. White, Rupkatha Banerjee and Shermali Gunawardena

Mar. Drugs 2016, 14(5), 102; https://doi.org/10.3390/md14050102 - 19 May 2016

Cited by 11 | Viewed by 8936

Abstract

Unlike virtually any other cells in the human body, neurons are tasked with the unique problem of transporting important factors from sites of synthesis at the cell bodies, across enormous distances, along narrow-caliber projections, to distally located nerve terminals in order to maintain [...] Read more.

Unlike virtually any other cells in the human body, neurons are tasked with the unique problem of transporting important factors from sites of synthesis at the cell bodies, across enormous distances, along narrow-caliber projections, to distally located nerve terminals in order to maintain cell viability. As a result, axonal transport is a highly regulated process whereby necessary cargoes of all types are packaged and shipped from one end of the neuron to the other. Interruptions in this finely tuned transport have been linked to many neurodegenerative disorders including Alzheimer’s (AD), Huntington’s disease (HD), and amyotrophic lateral sclerosis (ALS) suggesting that this pathway is likely perturbed early in disease progression. Therefore, developing therapeutics targeted at modifying transport defects could potentially avert disease progression. In this review, we examine a variety of potential compounds identified from marine aquatic species that affect the axonal transport pathway. These compounds have been shown to function in microtubule (MT) assembly and maintenance, motor protein control, and in the regulation of protein degradation pathways, such as the autophagy-lysosome processes, which are defective in many degenerative diseases. Therefore, marine compounds have great potential in developing effective treatment strategies aimed at early defects which, over time, will restore transport and prevent cell death. Full article

(This article belongs to the Special Issue Marine Compounds and Their Application in Neurological Disorders)

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Open AccessReview

Lipidomic Approaches towards Deciphering Glycolipids from Microalgae as a Reservoir of Bioactive Lipids

by Elisabete Da Costa, Joana Silva, Sofia Hoffman Mendonça, Maria Helena Abreu and Maria Rosário Domingues

Mar. Drugs 2016, 14(5), 101; https://doi.org/10.3390/md14050101 - 19 May 2016

Cited by 89 | Viewed by 12601

Abstract

In recent years, noteworthy research has been performed around lipids from microalgae. Among lipids, glycolipids (GLs) are quite abundant in microalgae and are considered an important source of fatty acids (FAs). GLs are rich in 16- and 18-carbon saturated and unsaturated fatty acids [...] Read more.

In recent years, noteworthy research has been performed around lipids from microalgae. Among lipids, glycolipids (GLs) are quite abundant in microalgae and are considered an important source of fatty acids (FAs). GLs are rich in 16- and 18-carbon saturated and unsaturated fatty acids and often contain polyunsaturated fatty acids (PUFAs) like n-3 α-linolenic (ALA 18:3), eicosapentaenoic (EPA, 20:5) and docosahexaenoic (DHA, 22:6). GLs comprise three major classes: monogalactosyldiacyl glycerolipids (MGDGs), digalactosyl diacylglycerolipids (DGDGs) and sulfoquinovosyl diacylglycerolipids (SQDGs), whose composition in FA directly depends on the growth conditions. Some of these lipids are high value-added compounds with antitumoral, antimicrobial and anti-inflammatory activities and also with important nutritional significance. To fully explore GLs’ bioactive properties it is necessary to fully characterize their structure and to understand the relation between the structure and their biological properties, which can be addressed using modern mass spectrometry (MS)-based lipidomic approaches. This review will focus on the up-to-date FA composition of GLs identified by MS-based lipidomics and their potential as phytochemicals. Full article

(This article belongs to the Special Issue Marine Fatty Acids-2016)

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Open AccessReview

Impact of Microalgae-Bacteria Interactions on the Production of Algal Biomass and Associated Compounds

by Juan Luis Fuentes, Inés Garbayo, María Cuaresma, Zaida Montero, Manuel González-del-Valle and Carlos Vílchez

Mar. Drugs 2016, 14(5), 100; https://doi.org/10.3390/md14050100 - 19 May 2016

Cited by 292 | Viewed by 20671

Abstract

A greater insight on the control of the interactions between microalgae and other microorganisms, particularly bacteria, should be useful for enhancing the efficiency of microalgal biomass production and associated valuable compounds. Little attention has been paid to the controlled utilization of microalgae-bacteria consortia. [...] Read more.

