Fibrinolytic Evaluation of Compounds Isolated from a Marine Fungus <i>Stachybotrys longispora</i> FG216

Guo, Ruihua; Zhang, Yiting; Duan, Dong Xia; Fu, Qiang; Zhang, Xiangyu; Yu, Xiaowei; Wang, Shujun; Bin, Bao; Wu, Wenhui

doi:10.1002/cjoc.201600623

Cited by 12 publications

(14 citation statements)

References 32 publications

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“…Diindolinonepyrane ( 14 ), 2,5-bis-[8-(4,8-dimethyl-nona-3,7-dienyl)-5,7-dihydroxy-8-methyl-3-keto-1,2,7,8-tertahydro-6H-pyran[a]isoindol-2-yl]-pentanoic acid (2,5-BHPA) isolated from marine fungi Stachybotrys longispora , possesses significant thrombolytic activity [ 108 , 109 ]. The linear pharmacokinetics was observed for 2,5-BHPA after i/v injection in rats at doses of 10–20 mg/kg.…”

Section: Pharmacokinetics Studies In Animalsmentioning

confidence: 99%

Pharmacokinetics of Marine-Derived Drugs

et al. 2020

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Marine organisms represent an excellent source of innovative compounds that have the potential for the development of new drugs. The pharmacokinetics of marine drugs has attracted increasing interest in recent decades due to its effective and potential contribution to the selection of rational dosage recommendations and the optimal use of the therapeutic arsenal. In general, pharmacokinetics studies how drugs change after administration via the processes of absorption, distribution, metabolism, and excretion (ADME). This review provides a summary of the pharmacokinetics studies of marine-derived active compounds, with a particular focus on their ADME. The pharmacokinetics of compounds derived from algae, crustaceans, sea cucumber, fungus, sea urchins, sponges, mollusks, tunicate, and bryozoan is discussed, and the pharmacokinetics data in human experiments are analyzed. In-depth characterization using pharmacokinetics is useful for obtaining information for understanding the molecular basis of pharmacological activity, for correct doses and treatment schemes selection, and for more effective drug application. Thus, an increase in pharmacokinetic research on marine-derived compounds is expected in the near future.

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Section: Pharmacokinetics Studies In Animalsmentioning

confidence: 99%

Pharmacokinetics of Marine-Derived Drugs

et al. 2020

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“…Therefore, 2,5-BHPA is a new marine lead compound (separated and purified from the rare marine fungus Stachybotrys longispora FG216) that has a novel structure, fibrinolytic activity, and low molecular weight [9][10][11][12]; our results suggest that that 2,5-BHPA has potential medicinal properties and can be used in the development of a thrombolytic drug candidate.…”

Section: Discussionmentioning

confidence: 97%

“…It was isolated from a rare marine fungi Stachybotrys longispora FG216 [10]. The structure of 2,5-BHPA has been elucidated by Guo et al [11]. 2,5-BHPA activates fibrinolytic enzyme activity, which decreases thrombolysis while minimizing bleeding risk [11][12][13].…”

Section: Introductionmentioning

confidence: 99%

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Evaluation of Marine Diindolinonepyrane in Vitro and in Vivo: Permeability Characterization in Caco-2 Cells Monolayer and Pharmacokinetic Properties in Beagle Dogs

Guo

Elango

et al. 2019

Marine Drugs

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A marine fibrinolytic compound was studied for use in thrombolytic therapy. Firstly, the absorption and transportation characteristics of 2,5-BHPA (2,5-BHPA:2,5-Bis-[8-(4,8-dimethyl-nona-3,7-dienyl)-5,7-dihydroxy-8-methyl-3-keto-1,2,7,8-tertahydro-6H-pyran[a]isoindol-2-yl]-pentanoic acid, a novel pyran-isoindolone derivative with bioactivity isolated from a rare marine microorganism in our laboratory) in the human Caco-2 cells monolayer model were investigated. We collected 2,5-BHPA in the cells to calculate the total recovery, and its concentration was analyzed by LC/MS/MS (Liquid Chromatography/ Mass Spectrum/ Mass Spectrum). The results showed that 2,5-BHPA has low permeability and low total recoveries in the Caco-2 cells membrane. Pharmacokinetics and tissue distribution of 2,5-BHPA were investigated in beagle dogs using HPLC (High Performance Liquid Chromatography) after intravenous administration of three different doses (7.5, 5.0, 2.5 mg·kg−1). Pharmacokinetic data indicated that 2,5-BHPA fitted well to a two-compartment model. Elimination half-lives (T1/2) were 49 ± 2, 48 ± 2, and 49 ± 2 min, respectively; the peak concentrations (Cmax) were 56.48 ± 6.23, 48.63 ± 5.53, and 13.64 ± 2.76 μg·mL−1, respectively; clearance rates (CL) were 0.0062 ± 0.0004, 0.0071 ± 0.0008, and 0.0092 ±0.0006 L·min−1·kg−1, respectively; mean retention times (MRT) were 28.17 ± 1.16, 26.23 ± 0.35, and 28.66 ± 0.84 min, respectively. The low penetrability of 2,5-BHPA indicated that the intravenous route of administration is more appropriate than the oral route. Meanwhile, 2,5-BHPA showed a good pharmacokinetic profile in beagle dogs. The tissue distribution showed that 2,5-BHPA could quickly distribute into the heart, intestines, liver, stomach, spleen, lungs, testicles, urine, intestine, kidneys, brain, and feces. The concentration of 2,5-BHPA was higher in the liver and bile. Interestingly, 2,5-BHPA was detected in the brain. Taken together, the above results suggested that our work might be beneficial in the development of agents for thrombolytic treatment.

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“…It reduces the average life expectancy and changes the living habits. [1,2] The current therapies (Heparin (ordinary heparin, low molecular weight heparin) and fondaparinux, and oral adjusted-dose vitamin K antagonists, [3] aspirin, adenosine monophosphate receptor antagonist and platelet membrane glycoprotein antibody antagonist) are effective for the treatment of thrombosis patients clinically, however, they still remain unsatisfactory, [3][4][5][6][7][8][9][10][11][12][13][14][15] Therefore, researchers are searching for small molecules with antithrombotic activities. [16][17][18][19][20][21][22][23][24][25] Natural products are divided into diverse chemical compounds isolated from varied biological sources such as plants, animals, marine organisms, microorganisms, minerals, and organic matters.…”

Section: Introductionmentioning

confidence: 99%