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Application of enniatine compound for preparing anti-drug-resistant tubercle bacillus drugs

A technology of enfusaricin and compound, which is applied in the application field of enfusarium compound in the preparation of anti-drug-resistant tuberculosis drugs, can solve problems such as infection, multidrug resistance, etc., achieves easy purification, strong Activity against drug-resistant tuberculosis bacteria and its effect on large-scale industrial production

Inactive Publication Date: 2010-03-17
SUN YAT SEN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, opportunistic infection of non-tuberculous mycobacteria (such as avium-mycobacterium intracellulare complex group) often occurs in immunocompromised populations (including AIDS patients), and symptoms similar to typical tuberculosis occur, which is one of the main causes of death in AIDS patients One; more seriously, these non-tuberculous mycobacteria are often naturally resistant to existing anti-tuberculosis drugs, showing natural multi-drug resistance

Method used

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  • Application of enniatine compound for preparing anti-drug-resistant tubercle bacillus drugs
  • Application of enniatine compound for preparing anti-drug-resistant tubercle bacillus drugs
  • Application of enniatine compound for preparing anti-drug-resistant tubercle bacillus drugs

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0025] Preparation of enfusarin compounds shown in embodiment 1 formula (I)

[0026] In this example, GTY medium (containing 2.5 mass % glucose, 0.8 mass % peptone, 20 mass % artificial seawater with an initial value of pH 6) was used to carry out suspension fermentation culture of the endogenous fungus Fusarium sp. Static cultivation for 15 days, filtration, separation of bacteria and fermentation broth.

[0027] The above-mentioned fermentation broth was extracted with ethyl acetate, the extract was mixed with silica gel and packed into a column, and eluted with a gradient of petroleum ether-ethyl acetate-methanol. Obtain the crude product of the enfusarium compound mixture shown in formula (I) in the dehydration, and use ethyl acetate / cyclohexane (volume ratio is 1 / 1) mixed solvent isocratic elution, obtain enfusarium successively enfusarin G, enfusarin B, and enfusarin B 4 .

[0028] The above-mentioned bacteria were extracted with methanol, the extract was mixed with s...

Embodiment 2

[0029] Example 2 Anti-mycobacterium avium-intracellular activity test of enfusarin compounds

[0030] This embodiment adopts the solid medium dilution method to enfusarin G, enfusarin B, enfusarin B 4 The anti-Mycobacterium avium-intracellular activities of the four substances, Beauveria and Beauveria, were detected.

[0031] Take the culture of Mycobacterium avium intracellulare cultured on the slant, add it to 3ml Middlebrook7H9 broth medium, add a small amount of glass beads, tighten the cap of the test tube, vibrate vigorously on a vortex shaker, and compare with the standard McFarland turbidity Tube (MacFarland No.1) turbidity, that is to prepare a 1 mg / ml suspension of Mycobacterium avium intracellulare.

[0032] enfusarin G, enfusarin B, enfusarin B 4 and beauverum were formulated with DMSO (dimethyl sulfoxide) to prepare a high-concentration stock solution, and the stock solution was diluted to 120 μg / ml with 5% Tween-80 sterile ultrapure water. The sporin compounds...

Embodiment 3

[0035] Example 3 Anti-ISRE MTB strain activity test of enfusarin compounds against Mycobacterium tuberculosis clinical isolation

[0036] This embodiment adopts the solid medium dilution method to enfusarin G, enfusarin B, enfusarin B 4 Anti-tuberculosis Mycobacterium clinical isolates resistant to ISRE MTB strains (isoniazid, streptomycin, rifampicin, ethambutol-resistant Mycobacterium tuberculosis clinical isolates) activities were detected.

[0037] Scrape the culture of clinically isolated ISRE-resistant MTB strain of Mycobacterium tuberculosis from the inclined surface, add it to 3ml Middlebrook7H9 broth medium, add a small amount of glass beads, tighten the test tube cap, vibrate vigorously on a vortex shaker, and grind with standard wheat Turbidimetric tube (MacFarland No.1) was used for turbidimetry, that is, a 1 mg / ml bacterial suspension was prepared. This operation is performed in a biosafety level 3 laboratory.

[0038] enfusarin G, enfusarin B, enfusarin B 4 an...

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Abstract

The invention discloses an application of enniatine compound for preparing anti-drug-resistant tubercle bacillus drugs; the enniatine compound has a general formula showed by a formula (I); aiming atthe conditions that tuberculosis has high morbidity at present, mycobacterium tuberculosis has multiple drug-resistant strains and human immune deficiency virus is infected doubly, so as to lead the tuberculosis morbidity and mortality to be on the rise, the invention provides a new application of the enniatine compound on the anti-drug-resistant tubercle bacillus by finding that the enniatine compound has strong anti-drug-resistant tubercle bacillus activity, thereby not only providing a new beneficial tool for the treatment of the drug-resistant tubercle bacillus, but also expanding the application range of the enniatine compound. In addition, the enniatine compound is derived from ocean mangrove endophytic fungi, the raw material is plentiful, and the collection and cultivation of the raw material are easy, the purification is easy and the cost is low, and the breeding cycle is short, thereby being large-scale industrial production.

Description

technical field [0001] The invention relates to the technical field of medicine, in particular to the medical research on Mycobacterium tuberculosis, in particular to the application of enfusarin compounds in the preparation of anti-drug-resistant Mycobacterium tuberculosis drugs. Background technique [0002] Due to their special environment, marine microorganisms have developed various unique metabolic methods, which not only ensure their survival in extreme environments, but also provide humans with a large number of novel metabolites that are difficult to find in terrestrial microorganisms, many of which It has potential practical application value and has been considered as a new source for finding pharmacologically active substances. In addition, marine microorganisms are easy to collect and cultivate, and the metabolites produced by artificial fermentation are easier to purify than substances contained in higher organisms, and the cost is lower, which is in line with ...

Claims

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Application Information

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IPC IPC(8): A61K31/395A61P31/06
Inventor 赖小敏王军林永成佘志刚陈伊
Owner SUN YAT SEN UNIV
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