An indole-3-aryl ketone derivative, its preparation method and application

Abstract

This invention relates to the field of anticancer drugs, and more particularly to an indole-3-aryl ketone derivative, its preparation method, and its applications. The indole-3-aryl ketone derivative is compound I-VI, which can be used to prepare drugs for the prevention and / or treatment of cancer, including at least one of breast cancer, liver cancer, lung cancer, colorectal cancer, leukemia, pancreatic cancer, glioma, osteosarcoma, cervical cancer, ovarian cancer, kidney cancer, and esophageal cancer. This invention screened the activity of various compounds and, for the first time, discovered that compound I-VI exhibits excellent inhibitory activity against multiple different types of human cancer cells, providing a potential option for broad-spectrum anticancer drugs.

Description

Technical Field

[0001] This invention relates to the field of anticancer drugs, and more particularly to an indole-3-aryl ketone derivative, its preparation method, and its application. Background Technology

[0002] Cancer is one of the leading causes of death worldwide, posing a serious threat to human health. Despite significant progress in cancer diagnosis and treatment in recent years, existing therapies, such as chemotherapy, radiotherapy, targeted therapy, and immunotherapy, still face numerous limitations and challenges. For example, many chemotherapy drugs have poor selectivity, causing severe toxic side effects on normal tissues and organs while killing tumor cells; tumor cells are prone to multidrug resistance, leading to treatment failure; some targeted drugs are only effective against specific gene mutations or specific types of tumors, limiting their applicability; and the response rate of immunotherapy varies greatly among different cancer types and patients, and may be accompanied by immune-related adverse reactions. Therefore, developing novel, highly effective, low-toxicity drugs with broad-spectrum anticancer activity remains an urgent need and a major challenge in the current field of anti-tumor drug development.

[0003] Among the many compound skeletons with potential antitumor activity, indole compounds have attracted much attention due to their broad range of biological activities. Natural and synthetic indole derivatives have been shown to inhibit tumor cell proliferation and induce apoptosis through multiple mechanisms. The indole-3-one structural unit is considered an important pharmacophore and is present in many biologically active molecules.

[0004] Researchers are modifying the structure of indole-3-one skeletons to obtain derivatives with higher activity, better selectivity, or novel mechanisms of action. Existing literature reports that some compounds with indole-3-one or similar indole structures exhibit inhibitory activity against specific tumor types, but they often lack broad-spectrum anticancer properties, failing to meet the needs of combating multiple cancers. Therefore, developing indole-3-arylone derivatives with broad-spectrum and highly effective antitumor activity is of great significance. Summary of the Invention

[0005] To address the shortcomings of existing technologies, this invention provides a class of indole-3-aryl ketone derivatives and their application in the preparation of drugs for the prevention and / or treatment of cancer. The indole-3-aryl ketone derivatives exhibit excellent inhibitory activity against a variety of different types of human cancer cells.

[0006] To solve the above-mentioned technical problems, the technical solution of the present invention is as follows: The present invention provides an indole-3-aryl ketone derivative, wherein the indole-3-aryl ketone derivative is selected from one or more of compounds I-VI, and has the following structural formula:

[0007] .

[0008] The indole-3-aryl ketone derivative is preferably compound I, compound II, compound V or compound VI;

[0009] The indole-3-aryl ketone derivative is further preferably compound I, with the following structural formula:

[0010] .

[0011] The selected compounds exhibit good inhibitory activity against cancer cells, which is superior to that of the positive control cisplatin.

[0012] The present invention also provides a method for preparing the indole-3-aryl ketone derivative, the method comprising the following steps: mixing compound M1, compound M2 and compound M3, adding cesium carbonate and reacting at room temperature under 460 nm light for 8-20 h, and separating by column chromatography to obtain compounds I-VI;

[0013] Compound M1 is acenaphthoquinone; compound M3 is trifluoroethanol or hexafluoroisopropanol;

[0014] The structural formula of compound M2 is as follows: , , , , or .

[0015] Preferably, the molar volume ratio of compounds M1, M2 and M3 is 2-4 mmol: 1-3 mmol: 15-30 mL; the amount of cesium carbonate added is 2-3 times the molar amount of compound M1.

