Marine Polysaccharides in Pharmaceutical Applications

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

Deadline for manuscript submissions: closed (15 January 2020) | Viewed by 63627

Special Issue Editor


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Guest Editor
Departamento de Química e Bioquímica (DQB) e Centro de Química Estrutural (CQE), Institute of Molecular Sciences, Faculdade de Ciências, Universidade de Lisboa, Lisboa, Portugal
Interests: neurodegenerative diseases; organic synthesis; natural products; antibiotics; antidiabetics; carbohydrate chemistry
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Special Issue Information

Dear Colleagues,

Marine glycans are remarkable molecules, playing a determinant role in biological processes. This Special Issue of Marine Drugs will be dedicated to marine glycans. Participants working in this area are encouraged to contact the Guest Editor, Prof. Amelia Pilar Rauter ([email protected]), with a title and a short abstract of their proposed contribution, until October 31, 2018.

Main topics to be addressed in this issue:

  • Marine glycans: Glycosaminogluycans—structure and biological function; sulfated glycans—infection and therapeutics; N- and O-glycans; Polysaccharides and gut microbiota fermentation; etc.
  • Marine algae lectins: Glycan recognition, biological activity
  • Glycan-based marine natural products—isolation, identification, synthesis, bioactivity
  • Marine glycan-based biopolymers

Other topics addressing marine glycan-related areas are also welcome.

Prof. Amélia Pilar Rauter
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Marine Drugs is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

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Published Papers (11 papers)

