Anticoagulant and antithrombotic activity of seaweed sulfated polysaccharides

2020 ◽  
Author(s):  
Т.А. Кузнецова
Keyword(s):  
Main Chain ◽  
Oral Anticoagulants ◽  
Monosaccharide Composition ◽  
Structural Features ◽  
Sulfated Polysaccharides ◽  
Clinical Use ◽  
Antithrombotic Activity ◽  
Glycosidic Bonds ◽  
Low Toxicity ◽  
Alternative Sources

Представлены современные литературные данные по антикоагулянтной, антитромботической и фибринолитической активности сульфатированных полисахаридов (ПС) морских водорослей в зависимости от их структурных особенностей (содержания и положения сульфатных групп на главной цепи ПС, молекулярной массы, моносахаридного состава и типа гликозидных связей, характера разветвления и др.). Обсуждаются механизмы действия ПС на систему гемостаза в сравнительном аспекте по отношению к гепарину. Рассматриваются вопросы пероральной биодоступности ПС, важные для их клинического использования в качестве пероральных антикоагулянтов и антитромботических средств. Сочетание свойств антикоагулянтов, ингибиторов тромбина, фибринолитиков наряду с низкой токсичностью и относительной дешевизной производства открывают перспективы для клинического использования ПС в качестве альтернативных источников новых антикоагулянтных и антитромботических соединений. Modern literature data on the anticoagulant, antithrombotic and fibrinolytic activity of sulfated polysaccharides of seaweed (PS) are presented, depending on their structural features (content and position of sulfate groups on the main chain of PS, molecular weight, monosaccharide composition and type of glycosidic bonds, the degree of PS chain branching, etc.). The mechanisms of PS action on hemostasis are discussed in a comparative to heparin. The questions of oral bioavailability of PS, important for their clinical use as oral anticoagulants and antithrombotic agents, are considered. The combination of the anticoagulant, thrombolytic, fibrinolytic properties together with low toxicity and relative cheapness of production open up prospects for the clinical use of PS as alternative sources of new anticoagulant and antithrombotic compounds.

scholarly journals The Potency of Seaweed Sulfated Polysaccharides for the Correction of Hemostasis Disorders in COVID-19

Molecules ◽  
2021 ◽  
Vol 26 (9) ◽  
pp. 2618
Author(s):  
Tatyana A. Kuznetsova ◽  
Boris G. Andryukov ◽  
Ilona D. Makarenkova ◽  
Tatyana S. Zaporozhets ◽  
Natalya N. Besednova ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Therapeutic Potential ◽  
Low Cost ◽  
Clinical Manifestations ◽  
Optimal Dose ◽  
Monosaccharide Composition ◽  
Structural Features ◽  
Sulfated Polysaccharides ◽  
Clinical Use ◽  
Hemostasis System

Hemostasis disorders play an important role in the pathogenesis, clinical manifestations, and outcome of COVID-19. First of all, the hemostasis system suffers due to a complicated and severe course of COVID-19. A significant number of COVID-19 patients develop signs of hypercoagulability, thrombocytopenia, and hyperfibrinolysis. Patients with severe COVID-19 have a tendency toward thrombotic complications in the venous and arterial systems, which is the leading cause of death in this disease. Despite the success achieved in the treatment of SARS-CoV-2, the search for new effective anticoagulants, thrombolytics, and fibrinolytics, as well as their optimal dose strategies, continues to be relevant. The wide therapeutic potential of seaweed sulfated polysaccharides (PSs), including anticoagulant, thrombolytic, and fibrinolytic activities, opens up new possibilities for their study in experimental and clinical trials. These natural compounds can be important complementary drugs for the recovery from hemostasis disorders due to their natural origin, safety, and low cost compared to synthetic drugs. In this review, the authors analyze possible pathophysiological mechanisms involved in the hemostasis disorders observed in the pathological progression of COVID-19, and also focus the attention of researchers on seaweed PSs as potential drugs aimed to correction these disorders in COVID-19 patients. Modern literature data on the anticoagulant, antithrombotic, and fibrinolytic activities of seaweed PSs are presented, depending on their structural features (content and position of sulfate groups on the main chain of PSs, molecular weight, monosaccharide composition and type of glycosidic bonds, the degree of PS chain branching, etc.). The mechanisms of PS action on the hemostasis system and the issues of oral bioavailability of PSs, important for their clinical use as oral anticoagulant and antithrombotic agents, are considered. The combination of the anticoagulant, thrombolytic, and fibrinolytic properties, along with low toxicity and relative cheapness of production, open up prospects for the clinical use of PSs as alternative sources of new anticoagulant and antithrombotic compounds. However, further investigation and clinical trials are needed to confirm their efficacy.

