A rotenoid-malonate-quaternary ammonium compound targeting mitochondria and its preparation method and application

Abstract

This invention belongs to the field of medicinal chemistry, specifically relating to a mitochondrial-malonic acid-dequinoline chloride compound, its preparation method, and its application. The rotenol-malonic acid-dequinoline chloride compound has the following structural formula. This invention uses malonic acid as a bridging molecule, covalently binding the rotenone derivative—rotenol—with the mitochondrial-targeting molecule—dequinoline chloride to obtain an anticancer prodrug molecule—rotenol-malonic acid-dequinoline chloride. This prodrug can promote drug accumulation in the mitochondria of cancer cells. Given that dequinoline chloride has a significant apoptosis-promoting function, the synergistic effect of rotenol and dequinoline chloride induces the production of a large amount of reactive oxygen species within cancer cells, thereby exhibiting high anticancer activity and achieving highly effective and low-toxicity anticancer treatment.

Description

Technical Field

[0001] This invention belongs to the field of medicinal chemistry technology, specifically relating to a mitochondrial-malonic acid-diquinoline chloride compound, its preparation method, and its application. Background Technology

[0002] Rotenone derivatives are a class of isoflavone compounds with insecticidal activity extracted from plants such as *Rotenone*. Since 1932, 47 rotenone compounds have been extracted and isolated from these plants. These compounds exhibit insecticidal activity by inhibiting mitochondrial respiration through the inhibition of reduced nicotinamide adenine dinucleotide (NADH). Studies have shown that rotenone can reduce environmental pollution, stimulate plant growth, and effectively delay the development of pesticide resistance in pests. However, rotenone is easily decomposed and inactivated under conditions such as sunlight, oxygen, and high temperature, which greatly limits its application. To reduce the limitations of rotenone, its structure can be modified or chemically modified to construct targeted prodrugs. Designing highly effective and low-toxicity rotenone derivatives and improving their biological activity is an urgent problem to be solved.

[0003] Recent studies have found that rotenone has inhibitory effects on various tumor cells, including lung cancer, breast cancer, gastric cancer, pancreatic cancer, and colon cancer cells. As an anticancer substance, rotenone can induce apoptosis in various cancer cells, including human breast cancer cells, B lymphocytes, promyelocytic leukemia cells, human neuroblastoma cells, and lung cancer cells. Therefore, the anticancer mechanism of rotenone targeting mitochondria is a research topic worthy of in-depth investigation, and rotenone is considered a very promising anticancer lead compound. However, when the dose of rotenone exceeds the effective concentration, it can cause damage to the heart, lungs, and nervous system, and can also induce Parkinson's syndrome, thus posing a significant obstacle to the practical application of rotenone. Therefore, how to structurally modify or chemically modify rotenone to increase its stability while retaining its anticancer activity and enabling it to target tumors, thereby reducing its toxic side effects on other tissues, especially the nervous system, and improving its biological activity, is an urgent problem to be solved. Summary of the Invention

[0004] To address the aforementioned problems, this invention provides a mitochondrial-targeting rotenol-malonic acid-dequinoline chloride compound, its preparation method, and its applications. Using malonic acid as a bridging molecule, this invention covalently binds the rotenone derivative rotenol to the mitochondrial-targeting molecule dequinoline chloride to obtain an anticancer prodrug molecule—rotenol-malonic acid-dequinoline chloride. This prodrug promotes drug accumulation in the mitochondria of cancer cells. Given that dequinoline chloride has a significant apoptosis-promoting function, the synergistic effect of rotenol and dequinoline chloride induces the production of large amounts of reactive oxygen species within cancer cells, thereby exhibiting high anticancer activity and achieving highly effective and low-toxicity anticancer treatment.

[0005] The present invention solves the above-mentioned technical problems through the following technical solutions.

[0006] The first objective of this invention is to provide a rotenol-malonic acid-dequinoline chloride compound targeting mitochondria, said rotenol-malonic acid-dequinoline chloride compound having the following structural formula:

[0007]

[0008] A second objective of this invention is to provide a method for preparing the above-mentioned mitochondrial-targeting rotenol-malonic acid-diquinoline chloride compound, characterized by comprising the following steps:

[0009] S1. Rotenone was dissolved in the first solvent, sodium borohydride was added and reacted at room temperature. After the reaction was completed, water was added while stirring to obtain compound 1.

