Mitochondrial-targeted genistein derivatives and their application in the preparation of drugs against myocardial ischemia-reperfusion injury

Abstract

The present invention belongs to the field of medicine, and specifically relates to a mitochondrial targeted genistein derivative and its application in the preparation of a drug for the prevention and treatment of myocardial ischemia-reperfusion injury. The general structural formula of the derivative is shown in (I): #imgabs0# Using an animal model of myocardial ischemia-reperfusion injury, experimental results show that the mitochondrial targeted genistein synthesized by the present invention can significantly improve cardiac function, reduce the area of ​​myocardial infarction, and has a significant protective effect on myocardial ischemia-reperfusion injury, and the effect is better than that of genistein.

Description

Technical Field

[0001] The invention belongs to the field of medicine, and specifically relates to a mitochondrial targeted genistein derivative and an application thereof in preparing a drug for preventing and treating myocardial ischemia-reperfusion injury. Background Art

[0002] Acute myocardial infarction is a common clinical cardiovascular emergency with high morbidity and mortality worldwide. Currently, vascular reconstruction strategies can effectively restore myocardial perfusion and reduce myocardial damage caused by myocardial infarction. However, after the heart restores blood perfusion, myocardial damage is secondary aggravated and destroys the myocardial tissue structure. This phenomenon is called myocardial ischemia-reperfusion injury (MI / RI). Currently, effective measures for the treatment of MI / RI in clinical practice are still very limited.

[0003] Studies have shown that there are many pathophysiological mechanisms that induce reperfusion injury, among which oxidative stress plays an important role. Isoflavones are a naturally occurring polyphenolic substance that is widely found in leguminous plants. They have excellent antioxidant properties and have potential preventive and therapeutic effects on MI / RI. Genistein (GEN), whose chemical name is 4',5,7-trihydroxyisoflavone, is an effective natural antioxidant that can improve MI / RI by scavenging free radicals, inhibiting lipid peroxidation and cell apoptosis. Considering that the free radicals in cells mainly come from mitochondria, although GEN can be absorbed by cells, it is difficult to enrich in mitochondria. Therefore, the present invention intends to deliver GEN to mitochondria through chemical modification in order to significantly improve the therapeutic effect on MI / RI. Summary of the invention

[0004] Based on the above-mentioned deficiencies of the prior art, the present invention provides a mitochondrial targeted genistein derivative and its use in preparing a drug for preventing and treating myocardial ischemia-reperfusion injury. The mitochondrial targeted genistein derivative provided by the present invention can enrich genistein in mitochondria, directly remove excess ROS, inhibit lipid peroxidation, and enhance the preventive or therapeutic effect on MI / RI.

[0005] The purpose of the present invention is specifically achieved through the following technical solutions:

[0006] In a first aspect, the present invention provides a mitochondrial targeted genistein derivative having a structure as shown in formula (I):

[0007]

[0008] In a second aspect, the present invention provides a method for synthesizing the mitochondrial targeted genistein derivative, comprising the following steps:

[0009] Using triphenylphosphine and 6-bromohexanoic acid as raw materials for coordination reaction, an intermediate is obtained;

[0010] The intermediate is mixed with 4',5,7-trihydroxyisoflavone to carry out a dehydration reaction to obtain the mitochondrial targeting genistein derivative.

[0011] Preferably, the molar ratio of the triphenylphosphine to the 6-bromohexanoic acid is 1:1.3-1.7.

[0012] Preferably, the coordination reaction is to mix triphenylphosphine and 6-bromohexanoic acid, use acetonitrile as solvent, and reflux for 20 to 30 hours.

[0013] Preferably, the dehydration reaction is carried out according to the following steps:

[0014] The intermediate is mixed with 4',5,7-trihydroxyisoflavone, a catalyst and a reaction solvent are added, dicyclohexylcarbodiimide is added at 0°C, the reaction is continued for 20 to 40 minutes, and then the temperature is raised to room temperature and the reaction is continued for 10 to 15 hours.

