CN115137733B - Application of ursodeoxycholic acid in preparation of MCR-3 enzyme inhibitor - Google Patents
Application of ursodeoxycholic acid in preparation of MCR-3 enzyme inhibitor Download PDFInfo
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- CN115137733B CN115137733B CN202211021342.2A CN202211021342A CN115137733B CN 115137733 B CN115137733 B CN 115137733B CN 202211021342 A CN202211021342 A CN 202211021342A CN 115137733 B CN115137733 B CN 115137733B
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- RUDATBOHQWOJDD-UHFFFAOYSA-N (3beta,5beta,7alpha)-3,7-Dihydroxycholan-24-oic acid Natural products OC1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)CC2 RUDATBOHQWOJDD-UHFFFAOYSA-N 0.000 title claims abstract description 49
- 229960001661 ursodiol Drugs 0.000 title claims abstract description 49
- RUDATBOHQWOJDD-UZVSRGJWSA-N ursodeoxycholic acid Chemical compound C([C@H]1C[C@@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)CC1 RUDATBOHQWOJDD-UZVSRGJWSA-N 0.000 title claims abstract description 48
- 229940125532 enzyme inhibitor Drugs 0.000 title abstract description 10
- 239000002532 enzyme inhibitor Substances 0.000 title abstract description 10
- 238000002360 preparation method Methods 0.000 title description 3
- JORAUNFTUVJTNG-BSTBCYLQSA-N n-[(2s)-4-amino-1-[[(2s,3r)-1-[[(2s)-4-amino-1-oxo-1-[[(3s,6s,9s,12s,15r,18s,21s)-6,9,18-tris(2-aminoethyl)-3-[(1r)-1-hydroxyethyl]-12,15-bis(2-methylpropyl)-2,5,8,11,14,17,20-heptaoxo-1,4,7,10,13,16,19-heptazacyclotricos-21-yl]amino]butan-2-yl]amino]-3-h Polymers CC(C)CCCCC(=O)N[C@@H](CCN)C(=O)N[C@H]([C@@H](C)O)CN[C@@H](CCN)C(=O)N[C@H]1CCNC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCN)NC(=O)[C@H](CCN)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC(C)C)NC(=O)[C@H](CCN)NC1=O.CCC(C)CCCCC(=O)N[C@@H](CCN)C(=O)N[C@H]([C@@H](C)O)CN[C@@H](CCN)C(=O)N[C@H]1CCNC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCN)NC(=O)[C@H](CCN)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC(C)C)NC(=O)[C@H](CCN)NC1=O JORAUNFTUVJTNG-BSTBCYLQSA-N 0.000 claims abstract description 39
- 108010078777 Colistin Proteins 0.000 claims abstract description 34
- XDJYMJULXQKGMM-UHFFFAOYSA-N polymyxin E1 Natural products CCC(C)CCCCC(=O)NC(CCN)C(=O)NC(C(C)O)C(=O)NC(CCN)C(=O)NC1CCNC(=O)C(C(C)O)NC(=O)C(CCN)NC(=O)C(CCN)NC(=O)C(CC(C)C)NC(=O)C(CC(C)C)NC(=O)C(CCN)NC1=O XDJYMJULXQKGMM-UHFFFAOYSA-N 0.000 claims abstract description 34
- YKQOSKADJPQZHB-YNWHQGOSSA-N n-[(2s)-4-amino-1-[[(2s,3r)-1-[[(2s)-4-amino-1-oxo-1-[[(3s,6s,9s,12s,15r,18s,21s)-6,9,18-tris(2-aminoethyl)-3-[(1s)-1-hydroxyethyl]-12,15-bis(2-methylpropyl)-2,5,8,11,14,17,20-heptaoxo-1,4,7,10,13,16,19-heptazacyclotricos-21-yl]amino]butan-2-yl]amino]-3-h Polymers CCC(C)CCCC(=O)N[C@@H](CCN)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCN)C(=O)N[C@H]1CCNC(=O)[C@H]([C@H](C)O)NC(=O)[C@H](CCN)NC(=O)[C@H](CCN)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC(C)C)NC(=O)[C@H](CCN)NC1=O YKQOSKADJPQZHB-YNWHQGOSSA-N 0.000 claims abstract description 32
- 239000003814 drug Substances 0.000 claims abstract description 14
- 241000607142 Salmonella Species 0.000 claims abstract description 13
- 241000894006 Bacteria Species 0.000 claims abstract description 12
- 230000000844 anti-bacterial effect Effects 0.000 claims abstract description 9
- 208000015181 infectious disease Diseases 0.000 claims abstract description 5
- 230000000694 effects Effects 0.000 abstract description 5
- 241000305071 Enterobacterales Species 0.000 abstract description 3
- 102000004190 Enzymes Human genes 0.000 abstract description 3
- 108090000790 Enzymes Proteins 0.000 abstract description 3
- 230000000797 effect on infection Effects 0.000 abstract description 3
- 201000010099 disease Diseases 0.000 abstract description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 2
- 238000004519 manufacturing process Methods 0.000 abstract description 2
- 230000001580 bacterial effect Effects 0.000 description 8
- 241000588724 Escherichia coli Species 0.000 description 7
- 229960003346 colistin Drugs 0.000 description 7