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Research

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16 pages, 2974 KiB  
Article
Protective Effect of Low-Molecular-Weight Fucoidan on Radiation-Induced Fibrosis Through TGF-β1/Smad Pathway-Mediated Inhibition of Collagen I Accumulation
by Szu-Yuan Wu, Yu-Ting Chen, Guo-Yu Tsai, Fu-Yin Hsu and Pai-An Hwang
Mar. Drugs 2020, 18(3), 136; https://doi.org/10.3390/md18030136 - 27 Feb 2020
Cited by 17 | Viewed by 3709
Abstract
Radiation-induced fibrosis (RIF) occurs after radiation therapy in normal tissues due to excessive production and deposition of extracellular matrix proteins and collagen, possibly resulting in organ function impairment. This study investigates the effects of low-molecular-weight fucoidan (LMF) on irradiated NIH3T3 cells. Specifically, we [...] Read more.
Radiation-induced fibrosis (RIF) occurs after radiation therapy in normal tissues due to excessive production and deposition of extracellular matrix proteins and collagen, possibly resulting in organ function impairment. This study investigates the effects of low-molecular-weight fucoidan (LMF) on irradiated NIH3T3 cells. Specifically, we quantified cellular metabolic activity, fibrosis-related mRNA expression, transforming growth factor beta-1 (TGF-β1), and collagen-1 protein expression, and fibroblast contractility in response to LMF. LMF pre + post-treatment could more effectively increase cellular metabolic activity compared with LMF post-treatment. LMF pre + post-treatment inhibited TGF-β1 expression, which mediates negative activation of phosphorylated Smad3 (pSmad3) and Smad4 complex formation and suppresses downstream collagen I accumulation. In addition, LMF pre + post-treatment significantly reduced actin-stress fibers in irradiated NIH3T3 cells. LMF, a natural substance obtained from brown seaweed, may be a candidate agent for preventing or inhibiting RIF. Full article
(This article belongs to the Special Issue Marine Polysaccharides in Pharmaceutical Applications)
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12 pages, 2485 KiB  
Article
Promotion of Wound Healing and Prevention of Frostbite Injury in Rat Skin by Exopolysaccharide from the Arctic Marine Bacterium Polaribacter sp. SM1127
by Mei-Ling Sun, Fang Zhao, Xiu-Lan Chen, Xi-Ying Zhang, Yu-Zhong Zhang, Xiao-Yan Song, Cai-Yun Sun and Jie Yang
Mar. Drugs 2020, 18(1), 48; https://doi.org/10.3390/md18010048 - 11 Jan 2020
Cited by 32 | Viewed by 5373
Abstract
Many marine microorganisms synthesize exopolysaccharides (EPSs), and some of these EPSs have been reported to have potential in different fields. However, the pharmaceutical potentials of marine EPSs are rarely reported. The EPS secreted by the Artic marine bacterium Polaribacter sp. SM1127 has good [...] Read more.
Many marine microorganisms synthesize exopolysaccharides (EPSs), and some of these EPSs have been reported to have potential in different fields. However, the pharmaceutical potentials of marine EPSs are rarely reported. The EPS secreted by the Artic marine bacterium Polaribacter sp. SM1127 has good antioxidant activity, outstanding moisture-retention ability, and considerable protective property on human dermal fibroblasts (HDFs) at low temperature. Here, the effects of SM1127 EPS on skin wound healing and frostbite injury prevention were studied. Scratch wound assay showed that SM1127 EPS could stimulate the migration of HDFs. In the full-thickness cutaneous wound experiment of Sprague–Dawley (SD) rats, SM1127 EPS increased the wound healing rate and stimulated tissue repair detected by macroscopic observation and histologic examination, showing the ability of SM1127 EPS to promote skin wound healing. In the skin frostbite experiment of SD rats, pretreatment of rat skin with SM1127 EPS increased the rate of frostbite wound healing and promoted the repair of the injured skin significantly, indicating the good effect of SM1127 EPS on frostbite injury prevention. These results suggest the promising potential of SM1127 EPS in the pharmaceutical area to promote skin wound healing and prevent frostbite injury. Full article
(This article belongs to the Special Issue Marine Polysaccharides in Pharmaceutical Applications)
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24 pages, 8561 KiB  
Article
Alginate Oligosaccharides Affect Mechanical Properties and Antifungal Activity of Alginate Buccal Films with Posaconazole
by Marta Szekalska, Magdalena Wróblewska, Monika Trofimiuk, Anna Basa and Katarzyna Winnicka
Mar. Drugs 2019, 17(12), 692; https://doi.org/10.3390/md17120692 - 9 Dec 2019
