Xanthone derivative as well as antibacterial application and preparation method thereof

Abstract

The invention discloses a xanthone derivative as well as a preparation method and antibacterial application thereof. The structural general formula of the derivative is formula I, a biological activity experiment shows that the derivative has the advantages of relatively strong antibacterial activity, high water solubility, good druggability and the like, and can effectively remove biofilm virulence factors of gram-negative bacteria such as escherichia coli. Natural alpha-MG is used as an initial raw material, and is reduced or selectively etherified or esterified, or novel groups are symmetrically or asymmetrically introduced, so that the designed xanthone derivative is prepared. The preparation method is simple, short in route, clean in process and easy for large-scale industrialization.

Description

Technical Field

[0001] The present invention belongs to the field of biomedicine, and relates to a new xanthone siderophore derivative and an antibacterial application thereof, and specifically relates to a new natural xanthone derivative and an antibacterial application thereof. Background Art

[0002] The extensive application and irrational use of antibiotics in clinical and animal husbandry have caused bacterial multidrug resistance and posed a huge health threat to animals, especially the animal husbandry industry. At the same time, it has raised new issues for the construction of major animal disease prevention and control systems. According to statistics, two-thirds of microbial infections are currently caused by biofilm formation, which aggravates pathogenicity and enhances the drug resistance of pathogenic bacteria. Therefore, in response to the current severe situation of drug resistance and the challenges of infection and drug resistance caused by biofilms, it is urgent to develop new antimicrobial drugs and enhancers that reduce drug resistance caused by biofilms.

[0003] Mangosteen is a fruit in Southeast Asia, traditionally used as medicine. It mainly contains xanthone compounds, which have various biological activities in vivo and in vitro. α-Mangostin has the highest content in mangosteen and is recognized as a xanthone compound with strong pharmacological activities, including antibacterial, anti-inflammatory, antifungal, antioxidant, and antiallergic activities. The xanthone core structure of α-Mangostin has the characteristics of natural targeting of cell membranes, which has inspired many scientists to use it as a lead compound for structural modification. Based on the amphiphilic characteristics of antimicrobial peptidomimetics, nitrogen-containing side chains are introduced into the 3 and 6 hydroxyl groups of α-Mangostin to increase polarity. The charged N atom interacts electrostatically with the negative charge on the bacterial membrane. α-MG is lipophilic, which obtains stronger anti-Gram-positive bacteria than the lead compound, including methicillin-resistant Staphylococcus aureus (MRSA), and exhibits strong antibacterial activity (Design and synthesis of amphiphilic xanthone membrane-targeted antibacterial agents with improved membrane selectivity, Medicinal Chemistry, 2013, 56, 2359-2373). The inventor team once introduced simple sugars such as mannose on the 6-hydroxyl group of α-mangostin to solve the problem of poor water solubility of the lead compound, while improving the targeted antibacterial activity of α-mangostin sugar compounds (CN115260146B). However, there have been no reports on xanthone derivatives for pathogenic infections and antibiotic resistance caused by biofilm bacterial communities, and changes in membrane permeability such as cell membrane pore protein deletion and mutation. Moreover, the prior art shows that α-MG has relatively obvious hemolytic activity (Bioorg.Med.Chem.83(2023),117232). Summary of the invention

[0004] The purpose of the present invention is to overcome the shortcomings of the above-mentioned prior art, using xanthone α-MG as a lead compound, introducing a new group structure in a symmetrical or asymmetrical manner, rationally modifying the chemical space of xanthone α-MG, improving its water solubility and targeting, and obtaining a series of new xanthone derivatives. Specifically, using α-MG as a lead compound, focusing on C-1, C-3, and C-6 on the structure of xanthone α-MG, symmetrical and asymmetrical modifications, introducing hydroxime, catechol, hydroxy acid and other groups, synthesizing a series of α-MG derivatives, and screening for antibacterial activity and anti-biofilm activity to obtain xanthone derivatives with good anti-biofilm properties.

