Isopsoralea corylifolia chromone-curcumin derivative, preparation method and application thereof, and antibacterial drug preparation

Abstract

The present invention provides an isopsoralen chalcone-curcumin derivative, its preparation method and application, and an antibacterial pharmaceutical preparation, belonging to the field of pharmaceutical chemistry technology. The isopsoralen chalcone-curcumin derivative of the present invention is based on the isopsoralen chalcone and curcumin structural framework. In vitro antibacterial experiments have shown that it has excellent broad-spectrum antibacterial activity, especially against drug-resistant Staphylococcus aureus (MRSA), with antibacterial activity that is more than 1,000 times that of the positive drug ofloxacin. At the same time, the isopsoralen chalcone-curcumin derivative has high biosafety.

Description

Technical Field

[0001] The present invention relates to the technical field of pharmaceutical chemistry, and in particular to an isopsoralea corylifolia chromone-curcumin derivative, a preparation method and application thereof, and an antibacterial drug preparation. Background Art

[0002] Bacteria are single-celled organisms that, despite their tiny size, pack a powerful punch. Bacterial infections can cause a wide range of health problems, from mild colds and skin infections to severe respiratory infections, meningitis, and sepsis. Bacterial infections are dangerous because they multiply rapidly and release toxins that attack human tissue, causing inflammation, tissue damage, and organ dysfunction. Certain bacteria can also trigger abnormal immune responses, leading to allergic reactions. Severe bacterial infections, if left untreated, can be life-threatening.

[0003] Antimicrobial drugs play a vital role in medicine. They are the primary tool for combating bacterial infections, killing or inhibiting bacterial growth. Antimicrobial drugs are not only used to treat existing bacterial infections but are also widely used to prevent postoperative infections during surgery, organ transplantation, cancer chemotherapy, and other treatments. Since their discovery, antimicrobial drugs have played a vital role in clinical practice, saving millions of lives. However, the effectiveness of antimicrobial drugs has faced increasing challenges over time. In particular, the emergence of increasingly resistant and super-resistant bacteria has limited the therapeutic effectiveness of existing antimicrobial drugs and increased the risk of infection. Furthermore, as the development of new antimicrobial drugs has become increasingly expensive and complex, most pharmaceutical companies have reduced their investment in antimicrobial research and development, resulting in a shortage of new antimicrobial drugs on the market. Furthermore, some antimicrobial drugs are associated with serious adverse reactions and side effects during treatment, negatively impacting patient health. Summary of the Invention

[0004] The object of the present invention is to provide an isopsoralea chromene chalcone-curcumin derivative and its preparation method and application, and an antibacterial pharmaceutical preparation. The isopsoralea chromene chalcone-curcumin derivative has good antibacterial activity.

[0005] In order to achieve the above-mentioned object of the invention, the present invention provides the following technical solutions:

[0006] The present invention provides an isopsoralea corylifolia chromone-curcumin derivative having a structure shown in Formula 1:

[0007]

[0008] The present invention provides a method for preparing the isopsoralea corylifolia chromene chalcone-curcumin derivative described in the above technical solution, comprising the following steps:

[0009] 3-methyl-2-butenal, calcium chloride, an alcohol solution of 2,4-dihydroxybenzaldehyde and triethylamine are mixed and subjected to a cyclization reaction to obtain a benzaldehyde intermediate;

[0010] The benzaldehyde intermediate, acetone and a first alkaline solution are mixed to perform a first Claisen-Schmidt reaction to obtain an α,β-unsaturated aldehyde ketone intermediate;

[0011] The α,β-unsaturated aldehyde ketone intermediate, 4-tert-butylbenzaldehyde, an alcohol solvent and a second alkali solution are mixed and subjected to a second Claisen-Schmidt reaction to obtain an isopsoralen chromene chalcone-curcumin derivative.

[0012] Preferably, the molar ratio of the 3-methyl-2-butenal, calcium chloride, 2,4-dihydroxybenzaldehyde and triethylamine is 28.86:14.48:14.48:28.86; the temperature of the cyclization reaction is 80° C., and the time is 2 h.

