CN116019793A - Medical application of phloretin in preparation of salmonella polyphosphate kinase inhibitor - Google Patents
Medical application of phloretin in preparation of salmonella polyphosphate kinase inhibitor Download PDFInfo
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- CN116019793A CN116019793A CN202310134537.6A CN202310134537A CN116019793A CN 116019793 A CN116019793 A CN 116019793A CN 202310134537 A CN202310134537 A CN 202310134537A CN 116019793 A CN116019793 A CN 116019793A
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- salmonella
- phloretin
- ppk
- polyphosphate kinase
- inhibitor
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- VGEREEWJJVICBM-UHFFFAOYSA-N phloretin Chemical compound C1=CC(O)=CC=C1CCC(=O)C1=C(O)C=C(O)C=C1O VGEREEWJJVICBM-UHFFFAOYSA-N 0.000 title claims abstract description 61
- 241000607142 Salmonella Species 0.000 title claims abstract description 39
- ZWTDXYUDJYDHJR-UHFFFAOYSA-N (E)-1-(2,4-dihydroxyphenyl)-3-(2,4-dihydroxyphenyl)-2-propen-1-one Natural products OC1=CC(O)=CC=C1C=CC(=O)C1=CC=C(O)C=C1O ZWTDXYUDJYDHJR-UHFFFAOYSA-N 0.000 title claims abstract description 31
- YQHMWTPYORBCMF-UHFFFAOYSA-N Naringenin chalcone Natural products C1=CC(O)=CC=C1C=CC(=O)C1=C(O)C=C(O)C=C1O YQHMWTPYORBCMF-UHFFFAOYSA-N 0.000 title claims abstract description 31
- 229940122465 Polyphosphate kinase inhibitor Drugs 0.000 title claims abstract description 5
- 238000002360 preparation method Methods 0.000 title abstract description 4
- 230000005764 inhibitory process Effects 0.000 claims abstract description 7
- 108020000161 polyphosphate kinase Proteins 0.000 claims abstract description 7
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- 230000002401 inhibitory effect Effects 0.000 claims abstract description 5
- 230000008827 biological function Effects 0.000 claims 1
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- 239000003112 inhibitor Substances 0.000 abstract description 9
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- 239000008272 agar Substances 0.000 abstract description 6
- 230000002265 prevention Effects 0.000 abstract description 4
- 206010039438 Salmonella Infections Diseases 0.000 abstract description 3
- 229940079593 drug Drugs 0.000 abstract description 3
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- 235000013399 edible fruits Nutrition 0.000 description 2
- -1 flavonoid compound Chemical class 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 239000001205 polyphosphate Substances 0.000 description 2
- 235000011176 polyphosphates Nutrition 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- FWBHETKCLVMNFS-UHFFFAOYSA-N 4',6-Diamino-2-phenylindol Chemical compound C1=CC(C(=N)N)=CC=C1C1=CC2=CC=C(C(N)=N)C=C2N1 FWBHETKCLVMNFS-UHFFFAOYSA-N 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
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- 208000005577 Gastroenteritis Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 239000006137 Luria-Bertani broth Substances 0.000 description 1
- 229940126902 Phlorizin Drugs 0.000 description 1
- 229920000037 Polyproline Polymers 0.000 description 1
- 241000220324 Pyrus Species 0.000 description 1
- 241000293869 Salmonella enterica subsp. enterica serovar Typhimurium Species 0.000 description 1
- 206010040047 Sepsis Diseases 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
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- 235000021016 apples Nutrition 0.000 description 1
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- 238000012258 culturing Methods 0.000 description 1
- QGGZBXOADPVUPN-UHFFFAOYSA-N dihydrochalcone Chemical group C=1C=CC=CC=1C(=O)CCC1=CC=CC=C1 QGGZBXOADPVUPN-UHFFFAOYSA-N 0.000 description 1
- 238000003113 dilution method Methods 0.000 description 1
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- 230000029578 entry into host Effects 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 229930003935 flavonoid Natural products 0.000 description 1
- 235000017173 flavonoids Nutrition 0.000 description 1
- 229930182470 glycoside Natural products 0.000 description 1
- 150000002338 glycosides Chemical class 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 244000144972 livestock Species 0.000 description 1
- 238000000034 method Methods 0.000 description 1
