New Delhi metallo-beta-lactamase-1 inhibitors (NDM-1)
A technology of lactams and metals, which is applied in the field of medicine, can solve the problems of ineffective killing of "super bacteria", limited treatment options, and increased mortality of critically ill patients and infected people with low immunity.
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experiment example 1
[0126] Experimental Example 1 NDM-1 Inhibitor Enzyme Activity Inhibition Experiment in Vitro
[0127] In this experiment, the NDM-1 inhibitors used were compound IMB-XH1, compound IMB-XH1Q and compounds IMB-XH1-1~IMB-XH1-110 in Table 1, and the NDM-1 inhibitors were first prepared with DMSO to a concentration The mother solution is 10mg / mL, and the mother solution is dissolved and diluted with DMSO as needed during the experiment. The substrate used in this experiment was meropenem (MEPM). MEPM was prepared into a mother solution with a concentration of 10mM with distilled water, and stored at -20°C. During the experiment, the mother solution was diluted with 10mM HEPES buffer as needed. The NDM-1 enzyme used in this experiment was first prepared with 10mM HEPES buffer solution to make a mother solution with a concentration of 2.8U (3.78nM). During the experiment, the mother solution was diluted with 10mM HEPES buffer solution as needed.
[0128] The inhibitory activity of ND...
experiment example 2
[0163] Experimental Example 2 Kinetic Study of NDM-1 Inhibitors on NDM-1
[0164]In this experiment, the NDM-1 inhibitors used were compound IMB-XH1 and compound IMB-XH1Q. First, the NDM-1 inhibitor was prepared with DMSO into a mother solution with a concentration of 10 mg / mL. During the experiment, it was dissolved and diluted with DMSO as needed. mother liquor. The substrate used in this experiment was meropenem (MEPM). MEPM was first prepared with water to make a mother solution with a concentration of 10 mM. During the experiment, the mother solution was diluted with 10 mM HEPES buffer as needed. The NDM-1 enzyme used in this experiment was first prepared with 10mM HEPES buffer solution to make a mother solution with a concentration of 2.8U (3.78nM). During the experiment, the mother solution was diluted with 10mM HEPES buffer solution as needed.
[0165] 2.1 Identification of reversible inhibition and irreversible inhibition
[0166] Experimental methods include:
[0...
experiment example 3
[0184] Experimental example 3 different NDM-1 inhibitors in vitro to the antibacterial activity evaluation of NDM-1 bacteria
[0185] In order to investigate whether different NDM-1 inhibitors have antibacterial effects on NDM-1-producing bacteria, drug sensitivity tests at the bacterial level were carried out using recombinant NDM-1-expressing engineering bacteria and other clinically isolated NDM-1-producing bacteria. The minimum inhibitory concentration (MIC) was determined by broth microdilution method.
[0186] In this experiment, the NDM-1 inhibitors used were compound IMB-XH1 and compound IMB-XH1Q. First, the NDM-1 inhibitor was prepared with DMSO into a mother solution with a concentration of 10 mg / mL. During the experiment, it was dissolved and diluted with DMSO as needed. mother liquor.
[0187] The substrates used in this experiment were β-lactam antibiotics (including ampicillin, ticarcillin, piperacillin, penicillin, cephalothin, cefoperazone, meropenem and aztre...
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