[0015] Preferably, the catalyst is 4-dimethylaminopyridine;

[0016] The reaction solvent is anhydrous tetrahydrofuran;

[0017] The molar ratio of the triphenylphosphine to the 4',5,7-trihydroxyisoflavone is 1:1-1.5;

[0018] The molar ratio of the 4',5,7-trihydroxyisoflavone to the dicyclohexylcarbodiimide is 1:1.2-1.8.

[0019] The third aspect of the present invention provides a use of the mitochondrial targeted genistein in the preparation of a drug for resisting myocardial ischemia-reperfusion injury.

[0020] The fourth aspect of the present invention provides a medicine for resisting myocardial ischemia-reperfusion injury, which comprises the mitochondrial targeting genistein and pharmaceutically acceptable adjuvants. Depending on the specific dosage form, different adjuvants are added, such as fillers, disintegrants, binders, lubricants, suspending agents, stabilizers, flavoring agents, suspending agents, emulsifiers, etc.

[0021] Preferably, the drug is an oral preparation.

[0022] Preferably, the dosage form of the drug is tablets, capsules, dispersants or granules. Appropriate disintegrants, fillers, binders and lubricants can be added to the selected tablets, appropriate fillers, binders and lubricants can be added to the selected capsules, microcrystalline cellulose, cross-linked sodium carboxymethyl cellulose and the like can be added to the selected dispersants as excipients, and dextrin, powdered sugar and the like can be added to the selected granules as excipients. The amount of each excipient can be specifically selected according to the amount of the derivative added and the like.

[0023] Preferably, the drug contains the mitochondrial targeting genistein as the only active pharmaceutical ingredient.

[0024] The present invention provides a mitochondrial targeted genistein derivative Mito-GEN, and proves through myocardial ischemia-reperfusion injury mouse model experiments that Mito-GEN can significantly improve the cardiac function of myocardial ischemia-reperfusion injury mice, reduce myocardial infarction area, and has a significant protective effect on myocardial ischemia-reperfusion injury, and the effect is better than genistein. Its mechanism of action may be related to the alleviation of oxidative stress, inflammatory response, cell apoptosis and mitochondrial damage caused by myocardial ischemia-reperfusion. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] Figure 1 is a comparison of myocardial infarction size in mice; * P﹤0.05, compared with the I / R group. AAR, area at risk; LV, left ventricle; IF, infarct size; the left picture shows the myocardial tissue of mice;

[0026] Figure 2 It is the expression of apoptosis-related proteins in mouse myocardial tissue; * P﹤0.05, ** P﹤0.01, compared with Sham; # P﹤0.05, ## P﹤0.01, compared with the I / R group. DETAILED DESCRIPTION

[0027] The technical solution of the present invention is further described in detail below in conjunction with embodiments.

[0028] Example 1

[0029] Synthesis of Mitochondria-Targeted Genistein Derivatives (Mito-GEN)

[0030]

[0031] Dissolve 1.31g (5mmol) triphenylphosphine and 1.46g (7.5mmol) 6-bromohexanoic acid in 50mL acetonitrile and reflux for 24h. Remove acetonitrile under reduced pressure, precipitate the residue with ether, wash with n-hexane to obtain a white solid. Add 1.35g (5mmol) GEN, 6mg 4-dimethylaminopyridine (DMAP) and 30mL anhydrous tetrahydrofuran (THF), cool the low-temperature reactor to 0°C, and add 1.54g (7.5mmol) dicyclohexylcarbodiimide (DCC) dissolved in 20mL anhydrous THF dropwise with stirring. After the dropwise addition, continue to react for 30min, then warm to room temperature and continue to react for 12h, filter, remove the solvent under reduced pressure, and separate Mito-GEN by rapid column chromatography. 2.41g of light yellow solid, yield 68% (based on GEN).

