Application of compound with NMN and/or NADH structure and pharmaceutically acceptable salt of compound to preparation of mycobacterium tuberculosis inhibitor

A technology of mycobacterium tuberculosis and compounds, applied in the field of biomedicine and chemistry, can solve the problem of high toxicity

Inactive Publication Date: 2021-01-22
深圳市旷逸生物科技有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] The main purpose of the present invention is to propose the application of a compound with NMN and / or NADH structure and its pharmaceutically acceptable salt in the preparation of Mycobacterium tuberculosis inhibitors, aiming to solve the technical problem of high toxicity of traditional inhibitors

Method used

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  • Application of compound with NMN and/or NADH structure and pharmaceutically acceptable salt of compound to preparation of mycobacterium tuberculosis inhibitor
  • Application of compound with NMN and/or NADH structure and pharmaceutically acceptable salt of compound to preparation of mycobacterium tuberculosis inhibitor
  • Application of compound with NMN and/or NADH structure and pharmaceutically acceptable salt of compound to preparation of mycobacterium tuberculosis inhibitor

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0037] Example 1 Inhibition experiment of NMN on Mycobacterium tuberculosis in macrophages

[0038] 1. Experimental operation:

[0039] 1.1 Obtain macrophages: THP-1 cells were mixed with 5*10 5 Cells / mL were inoculated in 96-well plates, 100 uL per well, differentiated with 100 ng / mL phorbol ester (PMA) for 24 hours, and the cells adhered to the wall to obtain macrophages derived from THP-1 cells;

[0040] 1.2 Co-incubation: Infect the macrophages derived from THP-1 cells obtained above with Mycobacterium bovis BCG 1173P2 to obtain a macrophage system infected with Mycobacterium tuberculosis; wash the macrophages infected with Mycobacterium tuberculosis The extracellular Mycobacterium bovis BCG 1173P2 of the phagocyte system was cultured by adding 1640 medium containing 10% (volume fraction) fetal bovine serum; adding 1mM, 5mM, and 10mM NMN (final concentration) respectively, and setting a blank at the same time For the control group, incubated for 48 hours;

[0041] 1.3 D...

Embodiment 2

[0043] Example 2 Inhibition experiment of NADH on Mycobacterium tuberculosis in macrophages

[0044] 1. Experimental operation:

[0045] 1.1 Obtain macrophages: THP-1 cells were mixed with 5*10 5 Cells / mL were inoculated in 96-well plates, 100 uL per well, differentiated with 100 ng / mL phorbol ester (PMA) for 24 hours, and the cells adhered to the wall to obtain macrophages derived from THP-1 cells;

[0046]1.2 Co-incubation: Infect the macrophages derived from THP-1 cells obtained above with Mycobacterium bovis BCG 1173P2 to obtain a macrophage system infected with Mycobacterium tuberculosis; wash the macrophages infected with Mycobacterium tuberculosis The extracellular Mycobacterium bovis BCG 1173P2 of the phagocyte system was cultured in 1640 medium containing 10% (volume fraction) fetal bovine serum; NADH (final concentration) of 1mM, 5mM, and 10mM was added respectively, and a blank was set at the same time For the control group, incubated for 48 hours;

[0047] 1.3 D...

Embodiment 3

[0049] Embodiment 3 NMN is to the inhibition test of Mycobacterium tuberculosis

[0050] 1. Experimental operation: adjust the concentration of Mycobacterium bovis BCG 1173P2 to an OD600 reading of 0.05, inoculate in a 96-well plate, 99 uL per well. Then add 1.0 uL of the concentration gradient dilution solution of the NMN (final concentration) of 1mM, 5mM and 10mM respectively, and incubate altogether for 48h at 37°C; Mycobacterium BCG1173P2, but did not add the test drug, but added rifampicin). And take samples at 4h and 8h to detect the GFP fluorescence intensity in the culture system, and obtain as follows: image 3 The results shown; wherein, 4 replicate holes were set at each time point.

[0051] 2. Analysis of the results: when incubated for 4 hours, each concentration of NMN had no obvious inhibitory effect compared with the control group; after incubation for 8 hours, each concentration of NMN had a significant inhibitory effect on Mycobacterium tuberculosis. Among...

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Abstract

The invention discloses a compound with an NMN and / or NADH structure and an application of a pharmaceutically acceptable salt of the compound to preparation of a mycobacterium tuberculosis inhibitor.According to the technical scheme provided by the invention, the compound with the NMN and / or NADH structure and the medicinal salt of the compound are / is used in the mycobacterium tuberculosis inhibitor, so that the technical problem of high toxicity of the traditional mycobacterium tuberculosis inhibitor is solved.

Description

technical field [0001] The invention relates to the technical fields of biomedicine and chemistry, in particular to the application of a compound with NMN and / or NADH structure and a pharmaceutically acceptable salt thereof in the preparation of mycobacterium tuberculosis inhibitors. Background technique [0002] Tuberculosis is a disease that occurs after Mycobacterium tuberculosis infects the human body. After being infected by Mycobacterium tuberculosis, it will exist in the human body for several months or years, resulting in wide spread of tuberculosis, strong infectivity, and high fatality rate, making it a One of the most serious diseases. According to the World Health Organization's 2018 annual report on tuberculosis, there are about 10 million newly discovered tuberculosis patients in the world, 90% of whom are adults, and 1.3 million patients died of tuberculosis, including patients co-infected with AIDS and tuberculosis. The number of latent infections is as high...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/7084A61P31/04A61K31/706
CPCA61K31/706A61K31/7084A61P31/04A61K2300/00
Inventor 沈洁沈艳
Owner 深圳市旷逸生物科技有限公司
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