[0010] S2. Place malonic acid in a container, add 1,4-dioxane under a protective gas atmosphere, add thionyl chloride dropwise and carry out the first oil bath reaction. After the reaction is completed, remove the solvent to obtain the residue, add the compound 1 solution to the residue, add triethylamine dropwise and carry out the second oil bath reaction. After the reaction is completed, remove the solvent, wash and dry to obtain compound 2.

[0011] S3. Compound 2, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide and 1-hydroxybenzotriazole were placed in a container, and a second solvent was added under a protective gas atmosphere to carry out the first activation reaction. After the reaction was completed, a dequinoline chloride solution was added to adjust the pH of the system to 9 and carry out the third oil bath reaction. After the reaction was completed, the mixture was filtered, concentrated, recrystallized and dried to obtain the mitochondrial-targeted rotenol-malonic acid-dequinoline chloride compound.

[0012] Preferably, in S1, the mass-to-volume ratio of rotenone, the first solvent, sodium borohydride, and water is 270-330 mg: 8-12 mL: 120-140 mg: 8-12 mL.

[0013] Preferably, in S1, the room temperature reaction time is 3-5 hours, and the first solvent is methanol.

[0014] Preferably, in S2, the mass-to-volume ratio of malonic acid, 1,4-dioxane, thionyl chloride, compound 1, and triethylamine is 40-60 mg: 10-12 mL: 100-110 μL: 230-240 mg: 60-70 μL; the compound 1 solution is obtained by mixing the compound and N,N-dimethylformamide at a mass-to-volume ratio of 237 mg: 10 mL.

[0015] Preferably, in S2, the temperature of the first oil bath reaction is 100-120℃, and the reaction time is 12-15h; the temperature of the second oil bath reaction is 60-80℃, and the reaction time is 12-15h.

[0016] Preferably, in S3, the mass-to-volume ratio of compound 2, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide, 1-hydroxybenzotriazole, the second solvent, and dequinoline chloride is 70-80 mg:120-140 mg:120-130 mg:25-30 mL:65-80 mg; the dequinoline chloride solution is obtained by mixing dequinoline chloride and methanol at a mass-to-volume ratio of 76 mg:7 mL; the second solvent is methanol.

[0017] Preferably, in step S3, the temperature of the first activation reaction is 0-4℃ and the time is 4-6h; the pH of the system is adjusted to 9 using N,N-diisopropylethylamine; and the temperature of the third oil bath reaction is 37℃ and the time is 20-24h.

[0018] A third objective of this invention is to provide the use of the above-mentioned mitochondrial-malonic acid-dequinoline chloride compound in the preparation of therapeutic and / or preventive cancer drugs.

[0019] Preferably, the cancer includes lung cancer, cervical cancer, liver cancer, breast cancer, pancreatic cancer, or colon cancer.

[0020] Compared with the prior art, the present invention has the following advantages:

[0021] (1) This invention uses malonic acid as a bridging molecule to covalently bind rotenone derivative rotenol to mitochondrial-targeting molecule dequinoline chloride, thus obtaining an anticancer prodrug molecule – rotenol-malonic acid-dequinoline chloride. This prodrug can promote the accumulation of drugs in the mitochondria of cancer cells. Given that dequinoline chloride has a significant apoptosis-promoting function in cancer cells, the synergistic effect of rotenol and dequinoline chloride promotes the production of a large amount of reactive oxygen species in cancer cells, thereby exhibiting high anticancer activity. In addition, since the cell membrane potential of cancer cells is much higher than that of normal cells, the positively charged dequinoline chloride can more easily enter the cytoplasm of cancer cells under the impetus of the cell transmembrane potential, giving the prodrug tumor-targeting function and ultimately achieving highly effective and low-toxicity anticancer effects.

[0022] (2) This invention starts with the raw material rotenone and uses a reduction reaction to obtain its derivative rotenol. Subsequently, it is covalently linked with malonic acid through an esterification reaction to obtain the rotenol-malonic acid intermediate. Under suitable conditions, another free carboxyl group in this intermediate will further react with the amino group on dequinoline chloride to generate the rotenol-malonic acid-dequinoline chloride prodrug molecule. Attached Figure Description

[0023] Figure 1 This is the proton NMR spectrum of compound 1 in Example 1 of the present invention;

[0024] Figure 2 This is the carbon spectrum of compound 1 in Example 1 of the present invention;

[0025] Figure 3 This is the mass spectrum of compound 1 in Example 1 of the present invention;