A greater insight on the control of the interactions between microalgae and other microorganisms, particularly bacteria, should be useful for enhancing the efficiency of microalgal biomass production and associated valuable compounds. Little attention has been paid to the controlled utilization of microalgae-bacteria consortia. However, the studies of microalgal-bacterial interactions have revealed a significant impact of the mutualistic or parasitic relationships on algal growth. The algal growth, for instance, has been shown to be enhanced by growth promoting factors produced by bacteria, such as indole-3-acetic acid. Vitamin B₁₂ produced by bacteria in algal cultures and bacterial siderophores are also known to be involved in promoting faster microalgal growth. More interestingly, enhancement in the intracellular levels of carbohydrates, lipids and pigments of microalgae coupled with algal growth stimulation has also been reported. In this sense, massive algal production might occur in the presence of bacteria, and microalgae-bacteria interactions can be beneficial to the massive production of microalgae and algal products. This manuscript reviews the recent knowledge on the impact of the microalgae-bacteria interactions on the production of microalgae and accumulation of valuable compounds, with an emphasis on algal species having application in aquaculture. Full article

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Open AccessReview

“The Good, the Bad and the Ugly” of Chitosans

by Barbara Bellich, Ilenia D’Agostino, Sabrina Semeraro, Amelia Gamini and Attilio Cesàro

Mar. Drugs 2016, 14(5), 99; https://doi.org/10.3390/md14050099 - 17 May 2016

Cited by 259 | Viewed by 12702

Abstract

The objective of this paper is to emphasize the fact that while consistent interest has been paid to the industrial use of chitosan, minor attention has been devoted to spread the knowledge of a good characterization of its physico-chemical properties. Therefore, the paper [...] Read more.

The objective of this paper is to emphasize the fact that while consistent interest has been paid to the industrial use of chitosan, minor attention has been devoted to spread the knowledge of a good characterization of its physico-chemical properties. Therefore, the paper attempts to critically comment on the conflicting experimental results, highlighting the facts, the myths and the controversies. The goal is to indicate how to take advantage of chitosan versatility, to learn how to manage its variability and show how to properly tackle some unexpected undesirable features. In the sections of the paper various issues that relate chitosan properties to some basic features and to advanced solutions and applications are presented. The introduction outlines some historical pioneering works, where the chemistry of chitosan was originally explored. Thereafter, particular reference is made to analytical purity, characterization and chain modifications. The macromolecular characterization is mostly related to molecular weight and to degree of acetylation, but also refers to the conformational and rheological properties and solution stability. Then, the antimicrobial activity of chitosan in relation with its solubility is reviewed. A section is dedicated to the formulation of chitosan biomaterials, from gel to nanobeads, exploring their innovative application as active carrier nanoparticles. Finally, the toxicity issue of chitosan as a polymer and as a constructed nanomaterial is briefly commented in the conclusions. Full article

(This article belongs to the Special Issue Advances in Marine Chitin and Chitosan II, 2017)

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Open AccessReview

Tiny Microbes with a Big Impact: The Role of Cyanobacteria and Their Metabolites in Shaping Our Future

by Sophie Mazard, Anahit Penesyan, Martin Ostrowski, Ian T. Paulsen and Suhelen Egan

Mar. Drugs 2016, 14(5), 97; https://doi.org/10.3390/md14050097 - 17 May 2016

Cited by 101 | Viewed by 14636

Abstract

Cyanobacteria are among the first microorganisms to have inhabited the Earth. Throughout the last few billion years, they have played a major role in shaping the Earth as the planet we live in, and they continue to play a significant role in our [...] Read more.

Cyanobacteria are among the first microorganisms to have inhabited the Earth. Throughout the last few billion years, they have played a major role in shaping the Earth as the planet we live in, and they continue to play a significant role in our everyday lives. Besides being an essential source of atmospheric oxygen, marine cyanobacteria are prolific secondary metabolite producers, often despite the exceptionally small genomes. Secondary metabolites produced by these organisms are diverse and complex; these include compounds, such as pigments and fluorescent dyes, as well as biologically-active compounds with a particular interest for the pharmaceutical industry. Cyanobacteria are currently regarded as an important source of nutrients and biofuels and form an integral part of novel innovative energy-efficient designs. Being autotrophic organisms, cyanobacteria are well suited for large-scale biotechnological applications due to the low requirements for organic nutrients. Recent advances in molecular biology techniques have considerably enhanced the potential for industries to optimize the production of cyanobacteria secondary metabolites with desired functions. This manuscript reviews the environmental role of marine cyanobacteria with a particular focus on their secondary metabolites and discusses current and future developments in both the production of desired cyanobacterial metabolites and their potential uses in future innovative projects. Full article

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Open AccessArticle

The Effect of the Molecular Architecture on the Antioxidant Properties of Chitosan Gallate

by Chunhua Wu, Liping Wang, Zhongxiang Fang, Yaqin Hu, Shiguo Chen, Tatsuya Sugawara and Xingqian Ye

Mar. Drugs 2016, 14(5), 95; https://doi.org/10.3390/md14050095 - 13 May 2016

Cited by 23 | Viewed by 6542

Abstract

To elucidate the structure–antioxidant activity relationships of chitosan gallate (CG), a series of CG derivatives with different degrees of substitution (DS’s) and molecular weights (MWs) were synthesized from chitosan (CS) and gallic acid (GA) via a free radical graft reaction. A higher MW [...] Read more.