[0032] Example 2

[0033] Synthesis of Mitochondria-Targeted Genistein Derivatives (Mito-GEN)

[0034]

[0035] Dissolve 1.31g (5mmol) triphenylphosphine and 1.27g (6.5mmol) 6-bromohexanoic acid in 50mL acetonitrile and reflux for 20h. Remove acetonitrile under reduced pressure, precipitate the residue with ether, wash with n-hexane to obtain a white solid. Add 1.35g (5mmol) GEN, 6mg 4-dimethylaminopyridine (DMAP) and 30mL anhydrous tetrahydrofuran (THF), cool the low-temperature reactor to 0°C, and add 1.54g (7.5mmol) dicyclohexylcarbodiimide (DCC) dissolved in 20mL anhydrous THF dropwise with stirring. After the dropwise addition, continue to react for 30min, then warm to room temperature and continue to react for 12h, filter, remove the solvent under reduced pressure, and separate Mito-GEN by rapid column chromatography. 2.41g of light yellow solid, yield 68% (based on GEN).

[0036] Example 3

[0037] Synthesis of Mitochondria-Targeted Genistein Derivatives (Mito-GEN)

[0038]

[0039] 1.31g (5mmol) triphenylphosphine and 1.66g (8.5mmol) 6-bromohexanoic acid were dissolved in 50mL acetonitrile and refluxed for 30h. The acetonitrile was removed under reduced pressure, and the residue was precipitated with ether and washed with n-hexane to obtain a white solid. 1.35g (5mmol) GEN, 6mg 4-dimethylaminopyridine (DMAP) and 30mL anhydrous tetrahydrofuran (THF) were added, the low temperature reactor was cooled to 0°C, and 1.54g (7.5mmol) dicyclohexylcarbodiimide (DCC) dissolved in 20mL anhydrous THF was added dropwise with stirring. After the addition, the reaction was continued for 30min, then the temperature was raised to room temperature and the reaction was continued for 12h, filtered, the solvent was removed under reduced pressure, and Mito-GEN was separated by rapid column chromatography. 2.41g of light yellow solid, yield 68% (based on GEN).

[0040] Example 4

[0041] Synthesis of Mitochondria-Targeted Genistein Derivatives (Mito-GEN)

[0042]

[0043] Dissolve 1.31g (5mmol) triphenylphosphine and 1.46g (7.5mmol) 6-bromohexanoic acid in 50mL acetonitrile and reflux for 24h. Remove acetonitrile under reduced pressure, precipitate the residue with ether, wash with n-hexane to obtain a white solid. Add 1.35g (5mmol) GEN, 6mg 4-dimethylaminopyridine (DMAP) and 30mL anhydrous tetrahydrofuran (THF), cool the low-temperature reactor to 0°C, and add 1.54g (7.5mmol) dicyclohexylcarbodiimide (DCC) dissolved in 20mL anhydrous THF dropwise with stirring. After the dropwise addition, continue to react for 20min, then warm to room temperature and continue to react for 15h, filter, remove the solvent under reduced pressure, and separate Mito-GEN by rapid column chromatography. 2.41g of light yellow solid, yield 68% (based on GEN).

[0044] Example 5

[0045] Synthesis of Mitochondria-Targeted Genistein Derivatives (Mito-GEN)

[0046]

[0047] Dissolve 1.31g (5mmol) triphenylphosphine and 1.46g (7.5mmol) 6-bromohexanoic acid in 50mL acetonitrile and reflux for 24h. Remove acetonitrile under reduced pressure, precipitate the residue with ether, wash with n-hexane to obtain a white solid. Add 1.35g (5mmol) GEN, 6mg 4-dimethylaminopyridine (DMAP) and 30mL anhydrous tetrahydrofuran (THF), cool the low-temperature reactor to 0°C, and add 1.54g (7.5mmol) dicyclohexylcarbodiimide (DCC) dissolved in 20mL anhydrous THF dropwise with stirring. After the dropwise addition, continue to react for 40min, then warm to room temperature and continue to react for 10h, filter, remove the solvent under reduced pressure, and separate Mito-GEN by rapid column chromatography. 2.41g of light yellow solid, yield 68% (based on GEN).