The Potential of Fucose-Containing Sulfated Polysaccharides As Scaffolds for Biomedical Applications

2019 ◽  
Vol 26 (35) ◽  
pp. 6399-6411 ◽  
Author(s):  
Cláudia Nunes ◽  
Manuel A. Coimbra
Keyword(s):  
Tissue Regeneration ◽  
Cell Walls ◽  
Biomedical Applications ◽  
Structural Features ◽  
Therapeutic Agents ◽  
Sulfated Polysaccharides ◽  
Clinical Use ◽  
Health Related ◽  
Pathogen Inhibition ◽  
Health Applications

Marine environments have a high quantity and diversity of sulfated polysaccharides. In coastal regions brown algae are the most abundant biomass producers and their cell walls have fucosecontaining sulfated polysaccharides (FCSP), known as fucans and/or fucoidans. These sulfated compounds have been widely researched for their biomedical properties, namely the immunomodulatory, haemostasis, pathogen inhibition, anti-inflammatory capacity, and antitumoral. These activities are probably due to their ability to mimic the carbohydrate moieties of mammalian glycosaminoglycans. Therefore, the FCSP are interesting compounds for application in health-related subjects, mainly for developing scaffolds for delivery systems or tissue regeneration. FCSP showed potential for these applications also due to their ability to form stable 3D structures with other polymers able to entrap therapeutic agents or cell and growth factors, besides their biocompatibility and biodegradability. However, for the clinical use of these biopolymers well-defined reproducible molecules are required in order to accurately establish relationships between structural features and human health applications.

On the diagnostics of Adonis L. species (Ranunculaceae) of the Russian flora

2020 ◽  
pp. 3-14
Author(s):  
Aleksandr Luferov
Keyword(s):  
Raw Materials ◽  
Natural Populations ◽  
Structural Features ◽  
Biologically Active ◽  
Scientific Medicine ◽  
Diagnostic Features ◽  
Plant Raw Materials ◽  
Similar Chemical ◽  
Chemical Studies ◽  
Alternative Sources

The article provides brief information about cardiotonic, sedative, cytostatic, diuretic, and antibacterial effects of biologically active compounds of Adonis L. (Ranunculaceae) species. Chemical studies allowed to identify the cardiac glycosides, or cardenolides: or cardenolides: adontoxin, adonitol, adonitoxigenin, acetyldigitoxin and others. In scientific medicine, it is currently allowed to use Adonis vernalis L. Other types of Adonis have a similar chemical composition and are offered as substitutes for this official species, for example, Adonis apennina L. Many Adonis species have limited natural resources, and in some regions are rare, requiring conservation of their natural populations. The search for alternative sources of medicinal plant raw materials, based on this, is relevant. The experimental part of our research was carried out using the morphological and geographical method with the involvement of information on ecology and phenology. For the first time summarizes the diagnostic features of Adonis flora of Russian flora. Previously unknown structural features (shape and size of anthers) were identified that characterize the subgenera Adonanthe and Adonis. Taxonomic study of the genus Adonis of the Russian flora allowed us to determine its species composition, clarify its systematic affiliation, and nomenclature synonyms. 9 species were identified. Of these, 6 are perennials belonging to the subgenus Adonanthe, section Consiligo, which includes 2 subsections: Amurenses (2 species) and Vernales, which is differentiated into 2 rows: Apenninae (2 species) and Vernales (2 species). Subgenus Adonis is represented by 2 sections: Adonis (1 species) and Lophocarpa with sections Aestivales (1 species) and Dentatae (1 species). For all the considered species and varieties, the main distribution areas are given. A key has been compiled to determine the wild Adonis species distributed in Russia.

