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High-efficiency and low-toxicity pimaricin derivative as well as preparation method and application thereof

A high-efficiency and low-toxicity technology of pimaricin, applied in the field of high-efficiency and low-toxic pimaricin derivatives and its preparation, can solve the problems of low pharmacological properties and limiting the application value of pimaricin

Active Publication Date: 2015-02-25
SHANGHAI JIAO TONG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Relatively low pharmacological properties severely limit the clinical application value of pimaricin

Method used

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  • High-efficiency and low-toxicity pimaricin derivative as well as preparation method and application thereof
  • High-efficiency and low-toxicity pimaricin derivative as well as preparation method and application thereof
  • High-efficiency and low-toxicity pimaricin derivative as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0031] Prepare 500ml seed medium and 5L fermentation medium according to the seed medium and fermentation culture formula, and divide them into 250ml three-sided flasks, 50ml each, sterilize at 115℃ for 30min, insert the spores of mutant QZ01 into the above seeds In the culture medium, the seed culture solution was obtained by culturing at a rotating speed of 220 rpm and a shaking table at 30° C. for 24 hours. The seed culture solution was connected to the fermentation medium at a 10% inoculum amount, and the fermentation culture of the mutant QZ01 was obtained by culturing at a rotating speed of 220 rpm and a shaking table at 30° C. for 5 days. Centrifuge the 5L fermentation culture obtained from the fermentation culture, collect the fermentation cells, wash the cells 3 times with water, remove the washing liquid, and freeze-dry the cells overnight; add 2L methanol to the lyophilized fermentation cells, and ultrasonically treat them for 30 minutes, The extract was obtained by ...

Embodiment 2

[0033] Prepare 1L seed medium and 10L fermentation medium according to the seed medium and fermentation culture formula, and divide them into 250ml three-sided flasks, 50ml each, sterilize at 115℃ for 30min, insert the spores of mutant QZ01 into the above seeds In the culture medium, the seed culture solution was obtained by culturing at a rotating speed of 220 rpm and a shaking table at 30° C. for 24 hours. The seed culture solution was inserted into the fermentation medium at a 10% inoculum amount, and the fermentation culture of the mutant QZ01 was obtained by culturing at a rotating speed of 220 rpm and a shaking table at 30° C. for 5 days. Centrifuge the 10L fermentation culture obtained from the fermentation culture, collect the fermentation cells, wash the cells 3 times with water, remove the washing liquid, and freeze-dry the cells overnight; add 3L methanol to the freeze-dried fermentation cells, and ultrasonically treat them for 30 minutes. The extract was obtained by...

Embodiment 3

[0035] In vitro determination of antifungal activity and hemolytic toxicity of pimamycin derivatives

[0036] The in vitro antifungal activity is determined by Candida albicans as the indicator bacteria, and the growth of Candida albicans at different antibiotic concentrations is determined to obtain the MIC of the corresponding antibiotic 50 And MIC 90 value. First, the overnight culture solution of Candida albicans was inoculated into LB medium at a ratio of 1 / 10000, and 200μl / well was divided into 96-well plates. The DMSO solutions of the pimamycin derivative and pimamycin of different concentrations (0-500 μg / ml) were prepared and added to the above-mentioned LB medium at a ratio of 2%. Place the 96-well plate in an incubator at 34°C and incubate for 12 hours. Use a microplate reader to determine the OD under different concentrations of antibiotics 660 . Draw a bacteriostasis curve against the concentration of antibiotics from the measured data to get the MIC 50 With MIC 90 ...

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Abstract

The invention discloses a high-efficiency and low-toxicity pimaricin derivative, of which the molecular formula is C33H49NO11, and the chemical structural formula is as shown in the specification. The high-efficiency and low-toxicity pimaricin derivative is obtained from a genetically engineered strain streptomyces chattanoogensis QZ01 zymophyte body as a raw material by bacterial treatment, organic reagent extraction, reverse phase chromatographic column chromatography and high-performance liquid chromatography. The compound disclosed by the invention is stable in structure, good in activity and low in toxicity, can be used as an antifungal drug and a food preservative, and has a good clinical application prospect and economic value.

Description

Technical field [0001] The invention relates to a separation technology of microbial secondary metabolites, in particular to a high-efficiency and low-toxicity pimamycin derivative, and a preparation method and application thereof. technical background [0002] Systemic fungal infection is a serious immune system deficiency complication, and its pathogens often have the characteristics of high transmission rate, high proliferation rate, high fatality rate and high drug resistance, which seriously threaten people's health. Due to the rapid development of the drug resistance of fungal pathogens and the interaction between drugs, the current antifungal drugs that can be used clinically to treat systemic fungal infections are very limited, and the therapeutic effect is very unsatisfactory. Among them, polyene antibiotics have high antibacterial and antibacterial activities against a variety of fungal pathogens, and the development of resistance to fungal pathogens is very slow, and t...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07H17/08A61P31/10C12P19/62A23L3/3562C12R1/465
CPCA23L3/3463C07H17/08C12P19/626
Inventor 白林泉齐震康前进姜春艳
Owner SHANGHAI JIAO TONG UNIV
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