A marine fungus, a novel skeleton heteroterpene derivative prepared therefrom, and its preparation method and application

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: 2021-11-26
GUANGZHOU UNIVERSITY OF CHINESE MEDICINE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

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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  • A marine fungus, a novel skeleton heteroterpene derivative prepared therefrom, and its preparation method and application
  • A marine fungus, a novel skeleton heteroterpene derivative prepared therefrom, and its preparation method and application
  • A marine fungus, a novel skeleton heteroterpene derivative prepared therefrom, and its preparation method and application

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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, a novel skeleton heteroterpene derivative prepared therefrom, a preparation method and application thereof. The marine fungus Aspergillus terreus GZU‑31‑1 was preserved in the Guangdong Provincial Microbial Culture Collection Center on December 17, 2019, and the preservation number is GDMCC No: 60789. From its fermentation broth, 6 novel skeleton hybrids were obtained. Terpene derivatives, which are novel in structure, also have significant triglyceride-lowering activity, especially compound 1‑5, when the concentration is 2 μM and 5 μM, the content of triglyceride in cells is significantly reduced, especially compound 1. Its lipid-lowering activity at a concentration of 5 μM is even better than the positive control berberine at the same concentration; the compound of the present invention has great application value in lipid-lowering, and can be prepared as a lipid-lowering drug for application.

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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Patent Type & Authority Patents(China)
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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