Indole-3-aryl ketone derivative as well as preparation method and application thereof

Abstract

The invention relates to the field of anti-cancer drugs, in particular to an indole-3-aryl ketone derivative as well as a preparation method and application thereof. The indole-3-aryl ketone derivative is a compound I-VI, the indole-3-aryl ketone derivative can be used for preparing drugs for preventing and / or treating cancers, and the cancers comprise 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. According to the invention, activity screening is carried out on various compounds, the fact that the compounds I-VI have excellent inhibitory activity on various different types of human cancer cells is found for the first time, and an optional scheme is provided for broad-spectrum anti-cancer drugs.

Description

Technical Field

[0001] The present invention relates to the field of anticancer drugs, and in particular to an indole-3-aryl ketone derivative, a preparation method and an application thereof. Background Art

[0002] Cancer is one of the leading causes of death worldwide and poses a serious threat to human health. Although significant progress has been made in the field of cancer diagnosis and treatment in recent years, existing therapies, such as chemotherapy, radiotherapy, targeted therapy, and immunotherapy, still have many limitations and challenges. For example, many chemotherapy drugs have poor selectivity and produce serious 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, and have a limited scope of application; and the response rate of immunotherapy varies greatly among different cancer types and patients, and may be accompanied by immune-related adverse reactions. Therefore, the development of new, highly effective, low-toxic drugs with broad-spectrum anti-cancer activity remains an urgent need and a major challenge in the current field of anti-tumor drug research and development.

[0003] Among the numerous chemical backbones with potential anti-tumor activity, indole compounds have attracted considerable attention due to their broad biological activity. Indole derivatives from both natural and synthetic sources have been shown to inhibit tumor cell proliferation and induce apoptosis through various mechanisms. Among them, the indole-3-one structural unit is considered an important pharmacophore, present in many biologically active molecules.

[0004] Researchers are modifying the indole-3-one skeleton in hopes of obtaining derivatives with increased activity, improved selectivity, or novel mechanisms of action. While some compounds with indole-3-one or indole-like structures have been reported to exhibit inhibitory activity against specific tumor types, they often lack broad-spectrum anticancer properties, making them inadequate for combating multiple cancers. Therefore, the development of indole-3-aryl ketone derivatives with broad-spectrum and highly effective antitumor activity is of great significance. Summary of the Invention

[0005] In response to the deficiencies of the prior art, the present invention provides a class of indole-3-aryl ketone derivatives and their use in the preparation of drugs for preventing and / or treating cancer. The indole-3-aryl ketone derivatives have excellent inhibitory activity against various types of human cancer cells.

[0006] To solve the above 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] The indole-3-aryl ketone derivative is preferably compound I, compound II, compound V or compound VI; The indole-3-aryl ketone derivative is further preferably compound I, having the following structural formula: .

[0008] The above preferred compounds have good inhibitory activity against cancer cells and are better than the positive control cisplatin.

[0009] The present invention also provides a method for preparing the indole-3-aryl ketone derivative, which is as follows: Compound M1, Compound M2, and Compound M3 are mixed, cesium carbonate is added, and the mixture is reacted at room temperature under 460 nm light for 8-20 hours, and the compounds I-VI are separated by column chromatography; The compound M1 is acenaphthenequinone; the compound M3 is trifluoroethanol or hexafluoroisopropanol; The structural formula of the compound M2 is as follows: 、 、 、 、 or .

[0010] Preferably, the molar volume ratio of the compounds M1, M2 and M3 is 2-4 mmol: 1-3 mmol: 15-30 mL; and the amount of cesium carbonate added is 2-3 times the molar amount of compound M1.

[0011] The present invention also provides the use of the indole-3-aryl ketone derivative in preparing a drug for preventing and / or treating 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.

[0012] Preferably, the cancer is breast cancer.

[0013] Preferably, the indole-3-aryl ketone derivative, its pharmaceutically acceptable salt, ester, stereoisomer, metabolite or prodrug can also be used as a pharmaceutical active ingredient.

