CN110950893A - Multifunctional fluorescent probe and preparation method and application thereof - Google Patents
Multifunctional fluorescent probe and preparation method and application thereof Download PDFInfo
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- CN110950893A CN110950893A CN201911226167.9A CN201911226167A CN110950893A CN 110950893 A CN110950893 A CN 110950893A CN 201911226167 A CN201911226167 A CN 201911226167A CN 110950893 A CN110950893 A CN 110950893A
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- lactamase
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- 238000002360 preparation method Methods 0.000 title claims abstract description 8
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- 239000003781 beta lactamase inhibitor Substances 0.000 claims abstract description 10
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- 229940126085 β‑Lactamase Inhibitor Drugs 0.000 claims abstract description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 27
- 238000006243 chemical reaction Methods 0.000 claims description 20
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- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 14
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- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 4
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- C07D501/14—Compounds having a nitrogen atom directly attached in position 7
- C07D501/16—Compounds having a nitrogen atom directly attached in position 7 with a double bond between positions 2 and 3
- C07D501/20—7-Acylaminocephalosporanic or substituted 7-acylaminocephalosporanic acids in which the acyl radicals are derived from carboxylic acids
- C07D501/57—7-Acylaminocephalosporanic or substituted 7-acylaminocephalosporanic acids in which the acyl radicals are derived from carboxylic acids with a further substituent in position 7, e.g. cephamycines
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- A61K31/542—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame ortho- or peri-condensed with heterocyclic ring systems
- A61K31/545—Compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins, cefaclor, or cephalexine
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Abstract
The invention relates to the technical field of specific molecular recognition materials, in particular to a multifunctional fluorescent probe which can detect AmpC β -lactamase, screen AmpC β -lactamase inhibitor and screen bacterial strain drug resistance, a preparation method and application thereof.
Description
Technical Field
The invention relates to the technical field of specific molecular recognition materials, in particular to a multifunctional fluorescent probe which can detect AmpC β -lactamase, screen AmpC β -lactamase inhibitor and screen drug resistance of a strain, and a preparation method and application of the multifunctional fluorescent probe.
Background
In 1940, β -lactam antibiotics were used for the first time to treat bacterial infection, because of its good therapeutic effect in treating infectious diseases, and then widely used, in recent 20 years, due to abuse and misuse of antibiotics, some bacteria have drug resistance to antibiotics, which causes poor therapeutic effect and endangers human health, research has found that a main reason why pathogenic bacteria have drug resistance is because bacteria produce a plurality of β -lactamase enzymes that can efficiently hydrolyze β -lactam antibiotics and inactivate them, if β -lactamase species produced by bacteria can be specifically detected, antibiotics that can be hydrolyzed by such enzymes can be avoided, other suitable antibiotics can be selected, or more accurate treatment can be achieved by using a combined enzyme inhibitor-antibiotic treatment method.
β -lactamases are classified into four classes A, B, C, D according to the Ambler classification, of which class A and class C are the two most important classes.recognition of class A β -lactamases has been reported, but there have been few studies on specific detection of class C β -lactamases, and the most common class C β -lactamase, AmpC β -lactamase, is the β -lactamase with the highest activity of the hydrolyzed β -lactam antibiotic.
On the other hand, because the phenomenon of drug resistance of bacteria is more and more common, and a plurality of antibiotics can not exert good treatment effect when being used independently, the treatment of patients can well ensure the treatment effect by adopting an antibiotic-inhibitor combination mode.
Therefore, the fluorescent probe is expected to have two functions of detecting AmpC β -lactamase and screening AmpC β -lactamase inhibitor, and can well guide the development and clinical medication of new drugs.
Disclosure of Invention
In order to solve the defects and shortcomings of the prior art, the invention provides the multifunctional fluorescent probe which can detect AmpC β -lactamase and screen AmpC β -lactamase inhibitor, can be used for screening the drug resistance of a strain and can identify the drug resistance mechanism of bacteria.
In another aspect of the present invention, a method for preparing the multifunctional fluorescent probe is provided.
In another aspect of the invention, the multifunctional fluorescent probe is applied to detection of AmpC β -lactamase, screening of AmpC β -lactamase inhibitor, preparation of antibacterial drugs and identification of bacterial drug resistance mechanism.
In order to achieve the purpose, the invention adopts the following technical scheme.
