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Pimaricin derivatives with high efficiency and low toxicity, their preparation methods and applications

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

Active Publication Date: 2016-11-16
SHANGHAI JIAOTONG 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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  • Pimaricin derivatives with high efficiency and low toxicity, their preparation methods and applications
  • Pimaricin derivatives with high efficiency and low toxicity, their preparation methods and applications
  • Pimaricin derivatives with high efficiency and low toxicity, their preparation methods and applications

Examples

Experimental program
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Effect test

Embodiment 1

[0031] Prepare 500ml of seed medium and 5L of fermentation medium according to the seed medium and fermentation culture formula, respectively, and pack them into 250ml triangular bottles, 50ml in each bottle, and sterilize at 115°C for 30min, insert the spores of the mutant strain QZ01 into the above seeds In the culture medium, at 220 rpm, at 30° C., on a shaker for 24 hours to obtain a seed culture solution. The seed culture liquid was added to the fermentation medium according to 10% inoculum amount, and cultured on a shaker at 220 rpm at 30° C. for 5 days to obtain a fermentation culture of the mutant strain QZ01. Centrifuge the 5L fermentation culture obtained from the fermentation culture, collect the fermented cells, wash the cells with water for 3 times, remove the washing liquid, and freeze-dry the cells overnight; Centrifuge to obtain the extract, repeat the ultrasonic extraction 3 times, combine the extracts, filter the extracts, and concentrate under reduced pressu...

Embodiment 2

[0033]According to the seed medium and fermentation culture formula, prepare 1L seed medium and 10L fermentation medium respectively, pack them into 250ml triangular bottles, fill each bottle with 50ml, and sterilize at 115°C for 30min, insert the spores of the mutant strain QZ01 into the above seeds In the culture medium, at 220 rpm, at 30° C., on a shaker for 24 hours to obtain a seed culture solution. The seed culture liquid was added to the fermentation medium according to 10% inoculum amount, and cultured on a shaker at 220 rpm at 30° C. for 5 days to obtain a fermentation culture of the mutant strain QZ01. Centrifuge the 10L fermentation culture obtained from the fermentation culture, collect the fermented cells, wash the cells with water for 3 times, remove the washing liquid, and freeze-dry the cells overnight; Centrifuge the extract, repeat the ultrasonic extraction 3 times, combine the extracts, filter the extracts, and concentrate under reduced pressure to obtain ab...

Embodiment 3

[0035] Determination of Antifungal Activity and Hemolytic Toxicity of Pimaricin Derivatives in Vitro

[0036] The determination of antifungal activity in vitro is based on Candida albicans as the indicator bacteria. By measuring the growth of Candida albicans at different concentrations of antibiotics, the MIC of the corresponding antibiotics can be obtained. 50 and MIC 90 value. First, the overnight culture solution of Candida albicans was inoculated in LB medium at a ratio of 1 / 10000, and distributed in 96-well plates at 200 μl / well. The DMSO solutions of the Pimaricin derivatives and Pimaricin in different concentrations (0-500 μg / ml) were prepared, and added to the above LB medium at a ratio of 2%. Place the 96-well plate in a 34°C incubator, culture it statically for 12 hours, and use a microplate reader to measure the OD under different concentrations of antibiotics 660 . MIC can be obtained by drawing the inhibition curve of the measured data against the concentrati...

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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 technology for separating secondary metabolites of microorganisms, in particular to a high-efficiency and low-toxicity picamamycin derivative and its preparation method and application. technical background [0002] Systemic fungal infection is a serious complication of immune system deficiency. Its pathogens often have the characteristics of high transmission rate, high proliferation rate, high lethality rate and high drug resistance, which seriously threaten people's health. Due to the rapid development of drug resistance of fungal pathogens and drug-drug interactions, currently there are very limited antifungal drugs that can be used clinically to treat systemic fungal infections, and the therapeutic effect is very unsatisfactory. Among them, polyene antibiotics have high antibacterial and antibacterial activities against a variety of fungal pathogens, and fungal pathogens develop resistance to them very slowly, and are cu...

Claims

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Application Information

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Patent Type & Authority Patents(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 JIAOTONG UNIV
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