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Alkaloid dimer, preparation method thereof and application of alkaloid dimer as antiviral agent

An alkaloid dimer, antiviral agent technology, applied in biochemical equipment and methods, antiviral agents, microorganism-based methods, etc., to achieve the effect of broad application prospects and strong inhibitory activity

Active Publication Date: 2015-09-02
OCEAN UNIV OF CHINA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, there are still relatively few reports on compounds with anti-HSV-1 and EV71 activities derived from marine microorganisms, especially reports on marine-derived compounds that have the potential to be developed into chiral drugs

Method used

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  • Alkaloid dimer, preparation method thereof and application of alkaloid dimer as antiviral agent
  • Alkaloid dimer, preparation method thereof and application of alkaloid dimer as antiviral agent
  • Alkaloid dimer, preparation method thereof and application of alkaloid dimer as antiviral agent

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0019] (1) Strain culture of soft coral endophytic fungus Pestalotiopsis sp. (ZJ-2009-7-6)

[0020] The culture medium used for strain culture contains glucose 1.0% (percentage by weight, the same below), yeast extract 0.2%, peptone 0.2%, agar 1.0%, sodium chloride 3.0%, and the rest is water. Strains were cultured at 30°C for 3 days.

[0021] (2) Fermentation of soft coral endophytic fungus Pestalotiopsis sp. (ZJ-2009-7-6)

[0022] The medium used for the fermentation culture contains 40.0% rice (percentage by weight, the same below), 3.0% sodium chloride, 0.2% calcium chloride, 2% potassium bromide, and the rest is water; the fungal strains are cultivated at 28° C. for 90 days.

[0023] (3) extraction and separation of formula I compound

[0024] Get 60 bottles of mycelia obtained in step (2), extract 3 times with chloroform-methanol mixed solution (1:1) and concentrate under reduced pressure, then extract 3 times with ethyl acetate to obtain crude extract; Extraction was...

Embodiment 2

[0030] (1) Strain culture of soft coral endophytic fungus Pestalotiopsis sp. (ZJ-2009-7-6)

[0031] The culture medium used for strain cultivation contains 0.1%-5.0% of glucose (percentage by weight, the same below), 0.01%-1% of yeast extract, 0.01%-1% of peptone, 0.1%-3.0% of agar, and 0.05% of sodium chloride- 5%, and the rest is water. When used, it is made into a test tube slant, and the fungal strains are cultivated at 0-30°C for 3-15 days.

[0032] (2) Fermentation of soft coral endophytic fungus Pestalotiopsis sp. (ZJ-2009-7-6)

[0033] The medium used for fermentation culture contains rice 1.0%-80.0% (weight percentage, the same below), sodium chloride 0.05%-5%, calcium chloride 0.01%-5%, potassium bromide 0.01%-5%, and the rest are In water, fungal strains are cultured at 0-30°C for 20-100 days.

[0034] (3) extraction and separation of formula I compound

[0035] Take 10-60 bottles of the obtained mycelium obtained in step (2), extract the obtained mycelium with c...

Embodiment 3

[0039] Take 1.5 mg of the compound of formula I and dissolve it in a vial filled with 500 μL of methanol, ethanol, water, tetrahydrofuran or acetone. After standing at 0° C. for 30 days, slowly crystallize to obtain the crystal of the compound of formula I.

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Abstract

The invention discloses an alkaloid dimer, a preparation method thereof and application of the alkaloid dimer as an antiviral agent. The method comprises the following steps: firstly, carrying out strain culture on fungus Pestalotiopsis sp.(ZJ-2009-7-6) during preparation, and carrying out fermental cultivation on the fungus; leaching the obtained mycelium with a chloroform-methanol mixed liquid (1 to 1) for three times, carrying out vacuum concentration, and extracting with ethyl acetate for three times, so as to obtain crude extractum; and sequentially carrying out positive slica column chromatography, Sephadex LH-20 gel column chromatography and HPLC (high-performance liquid chromatography) on ethyl acetate-phase crude extractum to obtain a compound shown in a formula I. The antiviral agent provided by the method has the characteristics that the compound shown in the formula I or a pharmaceutically acceptable salt is taken as an effective component for preventing and / or treating diseases caused by herpes simplex virus I (HSV-1) and / or enterovirus 71 (EV71).

Description

technical field [0001] The present invention relates to a kind of alkaloid dimer (alkaloid dimer) compound and its preparation method and application, especially relate to a kind of herpes simplex type I virus (HSV-1) and enterovirus 71 (EV71) have extremely strong Inhibitory alkaloid dimer and its preparation method and use. Background technique [0002] Herpes simplex type I virus is a wrapped DNA virus with high incidence, long incubation period, and neurotropic characteristics. It lurks in the peripheral nervous system and mainly infects children, immunocompromised persons and organ transplant recipients. Appropriate stimulation will cause large-scale outbreaks, causing encephalitis and keratitis, and severe cases can cause death. At present, the clinical antiviral drugs are mainly nucleoside antibiotics, such as acyclovir, but the population of drug-resistant infections has increased rapidly in recent years. Enterovirus 71 is a small single positive-sense RNA virus th...

Claims

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Application Information

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IPC IPC(8): C07D498/20C12P17/18A61K31/499A61P31/22A61P31/20C12R1/645
CPCC07D498/20C12P17/188
Inventor 邵长伦王长云贾彦来管菲菲王翠芳魏美燕
Owner OCEAN UNIV OF CHINA
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