[0005] The present invention is achieved by the following technical scheme: a xanthone derivative described in general formula I, whose general structural formula is as shown in formula I,

[0006]

[0007] At least one of R1, R2, and R3 is -(CH2) n COOH, -(CH2) n CONHOH or The rest are H, n = 1, 2, 3, 4, 5 or 6. The preferred embodiment is: R1, R2 are -(CH2) n COOH, R3 is H[A]; or R1, R2 are -(CH2) n CONHOH, R3 is H[B]; or R1, R3 are H, R2 is -(CH2) n COOH[C]; or R1, R3 are H, R2 is -(CH2) n CONHOH[D]; or R1 is -(CH2) n COOH, R2, R3 are H[E]; or R1 is -(CH2) n CONHOH, R2, R3 are H[F]; or R1, R2, R3 are -(CH2) n COOH[G]; or R1, R2, R3 are -(CH2) n CONHOH[H]; or R1 is H, R2, R3 are -(CH2) n COOH[I]; or R1 is H, R2, R3 are -(CH2) n CONHOH[J]; or R1, R3 are -(CH2) n COOH, R2 is H[K]; or R1, R3 are -(CH2) n CONHOH, R2 is H[L]; or R1, R2 are R3 is H[M] wherein n is preferably 2, 4 or 6.

[0008] One of the particularly preferred xanthone derivatives is that wherein R1, R2 are -(CH2) n COOH, R3 is H, n = 2, 4 or 6. One of the particularly preferred xanthone derivatives is that in which R1, R3 are H, R2 is -(CH2) n COOH, n = 2, 4 or 6. One of the particularly preferred xanthone derivatives is that in which R1, R3 are H, R2 is -(CH2) n CONHOH, n = 2, 4 or 6. One of the particularly preferred xanthone derivatives is that in which R1, R2, R3 are -(CH2) n CONHOH, n = 2, 4 or 6. One of the particularly preferred xanthone derivatives is the one in which R1 is H, R2, R3 are -(CH2) n COOH, n=2, 4 or 6.

[0009] The xanthone α-MG derivatives of the present invention target the inhibition of cell wall biosynthesis, focus on their drug-like properties and reduce bacterial resistance, and target the specificity of bacterial iron carriers for iron ion uptake. By symmetrically or asymmetrically introducing simple targeted bacterial iron carrier fragments, the transport system is taken into the membrane, destroying the membrane structure of the microorganism, resulting in enhanced permeability and outflow of contents, thereby inhibiting the activity of Gram-positive bacteria or eliminating the formation of Gram-negative bacterial biofilm. Therefore, on the one hand, it can be used to resist Gram-positive bacteria including MRSA and eliminate Gram-negative bacteria such as pathogenic Escherichia coli; on the other hand, it can improve the sensitivity to clinical antibiotics such as penicillin and amoxicillin, has a synergistic effect, and is used as a sensitizer and synergist for clinical drug-resistant strains. It can be used in animal husbandry to reduce the use of antibiotics or even replace antibiotics.

[0010] The preparation method of the xanthone derivative of the present invention is as follows: using α-MG precursor as the starting material, a compound represented by structural formula I is obtained through different chemical reactions. The synthesis conditions are mild, the reaction reagents are readily available, the reaction route is short, it is environmentally friendly, and it is easy to mass produce. Specifically, the preparation route schematic diagram is as follows Figure 2 and Figure 3 As shown, the specific steps include:

[0011] S1: Under nitrogen protection, at 0°C, α-MG is dissolved in anhydrous acetone solvent, 1 to 8 times of different carbon long bromates are added, and the reaction is carried out at 50°C for 4 to 10 hours. After separating and purifying the intermediate, hydroxylamine or a strong base is added to obtain compound AL. The route diagram is shown in FIG. Figure 2 shown.

[0012] Preferably, the anhydrous ether reagent includes tetrahydrofuran and 1,4-dioxane, the anhydrous reagent used is acetone, the strong base used is sodium hydroxide or hydroxylamine, the molar ratio of the selected strong base to α-MG is 1 to 4:1, and the selected reaction temperature is 50-75°C.

[0013] S2: Under nitrogen protection, at 0°C, α-MG is dissolved in an anhydrous solvent, 2 to 10 times of inorganic base is added, and stirred at 70-120°C for several hours. After purification, hydrobromic acid is used to remove the methyl group on the o-dimethyl to obtain catechol, and compound M is obtained. The route diagram is shown in FIG. Figure 3 shown.