[0014] Preferably, the active pharmaceutical ingredient is used in combination with a pharmaceutically acceptable carrier. Compounds I-VI can be used directly or in the form of a pharmaceutical composition. These can be administered orally or by injection to patients in need of treatment, and can be formulated into various pharmaceutical forms for use, thus providing a wide range of applications.

[0015] As a further description of the above scheme: the mass fraction of the active ingredient of the medicine is 0.1%~99%; preferably, the mass fraction of the active ingredient of the medicine is 0.1%~20%.

[0016] Currently marketed indole anticancer drugs (such as indirubin and sunitinib) all contain an indole or oxidized indole backbone. Their mechanisms of action involve inhibition of kinase activity, interference with tubulin polymerization, or induction of apoptosis. This suggests that the indole ring system is an effective carrier of anticancer activity. The type of substituent at the C-3 position of the indole significantly influences anticancer activity. The present invention introduces an aromatic ketone group at the C-3 position of the indole. The electronic effects of the aromatic group modulate target affinity, significantly enhancing anticancer activity. The steric hindrance of the aromatic substituent can influence molecular conformation. For example, ortho-substitution may enhance the ability to fit into the hydrophobic pocket of the target. This provides the structural foundation for the broad-spectrum anticancer activity of the compounds provided by the present invention.

[0017] Compared with the existing technology, the present invention has the following beneficial effects: the present invention screens the activity of 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 various types of human cancer cells, providing an alternative for broad-spectrum anticancer drugs.

[0018] In addition, the synthesis process provided by the present invention is simple to operate, has fewer by-products, high yield, and is environmentally friendly. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] Figure 1 The following are the structural formulas of 6 synthetic indole-3-aryl ketone derivatives; Figure 2 Compound I 1 H-NMR (400MHz, DMSO- d 6) Spectrum; Figure 3 Compound I 13 C-NMR (100MHz, DMSO- d 6) Spectrum; Figure 4 Compound I 19 F-NMR (376MHz, DMSO- d 6) Spectrum; Figure 5 For compound II 1 H-NMR (400MHz, DMSO- d 6) Spectrum; Figure 6 For compound II 13 C-NMR (100MHz, DMSO- d 6) Spectrum; Figure 7 For compound II 19 F-NMR (376MHz, DMSO- d 6) Spectrum; Figure 8 For compound III 1 H-NMR (400MHz, DMSO- d 6) Spectrum; Figure 9 For compound III 13 C-NMR (100MHz, DMSO- d 6) Spectrum; Figure 10 For compound III 19 F-NMR (376MHz, DMSO- d 6) Spectrum; Figure 11 For compound IV 1 H-NMR (400MHz, DMSO- d 6) Spectrum; Figure 12 For compound IV 13 C-NMR (100MHz, DMSO- d 6) Spectrum; Figure 13 For compound IV 19 F-NMR (376MHz, DMSO- d 6) Spectrum; Figure 14 For compound V 1 H-NMR (400MHz, DMSO- d 6) Spectrum; Figure 15 For compound V 13 C-NMR (100MHz, DMSO- d 6) Spectrum; Figure 16 For compound V 19 F-NMR (376MHz, DMSO- d 6) Spectrum; Figure 17 For compound VI 1 H-NMR (400MHz, DMSO- d 6) Spectrum; Figure 18 For compound VI 13 C-NMR (100MHz, DMSO-d 6) Spectrum; Figure 19 For compound VI 19 F-NMR (376MHz, DMSO- d 6) Spectrum; Figure 20 is the X-ray single crystal diffraction structure of compound 4e; Figure 21 This is the X-ray single crystal diffraction structure of compound 5b. DETAILED DESCRIPTION

[0020] The technical solutions of the present invention are 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.