[0026] Figure 4 This is the proton NMR spectrum of compound 2 in Example 1 of the present invention;

[0027] Figure 5 This is the carbon spectrum of compound 2 in Example 1 of the present invention;

[0028] Figure 6 This is the mass spectrum of compound 2 from Example 1 of the present invention;

[0029] Figure 7 This is the proton NMR spectrum of the rotenol-malonic acid-dequinoline chloride compound in Example 1 of the present invention;

[0030] Figure 8 This is the carbon spectrum of the rotenol-malonic acid-dequinoline chloride compound in Example 1 of the present invention;

[0031] Figure 9 This is the mass spectrum of the rotenol-malonic acid-dequinoline chloride compound from Example 1 of the present invention;

[0032] Figure 10 This is a graph showing the cell survival rate of three human cancer cell lines after treatment with the rotenol-malonic acid-dequinoline chloride compound of this invention. Detailed Implementation

[0033] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0034] It should be noted that the technical terms used in this invention are only for the purpose of describing specific embodiments and are not intended to limit the scope of protection of this invention. Unless otherwise specified, all raw materials, reagents, instruments and equipment used in the following embodiments of this invention can be purchased from the market or prepared by existing methods.

[0035] A rotenol-malonic acid-dequinoline chloride compound targeting mitochondria, wherein the rotenol-malonic acid-dequinoline chloride compound has the following structural formula:

[0036]

[0037] A second objective of this invention is to provide a method for preparing the above-mentioned mitochondrial-targeting rotenol-malonic acid-diquinoline chloride compound, comprising the following steps:

[0038] S1. Rotenone was dissolved in the first solvent, sodium borohydride was added and reacted at room temperature. After the reaction was completed, water was added while stirring to obtain compound 1.

[0039] S2. Place malonic acid in a container, add 1,4-dioxane under a protective gas atmosphere, add thionyl chloride dropwise and carry out the first oil bath reaction. After the reaction is completed, remove the solvent by vacuum distillation to obtain the residue. Add the compound 1 solution to the residue, add triethylamine dropwise and carry out the second oil bath reaction. After the reaction is completed, remove the solvent by vacuum distillation, wash and dry to obtain compound 2.

[0040] S3. Compound 2, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide and 1-hydroxybenzotriazole were placed in a container, and a second solvent was added under a protective gas atmosphere to carry out the first activation reaction. After the reaction was completed, a dequinoline chloride solution was added to adjust the pH of the system to 9 and carry out the third oil bath reaction. After the reaction was completed, the mixture was filtered, concentrated, recrystallized and dried to obtain the mitochondrial-targeted rotenol-malonic acid-dequinoline chloride compound.

[0041] The synthesis reaction equation is as follows:

[0042]

[0043] Example 1

[0044] A method for preparing mitochondrial-targeting rotenol-malonic acid-diquinoline chloride compounds includes the following steps:

[0045] S1. Dissolve 300 mg of rotenone in 10 mL of methanol, then add 127 mg of sodium borohydride, and stir at room temperature for 4 h. The reaction solution gradually becomes clear. Then, while stirring, add 10 mL of deionized water dropwise to the reaction solution. The solution gradually becomes turbid and a large amount of white solid precipitates. After filtration and vacuum drying at 60 °C for 12 h, a white powdery solid is obtained, which is compound 1.

[0046] The proton spectrum of compound 1 is as follows Figure 1 As shown, 1 H NMR(500MHz,DMSO-d6)δ7.26(s,1H),7.05(s,1H),6.37(s,2H),5.64(s,1H),5.18(s,1H),5.01(s,2H),4.86(s,2H),4.46(s,1 H),4.17(s,1H),3.64(d,J=28.0Hz,6H),3.39(d,J=4.7Hz,1H),3.22-3.09(m,1H),2.80(dd,J=15.6,7.8Hz,1H),1.69(s,3H).

[0047] The carbon spectrum of compound 1 is as follows: Figure 2 As shown, 13 C NMR (126MHz, DMSO) δ160.59,149.88,149.06,148.92,144.50,143.04,128.18,117.94,114.06,111.87,111.47,101.54,100. 77,85.85,70.54,66.53,66.22,56.61,55.83,49.07,40.50,40.34,40.17,40.00,39.84,39.67,39.50,36.97,31.90,17.52.

[0048] The mass spectrum of compound 1 is as follows Figure 3 As shown, HR-MS: 396.1 (M+Na) + ).