[0014] Preferably, the anhydrous solvent reagent includes N,N-dimethylformamide and acetonitrile, the selected base is triethylamine, potassium carbonate, etc., the molar ratio of α-MG, organic base and acylating agent is 1:3 to 12:2-6; the selected reaction temperature is 50-130°C. BRIEF DESCRIPTION OF THE DRAWINGS

[0015] Other features, objects and advantages of the present invention will become more apparent from the detailed description of non-limiting embodiments made with reference to the following drawings:

[0016] Figure 1 Schematic diagram of the structure of xanthone α-MG and its derivatives (i.e., compound AM);

[0017] Figure 2 is the synthetic route of compound AL;

[0018] Figure 3 is the synthetic route of compound M;

[0019] Figure 4 The results of hemolytic activity test of compounds A1 and A2;

[0020] Figure 5 The iron chelation test results of compound A1. DETAILED DESCRIPTION

[0021] The present invention is described in detail below with reference to the examples. The following examples are implemented on the premise of the technical solution of the present invention, using α-MG as a precursor, acetylation and substitution to prepare derivatives, and provide detailed implementation methods and specific operation processes, which will help those skilled in the art to further understand the present invention, but do not limit the invention in any form. It should be pointed out that for those of ordinary skill in the art, several adjustments and improvements can be made without departing from the concept of the present invention. These belong to the scope of protection of the present invention.

[0022] Examples 1-5 involve the synthesis of etherified α-MG derivatives at different positions. The reaction scheme is as follows: Figure 2.

[0023] Example 1 Synthesis of 3,6-etherified α-MG derivative (T1)

[0024] α-MG (1,1mmoL, 410mg) and anhydrous potassium carbonate (6mmoL, 828mg) were dissolved in 20mL DMF, heated to methyl bromoacetate under nitrogen protection, and reacted at 50°C overnight. After the reaction was completed, 100mL of ethyl acetate was added for dilution, and then 50mL of water was added for separation. The organic layer was washed with 100mL of water and 50mL of saturated brine successively, and the organic layer was dried over anhydrous sodium sulfate and dried under reduced pressure. The crude product was chromatographed on a 200-300 mesh silica gel column to obtain 402.5mg of a yellow solid compound with a yield of 75%. 1 H NMR (400MHz, CDCl3) δ14.10(s,1H),6.77(s,1H),6.32(s,1H),5.33(t,2H),4.36(s,2H),4 .10(s,2H),4.01(d,J=6Hz,2H),3.98–3.68(m,9H),3.40(d,2H),1.93(d,6H),1.88(s,6H). 13 CNMR (100MHz, CDCl3) δ182.11,169.31,169.00,163.33,161.11,157.45,155.43,155.11,144 .44,138.12,111.11,97.20,90.55,62.11,63.12,26.55,25.25,25.30,20.33,18.14,18.11.

[0025] Example 2 Synthesis of 3,6-acylated α-MG derivative (A1)

[0026] T1 (1,1 mmoL) and sodium hydroxide (6 mmoL, 828 mg) were dissolved in 20 mL of acetone and reacted at 50°C overnight. After the reaction was completed, 100 mL of ethyl acetate was added for dilution, and then 50 mL of dilute hydrochloric acid was added to separate the layers. The organic layer was washed with 100 mL of water and 50 mL of saturated brine successively, and the organic layer was dried over anhydrous sodium sulfate and dried under reduced pressure. The crude product was chromatographed on a 200-300 mesh silica gel column to obtain 402.5 mg of yellow solid compound A1, with a yield of 75%. 1H NMR (400MHz, CDCl3) δ13.42(s,1H),6.55(s,1H),6.12(s,1H),5.24(dt,J=21.1,7.0Hz,2H),4.76(s,2H),4.70 (s,2H),4.11(d,J=6.6Hz,2H),3.88–3.78(m,9H),3.39(d,J=7.2Hz,2H),1.82(d,J=16.7Hz,6H),1.67(s,6H). 13 C NMR (101MHz, CDCl3) δ181.90,168.51,168.14,161.34,160.24,155.98,154.79,154.76,144.18,137.96,131.86,131.7 1,122.97,122.05,112.17,98.94,89.15,65.38,65.24,61.02,52.46,52.30,26.16,25.85,25.79,21.47,18.14,17.75.