To elucidate the structure–antioxidant activity relationships of chitosan gallate (CG), a series of CG derivatives with different degrees of substitution (DS’s) and molecular weights (MWs) were synthesized from chitosan (CS) and gallic acid (GA) via a free radical graft reaction. A higher MW led to a lower DS of CG. The structures of CG were characterized by FT-IR and ¹H NMR, and results showed that GA was mainly conjugated to the C-2 and C-6 positions of the CS chain. The antioxidant activity (the DPPH radical scavenging activity and reducing power) were enhanced with an increased DS and a decreased MW of CG. A correlation between antioxidant activities and the DS and MW of CG was also established. In addition, a suitable concentration (0~250 μg/mL) of CG with different MWs (32.78~489.32 kDa) and DS’s (0~92.89 mg·GAE/g CG) has no cytotoxicity. These results should provide a guideline to the application of CG derivatives in food or pharmacology industries. Full article

(This article belongs to the Special Issue Advances in Marine Chitin and Chitosan II, 2017)

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Open AccessFeature PaperReview

Bacterial Long-Chain Polyunsaturated Fatty Acids: Their Biosynthetic Genes, Functions, and Practical Use

by Kiyohito Yoshida, Mikako Hashimoto, Ryuji Hori, Takumi Adachi, Hidetoshi Okuyama, Yoshitake Orikasa, Tadashi Nagamine, Satoru Shimizu, Akio Ueno and Naoki Morita

Mar. Drugs 2016, 14(5), 94; https://doi.org/10.3390/md14050094 - 12 May 2016

Cited by 81 | Viewed by 13403

Abstract

The nutritional and pharmaceutical values of long-chain polyunsaturated fatty acids (LC-PUFAs) such as arachidonic, eicosapentaenoic and docosahexaenoic acids have been well recognized. These LC-PUFAs are physiologically important compounds in bacteria and eukaryotes. Although little is known about the biosynthetic mechanisms and functions of [...] Read more.

The nutritional and pharmaceutical values of long-chain polyunsaturated fatty acids (LC-PUFAs) such as arachidonic, eicosapentaenoic and docosahexaenoic acids have been well recognized. These LC-PUFAs are physiologically important compounds in bacteria and eukaryotes. Although little is known about the biosynthetic mechanisms and functions of LC-PUFAs in bacteria compared to those in higher organisms, a combination of genetic, bioinformatic, and molecular biological approaches to LC-PUFA-producing bacteria and some eukaryotes have revealed the notably diverse organization of the pfa genes encoding a polyunsaturated fatty acid synthase complex (PUFA synthase), the LC-PUFA biosynthetic processes, and tertiary structures of the domains of this enzyme. In bacteria, LC-PUFAs appear to take part in specific functions facilitating individual membrane proteins rather than in the adjustment of the physical fluidity of the whole cell membrane. Very long chain polyunsaturated hydrocarbons (LC-HCs) such as hentriacontanonaene are considered to be closely related to LC-PUFAs in their biosynthesis and function. The possible role of LC-HCs in strictly anaerobic bacteria under aerobic and anaerobic environments and the evolutionary relationships of anaerobic and aerobic bacteria carrying pfa-like genes are also discussed. Full article

(This article belongs to the Special Issue Marine Fatty Acids-2016)

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Open AccessArticle

Anti-Oxidative Activity of Mytiloxanthin, a Metabolite of Fucoxanthin in Shellfish and Tunicates

by Takashi Maoka, Azusa Nishino, Hiroyuki Yasui, Yumiko Yamano and Akimori Wada

Mar. Drugs 2016, 14(5), 93; https://doi.org/10.3390/md14050093 - 11 May 2016

Cited by 20 | Viewed by 6246

Abstract

Anti-oxidative activities of mytiloxanthin, a metabolite of fucoxanthin in shellfish and tunicates, were investigated. Mytiloxanthin showed almost the same activities for quenching singlet oxygen and the inhibition of lipid peroxidation as those of astaxanthin, which is a well-known singlet oxygen quencher. Furthermore, mytiloxanthin [...] Read more.