[0013] Preferably, the first alkali solution and the second alkali solution are both NaOH solutions, and the mass concentration of the NaOH solution is 20%.

[0014] Preferably, the ratio of the benzaldehyde intermediate to acetone is 5.88 mmol:40 mL; the temperature of the first Claisen-Schmidt reaction is room temperature, and the time is 48 h.

[0015] Preferably, the molar ratio of the α,β-unsaturated aldehyde-ketone intermediate to 4-tert-butylbenzaldehyde is 0.818:1.64; the temperature of the second Claisen-Schmidt reaction is room temperature, and the time is 12 hours.

[0016] The present invention provides the use of the isopsoralea chromene chalcone-curcumin derivative described in the above technical solution or the isopsoralea chromene chalcone-curcumin derivative prepared by the preparation method described in the above technical solution in the preparation of antibacterial drugs.

[0017] Preferably, the fungi in the antibacterial drug include Pseudomonas aeruginosa, Staphylococcus aureus, Escherichia coli, Salmonella, Streptococcus, drug-resistant pneumococcus, Vibrio cholerae, Shigella dysenteriae, Clostridium or Hawkes's bacillus.

[0018] The present invention provides an antibacterial pharmaceutical preparation comprising an antibacterial active ingredient and a pharmaceutical excipient. The antibacterial active ingredient comprises the isopsoralea chromene chalcone-curcumin derivative described in the above technical solution or the isopsoralea chromene chalcone-curcumin derivative prepared by the preparation method described in the above technical solution.

[0019] Preferably, the dosage form of the antibacterial drug preparation is an injection, tablet, capsule, aerosol, suppository, film, pill, ointment, controlled release agent, sustained release agent or nano preparation.

[0020] The present invention provides an isopsoralen chalcone-curcumin derivative. The isopsoralen chalcone-curcumin derivative is based on the structural skeleton of isopsoralen chalcone and curcumin, and is an active hybrid compound of isopsoralen chalcone and curcumin. Chalcone and curcumin themselves have certain antibacterial activity, but curcumin is unstable due to its dicarbonyl structure. The isopsoralen chalcone-curcumin derivative provided by the present invention contains the antibacterial active sites of both chalcone and curcumin, thus having higher stability and better antibacterial activity. The results of antibacterial activity and wound healing experiments in the test examples show that the isopsoralen chalcone-curcumin derivative provided by the present invention has excellent broad-spectrum antibacterial activity, especially against drug-resistant Staphylococcus aureus (MRSA), with antibacterial activity more than 1000 times that of the positive drug ofloxacin. Chicken embryo experiments also show that the isopsoralen chalcone-curcumin derivative has high biosafety. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] Figure 1 The isopsoralea corylifolia chromone-curcumin derivative prepared in Example 1 1 HNMR nuclear magnetic resonance spectrum;

[0022] Figure 2 The isopsoralea corylifolia chromone-curcumin derivative prepared in Example 1 13 C NMR nuclear magnetic resonance spectrum;

[0023] Figure 3 The antibacterial and wound healing effects of the isopsoralen chromone chalcone-curcumin derivatives in Test Example 2;

[0024] Figure 4 This is a safety assessment of the isopsoralea corylifolia chromone-curcumin derivative in Test Example 3. DETAILED DESCRIPTION

[0025] The present invention provides an isopsoralea corylifolia chromone-curcumin derivative having a structure shown in Formula 1:

[0026]

[0027] The present invention provides a method for preparing the isopsoralea corylifolia chromene chalcone-curcumin derivative described in the above technical solution, comprising the following steps:

[0028] 3-methyl-2-butenal, calcium chloride, an alcohol solution of 2,4-dihydroxybenzaldehyde and triethylamine are mixed and subjected to a cyclization reaction to obtain a benzaldehyde intermediate;

[0029] The benzaldehyde intermediate, acetone and a first alkaline solution are mixed to perform a first Claisen-Schmidt reaction to obtain an α,β-unsaturated aldehyde ketone intermediate;

[0030] The α,β-unsaturated aldehyde ketone intermediate, 4-tert-butylbenzaldehyde, an alcohol solvent and a second alkali solution are mixed and subjected to a second Claisen-Schmidt reaction to obtain an isopsoralen chromene chalcone-curcumin derivative.