[0027] Example 3 Synthesis of 3,6-acylated α-MG derivative (B1)

[0028] T1 (1,1 mmol) and hydroxylamine were dissolved in 20 mL of acetone and reacted at 50°C overnight. After the reaction was completed, 100 mL of ethyl acetate was added for dilution, and then 50 mL of water was added for separation. The organic layer was washed with 100 mL of water and 50 mL of saturated brine successively, and the organic layer was dried over anhydrous sodium sulfate and dried under reduced pressure. The crude product was chromatographed on a 200-300 mesh silica gel column to obtain 402.5 mg of yellow solid compound B1 with a yield of 70%. 1 H NMR (400MHz, CDCl3) δ13.42(s,1H),6.55(s,1H),6.12(s,1H),5.24(dt,J=21.1,7.0Hz,2H),4.76(s,2H),4.70 (s,2H),4.11(d,J=6.6Hz,2H),3.88–3.78(m,9H),3.39(d,J=7.2Hz,2H),1.82(d,J=16.7Hz,6H),1.67(s,6H). 13C NMR (101MHz, CDCl3) δ181.90,168.51,168.14,161.34,160.24,155.98,154.79,154.76,144.18,137.96,131.86,131.7 1,122.97,122.05,112.17,98.94,89.15,65.38,65.24,61.02,52.46,52.30,26.16,25.85,25.79,21.47,18.14,17.75.

[0029] Example 4 Synthesis of α-MG derivatives (T2-T18)

[0030] The synthesis method of α-MG derivatives (T2-T18) is similar to that of T1. α-MG (1,1mmoL, 410mg) and anhydrous potassium carbonate (6mmoL, 828mg) are dissolved in 20mL acetone, heated to methyl bromate under nitrogen protection, and reacted at 40-75℃ overnight. After the reaction is completed, 100mL ethyl acetate is added to dilute, and then 50mL water is added to separate the layers. The organic layer is washed with 100mL water and 50mL saturated brine successively, and the organic layer is dried over anhydrous sodium sulfate, and dried under reduced pressure. The crude product is chromatographed on a 200-300 mesh silica gel column to obtain the product.

[0031] Example 5 Synthesis of α-MG derivative (A2-L3)

[0032] The synthesis method of α-MG derivative (A2-L3) is similar to A1. T2-T18 and sodium hydroxide are dissolved in 20 mL of acetone, and hydroxylamine is added under nitrogen protection. The reaction is carried out at 40-75°C overnight. After the reaction is completed, 100 mL of ethyl acetate is added to dilute, and then 50 mL of water is added to separate the layers. The organic layer is washed with 100 mL of water and 50 mL of saturated brine successively. The organic layer is dried over anhydrous sodium sulfate and dried under reduced pressure. The crude product is chromatographed on a 200-300 mesh silica gel column to obtain the product A2-L3.

[0033] Examples 6 and 7 involve the synthesis of etherified α-MG derivatives at different positions. The reaction scheme is shown in Figure 3 .

[0034] Example 6 Synthesis of α-MG derivatives T19-T21

[0035] α-MG (1mmoL) and catechol (3mmoL) were dissolved in 20mL acetone and reacted at 70-120°C overnight. After the reaction was completed, 100mL ethyl acetate was added for dilution, and then 50mL water was added for separation. The organic layer was washed with 100mL water and 50mL saturated brine successively, and the organic layer was dried over anhydrous sodium sulfate, and dried under reduced pressure. The crude product was chromatographed on a 200-300 mesh silica gel column to obtain 402.5mg of yellow solid compound T19, with a yield of 70%. The preparation method of T20-T21 is similar to the reaction of T19.

[0036] Example 7 Synthesis of α-MG derivatives (M1-M3)

[0037] T19-T21 (1 mmol) was dissolved in 20 mL of acetone, HBr was added under nitrogen protection, and the mixture was reacted at 130°C overnight. After the reaction was completed, 100 mL of ethyl acetate was added for dilution, and then 50 mL of water was added for separation. The organic layer was washed with 100 mL of water and 50 mL of saturated brine successively, and the organic layer was dried over anhydrous sodium sulfate and dried under reduced pressure. The crude product was chromatographed on a 200-300 mesh silica gel column to obtain the product M1-M3.

[0038] Examples 8-10 involve activity tests of α-MG and its derivatives, such as minimum inhibitory concentration test, biofilm inhibition and removal activity, and iron ion chelation test.

[0039] Example 8 Minimum inhibitory concentration test of α-MG and its derivatives

[0040] This experiment is based on the growth of bacteria in MH (Mueller-Hinton Broth) culture medium in a 96-well plate. After a period of time, white precipitate will be produced due to the large amount, which makes it easy to distinguish whether there is bacterial growth. The antibacterial agent is diluted in multiples and added to the bacterial suspension. After culturing for a period of time, the last well without precipitation is the minimum inhibitory concentration (MIC).