In a first aspect of the present invention, there is provided a multifunctional fluorescent probe, having a structural formula:
in another aspect of the present invention, there is provided a method for preparing the multifunctional fluorescent probe, comprising the steps of:
s1, reacting the compound 1 with NaI in a hydrophilic organic solvent, removing the hydrophilic organic solvent after the reaction is finished, adding a lipophilic organic solvent for dissolving, washing and drying an organic phase, adding triphenylphosphine for reacting, and separating a product after the reaction is finished to obtain an intermediate 2.
Preferably, the molar ratio of the compound 1 to the NaI to the triphenylphosphine is 1: 4-5: 1-1.5.
More preferably, the molar ratio of the compound 1, NaI and triphenylphosphine is 1: 4.4: 1.2.
Preferably, the reaction temperature in step S1 is 10-35 ℃.
S2, dissolving the intermediate 2 in a lipophilic organic solvent, adding an aqueous solution of NaOH to react, removing a water phase after the reaction is finished, drying an organic phase, adding the compound 3 to react, and separating a product after the reaction is finished to obtain an intermediate 4.
Preferably, the feeding molar ratio of the intermediate 2, NaOH and the compound 3 is 1 to (8-10) to (0.6-0.9).
More preferably, the molar ratio of the intermediate 2, NaOH and compound 3 is 1: 9: 0.7.
Preferably, the concentration of the aqueous NaOH solution is 1 mol/L.
Preferably, the reaction temperature in step S2 is 10-35 ℃.
S3, adding the intermediate 4, anisole and trifluoroacetic acid into a lipophilic organic solvent, and separating a product after the reaction is finished to obtain the multifunctional fluorescent probe.
Preferably, the feeding molar ratio of the intermediate 4, the anisole and the trifluoroacetic acid is 1: (10-15): (80-100).
More preferably, the molar ratio of intermediate 4, anisole and trifluoroacetic acid is 1: 12.3: 89.7.
Preferably, the reaction temperature in step S3 is 0 ℃.
The structural formulas of the compound 1, the intermediate 2, the compound 3 and the intermediate 4 are as follows.
The structural formula of compound 1 is:
the structural formula of the intermediate 2 is as follows:
the structural formula of compound 3 is:
the structural formula of the intermediate 4 is as follows:
in still another aspect of the present invention, there is provided a use of the multifunctional fluorescent probe described above.
The multifunctional fluorescent probe is used for detecting AmpC β -lactamase.
The multifunctional fluorescent probe is used for screening AmpC β -lactamase inhibitor.
The multifunctional fluorescent probe is applied to preparing antibacterial drugs.
Preferably, the bacteriostatic drug is a drug for inhibiting staphylococcus aureus.
The multifunctional fluorescent probe is applied to identifying a bacterial drug resistance mechanism.
Compared with the prior art, the invention has the beneficial effects that:
the invention synthesizes the multifunctional fluorescent probe which can detect AmpC β -lactamase and screen AmpC β -lactamase inhibitor and can be used for screening the drug resistance of bacterial strains by the compound 1 through three steps, has less synthesis steps, simple post-treatment process, easy operation and easy obtaining of products, is designed and modified based on cephalosporin nucleus, has high sensitivity, good specificity and better bacteriostatic effect, can be simultaneously used for detecting AmpC β -lactamase and screening AmpC β -lactamase inhibitor, and can detect the drug resistance of bacteria and identify the drug resistance mechanism of bacteria on the bacterial level.
Drawings
FIG. 1 is a synthetic scheme of the multifunctional fluorescent probe of example 1;
FIG. 2 shows a multi-functional fluorescent probe according to the present invention1H-NMR spectrum;
FIG. 3 shows a multi-functional fluorescent probe according to the present invention13A C-NMR spectrum;
FIG. 4a is a graph of the intensity of UV absorption of a multifunctional fluorescent probe of the present invention after mixing with 100U/mL AmpC β -lactamase over time (10 min);
FIG. 4b is a graph of fluorescence intensity over time (10min) for multifunctional fluorescent probes of the present invention after mixing with 100U/mL AmpC β -lactamase;
FIG. 5 is a graph showing the inhibitory effect of two inhibitors, sulbactam sodium and tazobactam acid, on AmpC β -lactamase when the multifunctional fluorescent probe of the present invention is used as a substrate;
FIG. 6a is a bacteriostatic circle diagram obtained by the interaction of the multifunctional fluorescent probe (2), oxacillin sodium (1), compound 1(3), cefazolin sodium (4), solvent (5, blank group) and Staphylococcus aureus ATCC 25923;
FIG. 6b is a bacteriostatic circle diagram obtained by the interaction of the multifunctional fluorescent probe (2), oxacillin sodium (1), compound 1(3), cefazolin sodium (4), solvent (5, blank group) and Staphylococcus aureus ATCC 29213;
FIG. 6c is a bacteriostatic circle diagram obtained by the interaction of the multifunctional fluorescent probe (2), oxacillin sodium (1), compound 1(3), cefazolin sodium (4), solvent (5, blank group) and Staphylococcus aureus ATCC 43300.
