Preparation and anti-tumor application of 9, 10-anthraquinone-(3-substituted salicylaldehyde) Schiff base dibutyltin complex

Abstract

The invention discloses a 9, 10-anthraquinone-(3-substituted salicylaldehyde) Schiff base dibutyltin complex, which is a compound with the following structural formula (I): # imgabs0 #, therefore, the inventor also establishes a corresponding preparation method, that is, 2-amino-3-hydroxy anthraquinone, 3-substituted salicylaldehyde and dibutyltin oxide are used as raw materials, absolute methanol is used as a solvent, and the reaction is completed under the condition of heating reflux. In-vitro anticancer activity research shows that the 9, 10-anthraquinone-(3-substituted salicylaldehyde) Schiff base dibutyltin complex has good inhibitory activity on human lung cancer cells, human liver cancer cells, human breast cancer cells and human oral cancer, and the in-vitro anticancer activity of the 9, 10-anthraquinone-(3-substituted salicylaldehyde) Schiff base dibutyltin complex is remarkably superior to that of a classic metal anticancer drug cis-platinum. Therefore, the compound has potential application value in research and development of anti-cancer drugs for human lung cancer, human liver cancer, human breast cancer and human oral cancer. In conclusion, the anthraquinone dibutyltin complex is good in anticancer activity, low in cost and simple in preparation method, and a new way is provided for developing new anticancer drugs.

Description

Technical Field

[0001] The present invention belongs to the technical field of anthraquinone derivatives, and particularly relates to the preparation and anti-tumor application of a dibutyltin complex of 9,10-anthraquinone-(3-substituted salicylaldehyde) Schiff base. Background Art

[0002] Anthraquinone anti-tumor drugs are one of the chemotherapy drugs widely used in current clinical treatments. These drugs have a common parent nucleus structure (9,10-anthraquinone skeleton structure). Anthraquinone anti-tumor drugs interfere with the metabolic process of tumor cells and inhibit the proliferation of tumor cells, thereby achieving the purpose of treating tumors. In clinical applications, anthraquinone anti-tumor drugs are widely used in the treatment of various types of tumors. In recent decades, researchers have designed and synthesized a large number of new 9,10-anthraquinone derivatives based on the 9,10-anthraquinone parent nucleus structure, and found that 9,10-anthraquinone derivatives have good inhibitory effects on the proliferation of various cancer cells. Therefore, designing and synthesizing new 9,10-anthraquinone derivatives with excellent anti-cancer activity has become an important research direction for the development of anthraquinone anti-cancer drugs.

[0003] Organotin is a unique organometallic compound formed by the direct combination of Sn atoms and C atoms. It has significant biological activities and has attracted much attention due to its cytotoxic effect and strong DNA-binding ability. These compounds can inhibit cell proliferation and induce apoptosis, showing potential drug treatment value in cancer chemotherapy. The exertion of its biological activities is affected by various parameters, including the number of tin atoms, the nature of the ligands, and the coordination number, etc. In particular, the organic groups connected to the organotin atoms and the ligands participating in coordination play a decisive role in the biological activities of organotin compounds. Therefore, selecting organic ligands with good biological activities to coordinate with the tin atoms in organotin has become the research focus of scientific researchers.

[0004] Upon investigation, reports on the anti-cancer drug applications of anthraquinone derivatives or organotin compounds include:

[0005] The Chinese patent application "An Anthraquinone Parent Nucleus Structure Compound and Its Preparation Method and Application" (Patent Application No. 2024107003413, Publication Date: September 13, 2024) discloses an anthraquinone parent nucleus structure compound and its preparation method and application. This compound is 1,8-dibenzyloxy-9,10-anthraquinone-N-(4-phenylethanol)-3-carboxamide, which can effectively inhibit the expression of MCL-1, significantly kill liver cancer cells with high expression of MCL-1 both in vivo and in vitro, and no obvious toxic effect on the heart is observed, providing a new and safe drug use route for the treatment of liver cancer.