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- 230000007918 pathogenicity Effects 0.000 description 1
- 235000021017 pears Nutrition 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- IOUVKUPGCMBWBT-UHFFFAOYSA-N phloridzosid Natural products OC1C(O)C(O)C(CO)OC1OC1=CC(O)=CC(O)=C1C(=O)CCC1=CC=C(O)C=C1 IOUVKUPGCMBWBT-UHFFFAOYSA-N 0.000 description 1
- IOUVKUPGCMBWBT-GHRYLNIYSA-N phlorizin Chemical compound O[C@@H]1[C@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=CC(O)=C1C(=O)CCC1=CC=C(O)C=C1 IOUVKUPGCMBWBT-GHRYLNIYSA-N 0.000 description 1
- 235000019139 phlorizin Nutrition 0.000 description 1
- 230000008092 positive effect Effects 0.000 description 1
- 244000144977 poultry Species 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 239000011535 reaction buffer Substances 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 208000013223 septicemia Diseases 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 235000015192 vegetable juice Nutrition 0.000 description 1
- 239000000304 virulence factor Substances 0.000 description 1
- 230000007923 virulence factor Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Images
Classifications
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- 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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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The salmonella polyphosphate kinase PPK is a potential target for developing salmonella infection anti-virus drugs, and the salmonella PPK inhibitor is researched and found to have important significance for prevention and control of salmonella. The invention relates to medical application of phloretin in preparation of salmonella polyphosphate kinase inhibitor, and verifies that phloretin can inhibit salmonella PPK enzyme activity through a minimum inhibitory concentration measurement test, a PPK enzyme activity inhibition test, a soft agar plate electrophoresis test and the like, so as to inhibit bacterial motility, thereby providing a new thought and a potential lead compound for research and development of salmonella polyphosphate kinase PPK inhibitor.
Description
Technical Field
The invention relates to medical application of phloretin in preparation of salmonella polyphosphate kinase (Polyphosphate kinase, PPK) inhibitors, and belongs to the technical field of medical pharmacy.
Background
Phloretin (phloretin), also known as triphenolacetone, is a flavonoid compound with a dihydrochalcone structure, and is widely distributed in different parts of plants at different stages mainly in the form of glycoside (phlorizin), and widely exists in fruit and various vegetable juices of apples, pears and the like, and especially the content of apple young fruits is most abundant. The research shows that phloretin has various pharmacological activities of antioxidation, anticancer, anti-inflammatory, prevention and treatment of cardiovascular diseases, and the like, and has the characteristics of safety, high efficiency, small toxic and side effects, and the like in clinical treatment.
Salmonella (Salmonella typhimurium) is an important food-borne pathogenic bacterium, and can infect people and animals through various transmission modes such as livestock and poultry, excrement, eggs, polluted water sources and the like, and cause septicemia, gastroenteritis and local tissue inflammation, thereby seriously threatening the health of people and animals. The pathogenicity of salmonella is closely related to various virulence factors, wherein Polyphosphate kinase (Polyphosphate kinase, PPK) can catalyze ATP to synthesize Polyphosphate (polyP), and plays an important role in the pathogenic process of salmonella, such as participation in and regulation of bacterial biofilm formation, bacterial motility and antibiotic sensitivity, adhesion and invasion of host cells, and adaptability to environmental pressure. Therefore, salmonella PPK is a potential target for salmonella infection anti-virulence drug development, and salmonella PPK inhibitors are explored and found to have important significance for prevention and control of salmonella. According to the invention, the phloretin can be used as a salmonella PPK inhibitor to obviously inhibit bacterial motility, so that a new thought and a lead compound are provided for prevention and control of salmonella.