- KNIWPHSUTGNZST-UHFFFAOYSA-N polymyxin E2 Natural products CC(C)CCCCC(=O)NC(CCN)C(=O)NC(C(C)O)C(=O)NC(CCN)C(=O)NC1CCNC(=O)C(C(C)O)NC(=O)C(CCN)NC(=O)C(CCN)NC(=O)C(CC(C)C)NC(=O)C(CC(C)C)NC(=O)C(CCN)NC1=O KNIWPHSUTGNZST-UHFFFAOYSA-N 0.000 description 7
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- 108010040201 Polymyxins Proteins 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- JAWSHISYWRRQQQ-HFAKWTLXSA-N patchoulenone Chemical compound C[C@@H]1CC[C@@H]2C(=O)C3=C(C)CC[C@]13C2(C)C JAWSHISYWRRQQQ-HFAKWTLXSA-N 0.000 description 4
- 238000004659 sterilization and disinfection Methods 0.000 description 4
- 239000003242 anti bacterial agent Substances 0.000 description 3
- 229940088710 antibiotic agent Drugs 0.000 description 3
- 235000012000 cholesterol Nutrition 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 125000001612 ursodeoxycholic acid group Chemical group 0.000 description 3
- 210000000941 bile Anatomy 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 208000027096 gram-negative bacterial infections Diseases 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 238000001000 micrograph Methods 0.000 description 2
- 238000007747 plating Methods 0.000 description 2
- 229940041153 polymyxins Drugs 0.000 description 2
- 241000588921 Enterobacteriaceae Species 0.000 description 1
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 1
- 101150004219 MCR1 gene Proteins 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 108010039918 Polylysine Proteins 0.000 description 1
- 241000607149 Salmonella sp. Species 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 238000010306 acid treatment Methods 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 230000031200 bile acid secretion Effects 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 210000002421 cell wall Anatomy 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000002158 endotoxin Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 208000001130 gallstones Diseases 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 229920006008 lipopolysaccharide Polymers 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000003032 molecular docking Methods 0.000 description 1
- 230000004660 morphological change Effects 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 230000009965 odorless effect Effects 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 239000013612 plasmid Substances 0.000 description 1
- 229920000656 polylysine Polymers 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 230000005180 public health Effects 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- -1 ursodeoxycholic acid compound Chemical class 0.000 description 1
Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/575—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/12—Cyclic peptides, e.g. bacitracins; Polymyxins; Gramicidins S, C; Tyrocidins A, B or C
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Oncology (AREA)
- Gastroenterology & Hepatology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Communicable Diseases (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
The invention relates to a new application of ursodeoxycholic acid, and discloses an application of ursodeoxycholic acid in preparing an MCR-3 enzyme inhibitor, comprising an application of ursodeoxycholic acid and polymyxin E in combination in preparing a medicament for resisting MCR-3 positive bacteria infection; use of ursodeoxycholic acid in combination with polymyxin E for the manufacture of a medicament for the treatment of a disease caused by infection with a MCR-3 salmonella, 15E464MCR-3 isolate. The invention provides a new medical application of ursodeoxycholic acid in preparing an MCR-3 enzyme inhibitor, and discloses that the ursodeoxycholic acid can inhibit the activity of MCR-3 enzyme and recover the bactericidal activity of polymyxin E on MCR-3 enterobacteria; the ursodeoxycholic acid combined polymyxin E has good treatment effect on infection caused by MCR-3 salmonella, and has wide medical application.