[0006] The Chinese patent application "Application of 1,8-dihydroxy-3-(monoethyl succinate)-6-methylanthraquinone in the preparation of anti-hepatocellular carcinoma drugs" (Patent Application No. 2024111138625, Publication Date: October 22, 2024) discloses the application of 1,8-dihydroxy-3-(monoethyl succinate)-6-methylanthraquinone in the preparation of anti-hepatocellular carcinoma drugs. This compound can inhibit tumor growth, has a significant effect on treating hepatocellular carcinoma, has the function of treating hepatocellular carcinoma, is beneficial to the absorption of organisms, has a large tolerance, no obvious toxic and side effects, good safety, simple and convenient medication, and is easily absorbed orally, etc.

[0007] The Chinese patent application "A binuclear dibutyltin complex of thiophenecarboxylic hydrazone" (Patent Application No. 2018115765292, Publication Date: February 12, 2019) discloses a binuclear dibutyltin complex of thiophenecarboxylic hydrazone, its preparation method and application in the preparation of anti-cancer drugs.

[0008] The Chinese patent "A poly-substituted benzoic acid organotin complex, its preparation method and application" (Patent No. 2014103527986, Publication Date: December 3, 2014) discloses that the poly-substituted benzoic acid organotin complex has strong inhibitory activity against human cervical cancer cells (Hela), providing a new way for the development of anti-cancer drugs.

[0009] The literature (Eur. J. Med. Chem. 2024, 268: 116222.) reports a class of novel azoanthraquinone compounds, which can inhibit the growth of K562 cells in a dose- and time-dependent manner, causing cell cycle arrest and apoptosis.

[0010] The literature (Eur. J. Med. Chem. 2025, 282: 117100.) reports a class of novel anthraquinone-artemisinin conjugates, which show good tumor inhibitory ability both in vitro and in vivo.

[0011] When researchers modify based on the 9,10-anthraquinone skeleton structure, they are almost all keen on synthesizing small organic molecules. However, there are few reports on substances that can significantly improve the anti-cancer activity of anthraquinone by synthesizing organotin complexes based on the 9,10-anthraquinone skeleton structure as ligands. Summary of the Invention

[0012] The technical problem to be solved by the present invention is to provide the preparation and anti-tumor application of 9,10-anthraquinone-(3-substituted salicylaldehyde) Schiff base dibutyltin complex.

[0013] To solve the above technical problems, the present invention adopts the following technical solutions:

[0014] The 9,10-anthraquinone-(3-substituted salicylaldehyde) Schiff base dibutyltin complex is a compound of the following structural formula (I):

[0015]

[0016] Among them, R is -H, -OH, -CH3, -C(CH3)3, -OCH3, -F, -Cl, -Br.

[0017] When R is -H, the complex is A1, and its crystal is triclinic system, space group P-1, α = 68.446(3)°, β = 85.290(3)°, γ = 85.264(3)°, Z = 6, Dc = 1.501 Mg·m -3 , F(000) = 1752.0; the tin atom in the molecule has a pentacoordinate trigonal bipyramidal configuration;

[0018] When R is -CH3, the complex is A3, and its crystal is monoclinic system, space group P21 / c, α = 90(3)°, β = 94.540(2)°, γ = 90°, Z = 4, Dc = 1.502 Mg·m -3 , F(000) = 1200.0; the tin atom in the molecule has a pentacoordinate trigonal bipyramidal configuration;

[0019] When R is -C(CH3)3, the complex is A4, and its crystal is orthorhombic system, space group Pbcn, α = 90°, β = 90°, γ = 90°, Z = 8, Dc = 1.457 Mg·m -3 , F(000) = 2592.0; the tin atom in the molecule has a pentacoordinate trigonal bipyramidal configuration;

[0020] When R is -OCH3, the complex is A5, and its crystal is triclinic system, space group P-1, α = 105.4590(10)°, β = 103.8170(10)°, γ = 97.4450(10)°, Z = 2, Dc = 1.523 Mg·m -3 , F(000) = 616.0; the tin atom in the molecule has a pentacoordinate trigonal bipyramidal configuration;

[0021] When R is -F, the complex is A6, and its crystal is monoclinic system, space group P21 / c, α = 90°, β = 110.0830(10)°, γ = 90°, Z = 4, Dc = 1.540 Mg·m -3 , F(000) = 1200.0; the tin atom in the molecule has a pentacoordinate trigonal bipyramidal configuration;

[0022] When R is -Cl, the complex is A7, and its crystal is monoclinic system, space group P21 / c, α = 90°, β = 113.160(2)°, γ = 90°, Z = 4, Dc = 1.525 Mg·m -3 , F(000) = 1232.0; the tin atom in the molecule has a pentacoordinate trigonal bipyramidal configuration;

[0023] When R is -Br, the complex is A8, and its crystal is triclinic system, space group P-1, α = 76.1480(10)°, β = 79.2200(10)°, γ = 87.9860(10)°, Z = 4, Dc = 1.660 Mg·m -3 , F(000) = 1304.0; the tin atom in the molecule has a pentacoordinate trigonal bipyramidal configuration.