[0031] In the present invention, the reaction formula of the isopsoralea corylifolia chromene chalcone-curcumin derivative is:

[0032]

[0033] The invention mixes 3-methyl-2-butenal, calcium chloride, an alcohol solution of 2,4-dihydroxybenzaldehyde and triethylamine, and performs a cyclization reaction to obtain a benzaldehyde intermediate.

[0034] In the present invention, the molar ratio of the 3-methyl-2-butenal, calcium chloride, 2,4-dihydroxybenzaldehyde and triethylamine is preferably 28.86:14.48:14.48:28.86; the alcohol solution of 2,4-dihydroxybenzaldehyde is preferably an anhydrous ethanol solution of 2,4-dihydroxybenzaldehyde, and the concentration is preferably 0.05 g / mL.

[0035] In the present invention, the temperature of the cyclization reaction is preferably 80° C., and the time is preferably 2 h.

[0036] In the present invention, the process of the cyclization reaction is preferably: 3-methyl-2-butenal and calcium chloride are added to an anhydrous ethanol solution of 2,4-dihydroxybenzaldehyde (compound 1), and triethylamine is added, and the resulting reaction solution is subjected to a cyclization reaction under stirring and reflux conditions; after the reaction is completed, water is added to the resulting product to quench the reaction, the solvent anhydrous ethanol is removed by distillation under reduced pressure, the resulting residue is dissolved in ethyl acetate and distilled water and extracted three times, the organic layer is dried over anhydrous magnesium sulfate, and ethyl acetate is removed by distillation under reduced pressure. The resulting residue is purified by silica gel column chromatography to obtain a benzaldehyde intermediate, i.e., compound 2. The present invention has no particular limitation on the specific amount of the reagents used after the reaction is completed, and can be adjusted according to actual needs; the reagent used for the silica gel column chromatography is preferably petroleum ether: ethyl acetate = 100: 1 (volume ratio).

[0037] After obtaining the benzaldehyde intermediate, the present invention mixes the benzaldehyde intermediate, acetone and a first alkaline solution to perform a first Claisen-Schmidt reaction to obtain an α,β-unsaturated aldehyde ketone intermediate.

[0038] In the present invention, the first alkali solution is preferably a NaOH solution, and the mass concentration of the NaOH solution is preferably 20%. The amount of the first alkali solution used is not particularly limited in the present invention and can be adjusted according to actual needs to ensure smooth reaction. More preferably, the molar ratio of the alkali to the benzaldehyde intermediate in the alkali solution is 3:1.

[0039] In the present invention, the ratio of the benzaldehyde intermediate to acetone is preferably 5.88 mmol:40 mL; the temperature of the first Claisen-Schmidt reaction is preferably room temperature, and the time is preferably 48 h.

[0040] In the present invention, the process of the first Claisen-Schmidt reaction is preferably: benzaldehyde intermediate 2 is added to acetone, and then the first alkali solution is added, and the resulting reaction solution is stirred at room temperature to perform the first Claisen-Schmidt reaction. After the reaction is completed, the solvent acetone is removed by vacuum distillation, and the residue is dissolved in ethyl acetate and distilled water and extracted three times. The organic layer is dried over anhydrous magnesium sulfate, and the ethyl acetate is removed by vacuum distillation. The residue is purified by silica gel column chromatography to obtain an α,β-unsaturated aldehyde ketone intermediate, i.e., compound 3. The present invention does not specifically limit the amount of the post-treatment reagent used after the completion of the first Claisen-Schmidt reaction, and can be adjusted according to actual needs. The reagent used for the silica gel column chromatography is preferably petroleum ether: ethyl acetate = 10:1 (volume ratio).

[0041] After obtaining the α,β-unsaturated aldehyde ketone intermediate, the present invention mixes the α,β-unsaturated aldehyde ketone intermediate, 4-tert-butylbenzaldehyde, an alcohol solvent and a second alkali solution, and performs a second Claisen-Schmidt reaction to obtain an isopsoralen chromene chalcone-curcumin derivative.