Anti-oxidative activities of mytiloxanthin, a metabolite of fucoxanthin in shellfish and tunicates, were investigated. Mytiloxanthin showed almost the same activities for quenching singlet oxygen and the inhibition of lipid peroxidation as those of astaxanthin, which is a well-known singlet oxygen quencher. Furthermore, mytiloxanthin showed excellent scavenging activity for hydroxyl radicals and this activity was markedly higher than that of astaxanthin. Full article

(This article belongs to the Special Issue Marine Carotenoids)

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Open AccessArticle

cDNA and Gene Structure of MytiLec-1, A Bacteriostatic R-Type Lectin from the Mediterranean Mussel (Mytilus galloprovincialis)

by Imtiaj Hasan, Marco Gerdol, Yuki Fujii, Sultana Rajia, Yasuhiro Koide, Daiki Yamamoto, Sarkar M. A. Kawsar and Yasuhiro Ozeki

Mar. Drugs 2016, 14(5), 92; https://doi.org/10.3390/md14050092 - 11 May 2016

Cited by 33 | Viewed by 8369

Abstract

MytiLec is an α-d-galactose-binding lectin with a unique primary structure isolated from the Mediterranean mussel (Mytilus galloprovincialis). The lectin adopts a β-trefoil fold that is also found in the B-sub-unit of ricin and other ricin-type (R-type) lectins. We are [...] Read more.

MytiLec is an α-d-galactose-binding lectin with a unique primary structure isolated from the Mediterranean mussel (Mytilus galloprovincialis). The lectin adopts a β-trefoil fold that is also found in the B-sub-unit of ricin and other ricin-type (R-type) lectins. We are introducing MytiLec(-1) and its two variants (MytiLec-2 and -3), which both possess an additional pore-forming aerolysin-like domain, as members of a novel multi-genic “mytilectin family” in bivalve mollusks. Based on the full length mRNA sequence (911 bps), it was possible to elucidate the coding sequence of MytiLec-1, which displays an extended open reading frame (ORF) at the 5′ end of the sequence, confirmed both at the mRNA and at the genomic DNA sequence level. While this extension could potentially produce a polypeptide significantly longer than previously reported, this has not been confirmed yet at the protein level. MytiLec-1 was revealed to be encoded by a gene consisting of two exons and a single intron. The first exon comprised the 5′UTR and the initial ATG codon and it was possible to detect a putative promoter region immediately ahead of the transcription start site in the MytiLec-1 genomic locus. The remaining part of the MytiLec-1 coding sequence (including the three sub-domains, the 3′UTR and the poly-A signal) was included in the second exon. The bacteriostatic activity of MytiLec-1 was determined by the agglutination of both Gram-positive and Gram-negative bacteria, which was reversed by the co-presence of α-galactoside. Altogether, these data support the classification of MytiLec-1 as a member of the novel mytilectin family and suggest that this lectin may play an important role as a pattern recognition receptor in the innate immunity of mussels. Full article

(This article belongs to the Special Issue Structures, Functions and Applications of Marine Lectins)

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Open AccessArticle

Effect of Chitosan Properties on Immunoreactivity

by Sruthi Ravindranathan, Bhanu Prasanth Koppolu, Sean G. Smith and David A. Zaharoff

Mar. Drugs 2016, 14(5), 91; https://doi.org/10.3390/md14050091 - 11 May 2016

Cited by 47 | Viewed by 6577

Abstract

Chitosan is a widely investigated biopolymer in drug and gene delivery, tissue engineering and vaccine development. However, the immune response to chitosan is not clearly understood due to contradicting results in literature regarding its immunoreactivity. Thus, in this study, we analyzed effects of [...] Read more.

Chitosan is a widely investigated biopolymer in drug and gene delivery, tissue engineering and vaccine development. However, the immune response to chitosan is not clearly understood due to contradicting results in literature regarding its immunoreactivity. Thus, in this study, we analyzed effects of various biochemical properties, namely degree of deacetylation (DDA), viscosity/polymer length and endotoxin levels, on immune responses by antigen presenting cells (APCs). Chitosan solutions from various sources were treated with mouse and human APCs (macrophages and/or dendritic cells) and the amount of tumor necrosis factor-α (TNF-α) released by the cells was used as an indicator of immunoreactivity. Our results indicate that only endotoxin content and not DDA or viscosity influenced chitosan-induced immune responses. Our data also indicate that low endotoxin chitosan (<0.01 EU/mg) ranging from 20 to 600 cP and 80% to 97% DDA is essentially inert. This study emphasizes the need for more complete characterization and purification of chitosan in preclinical studies in order for this valuable biomaterial to achieve widespread clinical application. Full article

(This article belongs to the Special Issue Advances in Marine Chitin and Chitosan II, 2017)

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Open AccessArticle

Effect of Experimental Parameters on Alginate/Chitosan Microparticles for BCG Encapsulation

by Liliana A. Caetano, António J. Almeida and Lídia M.D. Gonçalves

Mar. Drugs 2016, 14(5), 90; https://doi.org/10.3390/md14050090 - 11 May 2016

Cited by 77 | Viewed by 9900

Abstract

The aim of the present study was to develop novel Mycobacterium bovis bacille Calmette-Guérin (BCG)-loaded polymeric microparticles with optimized particle surface characteristics and biocompatibility, so that whole live attenuated bacteria could be further used for pre-exposure vaccination against Mycobacterium tuberculosis by the intranasal [...] Read more.