[0049] The synthesis reaction equation is as follows:

[0050]

[0051] S2. Add 50 mg (0.48 mmol) of malonic acid to a 25 mL brown three-necked round-bottom flask. Under nitrogen protection, add 10 mL of 1,4-dioxane, heat in an oil bath at 105 °C, reflux, and add 104 μL of thionyl chloride (1.44 mmol). After reacting for 4 h, remove the solvent by vacuum distillation. Add 10 mL of anhydrous DMF (N,N-dimethylformamide) to the residue and 237 mg (0.6 mmol) of compound 1, add 66 μL of TEA (0.48 mmol of triethylamine), heat in an oil bath at 60 °C, and reflux for 12 h. After the reaction is complete, remove the solvent by vacuum distillation. Wash the residue three times with 0.5 mol / L hydrochloric acid, then dissolve it in methanol, evaporate the solvent by rotary evaporation, and finally dry it under vacuum at 60 °C for 12 h to obtain a brownish-yellow powder (compound 2).

[0052] The proton spectrum of compound 2 is as follows Figure 4 As shown, 1 H NMR(500MHz,DMSO-d6)δ7.28(s,2H),7.03(d,J=2.4Hz,2H),6.99(d,J=8.0Hz,2H),6.55(s,2H),6.47(d,J=8.1Hz,2H), 5.41-5.31(m,2H),5.27(t,J=8.7Hz,2H),5.10(d,J=2.2Hz,2H),4.96(t,J=1.8Hz,2H),4.62(dd,J=9.9,5.4Hz,2H),4.0 9(dd,J=10.9,9.9Hz,4H),3.84(s,6H),3.80(s,6H),3.50(q,J=7.0Hz,6H),3.30(dd,J=15.7,9.6Hz,2H),2.94(dd,J=15 .7,7.8Hz,2H),2.10-2.00(m,1H),1.79(s,5H),1.32-1.28(m,3H),1.23(dt,J=14.0,7.1Hz,3H),1.12(t,J=7.0Hz,9H).

[0053] The carbon spectrum of compound 2 is as follows Figure 5 As shown, 13 C NMR (126MHz, DMSO) δ161.07,150.64,149.47,149.07,145.04,144.21,127.16,123.42,117.29,112.91,112. 66,112.17,110.90,106.57,103.05,101.61,86.16,71.05,67.54,56.54,56.49,56.11,31.44,19.02,17.56.

[0054] The mass spectrum of compound 2 is as follows Figure 6 As shown, HR-MS: 482.1 (M+H + ).

[0055] The synthesis reaction equation is as follows:

[0056]

[0057] S3. Take 275 mg (0.24 mmol) of the compound, 136 mg of EDCI (1-(3-dimethylaminopropyl)-3-ethylcarbodiimide and 0.69 mmol of 1-hydroxybenzotriazole), and 124 mg of HOBT (0.29 mmol of 1-hydroxybenzotriazole) and add them to a 50 mL brown three-necked round-bottom flask. Under nitrogen protection, add 25 mL of methanol and stir in an ice-water bath for 5 h to activate. Then, add 7 mL of 76 mg (0.14 mmol) of dequinoline chloride dissolved in methanol and 900 μL of DIPEA (N,N-diisopropylethylamine) to adjust the pH of the system to 9. Heat in an oil bath at 37 °C for 24 h. After the reaction is complete, filter to remove the residue, and obtain a yellow filtrate. Concentrate by rotary evaporation, recrystallize by ice-crystallated diethyl ether, filter and dry to obtain a yellow powder, which is the rotenol-malonic acid-dequinoline chloride compound.

[0058] The proton NMR spectrum of the rotenol-malonic acid-diquinoline chloride compound is as follows: Figure 7 As shown, 1H NMR (500MHz, DMSO-d6) δ8.93(d,J=16.2Hz,2H),8.49(d,J=8.3Hz,1H),8.14(d,J= 9.0Hz,1H),8.04-7.97(m,1H),7.71(t,J=7.6Hz,1H),7.22(s,3H),6.97(d,J=2.4H z,3H),6.93(d,J=8.0Hz,3H),6.75(s,1H),6.50(s,3H),6.42(d,J=8.0Hz,3H),5. 33-5.25(m,3H),5.22(t,J=8.7Hz,3H),5.04(s,3H),4.90(t,J=1.8Hz,3H),4.56(d d,J=9.9,5.4Hz,3H),4.44(t,J=8.2Hz,2H),4.03(t,J=10.4Hz,3H),3.78(s,9H), 3.74(s,9H),3.25(dd,J=15.7,9.6Hz,5H),3.08(qd,J=7.3,4.8Hz,1H),2.89(dd,J =15.6,7.9Hz,3H),2.72(s,3H),2.04-1.94(m,1H),1.73(s,8H),1.44(d,J=8.8Hz, 2H),1.34(d,J=7.7Hz,1H),1.30(s,2H),1.26-1.14(m,5H),0.85(t,J=6.8Hz,1H).