[0042] In the present invention, the molar ratio of the α,β-unsaturated aldehyde-ketone intermediate to 4-tert-butylbenzaldehyde is preferably 0.818:1.64; the alcohol solvent is preferably anhydrous ethanol; the amount of the alcohol solvent used is not particularly limited, as long as it ensures smooth reaction; the second alkali solution is preferably a NaOH solution, and the mass concentration of the NaOH solution is preferably 20%. The amount of the second alkali solution used is not particularly limited, and can be adjusted according to actual needs to ensure smooth reaction.

[0043] In the present invention, the temperature of the second Claisen-Schmidt reaction is preferably room temperature, and the time is preferably 12 hours.

[0044] In the present invention, the second Claisen-Schmidt reaction preferably comprises the following steps: adding an α,β-unsaturated aldehyde-ketone intermediate 3 and 4-tert-butylbenzaldehyde to an alcohol solution, adding a second alkali solution dropwise, and stirring the resulting reaction mixture at room temperature to perform a second Claisen-Schmidt reaction; after completion of the reaction, quenching is performed by adding a saturated ammonium chloride solution, followed by extraction three times with ethyl acetate and distilled water, drying the organic layer over anhydrous magnesium sulfate, removing the ethyl acetate by vacuum distillation, and purifying the residue by silica gel column chromatography to obtain an isopsoralea corylifolia chromene chalcone-curcumin derivative, namely, compound 4. The present invention does not specifically limit the quenching, extraction, drying, and vacuum distillation processes or the reagent amounts used, and these can be adjusted according to actual needs; the reagent used for the silica gel column chromatography is preferably petroleum ether:ethyl acetate = 6:1 (volume ratio).

[0045] The present invention provides the use of the isopsoralea chromene chalcone-curcumin derivative described in the above technical solution or the isopsoralea chromene chalcone-curcumin derivative prepared by the preparation method described in the above technical solution in the preparation of an antibacterial drug. The present invention does not particularly limit the method of application, and the application can be carried out according to methods well known in the art.

[0046] In the present invention, the fungi in the antibacterial drug preferably include Pseudomonas aeruginosa, Staphylococcus aureus, Escherichia coli, Salmonella, Streptococcus, drug-resistant pneumococcus, Vibrio cholerae, Shigella dysenteriae, Clostridium or Hawkes's bacillus.

[0047] The present invention provides an antibacterial pharmaceutical preparation comprising an antibacterial active ingredient and a pharmaceutical excipient. The antibacterial active ingredient comprises the isopsoralea chromene chalcone-curcumin derivative described in the above technical solution or the isopsoralea chromene chalcone-curcumin derivative prepared by the preparation method described in the above technical solution.

[0048] The present invention has no particular limitation on the pharmaceutical excipients, and any corresponding excipient well known in the art can be used.

[0049] In the present invention, the content of the antibacterial active ingredient in the antibacterial pharmaceutical preparation is preferably 98.0-100.0%.

[0050] In the present invention, the dosage form of the antibacterial drug preparation is preferably an injection, tablet, capsule, aerosol, suppository, film, pill, ointment, controlled-release agent, sustained-release agent or nano preparation.

[0051] The technical solutions provided by the present invention are described in detail below with reference to the embodiments, but they should not be construed as limiting the scope of protection of the present invention.

[0052] Example 1

[0053]

[0054] 1) Synthesis steps:

[0055] Step a: Synthesis of 5-hydroxy-2,2-dimethyl 2H-benzopyran-6-carbaldehyde (2): 3-methyl-2-butenal (2.80 mL, 28.86 mmol) and calcium chloride (1.61 g, 14.48 mmol) were added to a solution of 2,4-dihydroxybenzaldehyde (2.0 g, 14.48 mmol) in anhydrous ethanol (40 mL), and triethylamine (4.02 mL, 28.86 mmol) was added. The resulting reaction solution was stirred at 40°C for 1 h. The mixture was stirred and refluxed at 80° C. for 2 hours. After the reaction was completed, water was added to quench the reaction, and the solvent, anhydrous ethanol, was distilled off under reduced pressure. The residue was dissolved in ethyl acetate (30 mL) and distilled water (30 mL), and extracted three times. The organic layer was dried over anhydrous magnesium sulfate, and the ethyl acetate was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (petroleum ether:ethyl acetate=100:1, volume ratio) to obtain benzaldehyde intermediate 2 (1.89 g, yield: 63.9%, yellow oily liquid).

