As a part of our continuing work to discover bioactive leading molecules from marine microorganism, ethyl acetate fraction of organic extract of the train Stachybotrys longispora FG216 showed fibrinolytic activity in ...As a part of our continuing work to discover bioactive leading molecules from marine microorganism, ethyl acetate fraction of organic extract of the train Stachybotrys longispora FG216 showed fibrinolytic activity in our primary screen. The bioassay-guided purification of the active fractions resulted in isolation of a new isoindolone, FGFC2 （1） （FGFC2, Fungi fibrinolytic compound 2）, together with two known compounds, LL-Zl272β （2） and ergosterol （3）. The structure of compound 1 was elucidated by the spectral analysis of 1D （^1H, ^13C） NMR, 2D （COSY, HSQC, and HMBC） and ESI-MS. Three compounds were evaluated for fibrinolytic activities in vitro. Compared to FGFC1 （EC50=47 μmol/L） as a reference drug, compound 1 and ergosterol （3） showed moderate fibrinolytic activities in vitro with EC50 values of 108.16 and 156.30 μmol/L, respectively. LL-Z127213 （2） had no fibrinolytic activity.展开更多
An isoindolone derivative, Fungi fibrinolytic compound （R）-2,5-bis（（2R,3R）-2-（（E）-4,8-dimethylnona-3,7-dien- 1-y1）-3,5-dihydroxy-2-methy--7-oxo-3,4,7,9-tetrahydr pyrano[2,3-e]isoindol-8（2H）-yl）pentanoic ac...An isoindolone derivative, Fungi fibrinolytic compound （R）-2,5-bis（（2R,3R）-2-（（E）-4,8-dimethylnona-3,7-dien- 1-y1）-3,5-dihydroxy-2-methy--7-oxo-3,4,7,9-tetrahydr pyrano[2,3-e]isoindol-8（2H）-yl）pentanoic acid （FGFC1, Fungi fibrinolytic compound 1）, was isolated from a rare marine microorganism strain Stachybotrys longispora FG216. The structure of FGFC1 was elucidated by 1H NMR, 13C NMR, IR, and MS data; moreover, it was also evaluated for fibrinolytic activity in vitro and in vivo. The results showed that 0.1--0.4 mmol/L of FGFC1 could stimulate generation of plasmin activity （increased by 2.05--11.44 folds） by measuring Glu-plasminogen and Lys-plasminogen activation in vitro. The experiment of fluorescein isothiocyanate （FITC）-fibrinogen degradation indicated that the effect of FGFCI on fibrinolytic activity was mediated by plasminogen and scuPA. In addition, FGFC 1 （10 mg/kg） could dissolve most of pulmonary thrombus of Wistar rat in vivo. It is possible that FGFC 1 is a potential thrombolytic agent in the future.展开更多
基金The work was supported by the National Natural Science Foundation of China （No. 81502955）, the Doctoral Scientific Research Foundation of Shanghai Ocean University （No. A2030214300077）, the Young Teachers Training Program of Shanghai （No. A12056160002）, and the Project Funded by Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening.
文摘As a part of our continuing work to discover bioactive leading molecules from marine microorganism, ethyl acetate fraction of organic extract of the train Stachybotrys longispora FG216 showed fibrinolytic activity in our primary screen. The bioassay-guided purification of the active fractions resulted in isolation of a new isoindolone, FGFC2 （1） （FGFC2, Fungi fibrinolytic compound 2）, together with two known compounds, LL-Zl272β （2） and ergosterol （3）. The structure of compound 1 was elucidated by the spectral analysis of 1D （^1H, ^13C） NMR, 2D （COSY, HSQC, and HMBC） and ESI-MS. Three compounds were evaluated for fibrinolytic activities in vitro. Compared to FGFC1 （EC50=47 μmol/L） as a reference drug, compound 1 and ergosterol （3） showed moderate fibrinolytic activities in vitro with EC50 values of 108.16 and 156.30 μmol/L, respectively. LL-Z127213 （2） had no fibrinolytic activity.
文摘An isoindolone derivative, Fungi fibrinolytic compound （R）-2,5-bis（（2R,3R）-2-（（E）-4,8-dimethylnona-3,7-dien- 1-y1）-3,5-dihydroxy-2-methy--7-oxo-3,4,7,9-tetrahydr pyrano[2,3-e]isoindol-8（2H）-yl）pentanoic acid （FGFC1, Fungi fibrinolytic compound 1）, was isolated from a rare marine microorganism strain Stachybotrys longispora FG216. The structure of FGFC1 was elucidated by 1H NMR, 13C NMR, IR, and MS data; moreover, it was also evaluated for fibrinolytic activity in vitro and in vivo. The results showed that 0.1--0.4 mmol/L of FGFC1 could stimulate generation of plasmin activity （increased by 2.05--11.44 folds） by measuring Glu-plasminogen and Lys-plasminogen activation in vitro. The experiment of fluorescein isothiocyanate （FITC）-fibrinogen degradation indicated that the effect of FGFCI on fibrinolytic activity was mediated by plasminogen and scuPA. In addition, FGFC 1 （10 mg/kg） could dissolve most of pulmonary thrombus of Wistar rat in vivo. It is possible that FGFC 1 is a potential thrombolytic agent in the future.