Description
Technical Field
The invention relates to a new application of ursodeoxycholic acid, in particular to an application of ursodeoxycholic acid in preparing an MCR-3 enzyme inhibitor.
Background
To date, variants of the MCR-3 gene have been identified in different bacterial species isolated from humans, foods, animals, farms and environments. 2015. The plasmid-mediated colistin resistance gene MCR-3 and MCR-1 have been found in china throughout the years by global spread of conjugation in bacteria.
Polymyxins are small lipid polypeptides of molecular weight 1200 Da with polycationic rings attached to hydrophobic fatty acids. Polymyxins, including colistin, are well-organized drugs and the incidence of multiple resistant gram-negative bacterial infections is increasing. The mechanism of colistin is mediated by binding to lipopolysaccharide of gram negative bacteria and subsequent breakdown of the membrane. Colistin (polymyxin E) is considered the last antibiotic in clinical use to treat gram-negative bacterial infections, and thus colistin-resistant enterobacteriaceae is a globally recognized important threat to public health. There is a need today to find a natural compound that can replace antibiotics.
Ursodeoxycholic acid, chemical name 3a,7β -dihydroxy-5β -cholestane-24-acid, is organic compound, odorless and bitter. The medicine is used for increasing bile acid secretion, changing bile components, reducing cholesterol and cholesterol fat in bile, and facilitating the gradual dissolution of cholesterol in gall-stone. However, the application of ursodeoxycholic acid in preparing the MCR-3 inhibitor is not disclosed at home and abroad up to now.
Disclosure of Invention
The invention aims to solve the defects in the prior art, and provides application of ursodeoxycholic acid in preparing an MCR-3 enzyme inhibitor.
In order to achieve the above purpose, the present invention adopts the following technical scheme:
use of ursodeoxycholic acid in preparing MCR-3 enzyme inhibitor is provided.
Preferably, the ursodeoxycholic acid and polymyxin E are combined for preparing the medicine for resisting MCR-3 positive bacteria infection;
the ursodeoxycholic acid and the polymyxin E can restore the bactericidal activity of the polymyxin E on MCR-3 salmonella, 15E464MCR-3 isolate after being combined.
Preferably, ursodeoxycholic acid is used in combination with polymyxin E for the preparation of a medicament for the treatment of diseases caused by infection with the MCR-3 salmonella, 15E464MCR-3 isolate.
Preferably, the ursodeoxycholic acid has the formula C 24 H 40 O 4 The molecular weight is 392.572.
The invention provides a new medical application of ursodeoxycholic acid in preparing an MCR-3 enzyme inhibitor, and discloses that the ursodeoxycholic acid can inhibit the activity of MCR-3 enzyme and recover the bactericidal activity of polymyxin E on MCR-3 enterobacteria; the ursodeoxycholic acid combined polymyxin E has good treatment effect on infection caused by MCR-3 salmonella, and has wide medical application.
Drawings
FIG. 1 shows the growth curve of ursodeoxycholic acid in combination with polymyxin E for the MCR-3 Salmonella, 15E464MCR-3 isolate;
FIG. 2 shows the growth curve of ursodeoxycholic acid in combination with polymyxin E on MCR-3 E.coli, KY924928MCR-3 isolate;
FIG. 3 is a time-sterilization curve of ursodeoxycholic acid in combination with polymyxin E for the MCR-3 Salmonella, 15E464MCR-3 isolate;
FIG. 4 is a scanning electron microscope image of E.coli treated with ursodeoxycholic acid and colistin;
FIG. 5 is a scanning electron microscope image of untreated E.coli.
Detailed Description
The following description of the embodiments of the present invention will be made clearly and completely with reference to the accompanying drawings, in which it is apparent that the embodiments described are only some embodiments of the present invention, but not all embodiments.
