Purpose of L-cysteine compound for restraining new delhi metallo (NDM)-1 activity

A cysteine ​​ester and compound technology, applied in the field of pharmacy, can solve problems such as L-cysteine ​​ester compounds that have not yet been found, and achieve the effects of solving drug resistance, improving curative effect, and eliminating hydrolysis

Inactive Publication Date: 2013-06-05
TIANJIN INT JOINT ACADEMY OF BIOTECH & MEDICINE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The application of L-cysteine ​​ester compounds in inhibiting bacterial activity has not been found so far

Method used

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  • Purpose of L-cysteine compound for restraining new delhi metallo (NDM)-1 activity
  • Purpose of L-cysteine compound for restraining new delhi metallo (NDM)-1 activity
  • Purpose of L-cysteine compound for restraining new delhi metallo (NDM)-1 activity

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0037] Step 1. Preparation of NDM-1 substrate stock solution

[0038] Imipenem monohydrate (Imipenem monohydrate, purchased from Sigma Company) was dissolved in 50 mM HEPES (purchased from BioBasie Company) to prepare a 10 mM substrate stock solution for future use.

[0039] Step 2. Treatment of Compounds

[0040] Compounds in 95% DMSO+5% ddH 2 O, and prepared to a solution with a concentration of 100mM, and then placed the prepared compound solution in a 1.5ml ep tube, and stored it at 4°C for use.

[0041] Step 3. Preparation of NDM-1 protein buffer

[0042] NDM-1 (provided by the MDC protein purification group of our laboratory, the preparation method refers to Yu Guo, Jing Wang et al., A structural view of the antibiotic degradation enzyme NDM-1 from a superbug. Protein & Cell, 2011, 2(5): 384 -394) was dissolved in protein buffer (pH=6.8), and was prepared into 50nM NDM-1 protein buffer, wherein the protein buffer contained 50mM HEPES, 5μM ZnCl 2 (purchased from BioBa...

Embodiment 1

[0054] Example 1 Determination of NDM-1 activity inhibited by N-benzyloxycarbonyl-L-cysteine ​​methyl ester

[0055]

[0056] The N-benzyloxycarbonyl-L-cysteine ​​methyl ester used was purchased from Bailingwei with a purity of 98%.

[0057] Dissolve N-benzyloxycarbonyl-L-cysteine ​​methyl ester (4 mg) in 95% DMSO double distilled water (148.5 μL) to prepare a solution with a concentration of 100 mM, and then place the solution in a 1.5 ml ep tube , stored at 4°C.

[0058] Then according to the above activity test method step 5 (preliminary screening of compound) and step 6 (IC of compound) 50 Determination of the value) described in the operation. Then take the concentration logarithm of N-benzyloxycarbonyl-L-cysteine ​​methyl ester as the abscissa, and the remaining active fraction of NDM-1 as the ordinate to draw a curve, see image 3 . Finally, according to the curve, using GraphPad Prism version 5.0 software to calculate, the obtained IC 50 The value is 1.814±0.12...

Embodiment 2

[0059] Example 2 Determination of NDM-1 activity inhibited by N-acetyl-L-cysteine ​​methyl ester

[0060]

[0061] The N-acetyl-L-cysteine ​​methyl ester used was purchased from Bailingwei with a purity of 99%.

[0062] N-acetyl-L-cysteine ​​methyl ester (4 mg) was dissolved in 95% DMSO double distilled water (225.8 μ L) to prepare a solution with a concentration of 100 mM, and then the solution was placed in a 1.5 ml ep tube, Store at 4°C.

[0063] Proceed as described in steps 5 and 6 of the activity test method above. Then take the logarithm of the concentration of N-acetyl-L-cysteine ​​methyl ester as the abscissa, and the remaining active fraction of NDM-1 as the ordinate to draw a curve, see Figure 4 . Finally, according to the curve, the GraphPad Prismversion 5.0 software is used to calculate the obtained IC 50 The value is 33.94±2.8 μM.

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Abstract

The invention provides L-cysteine compound of a following general formula for restraining new delhi metallo (NDM)-1 activity in medicine. R1 is hydrogen or aromatic oxygen carbonyl or C1-C4 alkyl acyl, and R2 is C1-C4 alkyl. The compound can well restrain NDM-1 activity.

Description

technical field [0001] The present invention relates to the field of pharmacy, in particular to the use of L-cysteine ​​ester compounds. Background technique [0002] In the 1950s and 1960s, known as the "golden age" of antibiotics, about 7 million people died of infectious diseases worldwide every year, and this number rose to 20 million by 1999. The main reason for the increase in the fatality rate is the difficulty in medication brought by drug-resistant bacteria. [0003] At present, the problem of bacterial resistance has become very serious. In developed countries, 5% to 10% of hospitalized patients have one or more infections. There are about 2 million patients with nosocomial infection in the United States every year, 90,000 people die, and the economic loss reaches 4.5 billion to 5.7 billion US dollars. In developing countries, the risk of nosocomial infection is 2 to 20 times higher than in developed countries. The incidence rate of nosocomial infection in our ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/27A61K31/223A61P31/04
CPCY02A50/30
Inventor 饶子和陈悦杨诚白翠改郭宇徐寅通李宁宁夏强娄智勇
Owner TIANJIN INT JOINT ACADEMY OF BIOTECH & MEDICINE
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