FIG. 6d is a bacteriostatic circle diagram obtained by the interaction of the multifunctional fluorescent probe (2), oxacillin sodium (1), compound 1(3), cefazolin sodium (4), solvent (5, blank group) and Enterobacter cloacae ATCC 13047.
FIG. 7 is a graph showing the change of fluorescence intensity with time (10min) after mixing the multifunctional fluorescent probe of the present invention with 4 kinds of bacteria (Staphylococcus aureus ATCC 25923, ATCC29213, ATCC 43300, and Enterobacter cloacae ATCC 13047).
Detailed Description
In order to more fully understand the technical contents of the present invention, the technical solutions of the present invention will be further described and illustrated with reference to the following specific embodiments.
In addition to the reaction conditions selected for the synthesis process shown in the examples (e.g., charge ratios between reactants, reaction temperatures, etc.), in other embodiments, the molar ratio of compound 1, NaI, triphenylphosphine in the synthesis of intermediate 2 may be in the range of 1: (4-5): (1-1.5), and the reaction temperature may be in the range of 10-35 ℃; when the intermediate 4 is synthesized, the feeding molar ratio of the intermediate 2, NaOH and the compound 3 can be in the range of 1 to (8-10) to (0.6-0.9), and the reaction temperature can be in the range of 10-35 ℃; when the multifunctional fluorescent probe CDC-559 is synthesized, the feeding molar ratio of the intermediate 4, the anisole and the trifluoroacetic acid can be in the range of 1: 10-15: 80-100. Examples are provided to further illustrate the technical content of the present invention so that the reader can easily understand that the embodiments of the present invention are not limited to the following examples.
For parameters not particularly noted, it can be carried out with reference to conventional techniques. The nuclear magnetic spectrum is measured by AVANCE II 400M/600M nuclear magnetic resonance instrument of Bruker company, Germany, and deuterated chloroform and deuterated DMSO are used as solvents. The ultraviolet spectrum was measured by using a UV-Vis 2450 ultraviolet spectrometer manufactured by SHIMADZU, Japan. Fluorescence Spectroscopy and semi-Inhibitory Concentration (IC)50) The measurement was carried out using EnSpire-2300 multi-functional microplate reader Perkinelmer, USA.
Examples
This example provides a multifunctional fluorescent probe and a method for synthesizing the multifunctional fluorescent probe, wherein the synthetic route is shown in FIG. 1, and CDC-559 is a target fluorescent compound, i.e., a multifunctional fluorescent probe. The specific synthesis steps are as follows:
1. synthesis of intermediate 2
Compound 1(3.0g, 6.1mmol) was dissolved in acetone (40mL), NaI (4.0g, 26.7mmol) was added, stirred at room temperature for 1h and then spun dry, dissolved in 100mL ethyl acetate, the organic phase was taken up with 10% Na in turn2S2O3(50 mL. times.1), water (50 mL. times.1) and saturated saline (50 mL. times.1),anhydrous MgSO (MgSO)4After drying, the organic phase was concentrated to 40mL and triphenylphosphine (1.9g, 7.2mmol) was added rapidly under nitrogen and reacted overnight at room temperature (25 ℃ C.) in the absence of light. The reaction solution was suction-filtered, and the obtained solid was washed with n-hexane to give 4.0g of a yellow solid, with a yield of 77%.
2. Synthesis of intermediate 4
Intermediate 2(4.0g) was dissolved in dichloromethane, 43mL of 1mol/L NaOH solution was added, the mixture was stirred vigorously at room temperature (25 ℃) for 30min, the organic phase was separated, and anhydrous MgSO4Drying, filtration and then addition of compound 3(0.8g, 3.3mmol) stirring at room temperature for 6 h. After spin-drying, column chromatography was performed to obtain 620mg of a red solid, the yield was 28%.