[0056] Step b: Synthesis of (E)-4-(5-hydroxy-2,2-dimethyl-2H-chromen-6-yl)but-3-en-2-one (3): The intermediate benzaldehyde 2 (1.2 g, 5.88 mmol) was added to acetone (40 mL), and then 3 mL of 20 wt% NaOH solution was added, and the resulting reaction solution was stirred at room temperature for 48 h; after the reaction was completed, the solvent acetone was removed by distillation under reduced pressure, and the residue was dissolved in ethyl acetate (30 mL) and distilled water (30 mL) and extracted three times, and the organic layer was dried over anhydrous magnesium sulfate. The ethyl acetate was removed by distillation under reduced pressure, and the residue was purified by silica gel column chromatography (petroleum ether:ethyl acetate=10:1, volume ratio) to obtain α,β-unsaturated aldehyde ketone intermediate 3 (1.03 g, yield: 71.5%, yellow solid);

[0057] Step c: Synthesis 4: α,β-unsaturated aldehyde ketone intermediate 3 (200 mg, 0.818 mmol) and 4-tert-butylbenzaldehyde (265.64 mg, 1.64 mmol) were added to anhydrous ethanol, and 0.50 mL of 20 wt% NaOH solution was added dropwise. The reaction mixture was stirred at room temperature overnight; after the reaction was completed, saturated ammonium chloride solution was added to quench the reaction, and then extracted three times with ethyl acetate (30 mL) and distilled water (30 mL). The organic layer was dried over anhydrous magnesium sulfate, and the ethyl acetate was removed by distillation under reduced pressure. The residue was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 6:1, volume ratio) to obtain compound 4 (97 mg, yield: 30.5%, yellow solid).

[0058] Compound 4 prepared in Example 1 was characterized by nuclear magnetic resonance, and the results were shown in Figures 1-2 , the data obtained is:

[0059] 1 H-NMR (400MHz, DMSO-d6) δ (ppm): 9.78 (s, 1H), 8.03 (d, J = 15.8Hz, 1H), 7.79-7.67 (m, 3H), 7.61 (d, J = 8.6Hz, 1H), 7.49 (d, J = 8.4Hz, 2H),7.21(dd,J=15.9,1.2Hz,2H),6.78(d,J=10.0Hz,1H),6.43(d,J=8.6Hz,1H),5.75(d,J=10.0Hz,1H),1.40(s,6H),1.32(s,9H). 13 C-NMR(101MHz,DMSO-d6)δ188.75,156.40,153.78,153.43,142.25,138.59,132.66,129.45,128.85,1 28.77×2,126.31×2,126.27,122.94,117.16,116.54,110.65,109.67,76.64,35.12,31.41×3,28.04×2.

[0060] The above data show that compound 4 (isopsoralea chromene chalcone-curcumin derivative) prepared by the present invention is: 1E, 4E)-1-(4-(tert-butyl)phenyl)-5-(5-hydroxy-2,2-dimethyl-2H-benzopyran-6-yl)penta-1,4-diene-3-one.

[0061] The following test examples all used the isopsoralea corylifolia chromone chalcone-curcumin derivative prepared in Example 1.