[0016] The present invention also provides the use of the indole-3-aryl ketone derivative in the preparation of drugs for the prevention and / or treatment of cancer, wherein the cancer is at least one of breast cancer, liver cancer, gastric cancer, leukemia, lung cancer, pancreatic cancer, glioma, osteosarcoma, ovarian cancer, kidney cancer and skin cancer.

[0017] Preferably, the cancer is breast cancer.

[0018] Preferably, the indole-3-aryl ketone derivative, its pharmaceutically acceptable salt, ester, stereoisomer, metabolite or prodrug can also be used as the active pharmaceutical ingredient.

[0019] Preferably, the active pharmaceutical ingredient is used in combination with a pharmaceutically acceptable carrier. That is, when compounds I-VI are used as drugs, they can be used directly or in the form of a pharmaceutical composition. They can be administered orally or by injection to patients in need of treatment, thus enabling the formulation of various drug forms for wide application.

[0020] As a further description of the above scheme: the mass fraction of the active pharmaceutical ingredient is 0.1% to 99%; preferably, the mass fraction of the active pharmaceutical ingredient is 0.1% to 20%.

[0021] Currently marketed indole anticancer drugs (such as indirubin and sunitinib) all contain indole or oxidized indole skeletons, and their mechanisms of action involve inhibiting kinase activity, interfering with microtubule polymerization, or inducing apoptosis. This indicates that the indole ring system is an effective carrier of anticancer activity. The type of substituent at the C-3 position of indole significantly affects anticancer activity. In this invention, an aromatic ketone group is introduced at the C-3 position of indole. The aryl electronic effect regulates the target affinity, which can significantly enhance anticancer activity. The steric hindrance of the aryl substituent can affect the molecular conformation. For example, ortho-substitution may enhance the intercalation ability into the hydrophobic pocket of the target, which lays the structural foundation for the broad-spectrum anticancer activity of the compound provided by this invention.

[0022] Compared with the prior art, the present invention has the following beneficial effects: The present invention conducts activity screening on indole-3-aryl ketone derivatives and discovers for the first time that indole-3-aryl ketone derivatives (compounds I-VI) have excellent inhibitory activity against a variety of different types of human cancer cells, providing an option for broad-spectrum anticancer drugs.

[0023] In addition, the synthesis process provided by this invention is simple to operate, produces fewer byproducts, has a high yield, and is environmentally friendly. Attached Figure Description

[0024] Figure 1 The structural formulas of six synthetic indole-3-aryl ketone derivatives are shown.

[0025] Figure 2 For compound I 1 H-NMR (400MHz, DMSO- d 6) Spectrum;

[0026] Figure 3 For compound I 13 C-NMR (100MHz, DMSO- d 6) Spectrum;

[0027] Figure 4 For compound I 19 F-NMR (376MHz, DMSO- d 6) Spectrum;

[0028] Figure 5 For compound II 1 H-NMR (400MHz, DMSO- d 6) Spectrum;

[0029] Figure 6For compound II 13 C-NMR (100MHz, DMSO- d 6) Spectrum;

[0030] Figure 7 For compound II 19 F-NMR (376MHz, DMSO- d 6) Spectrum;

[0031] Figure 8 For compound III 1 H-NMR (400MHz, DMSO- d 6) Spectrum;

[0032] Figure 9 For compound III 13 C-NMR (100MHz, DMSO- d 6) Spectrum;

[0033] Figure 10 For compound III 19 F-NMR (376MHz, DMSO- d 6) Spectrum;

[0034] Figure 11 For compound IV 1 H-NMR (400MHz, DMSO- d 6) Spectrum;

[0035] Figure 12 For compound IV 13 C-NMR (100MHz, DMSO- d 6) Spectrum;

[0036] Figure 13 For compound IV 19 F-NMR (376MHz, DMSO- d 6) Spectrum;

[0037] Figure 14 For compound V 1 H-NMR (400MHz, DMSO- d 6) Spectrum;

[0038] Figure 15 For compound V 13 C-NMR (100MHz, DMSO- d 6) Spectrum;

[0039] Figure 16 For compound V 19F-NMR (376MHz, DMSO- d 6) Spectrum;

[0040] Figure 17 For compound VI 1 H-NMR (400MHz, DMSO- d 6) Spectrum;

[0041] Figure 18 For compound VI 13 C-NMR (100MHz, DMSO- d 6) Spectrum;

[0042] Figure 19 For compound VI 19 F-NMR (376MHz, DMSO- d 6) Spectrum;

[0043] Figure 20 The X-ray single-crystal diffraction structure of compound 4e is shown.