Cited by 39 | Viewed by 4749
Abstract
Sodium alginate and its oligosaccharides through potential antifungal properties might improve the activity of antifungal drugs enhancing their efficacy and potentially reducing the frequency of application. Mucoadhesive buccal films are oral dosage forms designed for maintaining both local or systemic drug effects and [...] Read more.
Sodium alginate and its oligosaccharides through potential antifungal properties might improve the activity of antifungal drugs enhancing their efficacy and potentially reducing the frequency of application. Mucoadhesive buccal films are oral dosage forms designed for maintaining both local or systemic drug effects and seem to be a very promising alternative to conventional oral formulations. Hence, in this study, mucoadhesive buccal films based on the alginate and its oligosaccharide oligomer composed predominantly of mannuronic acid for the administration of posaconazole-antifungal drug from the azole group were developed. As the polymer gelation method, a relatively new freeze-thaw technique was chosen. All prepared formulations were examined for pharmaceutical tests, swelling, mechanical, and mucoadhesive properties. In addition, the influence of sodium alginate (ALG) and alginate oligosaccharides (OLG) on POS antifungal activity on Candida species was performed. It was observed that film formulation containing 1% ALG and 1% OLG (F2) was characterized by optimal mucoadhesive and swelling properties and prolonged drug release up to 5 h. Additionally, it was shown that OLG affected the growth reduction of all tested Candida spp. The obtained data has opened the way for future research for developing OLG-based dosage forms, which might increase the activity of antifungal drugs. Full article
(This article belongs to the Special Issue Marine Polysaccharides in Pharmaceutical Applications)
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16 pages, 2269 KiB  
Article
In Vitro Immunostimulating Activity of Sulfated Polysaccharides from Caulerpa cupressoides Var. Flabellata
by Jefferson da Silva Barbosa, Mariana Santana Santos Pereira Costa, Luciana Fentanes Moura de Melo, Mayara Jane Campos de Medeiros, Daniel de Lima Pontes, Katia Castanho Scortecci and Hugo Alexandre Oliveira Rocha
Mar. Drugs 2019, 17(2), 105; https://doi.org/10.3390/md17020105 - 9 Feb 2019
Cited by 25 | Viewed by 4094
Abstract
Green seaweeds are rich sources of sulfated polysaccharides (SPs) with potential biomedical and nutraceutical applications. The aim of this work was to evaluate the immunostimulatory activity of SPs from the seaweed, Caulerpa cupressoides var. flabellata on murine RAW 264.7 macrophages. SPs were evaluated [...] Read more.
Green seaweeds are rich sources of sulfated polysaccharides (SPs) with potential biomedical and nutraceutical applications. The aim of this work was to evaluate the immunostimulatory activity of SPs from the seaweed, Caulerpa cupressoides var. flabellata on murine RAW 264.7 macrophages. SPs were evaluated for their ability to modify cell viability and to stimulate the production of inflammatory mediators, such as nitric oxide (NO), intracellular reactive oxygen species (ROS), and cytokines. Additionally, their effect on inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) gene expression was investigated. The results showed that SPs were not cytotoxic and were able to increase in the production of NO, ROS and the cytokines, tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6). It was also observed that treatment with SPs increased iNOS and COX-2 gene expression. Together, these results indicate that C. cupressoides var. flabellata SPs have strong immunostimulatory activity, with potential biomedical applications. Full article
(This article belongs to the Special Issue Marine Polysaccharides in Pharmaceutical Applications)
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15 pages, 3888 KiB  
Article
Microcarriers Based on Glycosaminoglycan-Like Marine Exopolysaccharide for TGF-β1 Long-Term Protection
by Agata Zykwinska, Mélanie Marquis, Mathilde Godin, Laëtitia Marchand, Corinne Sinquin, Catherine Garnier, Camille Jonchère, Claire Chédeville, Catherine Le Visage, Jérôme Guicheux, Sylvia Colliec-Jouault and Stéphane Cuenot
Mar. Drugs 2019, 17(1), 65; https://doi.org/10.3390/md17010065 - 19 Jan 2019
Cited by 22 | Viewed by 4853
Abstract