The aim of the present study was to develop novel Mycobacterium bovis bacille Calmette-Guérin (BCG)-loaded polymeric microparticles with optimized particle surface characteristics and biocompatibility, so that whole live attenuated bacteria could be further used for pre-exposure vaccination against Mycobacterium tuberculosis by the intranasal route. BCG was encapsulated in chitosan and alginate microparticles through three different polyionic complexation methods by high speed stirring. For comparison purposes, similar formulations were prepared with high shear homogenization and sonication. Additional optimization studies were conducted with polymers of different quality specifications in a wide range of pH values, and with three different cryoprotectors. Particle morphology, size distribution, encapsulation efficiency, surface charge, physicochemical properties and biocompatibility were assessed. Particles exhibited a micrometer size and a spherical morphology. Chitosan addition to BCG shifted the bacilli surface charge from negative zeta potential values to strongly positive ones. Chitosan of low molecular weight produced particle suspensions of lower size distribution and higher stability, allowing efficient BCG encapsulation and biocompatibility. Particle formulation consistency was improved when the availability of functional groups from alginate and chitosan was close to stoichiometric proportion. Thus, the herein described microparticulate system constitutes a promising strategy to deliver BCG vaccine by the intranasal route. Full article

(This article belongs to the Collection Marine Polysaccharides)

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Open AccessArticle

Dimethylsulfoniopropionate Promotes Process Outgrowth in Neural Cells and Exerts Protective Effects against Tropodithietic Acid

by Heidi Wichmann, Thorsten Brinkhoff, Meinhard Simon and Christiane Richter-Landsberg

Mar. Drugs 2016, 14(5), 89; https://doi.org/10.3390/md14050089 - 06 May 2016

Cited by 10 | Viewed by 6326

Abstract

The marine environment harbors a plethora of bioactive substances, including drug candidates of potential value in the field of neuroscience. The present study was undertaken to investigate the effects of dimethylsulfoniopropionate (DMSP), produced by several algae, corals and higher plants, on cells of [...] Read more.

The marine environment harbors a plethora of bioactive substances, including drug candidates of potential value in the field of neuroscience. The present study was undertaken to investigate the effects of dimethylsulfoniopropionate (DMSP), produced by several algae, corals and higher plants, on cells of the mammalian nervous system, i.e., neuronal N2a and OLN-93 cells as model system for nerve cells and glia, respectively. Additionally, the protective capabilities of DMSP were assessed in cells treated with tropodithietic acid (TDA), a marine metabolite produced by several Roseobacter clade bacteria. Both cell lines, N2a and OLN-93, have previously been shown to be a sensitive target for the action of TDA, and cytotoxic effects of TDA have been connected to the induction of oxidative stress. Our data shows that DMSP promotes process outgrowth and microtubule reorganization and bundling, accompanied by an increase in alpha-tubulin acetylation. Furthermore, DMSP was able to prevent the cytotoxic effects exerted by TDA, including the breakdown of the mitochondrial membrane potential, upregulation of heat shock protein Hsp32 and activation of the extracellular signal-regulated kinases 1/2 (ERK1/2). Our study points to the conclusion that DMSP provides an antioxidant defense, not only in algae but also in mammalian neural cells. Full article

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Open AccessCommunication

4-Hydroxy-2,3-Dimethyl-2-Nonen-4-Olide Has an Inhibitory Effect on Pro-Inflammatory Cytokine Production in CpG-Stimulated Bone Marrow-Derived Dendritic Cells

by Zahid Manzoor, Jung-Eun Koo, Irshad Ali, Jung-Eun Kim, Sang-Hee Byeon, Eun-Sook Yoo, Hee-Kyoung Kang, Jin-Won Hyun, Nam-Ho Lee and Young-Sang Koh

Mar. Drugs 2016, 14(5), 88; https://doi.org/10.3390/md14050088 - 04 May 2016

Cited by 9 | Viewed by 5732

Abstract

This study was intended to assess the anti-inflammatory properties of 4-hydroxy-2,3-dimethyl-2-nonen-4-olide (Comp) isolated from Ulva pertusa Kjellman on production of pro-inflammatory cytokines. Comp revealed remarkable inhibitory effects on production of pro-inflammatory cytokines in bone marrow-derived dendritic cells (BMDCs). Comp pre-treatment in the CpG [...] Read more.

