Inhibitor for acetylcoenzyme A synthetase in human pathogen clostridium difficile

A technology of Clostridium difficile and acetyl coenzyme, applied in the field of biomedicine, can solve problems such as death, growth inhibition, and failure of Clostridium to perform normal energy and material metabolism

Inactive Publication Date: 2010-08-11
FUDAN UNIV
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  • Application Information

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Problems solved by technology

If the activity of this enzyme is inhibited, the pathogen Clostridium difficile will not be ab

Method used

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  • Inhibitor for acetylcoenzyme A synthetase in human pathogen clostridium difficile
  • Inhibitor for acetylcoenzyme A synthetase in human pathogen clostridium difficile
  • Inhibitor for acetylcoenzyme A synthetase in human pathogen clostridium difficile

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Embodiment Construction

[0016] Taking 8-hydroxyquinoline as an example, the specific operation process is as follows:

[0017] First prepare a titanium citrate solution, and use potassium ferricyanide to calibrate its precise concentration to 15.8mM. Weigh 145 mg of 8-hydroxyquinoline and dissolve it with 1 mL of absolute ethanol. The extracted methyl cobalt iron sulfur protein (CoFeSP) has a concentration of 40μM, ACS cd It is 198μM. Prepare 1.2mL reaction solution A, which contains 20μM ACS cd , 1mM titanium citrate, and 50mM tris buffer solution (pH=8.0), after half an hour of combination, add 1μL of 1M 8-hydroxyquinoline for more than 1 hour; prepare 1.2mL reaction solution B, which contains 10μM CoFeSP, 1mM titanium citrate And 50mM tris buffer solution (pH=8.0).

[0018] Use a 2.5mL disposable syringe to transfer the reaction solutions A and B to the intercepting spectrophotometer, and monitor the curve of the absorbance at 390nm over time after the two are mixed. This curve reflects the ACS cd Th...

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Abstract

The invention belongs to the technical field of biological medicine, and specifically provides a human pathogen clostridium difficile inhibitor taking acetylcoenzyme A synthetase (ACS) as a target. This invention utilizes a fast reaction kinetics technique to successfully find an acetylcoenzyme A synthetase inhibitor with high inhibitory activity, which comprises 1,10-o-phenanthroline, 2,2-bipyridyl and 8-hydroxyquinoline, wherein the conventional clinically applied medicament, namely 8-hydroxyquinoline, can inhibit methyl transfer activity of acetylcoenzyme A nearly by 100 percent in a low concentration. A method of the invention is the only reported method at present for an efficient inhibitor of human pathogen clostridium difficile acetylcoenzyme A synthetase. The inhibitor is of important application value in the field of biological medicine.

Description

Technical field [0001] The invention belongs to the field of biomedicine technology, and specifically relates to being an acetyl-CoA synthase (ACS) inhibitor in the human pathogen Clostridium difficile. Background technique [0002] Clostridium difficile (clostridium difficile) is a gram-positive anaerobic bacillus that can produce toxin A and toxin B, which can lead to diarrhea, pseudomembranous colitis, colon cancer and other serious diseases, collectively referred to as CDAD. This disease mostly occurs in patients who took antibiotics in hospitals. It has been prevalent in North America and Europe for many years, and the number of cases has increased year by year. Only in the United States, the number of diagnosed CDAD cases has doubled in the four years from 2001 to 2005, 2006 Up to 300,000 cases were reported annually. In recent years, CDAD has spread to Australia, Asia, Japan, Taiwan and other places, and has a tendency to spread to the world. [0003] Currently, the drugs ...

Claims

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Application Information

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IPC IPC(8): A61K31/4745A61K31/444A61K31/47A61P31/04G01N21/31
Inventor 谭相石朱小飞
Owner FUDAN UNIV
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