The data of nuclear magnetic hydrogen spectrum and nuclear magnetic carbon spectrum of the intermediate 4 are as follows:
1H NMR(400MHz，CDCl3)δ7.74(d，J＝16.5Hz，1H)，7.58(s，1H)，7.40-7.21(m，8H)，6.91-6.83(m，3H)，6.57(d，J＝8.6Hz，1H)，6.43-6.38(m，2H)，5.81(dd，J＝9.1，4.8Hz，1H)，5.25(q，J＝12.1Hz，2H)，4.96(d，J＝4.7Hz，1H)，3.78(s，3H)，3.66(m，2H)，3.65(d，J＝2.8Hz，2H)，3.42(q，J＝6.9Hz，4H)，1.22(t，J＝6.9Hz，6H).
13C NMR(101MHz，CDCl3)δ171.20，164.67，162.05，161.56，159.85，155.96，150.89，137.77，133.86，130.69，129.45，129.38，129.13，128.57，127.66，127.08，126.61，123.70，123.18，116.69，114.01，109.29，108.92，97.12，67.87，59.17，57.90，55.26，44.92，43.35，24.52，12.53.
HRMS(ESI，m/z)Calcd.for C38H37N3O7S 679.2352；found：702.2254[M+Na]+(Calcd.702.2352).
3. synthesis of multifunctional fluorescent probe CDC-559
Intermediate 4(100mg, 0.15mmol) was dissolved in dichloromethane (5mL), cooled to 0 deg.C, and then anisole (200. mu.L) and trifluoroacetic acid (1mL) were added, and the reaction was continued at this temperature for 1 h. After completion of the reaction, the solvent was dried by spinning, 1mL of diethyl ether was added, and the precipitated solid was filtered and washed with diethyl ether (1 mL. times.3) to obtain 24mg of a red solid with a yield of 30%. The nuclear magnetic hydrogen spectrum and nuclear magnetic carbon spectrum of the obtained product are respectively shown in FIG. 2 and FIG. 3.
The nuclear magnetic hydrogen spectrum, nuclear magnetic carbon spectrum and mass spectrum data of the product are as follows:
1H NMR(600MHz，DMSO-d6)δ9.09(d，J＝8.2Hz，1H)，7.76(s，1H)，7.68(d，J＝16.6Hz，1H)，7.47(d，J＝8.7Hz，1H)，7.27(m，6H)，6.70(d，J＝8.3Hz，1H)，6.53(s，1H)，6.43(d，J＝16.6Hz，1H)，5.48(dd，J＝7.6，4.8Hz，1H)，5.00(d，J＝4.3Hz，1H)，3.65-3.49(m，4H)，3.43(q，J＝6.9Hz，4H)，1.13(t，J＝6.6Hz，6H).
13C NMR(151MHz，DMSO)δ171.44，164.85，163.85，160.36，155.84，151.15，141.18，136.31，130.18，129.50，128.70，126.97，125.64，125.47，125.39，116.20，109.92，108.81，96.69，65.39，59.72，58.38，44.64，42.07，31.16，23.93，15.64，12.84.
HRMS(ESI，m/z)calcd.for C30H29N3O6S+559.1777，found 582.1669(M+Na+)(Calcd.582.1777).
the multifunctional fluorescent compound CDC-559 prepared in the embodiment is used for respectively carrying out an in vitro response experiment on AmpC β -lactamase, a function verification experiment which can be used for screening AmpC β -lactamase, a bacteriostasis experiment and a test for identifying a bacterial drug resistance mechanism.
The experimental method comprises the steps of dissolving the compound CDC-559 in dimethyl sulfoxide to prepare 10mmol/L stock solution, diluting the stock solution with HEPES buffer solution to 10 mu mol/L solution to be detected, mixing the solution to be detected with 100U/mLAMPC β -lactamase, and then rapidly scanning with a fluorescence spectrophotometer (scanning 10 times, each time interval is 1 min).
The change of the ultraviolet absorbance and the relative fluorescence intensity of the compound CDC-559 and 100U/mL AmpC β -lactamase within 10min after mixing are shown in FIG. 4a and FIG. 4 b.