[0021] In the following examples, the human liver cancer cells are human liver cancer cell line SNU-387, the human lung cancer cells are human lung cancer cell line H460, the human breast cancer cells are human breast cancer cell lines HCC1937 and MDA-MB-231, the human leukemia cells are human leukemia cell line Jurkat, the human gastric cancer cells are human gastric cancer cell line SGC-7901, the human renal cancer cells are human renal cancer cell line G401, the human ovarian cancer cells are human ovarian cancer cell line SKOV3, the human glioma cells are human glioblastoma cell line U251, the human pancreatic cancer cells are human pancreatic cancer cell line SW1990, the human osteosarcoma cells are human osteosarcoma cell line MG63, and the human skin cancer cells are human skin cancer cell line A375. All conventional cancer cells used above were obtained from Kunming Medical University.

[0022] Unless otherwise specified, all reagents in the examples of the present invention can be purchased from commercial sources. RPMI1640 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.

[0023] The cell lines were cultured in DMEM or RPMI1640 medium containing 10% fetal bovine serum at 37°C, 5% CO2 and 90% humidity.

[0024] Example 1 Specific Synthesis Process of Compounds I-VI The structural formula of the indole-3-aryl ketone derivatives used in the following examples is as follows: Figure 1 shown.

[0025] General reaction formula of the synthesis method

[0026] Synthesis steps for the target products of formula (I-VI): Under air, acenaphthenequinone (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 at room temperature under 24 W light at a wavelength of 460 nm for 12 hours. The reaction was quenched with saturated aqueous NaCl 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 mixture was evaporated under reduced pressure. The residue was purified by silica gel flash column chromatography (dichloromethane:petroleum ether = 1:10) to afford compounds I-VI. The products were further identified by NMR and HRMS.

[0027] The structural characterization process of compounds I-VI is as follows: 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 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- d6) 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 such as Figure 2-Figure 4 shown.

[0028] 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 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; related spectra such as Figure 5-Figure 7 shown.

[0029] 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 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 such as Figures 8-10 shown.

[0030] 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 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 for C 22 H 13F3ClNNaO3:454.0429, Found: 454.0433; related spectra such as Figure 11-13 shown.

[0031] 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, 653cm -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). 13 C 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 such as Figure 14-16 shown.

[0032] Compound VI: Yellow solid; Mp: 172.6 °C; 82 mg, yield: 81%; IR (KBr): 3490, 3231, 3147, 1675, 1589, 1531, 1481, 867, 794, 761,672 cm -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). 19F 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 such as Figure 17-Figure 19 shown.

[0033] In the early stage of the present invention, compounds 4e and 5b were obtained by the same method, and the structures of the above compounds were confirmed by X-ray single crystal diffraction data of compounds with similar structures (4e and 5b), as shown in Table 1, Table 2, Figure 20 and Figure 21 shown.

[0034]

[0035] Table 1 X-ray single crystal diffraction results of compound 4e

[0036] Table 2 X-ray single crystal diffraction results of compound 5b

[0037] Example 2 Antitumor Activity Test of Indole-3-aryl ketone Derivatives The CCK-8 assay was used to detect cell growth inhibition. The CCK-8 assay, also known as the Cell Counting Kit-8, is a commonly used assay for detecting cell proliferation and cytotoxicity. The CCK-8 assay is based on the compound WST-8 (2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfonate phenyl)-2H-tetrazolium monosodium salt). In the presence of the electron carrier 1-Methoxy PMS (menadione phosphate), WST-8 is reduced by intracellular mitochondrial dehydrogenases to produce a highly water-soluble orange-yellow formazan product. The amount of formazan produced is proportional to the number of viable cells, and the color intensity reflects cellular metabolic activity. The absorbance at 450 nm using a microplate reader indirectly reflects the number of viable cells. Therefore, the CCK-8 assay can be used to assess cell proliferation, cytotoxicity, or the cellular effects of drugs.

[0038] Compounds (I-VI) were dissolved in DMSO (dimethyl sulfoxide). DMSO was then used to prepare solutions with concentrations of 50 μM, 10 μM, 1 μM, 500 nM, 100 nM, 50 nM, 10 nM, and 5 nM, respectively. These solutions were used as test solutions.