[0044] Figure 21 This is the X-ray single-crystal diffraction structure of compound 5b. Detailed Implementation

[0045] The technical solutions of the present invention will be further described in detail below with reference to the accompanying drawings and specific embodiments, but the present invention is not limited to the following technical solutions.

[0046] The human liver cancer cells used in the following examples are human liver cancer cells SNU-387, human lung cancer cells are human lung cancer cells H460, human breast cancer cells are human breast cancer cells HCC1937 and MDA-MB-231, human leukemia cells are human leukemia cells Jurkat, human gastric cancer cells are human gastric cancer cells SGC-7901, human kidney cancer cells are human kidney cancer cells G401, human ovarian cancer cells are human ovarian cancer cells SKOV3, human glioma cells are human glioma cells U251, human pancreatic cancer cells are human pancreatic cancer cells SW1990, human osteosarcoma cells are human osteosarcoma cells MG63, and human skin cancer cells are human skin cancer cells A375. All conventional cancer cells used were obtained from Kunming Medical University.

[0047] Unless otherwise specified, all reagents used in the embodiments of this invention are commercially available. RPMI 1640 medium, DMEM medium, and fetal bovine serum were purchased from Biological Industries; phosphate-buffered saline (PBS) and 0.25% trypsin (containing EDTA) were purchased from Gibco.

[0048] Cell lines were cultured in DMEM or RPMI 1640 medium containing 10% fetal bovine serum at 37°C, 5% CO2 and 90% humidity.

[0049] Example 1: Specific synthesis process of compounds I-VI

[0050] The structural formulas of the indole-3-aryl ketone derivatives used in the following examples are as follows: Figure 1 As shown.

[0051] General reaction formula for synthetic methods

[0052]

[0053] Synthetic steps of the target products (I-VI): Under air atmosphere, acenaphthene (M1) (0.3 mmol), indole (M2) (0.2 mmol), cesium carbonate (0.4 mmol), and trifluoroethanol (TFE) or hexafluoroisopropanol (HFIP) (M3) (2 mL) were added to a 10 mL transparent open reaction tube. The mixture was stirred for 12 hours at room temperature under a light source of 460 nm and 24 W. The reaction was quenched with saturated NaCl aqueous solution and extracted with 30 mL of ethyl acetate. The organic layers were then combined, dried over anhydrous Na2SO4, filtered, and the ethyl acetate in the reaction system was evaporated under reduced pressure. The residue was purified by silica gel rapid column chromatography (dichloromethane:petroleum ether = 1:10) to give compounds I-VI. The products were further identified by NMR and HRMS.

[0054] The structural characterization process of compounds I-VI is as follows:

[0055] Compound I: Yellow solid; Mp: 147.9 ℃; 89 mg, yield: 91%; IR (KBr): 3447, 2877, 2801, 1697, 1559, 1488, 1475, 1468, 858, 809, 669 cm⁻¹ -1 ; 1 H NMR (400 MHz, DMSO- d 6) δ 8.41 (d, J = 8.4 Hz, 1H, ArH), 8.31 (dd, J = 8.3, 1.4 Hz, 1H, ArH), 8.27–8.21 (m, 2H, ArH), 7.98 (dd, J= 7.1, 1.3 Hz,1H, ArH), 7.93–7.86 (m, 2H, ArH), 7.72 (q, J = 7.6 Hz, 2H, ArH), 7.58 (dd, J = 8.4, 1.7 Hz, 1H, ArH), 4.39 (q, J = 8.9 Hz, 2H, CH2). 13 C NMR (100 MHz, DMSO- d 6) δ 191.5, 166.9, 139.0, 137.6, 136.4, 134.7, 133.7, 132.0, 130.4,130.2, 129.4, 128.7, 127.1, 126.3, 126.0, 125.5 (q, J = 272.7 Hz), 124.0 (q, J =33.3 Hz), 123.6 (q, J = 278.8 Hz), 122.5, 118.8 (q, J = 3.0 Hz), 116.4, 110.3 (q, J = 5.0 Hz), 60.4 (q, J = 35.4 Hz). 19 F NMR (376 MHz, DMSO- d 6) δ-59.33,-72.35 (t, J =9.0 Hz). HRMS (ESI-TOF) m / z: [M+Na] + calcd for C 23 H 13 F6NNaO3: 488.0692, Found: 488.0697; related spectra are as follows Figures 2-4 As shown.