This study was intended to assess the anti-inflammatory properties of 4-hydroxy-2,3-dimethyl-2-nonen-4-olide (Comp) isolated from Ulva pertusa Kjellman on production of pro-inflammatory cytokines. Comp revealed remarkable inhibitory effects on production of pro-inflammatory cytokines in bone marrow-derived dendritic cells (BMDCs). Comp pre-treatment in the CpG DNA-stimulated BMDCs exhibited strong inhibition of interleukin (IL)-12 p40 and IL-6 production with IC₅₀ values ranging from 7.57 ± 0.2 to 10.83 ± 0.3, respectively. It revealed an inhibitory effect on the phosphorylation of ERK1/2, JNK1/2, and p38, and on activator protein (AP)-1 reporter activity. Comp displayed noteworthy inhibitory effects on phosphorylation and degradation of IκBα, and on NF-κB reporter activity. In summary, these data propose that Comp has substantial anti-inflammatory properties and warrants further study concerning its potential use as a therapeutic agent for inflammation-associated maladies. Full article

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Open AccessArticle

Ergosterols from the Culture Broth of Marine Streptomyces anandii H41-59

by Yang-Mei Zhang, Hong-Yu Li, Chen Hu, Hui-Fan Sheng, Ying Zhang, Bi-Run Lin and Guang-Xiong Zhou

Mar. Drugs 2016, 14(5), 84; https://doi.org/10.3390/md14050084 - 04 May 2016

Cited by 16 | Viewed by 6136

Abstract

An actinomycete strain, H41-59, isolated from sea sediment in a mangrove district, was identified as Streptomyces anandii on the basis of 16S rDNA gene sequence analysis as well as the investigation of its morphological, physiological and biochemical characteristics. Three new ergosterols, ananstreps A–C [...] Read more.

An actinomycete strain, H41-59, isolated from sea sediment in a mangrove district, was identified as Streptomyces anandii on the basis of 16S rDNA gene sequence analysis as well as the investigation of its morphological, physiological and biochemical characteristics. Three new ergosterols, ananstreps A–C (1–3), along with ten known ones (4–13), were isolated from the culture broth of this strain. The gross structures of these new compounds were elucidated on the basis of extensive analysis of spectroscopic data, including HR-ESI-MS, and NMR. The cytotoxicities of these isolates against human breast adenocarcinoma cell line MCF-7, human glioblastoma cell line SF-268, and human lung cancer cell line NCI-H460 and their antibacterial activities in inhibiting the growth of Candida albicans and some other pathogenic microorganisms were tested. Compounds 3–8, 10 and 11 displayed cytotoxicity with IC₅₀ values in a range from 13.0 to 27.8 μg/mL. However, all the tested compounds showed no activity on C. albicans and other bacteria at the test concentration of 1 mg/mL with the paper disc diffusion method. Full article

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Open AccessFeature PaperReview

Bioprospecting Sponge-Associated Microbes for Antimicrobial Compounds

by Anak Agung Gede Indraningrat, Hauke Smidt and Detmer Sipkema

Mar. Drugs 2016, 14(5), 87; https://doi.org/10.3390/md14050087 - 02 May 2016

Cited by 131 | Viewed by 18423

Abstract

Sponges are the most prolific marine organisms with respect to their arsenal of bioactive compounds including antimicrobials. However, the majority of these substances are probably not produced by the sponge itself, but rather by bacteria or fungi that are associated with their host. [...] Read more.

Sponges are the most prolific marine organisms with respect to their arsenal of bioactive compounds including antimicrobials. However, the majority of these substances are probably not produced by the sponge itself, but rather by bacteria or fungi that are associated with their host. This review for the first time provides a comprehensive overview of antimicrobial compounds that are known to be produced by sponge-associated microbes. We discuss the current state-of-the-art by grouping the bioactive compounds produced by sponge-associated microorganisms in four categories: antiviral, antibacterial, antifungal and antiprotozoal compounds. Based on in vitro activity tests, identified targets of potent antimicrobial substances derived from sponge-associated microbes include: human immunodeficiency virus 1 (HIV-1) (2-undecyl-4-quinolone, sorbicillactone A and chartarutine B); influenza A (H1N1) virus (truncateol M); nosocomial Gram positive bacteria (thiopeptide YM-266183, YM-266184, mayamycin and kocurin); Escherichia coli (sydonic acid), Chlamydia trachomatis (naphthacene glycoside SF2446A2); Plasmodium spp. (manzamine A and quinolone 1); Leishmania donovani (manzamine A and valinomycin); Trypanosoma brucei (valinomycin and staurosporine); Candida albicans and dermatophytic fungi (saadamycin, 5,7-dimethoxy-4-p-methoxylphenylcoumarin and YM-202204). Thirty-five bacterial and 12 fungal genera associated with sponges that produce antimicrobials were identified, with Streptomyces, Pseudovibrio, Bacillus, Aspergillus and Penicillium as the prominent producers of antimicrobial compounds. Furthemore culture-independent approaches to more comprehensively exploit the genetic richness of antimicrobial compound-producing pathways from sponge-associated bacteria are addressed. Full article