Test example 1
Minimum inhibitory concentration test:
antibacterial activity experiments of single use of ursodeoxycholic acid and polymyxin E and combined use of the ursodeoxycholic acid and polymyxin E against production of MCR-3 salmonella and 15E464MCR-3 isolate are carried out in a 96-well sterile microplate according to a chessboard method, MIC values of the two are determined to be used independently and jointly, and partial antibacterial concentration index (FIC) is calculated. FIC = MIC (polymyxin E combination)/MIC (polymyxin E alone) +mic (ursodeoxycholic acid combination)/MIC (ursodeoxycholic acid alone), and results of experiments on MIC and FIC values of MCR-3 positive bacterial isolates using polymyxin E in combination are shown in table 1:
TABLE 1
Conclusion: ursodeoxycholic acid alone has no antibacterial effect, and can reduce MIC value of Salmonella sp. Strain 15E464 (mcr-3) and E.coli trapinKY 924928 (mcr-3) by 16 times when being combined with polymyxin E, and FIC value indicates that the two have synergistic effect.
Test example 2
Growth curve test:
the MCR-3 salmonella, 15E464MCR-3 isolate was inoculated into LB liquid medium and cultured overnight (37 ℃,200 rpm), followed by 1:100 expansion to OD the next day 600nm About 0.3, and is divided into 5 conical flasks (20 ml/flask), and a group without adding medicine and a group treated with ursodeoxycholic acid with different concentrations are set. 37. Culture was continued at 200 rpm at C, and OD of each group of samples was measured and recorded every 1 hour 600nm Until the bacteria grew to the plateau, a growth curve was drawn (fig. 1).
Conclusion: in the culture period of 4h or 6h, ursodeoxycholic acid treatment group (32-256 μg/ml) grew to the plateau OD compared with the non-drug-treated group 600nm The values have no obvious difference, which indicates that the patchoulenone does not influence the normal growth of bacteria in the effective concentration range.
Inoculating MCR-3 Escherichia coli KY924928MCR-3 isolate into LB liquid medium, culturing overnight (37 deg.C, 200 rpm), and amplifying culture to OD 1:100 the next day 600nm About 0.3, and is divided into 5 conical flasks (20 ml/flask), and a group without adding medicine and a group treated with ursodeoxycholic acid with different concentrations are set. 37. Culture was continued at 200 rpm at C, and OD of each group of samples was measured and recorded every 1 hour 600nm Until the bacteria grew to the plateau, a growth curve was drawn (fig. 2).
Conclusion: in the culture period of 4 or 6 hours, ursodeoxycholic acid treated group (32-256 μg/ml) grew to the plateau OD compared with the untreated group 600nm The values have no obvious difference, which indicates that the patchoulenone does not influence the normal growth of bacteria in the effective concentration range.
Test example 3
Time-sterilization curve test:
cultures of Salmonella MCR-3, 15E464MCR-3 isolates overnight were adjusted to 1X 10 8 CFUs/mL, ready for use. Taking 4 groups (no-drug control group, 64 mug/mL) of ursodeoxycholic acid groups, 4 mug/mL of polymyxin E groups and polymyxin E groups combined with ursodeoxycholic acid) of sterile test tubes respectively, marking each group as 1, 3, 5, 7 and 9 hours, adding 1 mL autoclaved LB culture medium into all test tubes, adding 10 mug of adjusted bacterial liquid into each tube, and enabling the bacterial liquid concentration in each test tube to be 5 multiplied by 10 5 CFUs/mL. Wherein, the ursodeoxycholic acid group, the polymyxin E group and the polymyxin E group combined with ursodeoxycholic acid are respectively added with antibiotics and inhibitors with corresponding amounts, and bacterial liquid of the antibiotic-free control group is immediately subjected to plating count after uniform mixing to be used as the colony number of 0 h. Then, bacterial solutions in corresponding test tubes are respectively taken out every 1, 3, 5, 7 and 9h, counted by plating, and a time-sterilization curve is drawn (figure 3).
Conclusion: the combination of ursodeoxycholic acid and polymyxin E has remarkable sterilization effect and stable effect within 10 h compared with the no-drug control group, the ursodeoxycholic acid group and the polymyxin E group.