[0056] Compound II: White solid; Mp: 135.8 ℃; 77 mg, yield: 81%; IR (KBr): 3455, 2904, 2871, 1689, 1577, 1508, 1469, 1443, 886, 824, 641, 542 cm⁻¹ -1 ; 1 H NMR (400 MHz, DMSO-d 6) δ 12.38–12.19 (m, 1H, NH), 8.37 (d, J = 2.4Hz, 1H, ArH), 8.30 (dd, J = 8.3, 1.4 Hz, 1H, ArH), 8.24 (d, J = 8.2 Hz, 1H,ArH), 8.08 (d, J = 3.1 Hz, 1H, ArH), 7.96 (dd, J = 7.0, 1.4 Hz, 1H, ArH),7.89 (dd, J = 7.2, 1.4 Hz, 1H, ArH), 7.71 (td, J = 7.7, 5.9 Hz, 2H, ArH),7.54 (d, J = 8.6 Hz, 1H, ArH), 7.42 (dd, J = 8.6, 2.0 Hz, 1H, ArH), 4.40 (q, J = 9.0 Hz, 2H, CH2). 13 C NMR (100 MHz, DMSO- d 6) δ191.5, 166.8, 137.6, 136.1,134.7, 133.7, 131.9, 130.3, 130.1, 128.7, 128.5, 127.1, 126.3, 126.2, 126.0,123.9, 123.6 (q, J C-F = 276 Hz), 115.8, 115.3, 115.0, 60.4 (q, J C-F =36 Hz). HRMS (ESI-TOF) m / z [M+H] + calcd for C 22 H 14 BrF3NO3: 476.0104, Found: 476.0109; Relevant spectra are shown below. Figures 5-7 As shown.

[0057] Compound III: Yellow solid; Mp: 161.5 ℃; 69 mg, yield: 79%; IR (KBr): 3436, 2913, 2802, 1698, 1584, 1476, 1457, 1407, 874, 835, 663 cm⁻¹ -1 ; 1 H NMR (400 MHz, DMSO- d 6) δ 12.16 (s, 1H, NH), 8.28 (dd, J = 8.3, 1.4Hz, 1H, ArH), 8.26–8.18 (m, 2H, ArH), 8.02–7.93 (m, 2H, ArH), 7.88 (dd, J =7.1, 1.4 Hz, 1H, ArH), 7.70 (q, J = 7.6 Hz, 2H, ArH), 7.36 (dd, J = 9.6, 2.4Hz, 1H, ArH), 7.14 (td, J = 9.3, 2.4 Hz, 1H, ArH), 4.36 (q, J = 8.9 Hz, 2H,CH2). 13 C NMR (100 MHz, DMSO- d 6) δ 191.5, 166.9, 159.9 ( J = 234 Hz), 137.7, 137.5 ( J = 12 HZ), 137.3, 134.7, 133.6, 131.9, 130.3, 130.1, 128.8, 127.1,126.3, 125.9, 123.6 ( J C-F = 276 Hz), 123.4, 122.9 ( J =10 Hz), 116.3, 110.8 ( J =23 Hz), 99.1 ( J =25 Hz), 60.4( J = 35 Hz). 19 F NMR (376 MHz, DMSO- d 6) δ -72.34(t, J= 9.0 Hz), -119.20 (d, J = 5.6 Hz). HRMS (ESI-TOF) m / z [M+Na] + calcdfor C 22 H 13 F4NNaO3: 438.0724, Found: 438.0718; related spectra are as follows Figures 8-10 As shown.