Disclosure of Invention
The invention provides a medical application of phloretin in preparing salmonella PPK inhibitor, and provides a new research thought and candidate compound for preventing and treating salmonella infection.
The molecular structure of phloretin is as follows:
the phloretin provided by the invention has the following molecular formula: c (C) 15 H 14 O 5 Molecular weight: 274.27.
according to the invention, the phloretin can obviously inhibit the enzyme activity of salmonella PPK through a minimum inhibitory concentration measurement test, a PPK enzyme activity inhibition test, a soft agar plate electrophoresis test and the like, so that the bacterial motility is reduced, and the salmonella used in the test is SL1344.
The invention has the positive effects that:
provides a new medical application of phloretin in preparing salmonella PPK inhibitor, and discloses that phloretin can remarkably inhibit salmonella PPK enzyme activity.
Drawings
FIG. 1 shows the inhibition of salmonella PPK enzyme activity by phloretin of the present invention.
FIG. 2 is a graph showing the inhibition of sliding movement of Salmonella SL1344 by phloretin according to the invention.
Fig. 3 shows the measurement result of the sliding movement diameter of salmonella SL1344 by phloretin according to the present invention.
Detailed Description
The invention is further illustrated by the following examples, which are not intended to limit the invention in any way, and any modifications or alterations to the invention, which would be readily apparent to a person of ordinary skill in the art, without departing from the technical solutions of the invention, are intended to fall within the scope of the claims of the invention.
Example 1
Phloretin can be used as a salmonella PPK inhibitor for any carrier that is pharmaceutically acceptable.
Example 2
Phloretin can be used as a salmonella PPK inhibitor for preparing medicines for treating infectious diseases.
Test example 1
Determination of the minimum inhibitory concentration (Minimal inhibition concentration, MIC) value of phloretin for Salmonella SL1344
Determination of phloretin versus Salmonella according to the minimum inhibitory concentration value determination test Standard dilution method published by the American clinical and laboratory standards AssociationMIC values for SL1344. The phloretin compound was diluted in a sterile 96-well plate using LB broth-fold ratio to a final concentration of 1024. Mu.g/mL, 512. Mu.g/mL, 256. Mu.g/mL, 128. Mu.g/mL, 64. Mu.g/mL, 32. Mu.g/mL, 16. Mu.g/mL, 8. Mu.g/mL, 4. Mu.g/mL, while inoculating overnight-cultured Salmonella SL1344 (the amount of the strain was adjusted to 5X 10) 5 CFU/mL). Shaking and mixing uniformly, placing in a constant temperature incubator at 37 ℃ for culturing for 20-24 hours, and observing the growth condition of bacteria. The concentration of the compound that inhibits bacterial growth that is visible to the naked eye is determined as the MIC value of the compound for salmonella.
Conclusion: the MIC value of phloretin on salmonella is greater than 1024 mug/mL.
Test example 2
PPK enzyme Activity inhibition assay
1 μg PPK protein and phloretin (0 μg/mL,8 μg/mL,16 μg/mL,32 μg/mL) at various concentrations were added to reaction buffer (50 mM hepes, pH=7.5, 50mM (NH) 4 ) 2 SO 4 ,5mM MgCl 2 ) Incubation was performed at room temperature for 20min, then 1mM ATP and 40. Mu.M DAPI were added, shaking and mixing were performed, and incubation was performed in the dark for 15min, and the fluorescence intensity at 430/550 (excitation/emission) wavelength was measured to evaluate the effect of the drug on PPK enzyme activity.
Conclusion: treatment with phloretin (8-32 μg/mL) at various concentrations significantly inhibited Salmonella PPK enzyme activity (see FIG. 1).