As can be seen from FIGS. 4a and 4b, after the compound CDC-559 was combined with AmpC β -lactamase, the maximum UV absorption was slightly reduced in intensity at 440nm, while the fluorescence intensity was rapidly reduced by 93% at 539 nm.
The experimental method comprises the steps of dissolving a compound CDC-559 in dimethyl sulfoxide to prepare 10mmol/L stock solution, diluting the stock solution into 15 mu mol/L to-be-detected solution by using HEPES buffer solution, dissolving sulbactam sodium and tazobactam acid in distilled water to prepare 10mmol/L stock solution, diluting the stock solution into different concentrations by using HEPES, mixing 62.5U/mL AmpC β -lactamase with sulbactam sodium or tazobactam acid with different concentrations, standing the mixture at room temperature for 10min, adding the compound CDC-559, and rapidly detecting the mixture by using a microplate reader.
The inhibitory effects of two inhibitors (sulbactam sodium and tazobactam acid) on AmpC-lactamase when compound CDC-559 was used as a substrate are shown in fig. 5.
As can be seen from FIG. 5, both sulbactam sodium and tazobactam acid had a very good inhibitory effect on AmpC β -lactamase, and IC of both inhibitors was tested using compound CDC-559 as a substrate50Values are within the reported range in the literature, indicating that compound CDC-559 can be used to screen AmpC β -lactamase inhibitors.
The experimental method comprises the steps of preparing 1 mu g/mu L of solution from oxacillin sodium (1), CDC-559(2), compound 1(3), cefazolin sodium (4) and a solvent (5, blank group), dripping 1 mu L of solution on a paper sheet, then respectively placing the paper sheet on culture dishes paved with staphylococcus aureus ATCC 25923, ATCC29213 (sensitive bacteria), ATCC 43300 (drug-resistant bacteria, wherein the drug-resistant mechanism is that the bacteria have genes expressing PBP2a protein) and Enterobacter cloacae ATCC13047 (drug-resistant bacteria, wherein the drug-resistant mechanism is that the bacteria can express AmpC β -lactamase in large quantity), placing the culture dishes in a 37 ℃ incubator for 18h, and observing and taking pictures.
The inhibition zones obtained by culturing the 5 samples on 3 staphylococcus aureus are shown in fig. 6a, fig. 6b and fig. 6c, and the inhibition zone obtained by culturing on enterobacter cloacae is shown in fig. 6 d.
As can be seen from FIGS. 6a-d, Staphylococcus aureus ATCC 25923 and ATCC29213 are sensitive to oxacillin sodium and cefazolin sodium, while Staphylococcus aureus ATCC 43300 and Enterobacter cloacae ATCC13047 are resistant to oxacillin sodium and cefazolin sodium, indicating that the test system meets the requirements. When the compound CDC-559 acts on sensitive bacteria ATCC 25923 and ATCC29213, compared with the cephalosporin nucleus (compound 1) before modification, the compound CDC-559 has a much larger antibacterial ring which is only a little smaller than the first generation antibiotic cefazolin sodium, which shows that the compound CDC-559 has better antibacterial activity; when the antibacterial activity of the compound CDC-559 is acted with drug-resistant bacteria ATCC 43300 and ATCC13047, no inhibition zone is generated, which is consistent with an expected result, and the compound CDC-559 is proved to be capable of detecting the drug resistance of bacteria on a bacterial level, and meanwhile, a thought is provided for developing a novel antibiotic later, and the compound CDC-559 can be applied to the preparation of antibacterial drugs.
The experimental method comprises the following steps: dissolving the compound CDC-559 in dimethyl sulfoxide to prepare a 10mmol/L stock solution. Will OD6000.5 of staphylococcus aureus ATCC 25923, ATCC29213 (sensitive bacteria), ATCC 43300 (drug-resistant bacteria, the drug-resistant mechanism is that bacteria carry genes for expressing PBP2a protein) and Enterobacter cloacae ATCC13047 (drug-resistant bacteria, the drug-resistant mechanism is that bacteria can express AmpC β -lactamase in large quantity) are subjected to ultrasonic disruption, 15 mu L of supernatant is taken to be mixed with the stock solution, the mixture is diluted by HEPES buffer solution to ensure that the initial concentration of the compound CDC-559 is 10 mu mol/L, and the mixture is quickly detected by a microplate reader after being mixed.