[0058] Compound IV: White solid; Mp: 155.8 ℃; 70 mg, yield: 77%; IR (KBr): 3452, 2907, 2855, 1647, 1602, 1506, 1481, 1437, 892, 843, 755, 674, 609 cm⁻¹ -1 ; 1 H NMR (400 MHz, DMSO- d 6) δ 8.30 (dd, J =8.3, 1.4 Hz, 1H, ArH),8.24 (dd, J = 8.3, 1.3 Hz, 1H, ArH), 8.19 (d, J =7.9 Hz, 1H, ArH), 7.99–7.93 (m,2H, ArH), 7.88 (dd, J = 7.1, 1.3 Hz, 1H, ArH), 7.71 (q, J =7.9 Hz, 2H, ArH), 7.38 (dd, J =7.7, 1.0 Hz, 1H, ArH), 7.27 (t, J =7.8 Hz, 1H, ArH), 4.37 (q, J =8.9Hz, 2H, CH2). 13 C NMR (100 MHz, DMSO- d 6) δ191.5, 166.9, 137.6, 137.0, 134.7,134.2, 133.7, 132.0, 130.4, 130.1, 128.7, 128.6, 127.1, 126.4, 125.9, 123.7,123.6 (q, J C-F= 276Hz), 123.2, 120.7, 117.3, 117.2, 60.4 ( J = 36Hz). 19 F NMR (376 MHz, DMSO- d 6) δ -72.31 (t, J =9.0Hz). HRMS (ESI-TOF) m / z [M+Na] + calcd forC 22 H 13 F3ClNNaO3: 454.0429, Found: 454.0433; Related spectra are as follows Figures 11-13 As shown.

[0059] Compound V: Yellow solid; Mp: 135.4℃; 75 mg, yield: 78%; IR (KBr): 3490, 2881, 2799, 1745, 1732, 1653, 1532, 1486, 1265, 1156, 867, 824, 653 cm⁻¹ -1 ; 1 H NMR (400 MHz, DMSO-d6) δ 8.94 (d, J = 1.7 Hz, 1H, NH), 8.32(dd, J = 8.3,1.4 Hz, 1H, ArH), 8.26 (dd, J = 8.3,1.4 Hz, 1H, ArH), 8.16 (s, 1H,ArH), 7.99 (dd, J = 7.2, 1.3 Hz, 1H, ArH), 7.92 (ddd, J = 9.1,7.9, 1.6 Hz,2H, ArH), 7.73 (q, J = 7.5 Hz, 3H, ArH), 7.66 (d, J = 8.6 Hz, 1H, ArH), 4.35(q, J = 8.9 Hz, 2H, CH2), 3.89 (s, 3H, OCH3). 13C NMR (100 MHz, DMSO-d6) δ191.6,167.5, 166.9, 140.0, 138.3, 137.6, 134.7,133.7, 132.0, 130.4, 130.2,128.7, 127.1, 126.3, 126.0, 124.6, 124.0, 123.6 (q, J C-F =275Hz), 123.89,117.04, 112.97, 60.42( J = 35Hz), 52.37. 19 F NMR (376 MHz, DMSO-d6) δ -72.35 (t, J = 9.0 Hz). HRMS (ESI-TOF) m / z [M+Na] + calcd for C 24 H 16 F3NNaO5: 478.0873, Found: 478.0869; related spectra are as follows Figures 14-16 As shown.