(This article belongs to the Collection Bioactive Compounds from Marine Invertebrates)

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Open AccessArticle

Polyketides from the Mangrove-Derived Endophytic Fungus Nectria sp. HN001 and Their α-Glucosidase Inhibitory Activity

by Hui Cui, Yayue Liu, Yang Nie, Zhaoming Liu, Senhua Chen, Zhengrui Zhang, Yongjun Lu, Lei He, Xishan Huang and Zhigang She

Mar. Drugs 2016, 14(5), 86; https://doi.org/10.3390/md14050086 - 28 Apr 2016

Cited by 51 | Viewed by 6619

Abstract

Four new polyketides: nectriacids A–C (1–3) and 12-epicitreoisocoumarinol (4), together with three known compounds: citreoisocoumarinol (5), citreoisocoumarin (6), and macrocarpon C (7) were isolated from the culture of the endophytic fungus Nectria sp. HN001, which was isolated from a fresh branch of the [...] Read more.

Four new polyketides: nectriacids A–C (1–3) and 12-epicitreoisocoumarinol (4), together with three known compounds: citreoisocoumarinol (5), citreoisocoumarin (6), and macrocarpon C (7) were isolated from the culture of the endophytic fungus Nectria sp. HN001, which was isolated from a fresh branch of the mangrove plant Sonneratia ovata collected from the South China Sea. Their structures were determined by the detailed analysis of NMR and mass spectroscopic data. The absolute configuration of the stereogenic carbons for compound 4 was further assigned by Mosher’s ester method. All of the isolated compounds were tested for their α-glucosidase inhibitory activity by UV absorbance at 405 nm, and new compounds 2 and 3 exhibited potent inhibitory activity with IC₅₀ values of 23.5 and 42.3 μM, respectively, which were more potent than positive control (acarbose, IC₅₀, 815.3 μM). Full article

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Open AccessArticle

Novel Azetidine-Containing TZT-1027 Analogues as Antitumor Agents

by Qi Yan, Yujie Wang, Wei Zhang and Yingxia Li

Mar. Drugs 2016, 14(5), 85; https://doi.org/10.3390/md14050085 - 28 Apr 2016

Cited by 11 | Viewed by 6783

Abstract

A conformational restriction strategy was used to design and synthesize nine TZT-1027 analogues. 3-Aryl-azetidine moiety was used to replace phenylethyl group of TZT-1027 at the C-terminus. These analogues exhibited moderate to excellent antiproliferative activities, and the most potent compound 1a showed IC₅₀ [...] Read more.

A conformational restriction strategy was used to design and synthesize nine TZT-1027 analogues. 3-Aryl-azetidine moiety was used to replace phenylethyl group of TZT-1027 at the C-terminus. These analogues exhibited moderate to excellent antiproliferative activities, and the most potent compound 1a showed IC₅₀ values of 2.2 nM against A549 and 2.1 nM against HCT116 cell lines, respectively. However, 1a could not achieve effective inhibition at all the dose levels in the A549 xenograft model (up to 5 mg/kg, injection, once a day), which is only 16%–35% inhibition at the end of the experiment. Full article

(This article belongs to the Special Issue Synthesis of Antitumor Marine Alkaloids and Related Analogues)

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Antimicrobial Activity of Monoramnholipids Produced by Bacterial Strains Isolated from the Ross Sea (Antarctica)

by Pietro Tedesco, Isabel Maida, Fortunato Palma Esposito, Emiliana Tortorella, Karolina Subko, Chidinma Christiana Ezeofor, Ying Zhang, Jioji Tabudravu, Marcel Jaspars, Renato Fani and Donatella De Pascale

Mar. Drugs 2016, 14(5), 83; https://doi.org/10.3390/md14050083 - 26 Apr 2016

Cited by 50 | Viewed by 8763

Abstract

Microorganisms living in extreme environments represent a huge reservoir of novel antimicrobial compounds and possibly of novel chemical families. Antarctica is one of the most extraordinary places on Earth and exhibits many distinctive features. Antarctic microorganisms are well known producers of valuable secondary [...] Read more.