Articular cartilage is an avascular, non-innervated connective tissue with limited ability to regenerate. Articular degenerative processes arising from trauma, inflammation or due to aging are thus irreversible and may induce the loss of the joint function. To repair cartilaginous defects, tissue engineering approaches [...] Read more.
Articular cartilage is an avascular, non-innervated connective tissue with limited ability to regenerate. Articular degenerative processes arising from trauma, inflammation or due to aging are thus irreversible and may induce the loss of the joint function. To repair cartilaginous defects, tissue engineering approaches are under intense development. Association of cells and signalling proteins, such as growth factors, with biocompatible hydrogel matrix may lead to the regeneration of the healthy tissue. One current strategy to enhance both growth factor bioactivity and bioavailability is based on the delivery of these signalling proteins in microcarriers. In this context, the aim of the present study was to develop microcarriers by encapsulating Transforming Growth Factor-β1 (TGF-β1) into microparticles based on marine exopolysaccharide (EPS), namely GY785 EPS, for further applications in cartilage engineering. Using a capillary microfluidic approach, two microcarriers were prepared. The growth factor was either encapsulated directly within the microparticles based on slightly sulphated derivative or complexed firstly with the highly sulphated derivative before being incorporated within the microparticles. TGF-β1 release, studied under in vitro model conditions, revealed that the majority of the growth factor was retained inside the microparticles. Bioactivity of released TGF-β1 was particularly enhanced in the presence of highly sulphated derivative. It comes out from this study that GY785 EPS based microcarriers may constitute TGF-β1 reservoirs spatially retaining the growth factor for a variety of tissue engineering applications and in particular cartilage regeneration, where the growth factor needs to remain in the target location long enough to induce robust regenerative responses. Full article
(This article belongs to the Special Issue Marine Polysaccharides in Pharmaceutical Applications)
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18 pages, 3761 KiB  
Article
Anticoagulant Properties of a Green Algal Rhamnan-type Sulfated Polysaccharide and Its Low-molecular-weight Fragments Prepared by Mild Acid Degradation
by Xue Liu, Peng Du, Xiao Liu, Sujian Cao, Ling Qin, Meijia He, Xiaoxi He and Wenjun Mao
Mar. Drugs 2018, 16(11), 445; https://doi.org/10.3390/md16110445 - 12 Nov 2018
Cited by 35 | Viewed by 4395
Abstract
The active sulfated polysaccharide from seaweed possesses important pharmaceutical and biomedical potential. In the study, Monostroma sulfated polysaccharide (MSP) was obtained from Monostroma angicava, and the low-molecular-weight fragments of MSP (MSP-Fs: MSP-F1–MSP-F6) were prepared by controlled acid degradation. The molecular weights of [...] Read more.
The active sulfated polysaccharide from seaweed possesses important pharmaceutical and biomedical potential. In the study, Monostroma sulfated polysaccharide (MSP) was obtained from Monostroma angicava, and the low-molecular-weight fragments of MSP (MSP-Fs: MSP-F1–MSP-F6) were prepared by controlled acid degradation. The molecular weights of MSP and MSP-F1–MSP-F6 were 335 kDa, 240 kDa, 90 kDa, 40 kDa, 24 kDa, 12 kDa, and 6.8 kDa, respectively. The polysaccharides were sulfated rhamnans that consisted of →3)-α-l-Rhap-(1→ and →2)-α-l-Rhap-(1→ units with partial sulfation at C-2 of →3)-α-l-Rhap-(1→ and C-3 of →2)-α-l-Rhap-(1→. Anticoagulant properties in vitro of MSP and MSP-F1–MSP-F6 were evaluated by studying the activated partial thromboplastin time, thrombin time, and prothrombin time. Anticoagulant activities in vivo of MSP and MSP-F4 were further evaluated; their fibrin(ogen)olytic activities in vivo and thrombolytic properties in vitro were also assessed by D-dimer, fibrin degradation products, plasminogen activator inhibitior-1, and clot lytic rate assays. The results showed that MSP and MSP-F1–MSP-F4 with molecular weights of 24–240 kDa had strong anticoagulant activities. A decrease in the molecular weight of MSP-Fs was accompanied by a decrease in the anticoagulant activity, and higher anticoagulant activity requires a molecular weight of over 12 kDa. MSP and MSP-F4 possessed strong anticoagulant activities in vivo, as well as high fibrin(ogen)olytic and thrombolytic activities. MSP and MSP-F4 have potential as drug or helpful food supplements for human health. Full article
(This article belongs to the Special Issue Marine Polysaccharides in Pharmaceutical Applications)