[0048] Example 6

[0049] Synthesis of Mitochondria-Targeted Genistein Derivatives (Mito-GEN)

[0050]

[0051] Dissolve 1.31g (5mmol) triphenylphosphine and 1.46g (7.5mmol) 6-bromohexanoic acid in 50mL acetonitrile and reflux for 24h. Remove acetonitrile under reduced pressure, precipitate the residue with ether, wash with n-hexane to obtain a white solid. Add 2.03g (7.5mmol) GEN, 6mg 4-dimethylaminopyridine (DMAP) and 30mL anhydrous tetrahydrofuran (THF), cool the low-temperature reactor to 0°C, and add 1.54g (7.5mmol) dicyclohexylcarbodiimide (DCC) dissolved in 20mL anhydrous THF dropwise with stirring. After the dropwise addition, continue to react for 30min, then warm to room temperature and continue to react for 12h, filter, remove the solvent under reduced pressure, and separate Mito-GEN by rapid column chromatography. 2.41g of light yellow solid, yield 45% (based on GEN).

[0052] Example 7

[0053] Synthesis of Mitochondria-Targeted Genistein Derivatives (Mito-GEN)

[0054]

[0055] Dissolve 1.31g (5mmol) triphenylphosphine and 1.46g (7.5mmol) 6-bromohexanoic acid in 50mL acetonitrile and reflux for 24h. Remove acetonitrile under reduced pressure, precipitate the residue with ether, wash with n-hexane to obtain a white solid. Add 1.35g (5mmol) GEN, 6mg 4-dimethylaminopyridine (DMAP) and 30mL anhydrous tetrahydrofuran (THF), cool the low-temperature reactor to 0°C, and add 1.24g (6.0mmol) dicyclohexylcarbodiimide (DCC) dissolved in 20mL anhydrous THF dropwise with stirring. After the dropwise addition, continue to react for 30min, then warm to room temperature and continue to react for 12h, filter, remove the solvent under reduced pressure, and separate Mito-GEN by rapid column chromatography. 2.41g of light yellow solid, yield 68% (based on GEN).

[0056] Example 8

[0057] Synthesis of Mitochondria-Targeted Genistein Derivatives (Mito-GEN)

[0058]

[0059] Dissolve 1.31g (5mmol) triphenylphosphine and 1.46g (7.5mmol) 6-bromohexanoic acid in 50mL acetonitrile and reflux for 24h. Remove acetonitrile under reduced pressure, precipitate the residue with ether, wash with n-hexane to obtain a white solid. Add 1.35g (5mmol) GEN, 6mg 4-dimethylaminopyridine (DMAP) and 30mL anhydrous tetrahydrofuran (THF), cool the low-temperature reactor to 0°C, and add 1.86g (9.0mmol) dicyclohexylcarbodiimide (DCC) dissolved in 20mL anhydrous THF dropwise with stirring. After the dropwise addition, continue to react for 30min, then warm to room temperature and continue to react for 12h, filter, remove the solvent under reduced pressure, and separate Mito-GEN by rapid column chromatography. 2.41g of light yellow solid, yield 68% (based on GEN).