Test example 4
Scanning Electron Microscope (SEM) analysis:
coli E.coli strain Y924928 (mcr-3) cultured overnight was treated with a combination of ursodeoxycholic acid (64. Mu.g/mL) and colistin (4. Mu.g/mL) at 37℃for 4h-5h, washed, centrifuged and resuspended in PBS to obtain 0.5. 0.5 OD 600nm Is a bacterial sample of the subject. Samples were pre-incubated with fresh PBS buffer containing polylysine (1%) and then fixed in glutaraldehyde at 4 ℃ overnight. Morphological changes of the bacteria were observed by SEM (Hitachi S3400, tokyo, japan).
Conclusion: under the scanning electron microscope, the bacterial morphology was significantly changed compared with the blank group in FIG. 4, and the cell wall of E.coli strain Y924928 (mcr-3) was significantly contracted and spherical in shape, as shown in FIG. 5.
The invention relates to an application of ursodeoxycholic acid in preparing an MCR-3 enzyme inhibitor, wherein the ursodeoxycholic acid can recover the bactericidal activity of polymyxin on MCR-3 salmonella through a chessboard method and a time-bactericidal curve method, and the Root Mean Square Fluctuation (RMSF) of an MCR-3 ursodeoxycholic acid compound and pure protein MCR3 is calculated through molecular docking.
In the presence of ursodeoxycholic acid, the fluctuation of amino acid can be weakened to a certain extent, so that the ursodeoxycholic acid can be combined with antibiotics, the selectivity of medicines for super drug-resistant bacteria is increased, the dosage of polymyxin is reduced, and the important significance of restoring the sensitivity of polymyxin to gram-negative bacteria is realized
The invention provides a new medical application of ursodeoxycholic acid in preparing an MCR-3 enzyme inhibitor, and discloses that the ursodeoxycholic acid can inhibit the activity of MCR-3 enzyme and recover the bactericidal activity of polymyxin E on MCR-3 enterobacteria; the ursodeoxycholic acid combined polymyxin E has good treatment effect on infection caused by MCR-3 salmonella, and has wide medical application.
The foregoing is only a preferred embodiment of the present invention, but the scope of the present invention is not limited thereto, and any person skilled in the art, who is within the scope of the present invention, should make equivalent substitutions or modifications according to the technical scheme of the present invention and the inventive concept thereof, and should be covered by the scope of the present invention.
Claims (1)
1. Application of ursodeoxycholic acid and polymyxin E in preparing medicine for resisting MCR-3 positive bacteria infection;
the ursodeoxycholic acid and the polymyxin E can recover the bactericidal activity of the polymyxin E on the MCR-3 salmonella 15E464MCR-3 isolate after being combined;
the concentration of ursodeoxychol is 64 mug/mL, and the concentration of polymyxin E is 4 mug/mL.
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| CN103857440A (en) * | 2011-06-22 | 2014-06-11 | 维奥姆生物科学有限公司 | Conjugate-based antifungal and antibacterial prodrugs |
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| DK1158989T3 (en) * | 1999-03-09 | 2007-10-22 | Anker Stefan | Use of inhibitors of endotoxin for the treatment of cachexia |
| US20120082659A1 (en) * | 2007-10-02 | 2012-04-05 | Hartmut Land | Methods And Compositions Related To Synergistic Responses To Oncogenic Mutations |
| KR101814895B1 (en) * | 2013-06-04 | 2018-01-04 | 바이옴 바이오사이언스 피브이티. 엘티디. | Coated particles and compositions comprising same |
| EP2923710A1 (en) * | 2014-03-27 | 2015-09-30 | Universitätsklinikum Heidelberg | Bacterial phospholipase inhibitors as modulator of colonic bacterial flora |
| JP2018535228A (en) * | 2015-11-25 | 2018-11-29 | ファイザー・インク | Therapeutic nanoparticles containing antibiotics and methods of making and using the same |
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| CN103857440A (en) * | 2011-06-22 | 2014-06-11 | 维奥姆生物科学有限公司 | Conjugate-based antifungal and antibacterial prodrugs |
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