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10 pages, 1305 KiB  
Article
Influence of Modified Fucoidan and Related Sulfated Oligosaccharides on Hematopoiesis in Cyclophosphamide-Induced Mice
by Natalia Yu. Anisimova, Nadezhda E. Ustyuzhanina, Maria I. Bilan, Fedor V. Donenko, Natalia A. Ushakova, Anatolii I. Usov, Mikhail V. Kiselevskiy and Nikolay E. Nifantiev
Mar. Drugs 2018, 16(9), 333; https://doi.org/10.3390/md16090333 - 13 Sep 2018
Cited by 23 | Viewed by 4192
Abstract
Immunosuppression derived after cytostatics application in cancer chemotherapy is considered as an adverse side effect that leads to deterioration of quality of life and risk of infectious diseases. A linear sulfated (1→3)-α-l-fucan M-Fuc prepared by chemical modification of a fucoidan isolated [...] Read more.
Immunosuppression derived after cytostatics application in cancer chemotherapy is considered as an adverse side effect that leads to deterioration of quality of life and risk of infectious diseases. A linear sulfated (1→3)-α-l-fucan M-Fuc prepared by chemical modification of a fucoidan isolated from the brown seaweed Chordaria flagelliformis, along with two structurally related synthetic sulfated oligosaccharides, were studied as stimulators of hematopoiesis on a model of cyclophosphamide immunosuppression in mice. Recombinant granulocyte colony-stimulating factor (r G-CSF), which is currently applied in medicine to treat low blood neutrophils, was used as a reference. Polysaccharide M-Fuc and sulfated difucoside DS did not demonstrate significant effect, while sulfated octasaccharide OS showed higher activity than r G-CSF, causing pronounced neutropoiesis stimulation. In addition, production of erythrocytes and platelets was enhanced after the octasaccharide administration. The assessment of populations of cells in blood and bone marrow of mice revealed the difference in mechanisms of action of OS and r G-CSF. Full article
(This article belongs to the Special Issue Marine Polysaccharides in Pharmaceutical Applications)
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14 pages, 2293 KiB  
Article
Anticoagulant and Antithrombotic Properties of Three Structurally Correlated Sea Urchin Sulfated Glycans and Their Low-Molecular-Weight Derivatives
by Ariana A. Vasconcelos, Isabela D. Sucupira, Alessandra L. Guedes, Ismael N. Queiroz, Flavia S. Frattani, Roberto J. Fonseca and Vitor H. Pomin
Mar. Drugs 2018, 16(9), 304; https://doi.org/10.3390/md16090304 - 30 Aug 2018
Cited by 19 | Viewed by 4760
Abstract
The anticoagulant and antithrombotic properties of three structurally correlated sea urchin-derived 3-linked sulfated α-glycans and their low molecular-weight derivatives were screened comparatively through various in vitro and in vivo methods. These methods include activated partial thromboplastin time, the inhibitory activity of antithrombin over [...] Read more.
The anticoagulant and antithrombotic properties of three structurally correlated sea urchin-derived 3-linked sulfated α-glycans and their low molecular-weight derivatives were screened comparatively through various in vitro and in vivo methods. These methods include activated partial thromboplastin time, the inhibitory activity of antithrombin over thrombin and factor Xa, venous antithrombosis, the inhibition of platelet aggregation, the activation of factor XII, and bleeding. While the 2-sulfated fucan from Strongylocentrotus franciscanus was observed to be poorly active in most assays, the 4-sulfated fucan from Lytechinus variegatus, the 2-sulfated galactan from Echinometra lucunter and their derivatives showed multiple effects. All marine compounds showed no capacity to activate factor XII and similar low bleeding tendencies regardless of the dose concentrations used to achieve the highest antithrombotic effect observed. The 2-sulfated galactan showed the best combination of results. Our work improves the background about the structure-function relationship of the marine sulfated glycans in anticoagulation and antithrombosis. Besides confirming the negative effect of the 2-sulfated fucose and the positive effect of the 2-sulfated galactose on anticoagulation in vitro, our results also demonstrate the importance of this set of structural requirements on antithrombosis in vivo, and further support the involvement of high-molecular weight and 4-sulfated fucose in both activities. Full article
(This article belongs to the Special Issue Marine Polysaccharides in Pharmaceutical Applications)
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Review