[0060] Compound VI: Yellow solid; Mp: 172.6 ℃; 82 mg, yield: 81%; IR (KBr): 3490, 3231, 3147, 1675, 1589, 1531, 1481, 867, 794, 761, 672 cm⁻¹ -1 ; 1 H NMR (400 MHz, DMSO-d6) δ 8.53 (s, 1H, NH), 8.45 (d, J = 2.1 Hz, 1H, ArH), 8.39 (dd, J = 8.3, 1.3 Hz, 1H, ArH), 8.33 – 8.26 (m, 2H, ArH), 8.12(dd, J = 8.9, 2.2 Hz, 1H, ArH), 8.01 (dd, J = 7.1, 1.3 Hz, 1H, ArH), 7.95(dd, J = 7.2, 1.3 Hz, 1H, ArH), 7.77 (q, J = 7.7 Hz, 2H, ArH), 6.77 (p,J =6.3 Hz, 1H, CH). 13 C NMR (100 MHz, DMSO-d6) δ 191.3, 164.7, 143.7, 141.0,137.5, 136.1, 135.0, 134.8, 132.2, 132.0, 130.8, 130.5, 127.3, 126.7, 126.6,126.1, 122.2, 121.2 ( J C-F =282Hz), 117.2, 116.8, 109.4, 67.0( J = 34Hz). 19 F NMR (376 MHz, DMSO-d6) δ -72.03 (d, J = 6.3 Hz). HRMS (ESI-TOF) m / z [MH] - C 23 H 11 F6N2O5: 509.0577, Found 509.0579; related spectra are as follows Figures 17-19 As shown.

[0061] In the early stages of this invention, compounds 4e and 5b were obtained using the same method, and their structures were corroborated by X-ray single-crystal diffraction data of compounds with similar structures (4e and 5b), as shown in Tables 1 and 2. Figure 20 and Figure 21 As shown.

[0062]

[0063] Table 1. X-ray single-crystal diffraction results of compound 4e

[0064]

[0065] Table 2. X-ray single-crystal diffraction results of compound 5b

[0066]

[0067] Example 2: Antitumor activity test of indole-3-aryl ketone derivatives

[0068] The CCK-8 assay was used to detect cell growth inhibition. The CCK-8 assay, short for Cell Counting Kit-8, is a commonly used method for detecting cell proliferation and cytotoxicity. The principle of the CCK-8 assay is based on the compound WST-8 (2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfonic acid phenyl)-2H-tetrazole monosodium salt). In the presence of the electron carrier 1-Methoxy PMS (menaquinone phosphate), WST-8 can be reduced by intracellular mitochondrial dehydrogenases to produce a highly water-soluble orange-yellow formazan product. The amount of formazan produced is directly proportional to the number of viable cells, and the color intensity reflects cellular metabolic activity. The number of viable cells can be indirectly reflected by measuring the absorbance at 450 nm using a microplate reader. Therefore, CCK-8 can be used to assess cell proliferation, cytotoxicity, or the cellular effects of drugs.

[0069] Compounds (I-VI) were dissolved in DMSO (dimethyl sulfoxide), and then solutions of each compound with concentrations of 50 μM, 10 μM, 1 μM, 500 nM, 100 nM, 50 nM, 10 nM, and 5 nM were prepared using DMSO. These solutions were used as test solutions.

[0070] Human breast cancer cells MDA-MB-231 and HCC1937 (4×10) were used. 3 Cells were seeded in 96-well plates with 99 μL of culture medium per well and incubated at 37°C with 5% CO2 for 24 h. Then, 1 μL of the test solution (I-VI) was added to each well. For the control group, only 1 μL of DMSO was added to the cell culture, and the plates were incubated for 72 h. Then, 10 μL of CCK-8 solution was added to each well, and the mixture was gently mixed to avoid air bubbles. The cells were incubated for another 1 h, and the absorbance of each well was measured at 450 nm using a microplate reader. The average OD value of each well was calculated, and the changes in cell proliferation or toxicity were analyzed by comparing the experimental group absorbance value with that of the control group (untreated cells). The percentage of the absorbance value of the experimental group relative to the absorbance value of the control group represents the cell viability or cell proliferation level; the control group was assumed to be 100%. The results are shown in Table 3.

[0071] Table 3. Half-maximal inhibitory concentrations (IC50) of indole-3-aryl ketone derivatives (I-VI) on human breast cancer cell lines MDA-MB-231 and HCC1937. 50 (μM)

[0072]

[0073] The results are shown in Table 3. The indole-3-aryl ketone derivatives (compounds I-VI) all have good anti-tumor activity. Among them, compound I showed the strongest breast cancer inhibitory activity at concentrations below 10 μM, which was stronger than that of the clinical chemotherapy drug cisplatin.