[0059] The carbon spectrum of the compound rotenol-malonic acid-diquinoline chloride is as follows: Figure 8 As shown, 13 C NMR (126MHz, DMSO-d6) δ161.06,155.40,150.62,149.46,149.06,145.03,144.20,127.17,126.34,123.42,117.29,112.92,112.66,112. 18,110.89,106.54,104.46,103.06,101.60,86.15,71.04,67.53,56 .53,56.11,48.36,31.44,29.44,29.13,28.52,26.35,21.99,17.57.

[0060] Mass spectra of rotenol-malonic acid-diquinoline chloride compound are as follows: Figure 9 As shown, HR-MS: 991.3 (M+H) + ).

[0061] The synthesis reaction equation is as follows:

[0062]

[0063] Example 2

[0064] Cytotoxicity test of rotenol-malonic acid-dequinoline chloride compound.

[0065] Different concentrations of the intermediate product and the rotenol-malonic acid-dequinoline chloride compound were co-incubated with cells for 48 h. The killing effects on three types of cancer cells—human lung cancer cells (A549), human cervical cancer cells (HeLa), and human liver cancer cells (HepG-2)—were detected using the tetramethylazazole salt colorimetric method. The intermediate product and the final product, rotenol-malonic acid-dequinoline chloride compound, gradually reduced cell viability in a dose-dependent manner. The IC50 was defined as the 50% inhibitory concentration, i.e., the concentration at which cell viability was half that of the control sample. A lower IC50 indicates higher cytotoxicity of the drug.

[0066] Figure 10 This is a graph showing the cell survival rate of three human cancer cell lines after treatment with the rotenol-malonic acid-dequinoline chloride compound of this invention. 50 Values ​​were calculated using GraphPadPrism 9.0. The vertical axis provides the viable cell fraction (%), and the horizontal axis provides log[concentration] (μM). Cells were treated for 48 h. Cytotoxicity was assessed by the MTT assay. These results are from a representative assay from one of three independent trials. Data are characterized as mean ± SD. Figure 10 In the figure, A is the survival rate of compound 1 against three types of cancer cells: A549, HeLa, and HepG-2, and B is the survival rate of rotenol-malonic acid-dequinoline chloride against three types of cancer cells: A549, HeLa, and HepG-2.

[0067] from Figure 10The results show that (1) for the three cancer cells A549, HeLa, and HepG-2, the cell survival rate decreased with increasing drug concentration regardless of the type of cancer cell, indicating a clear dose-dependent relationship between cell survival rate and drug concentration; (2) by observing the inhibitory effects of different drugs on cancer cells, it can be seen that the cytotoxicity of the rotenol-malonic acid-dequinoline chloride compound is the strongest, while the cytotoxicity of the intermediate product is weaker. This is because the final product is not only coupled with rotenol, but also with dequinoline chloride. Both drugs can target the mitochondria in cancer cells and can play a synergistic role to a certain extent, enhancing the toxicity of the drugs. Different types of cancer cells have different inhibitory rates on cells. For example, the inhibitory effect of the rotenol-malonic acid-dequinoline chloride compound on HepG-2 cells is more obvious than that on A549 cells. This may be because the mechanism by which this prodrug promotes apoptosis in HepG-2 cells is different from that in other cells such as A549, resulting in different results. However, overall, this prodrug has a good inhibitory effect on several types of cancer cells.

[0068] It should be noted that when numerical ranges are involved in this invention, it should be understood that both endpoints of each numerical range and any value between the two endpoints can be selected. Since the steps and methods used are the same as in the embodiments, preferred embodiments are described here to avoid redundancy. Although preferred embodiments of the invention have been described, those skilled in the art, once they understand the basic inventive concept, can make other changes and modifications to these embodiments. Therefore, the appended claims are intended to be interpreted as including the preferred embodiments as well as all changes and modifications falling within the scope of this invention.