Microorganisms living in extreme environments represent a huge reservoir of novel antimicrobial compounds and possibly of novel chemical families. Antarctica is one of the most extraordinary places on Earth and exhibits many distinctive features. Antarctic microorganisms are well known producers of valuable secondary metabolites. Specifically, several Antarctic strains have been reported to inhibit opportunistic human pathogens strains belonging to Burkholderia cepacia complex (Bcc). Herein, we applied a biodiscovery pipeline for the identification of anti-Bcc compounds. Antarctic sub-sea sediments were collected from the Ross Sea, and used to isolate 25 microorganisms, which were phylogenetically affiliated to three bacterial genera (Psychrobacter, Arthrobacter, and Pseudomonas) via sequencing and analysis of 16S rRNA genes. They were then subjected to a primary cell-based screening to determine their bioactivity against Bcc strains. Positive isolates were used to produce crude extracts from microbial spent culture media, to perform the secondary screening. Strain Pseudomonas BNT1 was then selected for bioassay-guided purification employing SPE and HPLC. Finally, LC-MS and NMR structurally resolved the purified bioactive compounds. With this strategy, we achieved the isolation of three rhamnolipids, two of which were new, endowed with high (MIC < 1 μg/mL) and unreported antimicrobial activity against Bcc strains. Full article

(This article belongs to the Special Issue Selected Papers from the 9th European Conference on Marine Natural Products)

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Cytotoxic Compounds from the Saudi Red Sea Sponge Xestospongia testudinaria

by Ali A. El-Gamal, Shaza M. Al-Massarani, Lamiaa A. Shaala, Abdulrahman M. Alahdald, Mansour S. Al-Said, Abdelkader E. Ashour, Ashok Kumar, Maged S. Abdel-Kader, Wael M. Abdel-Mageed and Diaa T. A. Youssef

Mar. Drugs 2016, 14(5), 82; https://doi.org/10.3390/md14050082 - 26 Apr 2016

Cited by 15 | Viewed by 7332

Abstract

Bioassay-guided fractionation of the organic extract of the Red Sea sponge Xestospongia testudinaria led to the isolation of 13 compounds including two new sterol esters, xestosterol palmitate (2) and xestosterol ester of l6′-bromo-(7′E,11′E,l5′E)-hexadeca-7′,11′,l5′-triene-5′,13′-diynoic acid (4), together with [...] Read more.

Bioassay-guided fractionation of the organic extract of the Red Sea sponge Xestospongia testudinaria led to the isolation of 13 compounds including two new sterol esters, xestosterol palmitate (2) and xestosterol ester of l6′-bromo-(7′E,11′E,l5′E)-hexadeca-7′,11′,l5′-triene-5′,13′-diynoic acid (4), together with eleven known compounds: xestosterol (1), xestosterol ester of 18′-bromooctadeca-7′E,9′E-diene-7′,15′-diynoic acid (3), and the brominated acetylenic fatty acid derivatives, (5E,11E,15E,19E)-20-bromoeicosa-5,11,15,19-tetraene-9,17-diynoic acid (5), 18,18-dibromo-(9E)-octadeca-9,17-diene-5,7-diynoic acid (6), 18-bromooctadeca-(9E,17E)-diene-7,15-diynoic acid (7), 18-bromooctadeca-(9E,13E,17E)-triene-7,15-diynoic acid (8), l6-bromo (7E,11E,l5E)hexadeca-7,11,l5-triene-5,13-diynoic acid (9), 2-methylmaleimide-5-oxime (10), maleimide-5-oxime (11), tetillapyrone (12), and nortetillapyrone (13). The chemical structures of the isolated compounds were accomplished using one- and two-dimensional NMR, infrared and high-resolution electron impact mass spectroscopy (1D, 2D NMR, IR and HREIMS), and by comparison with the data of the known compounds. The total alcoholic and n-hexane extracts showed remarkable cytotoxic activity against human cervical cancer (HeLa), human hepatocellular carcinoma (HepG-2), and human medulloblastoma (Daoy) cancer cell lines. Interestingly, the dibrominated C₁₈-acetylenic fatty acid (6) exhibited the most potent growth inhibitory activity against these cancer cell lines followed by Compounds 7 and 9. Apparently, the dibromination of the terminal olefinic moiety has an enhanced effect on the cytotoxic activity. Full article

(This article belongs to the Collection Bioactive Compounds from Marine Invertebrates)

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Mar. Drugs, Volume 14, Issue 5 (May 2016) – 22 articles

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