[0041] According to the NCCLS experimental operation requirements, strains including E. coli ATCC25922, S. aureus ATCC29213 and clinically isolated multidrug-resistant strain MRSA 2 (ATCC33591) were used. The strains were revived and cultured to the logarithmic growth phase for use. α-MG and its derivatives were dissolved in dimethyl sulfoxide to 2 mg / mL, and the 96-well plate was taken out. 25.6 μL was added to the first column, and MH (B) medium was added to 200 μL, and diluted 2 times to the 10th column. The 11th column is the culture medium (negative) control, and the 12th column is the bacterial solution (positive) control. Penicillin and amoxicillin were used as drug controls, and the results were observed at 37°C for 18-24 hours. The minimum inhibitory concentration of the drug control should be within the reference range, and the experimental results of the same batch are considered reliable.

[0042] The antibacterial activity of α-MG and its derivatives against standard strains and multidrug-resistant strains of Escherichia coli and Staphylococcus aureus was tested by microdilution method, and the results are shown in Table 1. From the data in Table 1, it can be seen that the lead compound α-MG and all derivatives have certain antibacterial activity against Gram-positive bacteria and multidrug-resistant strains isolated from clinical sites, but the antibacterial activity of the modified derivatives is significantly improved, especially A1, A2, A3, C1, C2, C3, D1, D2, D3, H1, H2, H3, I1, I2, and I3.

[0043] Table 1 Minimum inhibitory concentration of α-MG and its derivatives against bacteria

[0044]

[0045] Example 9: Inhibition and removal of biofilm by α-MG and its derivatives

[0046] Biomembrane crystal violet quantification is a commonly used biological experimental method used to determine the permeability of biological membranes such as cell membranes, mitochondria, and endoplasmic reticulum. This method is based on crystal violet dye, which can bind to biological membranes and diffuse into the interior of cells through the cell membrane. After staining, the permeability of the biological membrane can be indirectly reflected by measuring the degree of absorption of the dye in the cell. The absorbance (OD value) of the stained cells can be measured by a spectrophotometer. The absorbance is proportional to the concentration of crystal violet in the cell, and the concentration of crystal violet in the cell is related to the permeability of the biological membrane. Therefore, by measuring the absorbance, the permeability of the biological membrane can be indirectly calculated.

[0047] LB (3 mL) was inoculated with an overnight bacterial culture and incubated at 37°C until the culture reached mid-log phase, diluted 1:100 and set aside. The biofilm inhibition test was performed by adding bacterial suspension (100 μL) to a 96-well plate containing 100 μL of different concentrations (0 to 128 μg / ml) of the compound. The 96-well plate was then placed in an incubator at 37°C for 12-16 hours. Upon completion, the bacteria were removed from the 96-well plate, washed three times with phosphate-buffered saline (1× PBS), then 0.1% crystal violet was added and placed at room temperature for 15-20 minutes, then the crystal violet was removed and washed three times with PBS. Finally, ethanol was added to the 96-well plate to dissolve the crystal violet adsorbed on the plate, and the plate was placed on a zymometer to read the absorbance value at 595 nm. The minimum polymer concentration that resulted in a 90% reduction in biofilm compared to the untreated control will be reported as the minimum inhibitory biofilm concentration of the biomass. Each experiment was repeated at least three times. Biofilm inhibition rate (%) = (OD control-OD sample) / OD control × 100. The removal experiment was first incubated in a 96-well plate at 37°C for 12 hours to obtain a mature biofilm. After removing the planktonic cells, the biofilm was treated with different concentrations of compounds at 37°C for 12 hours. The other steps were similar to the inhibition experiment. The samples were analyzed for biofilm biomass, and the biofilm concentration and the removal rate of biofilm biomass were calculated. Biofilm eradication rate (%) = (OD control-OD sample) / OD control × 100. The inhibitory effect of 36 α-MG derivatives on the biofilms of Staphylococcus aureus and Escherichia coli was measured by the crystal violet method, and the results are shown in Table 2. It can be seen from the data in Table 2 that the inhibitory effect of α-MG derivatives on the biofilms of Staphylococcus aureus and Escherichia coli was significantly improved after modification, among which A1 and A2 had the best effect.