[0060] The spectral data results of the mitochondrial targeted genistein derivatives (Mito-GEN) synthesized in Examples 1 to 8 are as follows: 1 H-NMR (nuclear magnetic hydrogen spectrum, CDCl3, 400M) δ: 7.76 (1H, s), 7.48 (2H, d, J = 8.8 Hz), 7.38-7.32 (m, 15H), 6.93 (2H, d, J = 8.8 Hz,), 6.42 (1H, d, J = 2.0 Hz), 6.36 (1H, d, J = 2.0 Hz, C8-H), 3.57-3.50 (m, 4H), 2.48-2.46 (t, 2H), 2.32-2.30 (t, 2H), 1.51-1.48 (m, 2H), 1.31-1.29 (m, 4H). 13C-NMR (nuclear magnetic carbon spectrum, CDCl3, 400M) δ: 175.6, 172.4, 163.9, 161.6, 160.3, 159.5, 149.7, 135.2, 133.8, 133.7, 130.7, 130.6, 130.3, 118.8, 125.7, 124.5, 113.8, 109.8, 96.3, 92.6, 33.2, 29.3, 27.8, 26.8, 22.16. ESI-MS (mass spectrum, m / z): 629 [M-Br] + . High resolution mass spectrometry HRMS[C 39 H 34 O6P + ]: Calculated value: 629.2088; Measured value: 629.2091.

[0061] Example 9

[0062] A drug for preventing myocardial ischemia-reperfusion injury, in the form of tablets, with the specific ingredients and contents as follows:

[0063]

[0064] The tablets were prepared according to conventional methods, and a total of 1000 tablets were prepared, each tablet containing 10 mg of Mito-GEN.

[0065] Example 10

[0066] A drug for resisting myocardial ischemia-reperfusion injury, which is a capsule, and the specific ingredients and contents are as follows:

[0067]

[0068]

[0069] The capsules were prepared according to the conventional method, and a total of 1000 capsules were prepared, each containing 10 mg of Mito-GEN.

[0070] Embodiment 11

[0071] A drug for preventing myocardial ischemia-reperfusion injury, which is a dispersible tablet, and the specific ingredients and contents are as follows:

[0072]

[0073] Prepared according to the conventional method of dispersible tablets, a total of 1000 tablets were made, each containing 10 mg of Mito-GEN.

[0074] Example 12

[0075] A drug for preventing myocardial ischemia-reperfusion injury, which is a granule, and the specific ingredients and contents are as follows:

[0076]

[0077] The granules were prepared according to the conventional method, and a total of 1000 bags were made, each bag containing 10 mg of Mito-GEN.

[0078] In order to better understand the essence of the present invention, the excellent anti-myocardial ischemia-reperfusion injury activity of mitochondrial targeted genistein (Mito-GEN) will be illustrated by using the animal experiment and results of myocardial ischemia-reperfusion injury in mice.

[0079] 1. Experimental methods

[0080] Forty C57 / BL mice were randomly divided into four groups: sham operation group (Sham group), myocardial ischemia reperfusion group (I / R group), ischemia reperfusion + genistein group (I / R+Gen group) and ischemia reperfusion + Mito-GEN group (I / R+Mito-GEN group). The left anterior descending coronary artery was ligated to cause partial cardiac tissue ischemia for 30 minutes, followed by blood reperfusion for 120 minutes to establish the MI / RI mouse model. The mice in the Sham group were only opened without ligation; before the establishment of the MI / RI mouse model, the mice in the drug-treated group were given Mito-GEN (20 mg / kg) or genistein (200 mg / kg) by gavage every day for 7 consecutive days. The Sham group was given an equal amount of normal saline.

[0081] After the experiment, the mice were fixed on the operating table, and the cardiac function of each group of mice was detected by small animal ultrasound, and the left ventricular end-systolic diameter (LVESd), end-diastolic diameter (LVEDd), ejection fraction (LVEF) and shortening fraction (LVFS) were recorded. Then the eyeballs were removed for blood collection, and the blood was centrifuged at 4°C, 3000r / min for 15min to collect serum. After blood collection, the mice were killed, and the heart tissue was quickly removed for subsequent staining and biochemical index detection, all according to the instructions of the kit.

