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Marine fungus, novel skeleton meroterpenoid derivatives prepared from marine fungus as well as preparation method and application of novel skeleton meroterpenoid derivatives

A technology of marine fungi and derivatives, applied in the field of pharmaceutical compounds, can solve problems such as liver and kidney damage

Active Publication Date: 2020-05-15
GUANGZHOU UNIVERSITY OF CHINESE MEDICINE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, due to long-term use of these drugs and related research results, adverse reactions such as rhabdomyolysis and liver and kidney damage have brought serious pain to patients.

Method used

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  • Marine fungus, novel skeleton meroterpenoid derivatives prepared from marine fungus as well as preparation method and application of novel skeleton meroterpenoid derivatives
  • Marine fungus, novel skeleton meroterpenoid derivatives prepared from marine fungus as well as preparation method and application of novel skeleton meroterpenoid derivatives
  • Marine fungus, novel skeleton meroterpenoid derivatives prepared from marine fungus as well as preparation method and application of novel skeleton meroterpenoid derivatives

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0040] The acquisition of embodiment 1 marine fungus Aspergillus terreus GZU-31-1

[0041] 1. Isolation of strains: The inventor's team isolated and purified a marine fungus, Aspergillus terreus GZU-31-1, from the trunk of sulphurous sulphur, along the coast of Xuwen, Zhanjiang City, Guangdong Province.

[0042] The specific separation process is as follows: wash the back stone with clear water, sterilize the surface with 1% sodium hypochlorite aqueous solution for 30 seconds, and take it out. After sterilizing with 75% alcohol for 30 seconds, rinse with water. The slices were placed on Bengal red medium for culture and growth until a single colony grew.

[0043] 2. Identification of strains

[0044] Aspergillus terreus GZU-31-1 strain showed yellow filamentous fungal colonies on PDA medium.

[0045] Molecular identification:

[0046]The fungus was identified by DNA amplification and sequencing of the ITS region of the fungus. For specific steps, refer to the literature (N...

Embodiment 2

[0049] The separation of embodiment 2 compound

[0050] A novel skeleton heteroterpene derivative was isolated from the fermentation broth of the marine fungus Aspergillus terreus GZU-31-1. The specific method is as follows:

[0051] (1) Seed liquid culture of the fungus Aspergillus terreus GZU-31-1: The composition of the medium is by weight: 0.3% glucose, 0.1% yeast extract, 0.5% peptone, 2.5% agar, 3% sodium chloride, and 98% water %; Make a test tube slant, pick the strains and insert them into the slant, and cultivate them at 30°C for 6 days;

[0052] (2) Fermentation culture of the fungus Aspergillus terreus GZU-31-1: using solid rice fermentation medium: rice: seawater = 1:1 (mass ratio); ℃ for 2 months;

[0053] (3) extracting the above-mentioned fermented thallus with methanol for 3 times, concentrating the extract, and extracting the obtained concentrated extract with ethyl acetate to obtain a crude ethyl acetate extract;

[0054] (4) The ethyl acetate crude extra...

Embodiment 3

[0056] The structural analysis of embodiment 3 compound

[0057] Structural analysis of new compounds 1-6 was carried out, and the following experimental data were obtained:

[0058] New Compound 1: C 28 h 32 o 10 , HRESI-MS: 527.1912 [M-H] - (cald for C 28 h 31 o 10 527.1917).

[0059] New compound 2: C 28 h 32 o 10 , HRESI-MS: 527.1913 [M-H] - (cald for C 28 h 31 o 10 527.1917).

[0060] New Compound 3: C 28 h 32 o 10 , HRESI-MS: 527.1914 [M-H] - (cald for C 28 h 31 o 10 527.1917).

[0061] New Compound 4: C 28 h 34 o 10 , HRESI-MS: 529.2056 [M-H] - (cald for C 28 h 33 o 10 529.2073).

[0062] New Compound 5: C 28 h 34 o 11 , HRESI-MS: 545.2022 [M-H] - (cald for C 28 h 33 o 11 545.2022).

[0063] New compound 6: C 28 h 32 o 11 , HRESI-MS: 543.1932 [M-H] - (cald for C 28 h 31 o 11 543.1932).

[0064] The structural formulas and NMR data of compounds 1-6 are as follows:

[0065]

[0066] Table 1. NMR data of compounds 1-3...

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Abstract

The invention discloses a marine fungus, novel skeleton meroterpenoid derivatives prepared from the marine fungus as well as a preparation method and application of the novel skeleton meroterpenoid derivatives. The marine fungus Aspergillus terreus GZU-31-1 is preserved in Guangdong Microbiological Culture Collection Center on December 17, 2019 and has a preservation number of GDMCC No:60789. Sixnovel skeleton meroterpenoid derivatives are separated from fermented liquid of the marine fungus, have novel structures and are capable of remarkably reducing the activity of triglyceride; particularly, when the concentrations of the compounds 1-5 are 2 microliters and 5 microliters, the content of triglyceride in cells is remarkably reduced; especially the lipid decreasing activity of the compound 1 at a concentration of 5 microliters is even superior to that of a positive control, namely berberine at the same concentration. The compounds provided by the invention have a great application value to lipid decreasing and can be prepared into lipid decreasing drugs for use.

Description

technical field [0001] The present invention relates to the technical field of medical compounds, more specifically, to a marine fungus, a novel skeleton heteroterpene derivative prepared therefrom, and a preparation method and application thereof. Background technique [0002] Cardiovascular disease is one of the diseases with high mortality in human beings. The number of deaths due to cardiovascular disease is about 17 million every year. With the improvement of people's living standards, the annual morbidity and mortality are increasing year by year. Hyperlipidemia is one of the important factors inducing cardiovascular disease, and its most direct harm is that it can lead to atherosclerosis, coronary heart disease, obesity, diabetes and other diseases. Triglyceride is an important index parameter of hyperlipidemia, and its level can directly reflect the degree of hyperlipidemia. At present, the lipid-lowering drugs commonly used in clinical practice are mainly statins, ...

Claims

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Application Information

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IPC IPC(8): C12N1/14C12P17/18C12P17/06C07J73/00C07D493/10C07D493/06A61P3/06C12R1/66
CPCA61P3/06C07D493/06C07D493/10C07J73/003C07J73/008C12P17/06C12P17/181C12N1/145C12R2001/66
Inventor 崔辉唐渝茜赵钟祥
Owner GUANGZHOU UNIVERSITY OF CHINESE MEDICINE
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