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Application of derivative SKQ1 of plastoquinone in preparation of anti-mycobacterium tuberculosis drugs

A technology of mycobacterium tuberculosis and mycobacteria, applied in the field of microbial infectious diseases and pharmacy, can solve the problems of poor patient compliance, long treatment cycle, low treatment success rate, etc., and achieve the effect of small molecular weight and simple structure

Pending Publication Date: 2021-11-12
HUAZHONG AGRI UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, due to the special cell structure of M. tuberculosis, M. tuberculosis itself is resistant to some commonly used antibiotics
Nevertheless, there are still many challenges in the treatment and prevention of TB: 1) the low protection rate of existing vaccines and the lack of effective diagnosis of early TB; 2) the emergence of drug-resistant TB and the extremely low incidence of drug-resistant TB Treatment success rate; 3) Double infection of tuberculosis and AIDS; 4) The long treatment cycle and strong side effects of the existing standard tuberculosis treatment plan lead to poor patient compliance, low treatment success rate, and patients face a high risk of recurrence
These current situations have brought great challenges to the further spread of Mycobacterium tuberculosis.

Method used

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  • Application of derivative SKQ1 of plastoquinone in preparation of anti-mycobacterium tuberculosis drugs
  • Application of derivative SKQ1 of plastoquinone in preparation of anti-mycobacterium tuberculosis drugs
  • Application of derivative SKQ1 of plastoquinone in preparation of anti-mycobacterium tuberculosis drugs

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0014] Example 1 Bacterial Culture and Compound Storage Solution Preparation

[0015] Cultivation of test strains: Mycobacterium tuberculosis H37Rv (ATCC27294), Mycobacterium bovis M.bovis (ATCC19210) and 6 strains of drug-resistant Mycobacterium tuberculosis isolated from the hospital were inoculated in 7H9 liquid medium and cultured until the Several phases (optical density OD 600 0.8-1.0), the entire operation was carried out in a biosafety cabinet in a biosafety level 3 laboratory (BSL-3).

[0016] Streptococcus suis SC19 (isolated from a pig farm in Sichuan) was inoculated in TSB liquid medium and cultured to logarithmic phase (OD 600 0.8-1.0); Escherichia coli (ATCC25922), Listeria monocytogenes (ATCC19115), Pseudomonas aeruginosa (ATCC9027) and Klebsiella pneumoniae (CTCC46117) were all inoculated in LB liquid medium and cultivated to logarithmic Period (OD 600 is 0.6-0.8).

[0017] Preparation of the mother solution of the compound to be tested: the CSA number of S...

Embodiment 2

[0018] Embodiment 2 determines the minimum inhibitory concentration (MIC) of SKQ1

[0019] MIC is defined as the minimum concentration of a compound that inhibits 90% of the growth of bacteria in the medium. Carry out 2-fold serial dilution of the compound to be tested (the dilution gradient is 64 μg / mL-0.125 μg / mL), and the Mycobacterium tuberculosis, Mycobacterium bovis M.bovis, drug-resistant Mycobacterium tuberculosis and Streptococcus suis SC19 were diluted to OD with corresponding liquid medium 600 Escherichia coli, Listeria monocytogenes, Pseudomonas aeruginosa and Klebsiella pneumoniae that have grown to the logarithmic phase were diluted to OD with LB liquid medium 600 is 0.001. The diluted bacterial solution was added to the culture medium containing different concentrations of compounds, and a blank control group with only solvent was set, and cultured in a 37°C incubator. By measuring the OD value of each concentration gradient and blank control group, compared ...

Embodiment 3

[0023] Dilute the Mycobacterium tuberculosis H37Rv bacteria solution grown to the logarithmic phase with 7H9 liquid medium to OD 600 was 0.01, the stock solution of SKQ1 prepared in Example 1 was added to the diluted bacterial solution respectively to obtain the compound groups whose SKQ1 concentrations were 1.0 μg / mL, 4.0 μg / mL, 8.0 μg / mL and 16.0 μg / mL, In addition, 1% DMSO was set as the control group, cultured in a 37°C incubator for 12 days, and on the 0th, 2nd, 4th, 8th and 12th days of culture, each day was neutralized from the control group. 100 μl was taken out of the compound group with a concentration of 10 times and spread on the 7H11 solid plate medium for counting. The solid plate was cultured in an incubator for 21 days to count the counting results and calculate the colony forming units (CFU). The result is as figure 1 As shown, compared with Control 1, SKQ1 at 4.0 μg / mL was able to kill 99.99% of Mycobacterium tuberculosis.

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Abstract

The invention discloses an application of a derivative SKQ1 of plastoquinone in preparation of anti-mycobacterium tuberculosis drugs, and belongs to the field of microbial infectious diseases and pharmacy. The invention finds that the SKQ1 has the characteristics of inhibiting the growth of mycobacterium tuberculosis and finally killing the mycobacterium tuberculosis, has the application of resisting the mycobacterium tuberculosis, and can be used for preparing drugs for resisting the mycobacterium tuberculosis and drugs for treating tuberculosis; and meanwhile, the SKQ1 also has the characteristic of inhibiting streptococcus suis, has the application of resisting streptococcus suis, and can be used for preparing drugs for resisting streptococcus suis and drugs for treating streptococcus suis infection. The invention provides a novel drug for resisting mycobacterium tuberculosis and treating tuberculosis.

Description

technical field [0001] The invention relates to the fields of microbial infectious diseases and pharmacy, in particular to the application of SKQ1, a derivative of plastoquinone, in the preparation of anti-tuberculosis mycobacterium drugs. Background technique [0002] Tuberculosis is a respiratory disease caused by Mycobacterium tuberculosis infection. It is a chronic infectious disease that seriously threatens human health worldwide. About one quarter of the world's people are latently infected patients. The lack of new effective preventive vaccines, new anti-tuberculosis drugs and effective diagnostic techniques, as well as the emergence of multidrug-resistant and extensively drug-resistant Mycobacterium tuberculosis strains have brought great challenges to the prevention, control and treatment of tuberculosis. In the past few decades, people have been continuously optimizing the treatment strategy of tuberculosis: the most commonly used regimen for the treatment of sensi...

Claims

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Application Information

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IPC IPC(8): A61K31/66A61P31/04A61P31/06A01N57/34A01P1/00
CPCA61K31/66A61P31/04A61P31/06A01N57/34
Inventor 谭臣王高岩董文琪鲁浩王晨晨鲁文嘉王湘如陈焕春
Owner HUAZHONG AGRI UNIV
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