[0082] 2. Experimental results

[0083] As shown in Table 1, the results of cardiac ultrasound showed that compared with the Sham group, the LVEDd and LVESd of mice in the I / R group were significantly increased, while the LVEF and LVFS were significantly decreased (P<0.05); compared with the model group, the LVEDd and LVESd of mice in the Mito-GEN and GEN treatment groups were significantly decreased, while the LVEF and LVFS were significantly increased.

[0084] Table 1 Evaluation of cardiac function in mice ( n=10)

[0085]

[0086] Note:* P﹤0.05, ** P﹤0.01, compared with Sham; # P﹤0.05, ## P﹤0.01, compared with the I / R group.

[0087] TTC staining results Figure 1 Compared with the I / R group, there was no significant difference in the ratio of the area at risk to the left ventricle (AAR / LV%) in the Mito-GEN and GEN treated mice; the ratio of the infarct area to the area at risk (IF / AAR%) was significantly reduced.

[0088] The results of mouse serum myocardial enzymes are shown in Table 2.

[0089] Compared with the Sham group, the serum CK-MB, AST and cTnI levels of mice in the I / R group were significantly increased (P<0.01), while the serum CK-MB, AST and cTnI levels of mice in the Mito-GEN and GEN treatment groups were significantly decreased compared with the I / R group (P<0.01). The above results indicate that Mito-GEN can effectively alleviate myocardial injury in MI / RI mice.

[0090] Table 2 Evaluation of mouse myocardial enzymes ( n=10)

[0091]

[0092] Note: * P﹤0.05, ** P﹤0.01, compared with Sham; # P﹤0.05, ## P﹤0.01, compared with the I / R group.

[0093] The antioxidant results are shown in Table 3. Compared with the Sham group, the H2O2 and MDA contents in the myocardial tissue of mice in the I / R group were significantly increased, and the SOD activity was significantly decreased (P﹤0.01); compared with the I / R group, the H2O2 and MDA contents in the myocardial tissue of mice in the Mito-GEN and GEN treatment groups were significantly decreased (P﹤0.01), and the SOD activity was significantly increased (P﹤0.01). The above results show that Mito-GEN can effectively produce excessive free radicals in the myocardial tissue of I / R mice, alleviate lipid peroxidation, improve antioxidant capacity, and reduce MI / RI-induced oxidative stress damage.

[0094] Table 3 Changes of antioxidant system in mouse myocardial tissue ( n=10)

[0095]

[0096] Note:* P﹤0.05, ** P﹤0.01, compared with Sham; # P﹤0.05, ## P﹤0.01, compared with the I / R group.

[0097] The inflammatory indexes are shown in Table 4. Compared with the Sham group, the levels of TNF-α and IL-6 in myocardial tissue of mice in the I / R group were significantly increased (P﹤0.01), and the level of IL-10 was significantly decreased (P﹤0.01), while the levels of TNF-α and IL-6 in myocardial tissue of mice in the Mito-GEN and GEN treatment groups were significantly decreased (P﹤0.01or P﹤0.05), and the level of IL-10 was significantly increased (P﹤0.01). The above results show that Mito-GEN can alleviate the inflammatory response induced by MI / RI.

[0098] Table 4 Changes of inflammatory indicators in myocardial tissue of mice ( n=10)

[0099]

[0100] Note: * P﹤0.05, ** P﹤0.01, compared with Sham; # P﹤0.05, ## P﹤0.01, compared with the I / R group.

[0101] The results of the effects of Mito-GEN on myocardial apoptosis induced by MI / RI are as follows Figure 2 As shown. Compared with the Sham group, the expression of pro-apoptotic proteins Bax and cleaved Caspase-3 in the myocardial tissue of mice in the I / R group was significantly increased (P<0.01orP﹤0.05), while the expression of anti-apoptotic protein Bcl-2 was significantly decreased. Mito-GEN treatment can reverse these changes (P<0.01). The above results show that Mito-GEN can effectively alleviate the apoptosis of myocardial tissue cells in I / R mice.