[0039] Human breast cancer cells MDA-MB-231 and HCC1937 (4×10 3 Cells were seeded into 96-well plates (99 μL of culture medium per well) and incubated in a 37°C, 5% CO2 incubator for 24 hours. Then, 1 μL of test solution (I-VI) was added to each well. For the control group, only 1 μL of DMSO was added to the cell cultures. After incubation for 72 hours, 10 μL of CCK-8 solution was added to each well and gently mixed to avoid bubbles. Incubation continued for another hour. The absorbance of each well was measured at 450 nm using a microplate reader. The average OD value was calculated and compared with the control group (untreated cells) to analyze changes in cell proliferation or toxicity. The percentage of the absorbance of the experimental group relative to the control group represents the cell viability or proliferation level, with the control group assumed to be 100%. The results are shown in Table 3.

[0040] Table 3 IC50 of indole-3-aryl ketone derivatives (I-VI) on human breast cancer cell lines MDA-MB-231 and HCC1937 50 (μM)

[0041] The results are shown in Table 3. All indole-3-aryl ketone derivatives (Compounds I-VI) have good anti-tumor activity. Among them, Compound I exhibits the strongest inhibitory activity against breast cancer at a concentration of less than 10 μM, which is more active than the clinical chemotherapy drug cisplatin.

[0042] Example 3 Evaluation of the cytotoxicity of indole-3-aryl ketone derivatives (I) in different tumor cells The 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 glioblastoma cells U251, human osteosarcoma cells MG63, human ovarian cancer cells SKOV3, human kidney cancer cells G401, and human skin cancer cells A375. Other modifications were the same as in Example 2. 50 The results of the values ​​are shown in Table 4.

[0043] Table 4 IC50 of indole-3-aryl ketone derivatives (I) on various cancer cells 50 (μM)

[0044] According to the results in Table 4, the indole-3-aryl ketone derivative (Compound I) has strong cancer cell cytotoxicity 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 glioblastoma cells U251, human osteosarcoma cells MG63, human ovarian cancer cells SKOV3, human renal cancer cells G401 and human skin cancer cells A375.

[0045] In summary, indole-3-aryl ketone derivatives have good in vitro anti-cancer effects and can effectively inhibit the proliferation of various cancer cells.

[0046] It should be noted that the embodiments described above are only used to explain the present invention and do not constitute any limitation of the present invention. The present invention is described with reference to typical embodiments, but it should be understood that the words used therein are descriptive and explanatory words, rather than restrictive words. The present invention may be modified as specified within the scope of the claims of the present invention, and the present invention may be revised without departing from the scope and spirit of the present invention. Although the present invention described therein relates to specific methods, materials and embodiments, it does not mean that the present invention is limited to the specific examples disclosed therein. On the contrary, the present invention extends to all other methods and applications with 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-VI, and the structural formula is as follows: 。 2. The indole-3-aryl ketone derivative according to claim 1, characterized in that The indole-3-aryl ketone derivative is compound I, and its structural formula is as follows: 。 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 Compounds I-VI are obtained by column chromatography separation; The compound M1 is acenaphthenequinone; the compound M3 is trifluoroethanol or hexafluoroisopropanol; The structural formula of the compound M2 is as follows: 、 、 、 、 or .

4. The method for preparing an indole-3-aryl ketone derivative according to claim 3, wherein: The molar volume ratio of the 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. Use of the indole-3-aryl ketone derivative according to claim 1 in the preparation of a drug for preventing and / or treating cancer, characterized in that: 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.

6. Use of the indole-3-aryl ketone derivative according to claim 5 in the preparation of a drug for preventing and / or treating cancer, characterized in that: The cancer is breast cancer.

7. Use of the indole-3-aryl ketone derivative according to claim 5 in the preparation of a drug for preventing and / or treating cancer, characterized in that: The indole-3-aryl ketone derivative, its pharmaceutically acceptable salt, ester, stereoisomer, metabolite or prodrug is used as a pharmaceutical active ingredient.

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

Images