[0069] Obviously, those skilled in the art can make various modifications and variations to this invention without departing from its spirit and scope. Therefore, if these modifications and variations fall within the scope of the claims of this invention and their equivalents, this invention also intends to include these modifications and variations.

Claims

1. A rotenol-malonic acid-diquinoline chloride compound targeting mitochondria, characterized in that, The rotenol-malonic acid-dequinoline chloride compound has the following structural formula: The rotenol-malonic acid-dequinoline chloride compound is obtained by covalently binding rotenol, a rotenone derivative, with dequinoline chloride, a mitochondrial targeting molecule, using malonic acid as a bridging molecule.

2. A method for preparing the mitochondrial-targeting rotenol-malonic acid-diquinoline chloride compound according to claim 1, characterized in that, Includes the following steps: S1. Rotenone was dissolved in the first solvent, sodium borohydride was added, and the reaction was carried out at room temperature. After the reaction was completed, water was added while stirring to obtain compound 1. Compound 1 has the following structural formula: ； S2. Malonic acid was placed in a container, and 1,4-dioxane was added under a protective gas atmosphere. Thionyl chloride was added dropwise, and a first oil bath reaction was carried out. After the reaction was completed, the solvent was removed to obtain a residue. A solution of compound 1 was added to the residue, and triethylamine was added dropwise, and a second oil bath reaction was carried out. After the reaction was completed, the solvent was removed, the mixture was washed, and dried to obtain compound 2. Compound 2 has the following structural formula: ； S3. Compound 2, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide and 1-hydroxybenzotriazole were placed in a container, and a second solvent was added under a protective gas atmosphere to carry out the first activation reaction. After the reaction was completed, a dequinoline chloride solution was added to adjust the pH of the system to 9 and carry out the third oil bath reaction. After the reaction was completed, the mixture was filtered, concentrated, recrystallized and dried to obtain the mitochondrial-targeted rotenol-malonic acid-dequinoline chloride compound.

3. The method for preparing the mitochondrial-targeting rotenol-malonic acid-diquinoline chloride compound according to claim 2, characterized in that, In S1, the mass-to-volume ratio of rotenone, the first solvent, sodium borohydride, and water is 270-330 mg: 8-12 mL: 120-140 mg: 8-12 mL.

4. The method for preparing the mitochondrial-targeting rotenol-malonic acid-diquinoline chloride compound according to claim 2, characterized in that, In S1, the room temperature reaction time is 3-5 h, and the first solvent is methanol.

5. The method for preparing the mitochondrial-targeting rotenol-malonic acid-diquinoline chloride compound according to claim 2, characterized in that, In S2, the mass-to-volume ratio of malonic acid, 1,4-dioxane, thionyl chloride, compound 1, and triethylamine is 40-60 mg: 10-12 mL: 100-110 μL: 230-240 mg: 60-70 μL; the compound 1 solution is obtained by mixing the compound and N,N-dimethylformamide at a mass-to-volume ratio of 237 mg: 10 mL.

6. The method for preparing the mitochondrial-targeting rotenol-malonic acid-diquinoline chloride compound according to claim 2, characterized in that, In S2, the temperature of the first oil bath reaction is 100-120 ℃, and the reaction time is 12-15 h; the temperature of the second oil bath reaction is 60-80 ℃, and the reaction time is 12-15 h.

7. The method for preparing the mitochondrial-targeting rotenol-malonic acid-diquinoline chloride compound according to claim 2, characterized in that, In S3, the mass-to-volume ratio of compound 2, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide, 1-hydroxybenzotriazole, the second solvent, and dequinoline chloride is 70-80 mg:120-140 mg:120-130 mg:25-30 mL:65-80 mg; the dequinoline chloride solution is obtained by mixing dequinoline chloride and methanol at a mass-to-volume ratio of 76 mg:7 mL; the second solvent is methanol.

8. The method for preparing the mitochondrial-targeting rotenol-malonic acid-diquinoline chloride compound according to claim 2, characterized in that, In S3, the temperature of the first activation reaction is 0-4 ℃ and the time is 4-6 h; the pH of the system is adjusted to 9 using N,N-diisopropylethylamine; the temperature of the third oil bath reaction is 37 ℃ and the time is 20-24 h.

9. The use of the mitochondrial-targeting rotenol-malonic acid-dequinoline chloride compound of claim 1 in the preparation of a medicament for treating and / or preventing cancer, characterized in that, The cancer in question is lung cancer, cervical cancer, liver cancer, or breast cancer.

Images