[0102] Considering that Mito-GEN can improve the targeting effect of GEN on mitochondria, the present invention investigated the protective effect of Mito-GEN on mitochondria in myocardial tissue of mice in the I / R group. The results of relevant indicators are shown in Table 5: Compared with the Sham group, the ATP content in myocardial tissue of mice in the I / R group and the activities of mitochondrial respiratory chain complex I and complex IV were significantly reduced (P < 0.01); while the ATP level in myocardial tissue of mice in the Mito-GEN treatment group and the activities of complex I and complex IV were significantly increased (P < 0.01 or P < 0.05). Although GEN treatment can also increase the level of ATP, its effect on the activity of complex I and complex IV in mitochondria is smaller than that of Mito-GEN. The above results show that Mito-GEN can inhibit mitochondrial damage and improve MI / RI.

[0103] Table 5 Changes of related indicators in mitochondria of myocardial tissue of mice ( n=10)

[0104]

[0105] Note: * P﹤0.05, ** P﹤0.01, compared with Sham; # P﹤0.05, ## P﹤0.01, compared with the I / R group.

[0106] In summary, Mito-GEN has the effect of significantly improving myocardial ischemia-reperfusion injury, and its effect is still better than genistein when the dosage is significantly reduced. It can be used as an active ingredient to prepare drugs against myocardial ischemia-reperfusion injury.

[0107] Finally, it should be noted that the above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art can still modify the technical solutions described in the aforementioned embodiments or replace some of the technical features therein by equivalents. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.

Claims

1. A mitochondrial-targeted genistein derivative, characterized in that: It has a structure as shown in formula (I):

2. A method for synthesizing the mitochondrial targeted genistein derivative according to claim 1, characterized in that: The following steps are involved: Using triphenylphosphine and 6-bromohexanoic acid as raw materials for coordination reaction, an intermediate is obtained; The intermediate is mixed with 4',5,7-trihydroxyisoflavone to carry out a dehydration reaction to obtain the mitochondrial targeting genistein derivative; The synthetic route is:

3. The synthesis method according to claim 2, characterized in that The molar ratio of the triphenylphosphine to the 6-bromohexanoic acid is 1:1.3-1.

7.

4. The synthesis method according to claim 2, characterized in that The coordination reaction is to mix triphenylphosphine and 6-bromohexanoic acid, use acetonitrile as solvent, and reflux for 20 to 30 hours.

5. The synthesis method according to claim 2, characterized in that The dehydration reaction is carried out according to the following steps: The intermediate is mixed with 4',5,7-trihydroxyisoflavone, a catalyst and a reaction solvent are added, dicyclohexylcarbodiimide is added at 0°C, the reaction is continued for 20 to 40 minutes, and then the temperature is raised to room temperature and the reaction is continued for 10 to 15 hours.

6. The synthesis method according to claim 5, characterized in that The catalyst is 4-dimethylaminopyridine; The reaction solvent is anhydrous tetrahydrofuran; The molar ratio of the triphenylphosphine to the 4',5,7-trihydroxyisoflavone is 1:1-1.5; The molar ratio of the 4',5,7-trihydroxyisoflavone to the dicyclohexylcarbodiimide is 1:1.2-1.

8.

7. Use of the mitochondrial targeted genistein derivative according to claim 1 in the preparation of a drug for preventing myocardial ischemia-reperfusion injury.

8. A drug for treating myocardial ischemia-reperfusion injury, characterized in that: The invention comprises the mitochondrial targeting genistein derivative according to claim 1 and a pharmaceutically acceptable auxiliary material.

9. The drug for treating myocardial ischemia-reperfusion injury according to claim 8, characterized in that: The dosage form of the drug is tablet, capsule, dispersion or granule.

10. The drug for treating myocardial ischemia-reperfusion injury according to claim 8, characterized in that: The mitochondria-targeted genistein derivative is used as the only active pharmaceutical ingredient.

Images