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Polyketone compound derived from sponge endophytic fungi and application of polyketone compound in preparation of anti-inflammatory drugs

A technology of endophytic fungi and compounds, applied in the field of pharmaceutical compounds, can solve problems such as injury, adverse reactions, liver damage, etc.

Active Publication Date: 2021-10-22
KUNMING UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although they have anti-inflammatory effects to a certain extent, long-term large-scale use will produce a series of adverse reactions and tolerance, such as gastric mucosal damage, liver damage, kidney damage, etc.

Method used

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  • Polyketone compound derived from sponge endophytic fungi and application of polyketone compound in preparation of anti-inflammatory drugs
  • Polyketone compound derived from sponge endophytic fungi and application of polyketone compound in preparation of anti-inflammatory drugs
  • Polyketone compound derived from sponge endophytic fungi and application of polyketone compound in preparation of anti-inflammatory drugs

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0023] The acquisition of embodiment 1 sponge endophytic fungus

[0024] 1. Experimental method

[0025] The inventor team isolated a sponge endophytic fungus from the brown flat sponge (Phakellia fusca) collected from the Xisha Islands in China, which was identified as Pestalotiopsis heterocornis by rDNAits region analysis.

[0026] 2. Experimental results

[0027] The ITS-rRNA gene sequence of the sponge endophytic fungus is shown in SEQ ID NO.1:

Embodiment 2

[0028] Preparation identification of embodiment 2 polyketides

[0029] In this example, polyketide derivatives were obtained by fermenting endophytic fungi in sponges. The specific experimental methods and results are as follows:

[0030] 2.1. Preparation of derivatives

[0031] The preparation method of derivative comprises the following steps:

[0032] (1) insert the fungus Pestalopipsisheterocornis isolated from the brown flat sponge into the seed culture medium to obtain the seed culture liquid; the components of the seed culture medium (by specific gravity): malt soak Paste 5-20g, coarse sea salt 10-20g, distilled water 1000-2000ml, pH 7.4-8.2;

[0033] (2) Fungal fermentation culture: insert the seed culture solution into the solid fermentation medium, and let it stand for cultivation; the composition of the solid rice fermentation culture: 100-200g of rice, 2-10g of coarse sea salt, 200-1000m of tap water, and the cultivation time : 28-60 days, static culture tempera...

Embodiment 3

[0049] Anti-inflammatory activity research of embodiment 3 polyketide compounds

[0050] 1. Cell culture and anti-inflammatory activity detection

[0051] (1) RAW264.7 cells were inoculated in 10% FBS DMEM high-glucose medium, and routinely cultured and passaged at 37°C and 5% carbon dioxide.

[0052] (2) Anti-inflammatory activity detection

[0053] RAW264.7 cells grown in logarithmic phase were taken at 1×10 6 Cells / well were seeded in 6-well plates. After 24 h, the cells were pretreated with compound Ⅰ (0, 3, 11, 33 μM), Ⅱ (0, 3, 11, 33 μM) and the positive drug dexamethasone DXM (33 μ M) for 2 h, and then LPS (1 μg / mL ) to stimulate the cells for 24h. The supernatant was collected and the NO content was detected by the Griess method. The result is as follows figure 1 As shown, both compounds Ⅰ and Ⅱ can significantly inhibit LPS-induced NO release from macrophages, and compounds Ⅰ and Ⅱ have no cytotoxicity, so it can be preliminarily concluded that compounds Ⅰ and Ⅱ...

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Abstract

The invention discloses a polyketone compound derived from sponge endophytic fungi pestalotiopsis and application of the polyketone compound in preparation of anti-inflammatory drugs, and belongs to the technical field of medical compounds. The invention provides a polyketone derivative derived from sponge endophytic fungi and application of the polyketone derivative in preparation of anti-inflammatory drugs. According to the invention, a strain of sponge endophytic fungus pestalotiopsis is separated from brown flat sponge (Phakellifusca) in the Xisha of China, a polyketone derivative is separated and identified from a fermentation culture product of the fungus, the derivative has relatively strong activity of resisting NO generation, the anti-inflammatory activity of the derivative is equivalent to that of a positive drug dexamethasone, and the derivative has no cytotoxic activity and has high the safety coefficient. Therefore, the polyketone derivative provided by the invention has a good clinical application prospect in preparation of anti-inflammatory drugs, especially in preparation of drugs for inhibiting LPS-induced NO production.

Description

technical field [0001] The invention belongs to the technical field of medical compounds, and relates to a polyketide compound isolated from the spongy endophytic fungus Discopolyphades and its application in the preparation of anti-inflammatory drugs. Background technique [0002] Over the past few decades, sponge endophytes have been recognized as an important source of new drugs. Fungi have diverse metabolic pathways, abundant metabolites, sustainability, and environmental friendliness, and have always been an important source of drug screening. Secondly, the metabolites of fungi have a wide range of physiological activities, such as antibacterial, antitumor, immune regulation, anti-inflammatory, enzyme inhibition and other activities. At present, searching for new drug source molecules from endophytic fungi in sponges has become a research hotspot both at home and abroad. However, most biosynthetic gene clusters are silenced under laboratory conditions, while only a sm...

Claims

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Application Information

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IPC IPC(8): C07D307/87A61P29/00C12P17/04C12N1/14C12R1/645
CPCC07D307/87A61P29/00C12P17/04C12N1/14C07B2200/07
Inventor 毕晓旭雷辉刘子超何江波
Owner KUNMING UNIV
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