Click Reactions in Chemistry of Triterpenes - Advances Towards Development of Potential Therapeutics

2018 ◽  
Vol 25 (5) ◽  
pp. 636-658 ◽  
Author(s):  
Jan Pokorny ◽  
Lucie Borkova ◽  
Milan Urban
Keyword(s):  
Biological Activities ◽  
Synthetic Approach ◽  
Clinical Use ◽  
New Approach ◽  
Click Reactions ◽  
Drug Candidates ◽  
The Past ◽  
Low Toxicity ◽  
New Compounds ◽  
Potential Therapeutics

Triterpenoids are natural compounds with a large variety of biological activities such as anticancer, antiviral, antibacterial, antifungal, antiparazitic, antiinflammatory and others. Despite their low toxicity and simple availability from the natural resources, their clinical use is still severely limited by their higher IC50 and worse pharmacological properties than in the currently used therapeutics. This fact encouraged a number of researchers to develop new terpenic derivatives more suitable for the potential clinical use. This review summarizes a new approach to improve both, the activity and ADME-Tox properties by connecting active terpenes to another modifying molecules using click reactions. Within the past few years, this synthetic approach was well explored yielding a lot of great improvements of the parent compounds along with some less successful attempts. A large quantity of the new compounds presented here are superior in both activity and ADME-Tox properties to their parents. This review should serve the researchers who need to promote their hit triterpenic structures towards their clinical use and it is intended as a guide for the chemical synthesis of better drug candidates.

Contemporary Clinical Use of Aspirin: Mechanisms of Action, Current Concepts, Unresolved Questions, and Future Perspectives

2021 ◽  
Author(s):  
Mikael Christiansen ◽  
Erik Lerkevang Grove ◽  
Anne-Mette Hvas
Keyword(s):  
Cardiovascular Disease ◽  
Clinical Trials ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Bleeding Risk ◽  
Clinical Use ◽  
Action Current ◽  
Potential Clinical Benefit ◽  
Treatment Indications ◽  
Prevention Of Cardiovascular Disease

AbstractThe ability of aspirin to inhibit platelet aggregation has positioned this agent within the most frequently used drugs worldwide. The aim of this article is to review the contemporary clinical use of aspirin and also to discuss unresolved issues not yet translated into clinical practice. Results from several clinical trials have led to strong guideline recommendations for aspirin use in the acute management and secondary prevention of cardiovascular disease. On the contrary, guidelines regarding aspirin use as primary prevention of cardiovascular disease are almost conservative, supported by recent trials reporting that the bleeding risk outweighs the potential benefits in most patients. In pregnancy, aspirin has proved efficient in preventing preeclampsia and small-for-gestational-age births in women at high risk, and is hence widely recommended in clinical guidelines. Despite the vast amount of clinical data on aspirin, several unresolved questions remain. Randomized trials have reported that aspirin reduces the risk of recurrent venous thromboembolism, but the clinical relevance remains limited, because direct oral anticoagulants are more effective. Laboratory studies suggest that a twice-daily dosing regimen or evening intake may lead to more efficient platelet inhibition, and the potential clinical benefit of such strategies is currently being explored in ongoing clinical trials. Enteric-coated formulations of aspirin are frequently used, but it remains unclear if they are safer and as efficient as plain aspirin. In the future, aspirin use after percutaneous coronary interventions might not be mandatory in patients who also need anticoagulant therapy, as several trials support shorter aspirin duration strategies. On the other hand, new treatment indications for aspirin will likely arise, as there is growing evidence that aspirin may reduce the risk of colorectal cancer and other types of cancer.