[0062] Test Example 1

[0063] Bactericidal effects of isopsoralen chromone chalcone-curcumin derivatives against Pseudomonas aeruginosa and drug-resistant Staphylococcus aureus (MRSA):

[0064] Take out the glycerol-preserved strains of Pseudomonas aeruginosa or drug-resistant Staphylococcus aureus (MRSA) from the ultra-low temperature freezer (-80°C), inoculate them into 4 mL of LB liquid medium in a clean bench, place them in a constant temperature shaking incubator, set the temperature to 37°C, set the speed to 180 r / min, culture overnight, and add an appropriate amount of sterile LB liquid medium to dilute the bacterial solution to OD 600nm 0.1 (final bacterial count 1×10 8 CFU / mL) for later use. 100 μL of the designated concentrations of isopsoralen chromene chalcone and curcumin derivatives were added to a 96-well plate; at the same time, 1 μL of the above-mentioned standby bacterial solution was added to each well to make the final bacterial count 5×10 5CFU / well, with bacterial suspension serving as a positive control and LB medium serving as a negative control. After microvortexing to mix, a sterile inoculating loop was used to draw three lines on an LBBA plate within a clean bench. The plate was then incubated at 37°C for 12 hours. The absence of visible bacterial growth was considered bactericidal. The results are shown in Table 1.

[0065] Table 1 Minimum inhibitory concentration (MIC) of isopsoralen chalcone-curcumin derivatives against Pseudomonas aeruginosa (PA) and drug-resistant Staphylococcus aureus (MRSA)

[0066] drug PA MRSA Isopsoralen chromene chalcone-curcumin derivatives 0.86 μg / mL 0.15 ng / mL Ofloxacin 1.25 μg / mL 12.68 μg / mL

[0067] As shown in Table 1, the minimum inhibitory concentration (MIC) ofloxacin, a Yangshen drug, against Pseudomonas aeruginosa is 1.25 μg / mL, while the MIC of the isopsoralen chromone chalcone-curcumin derivative is 0.86 μg / mL. These experimental results demonstrate that the synthesized isopsoralen chromone chalcone-curcumin derivative exhibits stronger inhibitory activity against Pseudomonas aeruginosa growth than ofloxacin.

[0068] Furthermore, the minimum inhibitory concentration (MIC) ofloxacin, a Yangshen drug, against MRSA is 12.68 μg / mL, while the MIC of the isopsoralen chalcone-curcumin derivative against MRSA is as low as 0.15 ng / mL, a difference of nearly 1,000 times. This clearly demonstrates that the antibacterial effect of the isopsoralen chalcone-curcumin derivative against MRSA is more than 1,000 times greater than that ofloxacin, a positive drug.

[0069] In Test Example 1, the antibacterial efficacy of the synthesized isopsoralen chalcone-curcumin derivative was demonstrated using Pseudomonas aeruginosa and MRSA as examples. However, it should be understood that while only Pseudomonas aeruginosa and MRSA were used as examples to illustrate the use of the derivative for preparing an antibacterial drug, the "bacteria" referred to in the present invention include, but are not limited to, Pseudomonas aeruginosa, MRSA, and the like. Experiments have demonstrated that the isopsoralen chalcone-curcumin derivative has significant bactericidal efficacy against Pseudomonas aeruginosa and MRSA, including but not limited to Pseudomonas aeruginosa and MRSA.

[0070] Test Example 2

[0071] The antibacterial and wound healing effects of isopsoralen chromone chalcone-curcumin derivatives:

[0072] The mice were fed for one week. After anesthesia, the hair on the back of the mice was carefully removed with a razor. A circular wound with a diameter of 0.5 cm was made on the upper middle part of the back with a special punch. After the wound hemostasis, 1 mL of 2×10 6 CFU / mL of Staphylococcus aureus. The control group was given normal saline to disinfect the wound three times a day, and the treatment group was given normal saline solution containing 125μg / L of isopsoralen chromone chalcone-curcumin derivative three times a day. The wound healing and scarring of each group were tracked using transparent film on days 0, 4, 8, and 12 after injury. The experimental results are shown in Figure 3 .

[0073] like Figure 3 As shown, the wounds of mice in the normal saline group healed slowly, while the wounds of mice in the group administered with normal saline solution containing 125 μg / L isopsoralen chromone chalcone-curcumin derivatives healed significantly faster.

