Pharmacokinetics and tissue distribution of a novel marine fibrinolytic compound in Wistar rat following intravenous administrations

Su, Tongwei; Wu, Wenhui; Yan, Ting; Zhang, Chaoyan; Bao, Bin

doi:10.1016/j.jchromb.2013.10.031

Cited by 12 publications

(21 citation statements)

References 25 publications

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“…According to the experimental method, A405 nm was measured by S-2444 hydrolysis with different concentrations of plasmin (5,10,20,30,40, and 50 nmol·L -1 ). The plot of A405 versus t of the S-2444 hydrolysis by different concentrations of plasmin is shown in Figure 3.…”

Section: Kinetic Characteristics Of Plasminmentioning

confidence: 99%

“…The reaction mixture contained chromospheres substrates S-2444, Tris-HCl buffer (50 mmol/L, 100 mmol/L NaCl, pH7.4, 25 °C), and plasmin (5,10,20,30,40, and 50 nmol·L -1 ) was incubated in a 96-well plate with a round bottom at 37 °C for 90 min. The absorbance of reaction mixture was determined continuously at 37 °C for 44 min.…”

Section: Determination Of Standard Curve By S-2444 Hydrolysismentioning

confidence: 99%

“…The reaction mixture was made up of pro-uPA (20,30, and 40 nmol·L -1 ), 0.8 mmol·L -1 S-2444, Tris-HCl buffer (50 mmol/L, 100 mmol/L NaCl, pH7.4, 25 °C), and FGFC1 (10,20,30, and 40 μg/mL) at 37 °C. The absorbance of the reaction mixture was determined continuously at 37 °C for 44 min.…”

Section: Determination Of Kcatpro-upa Of Plasminogen Activation By Pmentioning

confidence: 99%

“…An isoindolone derivative, Fungi fibrinolytic compound (R)-2,5-bis((2R,3R)-2-((E)-4,8-dimethylnona-3,7-dien-1-yl)-3,5-dihydroxy-2-methyl-7-oxo-3,4,7,9-tetr ahydropyrano [2,3-e]isoindol-8(2H)-yl)pentanoic acid (FGFC1, Fungi fibrinolytic compound 1, Figure 2), was isolated from a rare marine microorganism strain Stachybotrys longispora FG216. This compound was also evaluated for fibrinolytic activity in vitro and in vivo [10,11]. The results showed that FGFC1 could stimulate the generation of plasmin activity by measuring Glu-plasminogen and Lys-plasminogen activation in vitro.…”

Section: Introductionmentioning

confidence: 99%

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A Marine Fibrinolytic Compound FGFC1 Stimulating Enzymatic Kinetic Parameters of a Reciprocal Activation System Based on a Single Chain Urokinase-Type Plasminogen Activator and Plasminogen

Guo¹,

Duan²,

Hong³

et al. 2017

Preprint

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A marine fibrinolytic compound FGFC1 enhancing fibrinolysis was obtained involving enzymatic kinetic parameters of a reciprocal activation system with a single chain urokinase type plasminogen activator and plasminogen. FGFC1, a kind of bisindole alkaloid from a metabolite of the rare marine fungi Starchbotrys longispora FG216, modulated enzymatic kinetic parameters including the fibrinolytic reaction rate and fibrin degradation characteristics. The enzymatic kinetics of fibrinolysis was described based on the enzymatic reaction of a chromogenic-substrate associated with p-nitroaniline (p-NA). While the single chain urokinase-type plasminogen activator (pro-uPA) activated plasminogen, kcat and kcat/Km increased significantly with an increase of FGFC1 concentration. Moreover, kcat and kcat/Km exhibited 26.5-fold and 22.8-fold enhanced activity at the concentration of 40 μg·mL −1 of FGFC1, respectively. The results suggested that FGFC1 significantly improved the maximum catalytic efficiency and the total catalytic activity of fibrinolysis base on the reciprocal activation of pro-uPA and plasminogen. Km increased with increasing FGFC1 concentration, which indicated that FGFC1 slightly decreased the affinity activity of the pro-uPA and plasminogen versus the enzyme substrate. The marine bisindole alkaloid FGFC1 enhanced fibrinolysis, which was taken on enzymatic kinetic characteristics.