[0074] Example 3: Evaluation of the cytotoxicity of indole-3-aryl ketone derivative (I) in different tumor cells

[0075] Human breast cancer cells MDA-MB-231 were replaced with human liver cancer cells SNU-387, human gastric cancer cells SGC-7901, human leukemia cells Jurkat, human lung cancer cells H460, human pancreatic cancer cells SW1990, human glioma cells U251, human osteosarcoma cells MG63, human ovarian cancer cells SKOV3, human kidney cancer cells G401, and human skin cancer cells A375, with the other parameters the same as in Example 2. IC 50 The results are shown in Table 4.

[0076] Table 4. Half-maximal inhibitory concentrations (IC50) of indole-3-aryl ketone derivatives (I) against various cancer cells. 50 (μM)

[0077]

[0078] According to the results in Table 4, the indole-3-aryl ketone derivative (compound I) exhibits strong cytotoxic activity against human liver cancer cells SNU-387, human gastric cancer cells SGC-7901, human leukemia cells Jurkat, human lung cancer cells H460, human pancreatic cancer cells SW1990, human glioma cells U251, human osteosarcoma cells MG63, human ovarian cancer cells SKOV3, human renal cancer cells G401, and human skin cancer cells A375.

[0079] In summary, indole-3-aryl ketone derivatives exhibit good in vitro anticancer effects and can effectively inhibit the proliferation of various cancer cells.

[0080] It should be noted that the embodiments described above are only for explaining the present invention and do not constitute any limitation on the present invention. The description of the present invention with reference to typical embodiments should be understood as descriptive and explanatory terms, not limiting terms. Modifications can be made to the present invention within the scope of the claims, and revisions can be made to the present invention without departing from its scope and spirit. Although the present invention described herein relates to specific methods, materials, and embodiments, it does not mean that the present invention is limited to the specific examples disclosed herein; on the contrary, the present invention extends to all other methods and applications having the same function.

Claims

1. An indole-3-aryl ketone derivative, characterized in that, The indole-3-aryl ketone derivative is selected from one or more of compounds I, II, V and VI, and has the following structural formula: 。 2. The indole-3-aryl ketone derivative according to claim 1, characterized in that, The indole-3-aryl ketone derivative is compound I, with the following structural formula: 。 3. The method for preparing the indole-3-aryl ketone derivative according to claim 1, characterized in that, The preparation method is as follows: Compound M1, Compound M2 and Compound M3 are mixed, cesium carbonate is added and reacted at room temperature under 460nm light for 8-20h, and then separated by column chromatography to obtain Compound I, II, V or VI; Compound M1 is acenaphthoquinone; compound M3 is trifluoroethanol or hexafluoroisopropanol; The structural formula of compound M2 is as follows: 。 4. The method for preparing the indole-3-aryl ketone derivative according to claim 3, characterized in that, The molar volume ratio of compounds M1, M2 and M3 is 2-4 mmol: 1-3 mmol: 15-30 mL; the amount of cesium carbonate added is 2-3 times the molar amount of compound M1.

5. The use of the indole-3-aryl ketone derivative according to claim 1 in the preparation of drugs for the prevention and / or treatment of cancer, characterized in that, The cancer mentioned is at least one of breast cancer, liver cancer, stomach cancer, leukemia, lung cancer, pancreatic cancer, glioma, osteosarcoma, ovarian cancer, kidney cancer, and skin cancer.

6. The use of the indole-3-aryl ketone derivative according to claim 5 in the preparation of drugs for the prevention and / or treatment of cancer, characterized in that, The cancer in question is breast cancer.

7. The use of the indole-3-aryl ketone derivative according to claim 5 in the preparation of drugs for the prevention and / or treatment of cancer, characterized in that, The indole-3-aryl ketone derivative or its pharmaceutically acceptable salt is used as the active pharmaceutical ingredient.

8. The use of the indole-3-aryl ketone derivative according to claim 7 in the preparation of drugs for the prevention and / or treatment of cancer, characterized in that, The active pharmaceutical ingredient is used in combination with a pharmaceutically acceptable carrier.

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