[0074] Test Example 3

[0075] Safety assessment of isopsoralen chromene chalcone and curcumin derivatives

[0076] Remove the chicken embryo from the incubator, illuminate it with light and position it properly. Make a small hole at the other end of the air chamber and carefully extract 2.5-3.0 mL of egg white with a syringe. Seal the hole with paraffin (paraffin, collodion). Make a skylight (1 cm × 1 cm) above the embryo, remove the film, expand the experimental area, and then add physiological saline (Control), 125 μg / L isopsoralen chromone-curcumin derivative physiological saline solution or 1M sodium hydroxide solution (NaOH) to the chicken embryo. The experimental results are shown in Figure 4 .

[0077] like Figure 4 As shown in the data, after 15 minutes of treatment with 1M NaOH, severe hemolysis occurred in the blood vessels of the chicken embryos. However, even after treatment with a 125 μg / L saline solution of isopsoralen chalcone-curcumin derivative for 120 minutes, the chicken embryos did not produce hemolytic reactions, indicating that it had no significant effect on angiogenesis in the chicken embryos and had high biosafety.

[0078] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principles of the present invention. These improvements and modifications should also be regarded as within the scope of protection of the present invention.

Claims

1. An isopsoralea corylifolia chromene chalcone-curcumin derivative, characterized in that: It has the structure shown in formula 1: Formula 1.

2. The method for preparing the isopsoralea corylifolia chromene chalcone-curcumin derivative according to claim 1, wherein: The following steps are involved: 3-methyl-2-butenal, calcium chloride, an alcohol solution of 2,4-dihydroxybenzaldehyde and triethylamine are mixed and subjected to a cyclization reaction to obtain a benzaldehyde intermediate; The benzaldehyde intermediate, acetone and a first alkaline solution are mixed to perform a first Claisen-Schmidt reaction to obtain an α,β-unsaturated aldehyde ketone intermediate; The α,β-unsaturated aldehyde ketone intermediate, 4-tert-butylbenzaldehyde, an alcohol solvent and a second alkali solution are mixed to perform a second Claisen-Schmidt reaction to obtain an isopsoralen chromene chalcone-curcumin derivative; The benzaldehyde intermediate is ; The α,β-unsaturated aldehyde ketone intermediate is .

3. The preparation method according to claim 2, characterized in that The molar ratio of the 3-methyl-2-butenal, calcium chloride, 2,4-dihydroxybenzaldehyde and triethylamine is 28.86:14.48:14.48:28.86; the temperature of the cyclization reaction is 80° C., and the time is 2 hours.

4. The preparation method according to claim 2, characterized in that The first alkali solution and the second alkali solution are both NaOH solutions, and the mass concentration of the NaOH solution is 20%.

5. The preparation method according to claim 2, characterized in that The ratio of the benzaldehyde intermediate to acetone is 5.88 mmol:40 mL; the temperature of the first Claisen-Schmidt reaction is room temperature, and the time is 48 h.

6. The preparation method according to claim 2, characterized in that The molar ratio of the α,β-unsaturated aldehyde ketone intermediate to 4-tert-butylbenzaldehyde is 0.818:1.64; the temperature of the second Claisen-Schmidt reaction is room temperature, and the time is 12 hours.

7. Use of the isopsoralea chromene chalcone-curcumin derivative according to claim 1 or the isopsoralea chromene chalcone-curcumin derivative prepared by the preparation method according to any one of claims 2 to 6 in the preparation of antibacterial drugs.

8. The use according to claim 7, characterized in that The fungi in the antibacterial drug are Pseudomonas aeruginosa or Staphylococcus aureus.

9. An antibacterial drug preparation comprising an antibacterial active ingredient and a pharmaceutical excipient, characterized in that: The antibacterial active ingredient includes the isopsoralea chromene chalcone-curcumin derivative according to claim 1 or the isopsoralea chromene chalcone-curcumin derivative prepared by the preparation method according to any one of claims 2 to 6.

10. The antibacterial drug preparation according to claim 9, characterized in that The dosage form of the antibacterial drug preparation is injection, tablet, capsule, aerosol, suppository, film, pill, ointment, controlled release agent, sustained release agent or nano preparation.

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