The change in fluorescence intensity within 10min after mixing of the compound CDC-559 with 4 bacteria (Staphylococcus aureus ATCC 25923, ATCC29213, ATCC 43300 and Enterobacter cloacae ATCC 13047) is shown in FIG. 7.
As can be seen from FIG. 7, Staphylococcus aureus ATCC 25923 and ATCC29213 have almost no influence on the fluorescence intensity of the compound CDC-559, Staphylococcus aureus ATCC 43300 slightly reduces the fluorescence intensity of the compound CDC-559, while the fluorescence intensity of the compound CDC-559 is reduced by 76% within 10 minutes under the action of Enterobacter cloacae ATCC13047, which indicates that the compound CDC-559 can distinguish not only bacterial sensitivity or drug resistance, but also even bacterial drug resistance mechanism.
The technical contents of the present invention are further illustrated by the examples, so as to facilitate the understanding of the reader, but the embodiments of the present invention are not limited thereto, and any technical extension or re-creation based on the present invention is protected by the present invention.
Claims (11)
1. A multifunctional fluorescent probe is characterized in that the structural formula of the multifunctional fluorescent probe is as follows:
2. the method for preparing the multifunctional fluorescent probe as claimed in claim 1, which comprises the following steps:
s1, reacting the compound 1 with NaI in a hydrophilic organic solvent, removing the hydrophilic organic solvent after the reaction is finished, adding a lipophilic organic solvent for dissolving, washing and drying an organic phase, adding triphenylphosphine for reacting, and separating a product after the reaction is finished to obtain an intermediate 2;
s2, dissolving the intermediate 2 in a lipophilic organic solvent, adding an aqueous solution of NaOH to react, removing a water phase after the reaction is finished, drying an organic phase, adding a compound 3 to react, and separating a product after the reaction is finished to obtain an intermediate 4;
s3, adding the intermediate 4, anisole and trifluoroacetic acid into a lipophilic organic solvent, and separating a product after the reaction to obtain the multifunctional fluorescent probe;
the structural formula of the compound 1 is as follows:
the structural formula of the intermediate 2 is as follows:
the structural formula of the compound 3 is as follows:
the structural formula of the intermediate 4 is as follows:
3. the method for preparing a multifunctional fluorescent probe according to claim 2, wherein in step S1, the molar ratio of the compound 1, NaI and triphenylphosphine is 1: 4-5: 1-1.5.
4. The method of claim 2, wherein the feeding molar ratio of the intermediate 2, NaOH and the compound 3 is 1: 8-10: 0.6-0.9 in step S2.
5. The method of claim 4, wherein the concentration of the aqueous solution of NaOH is 1mol/L in step S2.
6. The method for preparing a multifunctional fluorescent probe according to claim 2, wherein in step S3, the molar ratio of the intermediate 4, anisole and trifluoroacetic acid is 1: (10-15): (80-100).
7. The multifunctional fluorescent probe of claim 1 for detecting AmpC β -lactamase.
8. The multifunctional fluorescent probe of claim 1 for screening AmpC β -lactamase inhibitor.
9. The use of the multifunctional fluorescent probe of claim 1 in the preparation of a bacteriostatic drug.
10. The use of the multifunctional fluorescent probe of claim 9 in the preparation of a bacteriostatic drug, wherein the bacteriostatic drug is a drug that inhibits staphylococcus aureus.
11. Use of the multifunctional fluorescent probe of claim 1 for identifying a bacterial resistance mechanism.
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| CN115521324A (en) * | 2022-10-13 | 2022-12-27 | 山西医科大学 | Preparation of near-infrared fluorescent probe for detecting beta-lactamase in drug-resistant bacteria |
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| CN113912626A (en) * | 2021-08-24 | 2022-01-11 | 南开大学 | Broad spectrum resistant beta-lactam and cephalosporin antibiotics pathogen probe and synthetic method and application thereof |
| CN113912626B (en) * | 2021-08-24 | 2023-03-21 | 南开大学 | Broad spectrum resistant beta-lactam and cephalosporin antibiotics pathogen probe and synthetic method and application thereof |
| CN115521324A (en) * | 2022-10-13 | 2022-12-27 | 山西医科大学 | Preparation of near-infrared fluorescent probe for detecting beta-lactamase in drug-resistant bacteria |
| CN115521324B (en) * | 2022-10-13 | 2023-08-29 | 山西医科大学 | Preparation of near infrared fluorescent probe for detecting beta-lactamase in drug-resistant bacteria |
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