Test example 3
Soft agar plate sliding motion test
Salmonella SL1344 cultured overnight was used to adjust the bacterial concentration to OD using LB broth 600nm =0.5, and a 0.3% soft agar semisolid plate was prepared, 5uL of bacteria was pipetted into the center of the soft agar plate with or without phloretin treatment, and incubated overnight in a constant temperature incubator (37 ℃), and the size of bacterial chemotactic ring was observed and measured by photographing. The larger the chemotactic circle, the stronger the bacterial movement ability is indicated; and conversely, the weaker the exercise capacity is.
Conclusion: treatment with different concentrations of phloretin (4-32 μg/mL) significantly inhibited Salmonella motility on 0.3% soft agar solid plates (see FIGS. 2-3) compared to the control (no phloretin treatment added).
Claims (3)
1. The medical application of phloretin in preparing salmonella polyphosphate kinase inhibitor.
2. The use according to claim 1, wherein the medical use is the inhibition of the biological function of salmonella polyphosphate kinase by phloretin.
3. The use of claim 1, wherein the salmonella polyphosphate kinase inhibitor is effective in inhibiting salmonella motility.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202310134537.6A CN116019793A (en) | 2023-02-20 | 2023-02-20 | Medical application of phloretin in preparation of salmonella polyphosphate kinase inhibitor |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202310134537.6A CN116019793A (en) | 2023-02-20 | 2023-02-20 | Medical application of phloretin in preparation of salmonella polyphosphate kinase inhibitor |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN116019793A true CN116019793A (en) | 2023-04-28 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202310134537.6A Pending CN116019793A (en) | 2023-02-20 | 2023-02-20 | Medical application of phloretin in preparation of salmonella polyphosphate kinase inhibitor |
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| Country | Link |
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| CN (1) | CN116019793A (en) |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103156837A (en) * | 2013-03-27 | 2013-06-19 | 许翔 | Application of flavonoid in pharmacy |
| CN108358769A (en) * | 2018-04-23 | 2018-08-03 | 湖北尧生物科技有限公司 | A kind of method that phloretin is prepared by phloridzin hydrolysis in diphasic system |
| US20190307818A1 (en) * | 2016-04-08 | 2019-10-10 | The Trustees Of Princeton University | Novel antimicrobial compositions and methods of use |
-
2023
- 2023-02-20 CN CN202310134537.6A patent/CN116019793A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103156837A (en) * | 2013-03-27 | 2013-06-19 | 许翔 | Application of flavonoid in pharmacy |
| US20190307818A1 (en) * | 2016-04-08 | 2019-10-10 | The Trustees Of Princeton University | Novel antimicrobial compositions and methods of use |
| CN108358769A (en) * | 2018-04-23 | 2018-08-03 | 湖北尧生物科技有限公司 | A kind of method that phloretin is prepared by phloridzin hydrolysis in diphasic system |
Non-Patent Citations (4)
| Title |
|---|
| DAVIDE BARRECA等: "Biochemical and antimicrobial activity of phloretin and its glycosilated derivatives present in apple and kumquat", FOOD CHEMISTRY, vol. 160, pages 292 - 297, XP028660400, DOI: 10.1016/j.foodchem.2014.03.118 * |
| KARTIK T. NAKHATE等: "Therapeutic Potential and Pharmaceutical Development of a Multitargeted Flavonoid Phloretin", NUTRIENTS, vol. 14, no. 17, pages 3638 * |
| WU SHUAI-CHENG等: "Subinhibitory concentrations of phloretin repress the virulence of Salmonella typhimurium and protect against Salmonella typhimurium infection", ANTONIE VAN LEEUWENHOEK, vol. 109, pages 1503 - 1512 * |
| ZECAI ZHANG等: "Phloretin is protective in a murine salmonella enterica serovar typhimurium infection model", MICROBIAL PATHOGENESIS, vol. 161, pages 1 - 8 * |
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