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34 pages, 1694 KiB  
Review
The Antioxidant Activity of Polysaccharides Derived from Marine Organisms: An Overview
by Qiwu Zhong, Bin Wei, Sijia Wang, Songze Ke, Jianwei Chen, Huawei Zhang and Hong Wang
Mar. Drugs 2019, 17(12), 674; https://doi.org/10.3390/md17120674 - 29 Nov 2019
Cited by 165 | Viewed by 10309
Abstract
Marine-derived antioxidant polysaccharides have aroused extensive attention because of their potential nutritional and therapeutic benefits. However, the comprehensive comparison of identified marine-derived antioxidant polysaccharides is still inaccessible, which would facilitate the discovery of more efficient antioxidants from marine organisms. Thus, this review summarizes [...] Read more.
Marine-derived antioxidant polysaccharides have aroused extensive attention because of their potential nutritional and therapeutic benefits. However, the comprehensive comparison of identified marine-derived antioxidant polysaccharides is still inaccessible, which would facilitate the discovery of more efficient antioxidants from marine organisms. Thus, this review summarizes the sources, chemical composition, structural characteristics, and antioxidant capacity of marine antioxidant polysaccharides, as well as their protective in vivo effects mediated by antioxidative stress reported in the last few years (2013–2019), and especially highlights the dominant role of marine algae as antioxidant polysaccharide source. In addition, the relationships between the chemical composition and structural characteristics of marine antioxidant polysaccharides with their antioxidant capacity were also discussed. The antioxidant activity was found to be determined by multiple factors, including molecular weight, monosaccharide composition, sulfate position and its degree. Full article
(This article belongs to the Special Issue Marine Polysaccharides in Pharmaceutical Applications)
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20 pages, 1101 KiB  
Review
Possibilities of Fucoidan Utilization in the Development of Pharmaceutical Dosage Forms
by Aleksandra Citkowska, Marta Szekalska and Katarzyna Winnicka
Mar. Drugs 2019, 17(8), 458; https://doi.org/10.3390/md17080458 - 5 Aug 2019
Cited by 119 | Viewed by 9002
Abstract
Fucoidan is a polysaccharide built from L-fucose molecules. The main source of this polysaccharide is the extracellular matrix of brown seaweed (Phaeophyta), but it can be also isolated from invertebrates such as sea urchins (Echinoidea) and sea cucumbers ( [...] Read more.
Fucoidan is a polysaccharide built from L-fucose molecules. The main source of this polysaccharide is the extracellular matrix of brown seaweed (Phaeophyta), but it can be also isolated from invertebrates such as sea urchins (Echinoidea) and sea cucumbers (Holothuroidea). Interest in fucoidan is related to its broad biological activity, including possible antioxidant, anti-inflammatory, antifungal, antiviral or antithrombotic effects. The potential application of fucoidan in the pharmaceutical technology is also due to its ionic nature. The negative charge of the molecule results from the presence of sulfate residues in the C-2 and C-4 positions, occasionally in C-3, allowing the formation of complexes with other oppositely charged molecules. Fucoidan is non-toxic, biodegradable and biocompatible compound approved by Food and Drug Administration (FDA) as Generally Recognized As Safe (GRAS) category as food ingredient. Fucoidan plays an important role in the pharmaceutical technology, so in this work aspects concerning its pharmaceutical characteristics and designing of various dosage forms (nanoparticles, liposomes, microparticles, and semisolid formulations) with fucoidan itself and with its combinations with other polymers or components that give a positive charge were reviewed. Advantages and limitations of fucoidan utilization in the pharmaceutical technology were also discussed. Full article
(This article belongs to the Special Issue Marine Polysaccharides in Pharmaceutical Applications)
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31 pages, 5000 KiB  
Review
Antithrombotics from the Sea: Polysaccharides and Beyond
by Francisca Carvalhal, Ricardo R. Cristelo, Diana I. S. P. Resende, Madalena M. M. Pinto, Emília Sousa and Marta Correia-da-Silva
Mar. Drugs 2019, 17(3), 170; https://doi.org/10.3390/md17030170 - 16 Mar 2019
Cited by 49 | Viewed by 6875
Abstract
Marine organisms exhibit some advantages as a renewable source of potential drugs, far beyond chemotherapics. Particularly, the number of marine natural products with antithrombotic activity has increased in the last few years, and reports show a wide diversity in scaffolds, beyond the polysaccharide [...] Read more.
Marine organisms exhibit some advantages as a renewable source of potential drugs, far beyond chemotherapics. Particularly, the number of marine natural products with antithrombotic activity has increased in the last few years, and reports show a wide diversity in scaffolds, beyond the polysaccharide framework. While there are several reviews highlighting the anticoagulant and antithrombotic activities of marine-derived sulfated polysaccharides, reports including other molecules are sparse. Therefore, the present paper provides an update of the recent progress in marine-derived sulfated polysaccharides and quotes other scaffolds that are being considered for investigation due to their antithrombotic effect. Full article
(This article belongs to the Special Issue Marine Polysaccharides in Pharmaceutical Applications)
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