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A kind of preparation method of antifungal compound and antifungal use

A compound and anti-fungal technology, applied in the field of medicine, can solve problems such as human side effects

Active Publication Date: 2021-04-02
NORTHEASTERN UNIV LIAONING +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, antifungal drugs are mainly imidazoles (such as ketoconazole) and polyenes (such as amphotericin B), which have serious toxic and side effects on the human body.

Method used

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  • A kind of preparation method of antifungal compound and antifungal use
  • A kind of preparation method of antifungal compound and antifungal use
  • A kind of preparation method of antifungal compound and antifungal use

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0036]Preparation of Compound I

[0037]1.1 Streptomyces Albolongus seed culture.

[0038]Seed medium: 0.4 g of yeast paste 0.4g, glucose 0.4g, malt, 0.5 g of maltose 0.5g, 0.0ml composite vitamin, 1.0ml trace element, distilled water 100ml. Culture conditions: pH 7.2, culture temperature 28 degrees Celsius, 48 ​​hours of culture time.

[0039]1.2 Streptomyces Albolongus fermentation culture.

[0040]Fermentation medium: soy flour 10g / L, protein 胨 2g / L, glucose 20g / L, soluble starch 5g / L, yeast paste 2g / L, sodium chloride 4g / L, ltassium hydrogen phosphate 0.5 g / L, magnesium sulfate 0.5 g / L, calcium carbonate 2 g / L, distilled water 70L. Culture conditions: pH 7.8, culture temperature 28 degrees Celsius, and the culture time is 168 hours.

[0041]1.3 extraction.

[0042]The fermentation liquid obtained by step (2) is centrifuged, the supernatant passes through the XAD-16 macroporous adsorption resin (large pore adsorption resin volume of 35L) column chromatography, first elute the med...

Embodiment 2

[0051]Example 2: Antifungal Activity Experiment

[0052]Compound I was dissolved in DMSO, multiplied dilution was configured as 9 different concentrations (22.0, 11.0, 5.5, 0.36, 0.18, 0.09 mg / ml). Pathogen Conditions The pathogenic fungi is white Candida Albicans Atccmya-2876. Close-slot polyacea (Cryptococcus Neoformans ATCC 208821) is inoculated in RPMI-1640 medium (10.4 g L)-1RPMI-1640, 2G L-1Nahco334.53g L-1MOPS, PH 7.0) Montecerepe suspension, C.Albicans and close-flat glutinus (C. Parapsilosis) bacteria suspension concentration is 2 × 103CFU / mL, new binding pneumper bacteria suspension concentration is 5 × 104CFU / ml. The sample was diluted with RPMI-1640 medium diluted 10 times, 10 μl of samples and 100 μl of bacterial suspension to a 96-well plate, and the equivalent DMSO solution is a negative control, and myobialtomycin B is positive for positive controls. The results showed that Compound I showed strong inhibitory activity on white candida and near-flat glutini, the MI...

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Abstract

The invention relates to a preparation method for a novel antifungal compound and an antifungal application. The invention discloses a novel compound with a structure formula I as follows, wherein the novel compound is prepared by separating Streptomyces-albolongus which is used as a source; the chemical name is (1beta, 4beta, 4abeta, 8a alpha)-4,8a-dimethyloctahydronaphthalene-1,4a(2H)-diol; the molecular formula is C12H22O2. The invention also provides a preparation method and an application of the compound. The method provided by the invention comprises the following steps: performing fermenting culture on the strain S.albolongus, and then centrifuging, thereby acquiring a culture solution; absorbing the culture solution by a macroreticular resin column, reducing pressure and concentrating the 95% alcohol eluting part, thereby acquiring a crude extract; treating the crude extract with normal phase silica gel, dextrangel LH-20 and reverse phase silica gel column chromatography, thereby acquiring a monomer compound shown as structure I; and adopting nuclear magnetic resonance spectrum and mass spectrum for identifying the structure as the novel compound. An in vitro antifungal activity research proves that the compound I provided by the invention has obvious inhibiting effect to various pathogenic fungi, including candida albicans, candida parapsilosis and cryptococcus neoformans and is expected to be developed into a novel antifungal drug.

Description

Technical field[0001]The present invention relates to a compound having antifungal activity, and in particular, a compound that is extracted from the fermentation fluid extracted from a serial bacteria Streptomyces Albolongus fermentation liquid and its use in the treatment of fungal infection, belongs to the medical technology.Background technique[0002]In recent years, the number of people who have been infected with fungi infection in the immune function increases, especially the large increase in the incidence of deep fungi infections, anti-fungi drug research has become a hot spot. At present, antifungal drugs are primarily imidazole (such as ketozole) and polyene (such as amphotericin B), which have a serious poisonous side effect on the human body. At the same time, the continuous emergence of clinically resistant pathogens has made it difficult for new high-efficiency low-toxic antibacterial drugs.[0003]Candida is also known as fake yeast, which is a conditional pathogenic fu...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07C35/36C12P7/02A61K31/047A61P31/10C12R1/465
CPCC07C35/36C12P7/02
Inventor 黄学石韩力姜怡李莉娅王占友姜成林
Owner NORTHEASTERN UNIV LIAONING