INFLUENCE OF THE SULFATION PATTERN ON CERTAIN BIOLOGICAL PROPERTIES OF GALACTOSAMINOGLYCANS

1987 ◽  
Author(s):  
B Casu ◽  
L Marchese ◽  
A Naggi ◽  
G Torri ◽  
J Fareed ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Dermatan Sulfate ◽  
Anticoagulant Activity ◽  
Chlorosulfonic Acid ◽  
Biological Properties ◽  
Sulfated Polysaccharides ◽  
Low Molecular Weight ◽  
Antithrombotic Activity

In order to investigate the influence of charge distribution and chain length on the biological properties of sulfated polysaccharides, additional sulfate groups were introduced into the galactosaminoglycans, chondriotin sulfate and dermatan sulfate. Using a flexible method (with sulfuric acid and chlorosulfonic acid) for concurrent sulfation and controlled depolymerization, numerous products were obtained and characterized by chemical, enzymatic and nuclear magnetic resonance spectroscopic methods. The biologic actions of these products were profiled in both in vitro and in vivo assays for antithrombotic activity. Despite a weaker in vitro anticoagulant activity, low molecular weight over sulfated galactosaminoglycans produced significant dose-dependent antithrombotic actions in animal models which were similar to the actions observed with oversulfated low molecular weight heparins. These results suggest that a significant antithrombotic activity can be elicited through non-specific interactions of polysulfates with cellular and plasma components, and that clusters of sulfate groups such as the 4-6 disulfate group on D-galactosaminoglycan residues may be important for these interactions. Furthermore, these results, also suggest that supersulfation of glycosaminogly-cans results in products with biologic activity distinct from the native material.

An Analog Of Thiazole Which Has Potential Antithrombotic Activity With Low Toxicity

1981 ◽  
Author(s):  
E E Nishizawa ◽  
R H Rynbrandt ◽  
A R Mendoza ◽  
D P Balqoyen ◽  
K A Annis
Keyword(s):  
Platelet Aggregation ◽  
Chemical Modification ◽  
Intravenous Administration ◽  
Inhibitory Activity ◽  
Animal Species ◽  
Paw Edema ◽  
Antithrombotic Agent ◽  
Antithrombotic Activity ◽  
Low Toxicity ◽  
Induced Aggregation

Chemical modification of a compound found active in preventing death in mice following intravenous administration of collagen led to the development of an inhibitor of collagen-induced platelet aggregation which was active at 1 ng/ml in human PRP, namely 4,5-bis(p-methoxyphenyl)-2- (trifluoromethyl)-thiazole (TFT). It did not inhibit ADP, thrombin or PGH2-induced aggregation but inhibited the collagen-induced release of radioactivity from platelets labelled with radioactive serotonin. It was active in many animal species and in the rabbit it had a duration of activity of about 8 hours at 1 mg/kg (p.o.).TFT has cyclooxygenase inhibitory activity, but unlike aspirin (A) or flurbiprofen (F), it showed no incidence of ulcers at 500 mg/kg p.o. in rats. However, again unlike A or F, it had very little anti-inflammatory activity as measured by the carrageenan-induced hind paw edema assay in rats. Its LD50 in mice (i.p.) was greater than 1 gm/kg.Thus TFT appears to be a potential antithrombotic agent with high antiplatelet specificity and a wide therapeutic margin as compared with A or F. The anti platelet action of TFT may be due to its inhibition of cyclooxygenase.

Polysaccharides from the roots ofAlthaea officinalis L.: Structural features of D-glucans

1984 ◽  
Vol 49 (11) ◽  
pp. 2674-2679 ◽  
Author(s):  
Peter Capek ◽  
Rudolf Toman ◽  
Jozef Rosík ◽  
Alžbeta Kardošová ◽  
František Janeček
Keyword(s):  
Medicinal Plant ◽  
Structural Features ◽  
Gel Chromatography ◽  
Linear Character ◽  
Molecular Weights ◽  
Glycosidic Bonds ◽  
Althaea Officinalis ◽  
C Nmr

From the roots of the medicinal plant Althaea officinalis L., three D-glucans were isolated by gel chromatography which differed in molecular weights. The results of methylation analyses and 13C NMR measurements indicated predominantly linear character of the polysaccharide chains composed of α-D-glucopyranose units linked by 1 → 6 glycosidic bonds almost exclusively. The polymers had essentially the same structural features as D-glucan isolated from the leaves of this plant.