[0048] Table 2 Minimum inhibitory concentration of α-MG and its derivatives on bacterial biofilm

[0049]

[0050] Example 10 Metal Chelation Experiment

[0051] Metal chelation experiment is a commonly used experimental method to detect the ability of compounds to bind to metal ions. The principle is based on the coordination and chelation effect between compounds. MOPS buffer (Solarbio, China) was treated with Chelex 100 before use, and apoferritin was used as a positive control. The total sample volume was kept at 1.5 mL during the entire experiment. Fe-NTA (5 μM) was added to MOPS-prepared CP654 (6 μM) and incubated for 30 min to quench the fluorescence. Then compound A1 (30 μM) was added and incubated in the dark for 48 h. The fluorescence intensity was measured using a fluorescence spectrophotometer (PerkinElmer). The excitation wavelength was 435 nm, the emission wavelength was 440-550 nm, the scanning speed was 120 nm / min, and the excitation and emission wavelengths were both 5.0 nm. The fluorescence intensities of CP654 (6 μM) and CP654 (6 μM) bound to Fe (30 μM) were 100% and 0%, respectively. On this basis, the iron chelation constant was calculated. All experiments were performed three times, and the results are expressed as mean ± standard deviation. Figure 5 As shown, it indicates that A1 has a good binding ability with iron ions, which is statistically significant with its concentration, proving that the improvement of A1's antibacterial activity may be directly related to its binding with iron ions.

[0052] Example 11 Detection of hemolytic activity of α-MG derivatives

[0053] Hemolysis test is a commonly used test method to detect the activity of blood antibodies. Its principle is based on the phenomenon that red blood cells are lysed when exposed to specific antibodies.

[0054] 4% rabbit erythrocytes (100 μL) were added to a 96-well plate containing 100 μL of different concentrations (0 to 128 μg / ml) of the compound. The positive control was 1% Triton-X 100 and the negative control was PBS. The 96-well plate was incubated in a thermostat at 37°C and 60 rpm for 1 hour. After incubation, the plate was centrifuged at 1000 g for 3 minutes. The supernatant (100 μL) was taken and the absorbance of each well was measured at 540 nm. Each experimental data was repeated three times.

[0055] The results are as follows Figure 4 As shown in the figure: A1 does not hemolyze at a concentration less than 128 μg / mL, and A2 does not hemolyze at a concentration less than 64 μg / mL. This indicates that A1 and A2 are not likely to cause hemolysis of erythrocytes. Relatively speaking, α-MG has a relatively obvious hemolytic activity (HC 50 =26.2 μg / mL, reference Bioorg. Med. Chem. 83 (2023), 117232).

Claims

1. A xanthone derivative, the structure of which is shown in Formula I, At least one of R1, R2, and R3 is -(CH2) n COOH, -(CH2) n CONHOH or The rest are H, with n=1, 2, 3, 4, 5 or 6.

2. The xanthone derivative according to claim 1, characterized in that R1, R2 are -(CH2) n COOH, R3 is H; or R1, R2 are -(CH2) n CONHOH, R3 is H; or R1, R3 are H, R2 is -(CH2) n COOH; or R1, R3 are H, R2 is -(CH2) n CONHOH; or R1 is -(CH2) n COOH, R2, R3 are H; or R1 is -(CH2) n CONHOH, R2, R3 are H; or R1, R2, R3 are -(CH2) n COOH; or R1, R2, R3 are -(CH2) n CONHOH; or R1 is H, R2, R3 are -(CH2) n COOH; or R1 is H, R2, R3 are -(CH2) n CONHOH; or R1, R3 are -(CH2) n COOH, R2 is H; or R1, R3 are -(CH2) n CONHOH, R2 is H; or R1, R2 are R3 is H.

3. The xanthone derivative according to claim 1, characterized in that n=2, 4 or 6.

4. The xanthone derivative according to claim 2, characterized in that R1, R2 are -(CH2) n COOH, R3 is H, n=2, 4 or 6.

5. The xanthone derivative according to claim 2, characterized in that: R1, R3 are H, R2 is -(CH2) n COOH, n=2, 4 or 6.

6. The xanthone derivative according to claim 2, characterized in that R1, R3 are H, R2 is -(CH2) n CONHOH, n=2, 4 or 6.

7. The xanthone derivative according to claim 2, characterized in that: R1, R2, R3 are -(CH2) n CONHOH, n=2, 4 or 6.

8. The xanthone derivative according to claim 2, characterized in that: R1 is H, R2, R3 are -(CH2) n COOH, n=2, 4 or 6.

9. The use of the xanthone derivative according to any one of claims 1 to 8, characterized in that: The xanthone derivative is used for resisting Gram-positive bacteria or as a sensitizer for clinical drug-resistant strains.

10. The use of the xanthone derivative according to any one of claims 1 to 8, characterized in that: The xanthone derivatives are used for inhibiting and eliminating Gram-positive bacteria or Gram-negative biofilms.

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