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Section: Kinetic Characteristics Of Plasminmentioning

confidence: 99%

Section: Determination Of Standard Curve By S-2444 Hydrolysismentioning

confidence: 99%

Section: Determination Of Kcatpro-upa Of Plasminogen Activation By Pmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

A Marine Fibrinolytic Compound FGFC1 Stimulating Enzymatic Kinetic Parameters of a Reciprocal Activation System Based on a Single Chain Urokinase-Type Plasminogen Activator and Plasminogen

Guo¹,

Duan²,

Hong³

et al. 2017

Preprint

Self Cite

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“…1) (also referred to as SMTP7 in Stachybotrys microspora IFO 30018 [5]). FGFC1 shows good fibrinolytic activity and shows great potential for the development of antithrombotic agents [6]. Much effort has been made to produce a sustainable supply of FGFC1, as several grams to hundreds of grams are required for preclinical development, and multi-kilogram quantities will be required for clinical studies [3].…”

Section: Introductionmentioning

confidence: 99%

Designing novel glucose/ornithine replenishment strategies by biosynthetic and bioprocess analysis to improve fibrinolytic FGFC1 production by the marine fungus Stachybotrys longispora

Wang

et al. 2015

Process Biochemistry

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Effects of a novel marine natural product: pyrano indolone alkaloid fibrinolytic compound on thrombolysis and hemorrhagic activities in vitro and in vivo

Yan

et al. 2014

Arch. Pharm. Res.

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Fungi fibrinolytic compound 1 (FGFC1) is a novel marine natural product as a low-weight fibrinolytic pyranoindole molecule, whose thrombolytic effects were evaluated on FITC-fibrin (Fluorescein isothiocyanate, FITC) degradation methods in vitro and on acute pulmonary thromboembolism animal model in vivo. We determined the FGFC1 induced thrombolysis that stems from its fibrin(ogen)olytic activities as measured by fibrin(ogen) degradation products (FDPs) experiment, acute pulmonary thromboembolism animal model experiment, and euglobulin lysis assay. In vitro, measurement of FITC-fibrin degradation revealed that fibrin hydrolysis occurred in a concentration-dependent manner of FGFC1 from 5 to 25 μ mol/L. In vivo test of a classical acute pulmonary thromboembolism model in rat showed that when the injected dose was 5 mg/kg or above, FGFC1 was effective in dissolution of extrinsic FITC-fibrin induced blood clots. Euglobulin lysis time (ELT) in FGFC1-treated rats was shortened 30 s compared with rats in the positive control group, which were injected with clopidogrel sulfate and single-chain urokinase-type plasminogen activator. As compared to the control, FGFC1 (5-25 mg/kg) did not significantly alter the formation of fibrinogen and FDPs in vivo. Our research indicates that FGFC1 presents pharmacodynamic action in both the thrombolysis and the hemolytic procedure, which can be characterized by fibrinogenolysis in blood and FDPs in plasma. In vivo, increasing fibrinolytic doses of FGFC1 from 5 to 25 mg/kg did not induce fibrinogenolysis when compared with control group, this result corresponds to that FGFC1 did not induce the increasing of FDPs (compared with the saline-treated control). It indicates that the FGFC1 may act as a novel thrombolytic agent and represent an effective approach to the treatment of thrombus without significant risk of hemorrhagic activity.

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Pharmacokinetics and tissue distribution of a novel marine fibrinolytic compound in Wistar rat following intravenous administrations

Cited by 12 publications

References 25 publications

A Marine Fibrinolytic Compound FGFC1 Stimulating Enzymatic Kinetic Parameters of a Reciprocal Activation System Based on a Single Chain Urokinase-Type Plasminogen Activator and Plasminogen

A Marine Fibrinolytic Compound FGFC1 Stimulating Enzymatic Kinetic Parameters of a Reciprocal Activation System Based on a Single Chain Urokinase-Type Plasminogen Activator and Plasminogen

Designing novel glucose/ornithine replenishment strategies by biosynthetic and bioprocess analysis to improve fibrinolytic FGFC1 production by the marine fungus Stachybotrys longispora

Effects of a novel marine natural product: pyrano indolone alkaloid fibrinolytic compound on thrombolysis and hemorrhagic activities in vitro and in vivo

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