Highly CO2-Soluble Chelating Agents for Supercritical Extraction and Recovery of Heavy Metals

1994 ◽  
Vol 344 ◽  
Author(s):  
A. Yazdi ◽  
E. J. Beckman
Keyword(s):  
Carbon Dioxide ◽  
Chemical Process ◽  
Chelating Agents ◽  
Main Chain ◽  
Molecular Design ◽  
Metal Extraction ◽  
Extraction Recovery ◽  
Metal Chelating ◽  
Low Toxicity ◽  
Poor Solvent

AbstractCarbon dioxide is an attractive organic solvent in today's chemical process environment in that it is non-flammable, inexpensive, and exhibits low toxicity. Further, materials solubilized in carbon dioxide are easily and completely recovered/concentrated from solution via a simple pressure quench. Despite these favorable properties, CO2 is non-polar, and as such is a very poor solvent for materials such as conventional metal chelating agents, thus blocking application of carbon dioxide in metal extraction/recovery. Consequently, we are exploring the molecular design of materials which are highly CO2-philic, that is, they exhibit solubilities in carbon dioxide which are significantly greater than alkanes with the same number of main-chain atoms. By functionalizing chelating moieties with CO2-philic oligomers, we have generated materials which both effectively extract metals from solid matrices and which dissolve in carbon dioxide in significant quantities.

Antithrombotic and Anticoagulant Activities of a Low Molecular Weight Fucoidan by the Subcutaneous Route

1999 ◽  
Vol 81 (03) ◽  
pp. 391-395 ◽  
Author(s):  
S. Colliec Jouault ◽  
S. Mauray ◽  
J. Theveniaux ◽  
C. Sternberg ◽  
Boisson Vidal ◽  
...  
Keyword(s):  
Molecular Weight ◽  
High Molecular Weight ◽  
Subcutaneous Injection ◽  
Thrombin Generation ◽  
Sulfated Polysaccharides ◽  
Low Molecular Weight ◽  
High Molecular Weight Fraction ◽  
Antithrombotic Activity ◽  
Single Subcutaneous Injection ◽  
Chemical Structures

SummaryFucoidans (high-molecular-weight sulfated polysaccharides extracted from brown seaweeds) have anticoagulant and antithrombotic effects. They inhibit thrombin by catalyzing both serpins (antithrombin and heparin cofactor II) according to their chemical structures and origins. In this study, a low-molecular-weight (LMW) fucoidan of 8 kDa was obtained by chemical degradation of a high-molecular-weight fraction. The antithrombotic and anticoagulant activities of this new compound were compared to those of a low-molecular-weight heparin (LMWH), dalteparin, following subcutaneous administration to rabbits. This LMW fucoidan exhibited dose-related venous antithrombotic activity, with an ED80 of about 20 mg/kg, 2 h after a single subcutaneous injection. Its activity was comparable to that of dalteparin (close to 200 anti-Xa IU/kg) and was maximal 30 min after a single subcutaneous injection. The activity remained stable (about 70%) from 1 to 4 h after injection, but disappeared by 8 h. The antithrombotic activity was not associated with either a prolongation of the thrombin clotting time (TCT) or an increase in anti-Xa activity, contrary to dalteparin. A slight prolongation of APTT occurred with both compounds. This venous antithrombotic activity was associated with a decrease in ex vivo thrombin generation and with a significant increase in the lag phase in a thrombin generation test. LMW fucoidan thus has potent antithrombotic activity and a potentially weaker haemorrhagic effect (i.e. a smaller effect on coagulation tests and a smaller prolongation of the bleeding time) than dalteparin.

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