Marine Drugs
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2022
·Vol. 20
·期 10
·654
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IF 6.085
Pathum Chandika,Pipuni Tennakoon,Tae-Hee Kim,Se-Chang Kim,Jae-Young Je,Jae-Il Kim,Bonggi Lee,BoMi Ryu,Hyun Wook Kang,Hyun-Woo Kim,Young-Mog Kim,Chang Su Kim,Il-Whan Choi,Won Sun Park,Myunggi Yi,Won-Kyo Jung
Coagulation is a potential defense mechanism that involves activating a series of zymogens to convert soluble fibrinogen to insoluble fibrin clots to prevent bleeding and hemorrhagic complications. To prevent the extra formation and diffusion of clots, the counterbalance inhibitory mechanism is activated at levels of the coagulation pathway. Contrariwise, this system can evade normal control due to either inherited or acquired defects or aging which leads to unusual clots formation. The abnormal formations and deposition of excess fibrin trigger serious arterial and cardiovascular diseases. Although heparin and heparin-based anticoagulants are a widely prescribed class of anticoagulants, the clinical use of heparin has limitations due to the unpredictable anticoagulation, risk of bleeding, and other complications. Hence, significant interest has been established over the years to investigate alternative therapeutic anticoagulants from natural sources, especially from marine sources with good safety and potency due to their unique chemical structure and biological activity. This review summarizes the coagulation cascade and potential macromolecular anticoagulants derived from marine flora and fauna.Keywords:blood coagulation;anticoagulant;marine sources;marine anticoagulant macromolecules;chemically modified macromolecules
研究领域:
生物学
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医学
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产品关联
DOI
PubMed
高影响因子
ANALYTICAL LETTERS
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2022
·
IF 2.267
Ru Li,Xuan Zou,Pan Luan,Xiaokun Liu,Ning Wang,Qian Wang,Huashi Guan,Zhe Xu
Thrombosis is the main cause of many cardiovascular diseases. The conventional pharmaceuticals used for preventing thrombosis can induce significant adverse side effects, especially bleeding risk. Hence, the development of more effective and safe antithrombotic agents is strongly demanded to improve clinical treatment. In order to rapidly screen and identify novel antithrombotic substances from natural marine products, a multi-target screening strategy is reported to quantify the antithrombotic activity with high-performance liquid chromatography – mass spectrometry (HPLC-MS). Five key thrombosis-related targets, including thrombin, coagulation factors Xa, XIa and XIIa and platelet phosphodiesterase 3, were selected to establish the multi-target antithrombotic activity screening assay. The Michaelis-Menten constants (Km) were 8.16 µM, 58.85 µM, 120.03 µM, 35.24 µM and 79.67 µM, respectively. Five known inhibitors, namely argatroban, rivaroxaban, benzamidine, 3-carboxamide-coumarinand, and milrinone, were used for validation. The reproducibility of the screening strategy was verified by calculating the overall average Z′ value, which was 0.88. Subsequently, this method was assessed by screening a small marine library of 78 compounds. Five coumarin compounds were selected, and their antithrombotic activities were further validated in standard assessments of enzyme inhibition and on the coagulometer. According to the validation, the multi-target assay based on dried blood spots and HPLC-MS was suitable for screening antithrombotic substances with considerable reliability.
研究领域:
药理学
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分析化学
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心血管病学
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DOI
高影响因子
ANALYTICA CHIMICA ACTA
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2017
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IF 4.95
Zhe Xu,Ruonan Liu,Huashi Guan
An accurate, rapid, and cost-effective methodology for enzyme assay is highly demanded to screen the effect of compounds on target at the molecular level. Thrombin (EC 3.4.21.5) and factor Xa (FXa, EC 3.4.21.6) have been identified as the critical targets for the development of potential drugs with anticoagulant activity. In this study, a rapid, sensitive and accurate assay based on UHPLC-MS/MS method has been developed for inhibitor screening against thrombin and factor Xa simultaneously. For thrombin and factor Xa, the Michaelis-Menten constants ( K m ) were calculated to be 6.14 and 57.27 μM, respectively. The inhibition constants ( K i ) for two known inhibitors, argatroban and rivaroxaban , were determined to be 16.23 and 0.41 nM, respectively. The assay was further validated through the determination of a high Z′ factor value of 0.89. Finally, the developed assay was applied to screen a chemical library against two enzymes . Three hit compounds belonging to a class of sulfated polysaccharides were identified and their targets of inhibition action were further evaluated. The results indicated that the dual-target assay by UHPLC-MS/MS analysis could be used as a reliable method for screening anticoagulant agents.
研究领域:
药理学
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生物化学
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产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
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2022
·
IF 5.999
Jie Zheng,Jingjing Bi,Wei Zhao,Muhammad Sohail,Ninghua Fu,Xing Zhang
Heparin, the most widely used anticoagulant drug in the world today, suffers from the risk of overdose and a short serum half-life, limiting its clinical applications. Concerning the controlled, sustained, and targeted release of heparin, a delivery system was fabricated in this research using the layered composites of Fe 3 O 4 magnetic particles and pH-sensitive metal-organic framework, Fe 3 O 4 @ZIF-8. The composite demonstrated a high loading capacity for the heparin, 66.8 mg/g. The composite had a saturation magnetization of 1.5 emu/g and thus owned a magnetic targeting function, i.e. drug can be centered at a certain point using an external magnetic field. The anticoagulant activity was assessed by monitoring their activated partial thromboplastin time . The results showed that the pH-responsive and sustained release of the heparin reduced the systemic adverse effects associated with high concentrations. Moreover, control over the dose exhibited excellent anticoagulant features with fewer side effects.
研究领域:
药学
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材料科学
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纳米技术
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药物递送系统
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产品关联
DOI
PubMed
高影响因子
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