[0024] Application of anthraquinone dibutyltin complex in the preparation of anti-tumor drugs.

[0025] The tumor is lung cancer, liver cancer, breast cancer or oral cancer.

[0026] Lung cancer, liver cancer, breast cancer, and oral cancer originate from human lung cancer cell A549, human liver cancer cell HepG2, human breast cancer cell MDA-MB-231, and human oral cancer cell CAL-27, respectively.

[0027] The preparation method of the above anthraquinone dibutyltin complex uses 2-amino-3-hydroxyanthraquinone, 3-substituted salicylaldehyde, and dibutyltin oxide as raw materials, uses anhydrous methanol as a solvent, and reacts under the condition of heating and refluxing to complete.

[0028] The 3-substituted salicylaldehyde is salicylaldehyde, 3-hydroxysalicylaldehyde, 3-methylsalicylaldehyde, 3-tert-butylsalicylaldehyde, 3-methoxysalicylaldehyde, 3-fluorosalicylaldehyde, 3-chlorosalicylaldehyde, or 3-bromosalicylaldehyde.

[0029] The molar ratio of 2-amino-3-hydroxyanthraquinone, 3-substituted salicylaldehyde and dibutyltin oxide is 1:1:1.

[0030] In the above preparation method, 1 mmol of 2-amino-3-hydroxyanthraquinone, 1 mmol of 3-substituted salicylaldehyde, 1 mmol of dibutyltin oxide and 30 ml of anhydrous methanol as the solvent are added into a flask, and the reaction is carried out for 8 h under the condition of heating under reflux, cooled, filtered, and the solvent is volatilized and crystallized at room temperature to obtain the product.

[0031] Through in-depth research on the 9,10-anthraquinone skeleton structure compound, the inventor designed and prepared a 9,10-anthraquinone-(3-substituted salicylaldehyde) Schiff base dibutyltin complex, which is a compound of the following structural formula (I):

[0032]

[0033] Among them, R is -H, -OH, -CH3, -C(CH3)3, -OCH3, -F, -Cl, -Br. The tin atom in the compound molecule has a pentacoordinated trigonal bipyramidal configuration.

[0034] Accordingly, the inventor also established a corresponding preparation method, using 2-amino-3-hydroxyanthraquinone, 3-substituted salicylaldehyde and dibutyltin oxide as raw materials, and anhydrous methanol as the solvent, and the reaction is completed under the condition of heating under reflux. In vitro anti-cancer activity research shows that the 9,10-anthraquinone-(3-substituted salicylaldehyde) Schiff base dibutyltin complex of the present invention has good inhibitory activity against human lung cancer cells, human liver cancer cells, human breast cancer cells and human oral cancer, and its in vitro anti-cancer activity is significantly better than that of the classical metal anti-cancer drug cisplatin. Therefore, it has potential application value in the research and development of anti-cancer drugs for human lung cancer, human liver cancer, human breast cancer and human oral cancer. In summary, the anthraquinone dibutyltin complex of the present invention has good anti-cancer activity, low cost and simple preparation method, providing a new way for the development of new anti-cancer drugs. Description of the Drawings

[0035] Figure 1 It is the HRMS spectrum of the organotin complex A1 prepared in Example 1.

[0036] Figure 2 It is the HRMS spectrum of the organotin complex A2 prepared in Example 2.

[0037] Figure 3 It is the HRMS spectrum of the organotin complex A3 prepared in Example 3.

[0038] Figure 4 It is the HRMS spectrum of the organotin complex A4 prepared in Example 4.

[0039] Figure 5 The HRMS spectrum of the organotin complex A5 prepared in Example 5.

[0040] Figure 6 The HRMS spectrum of the organotin complex A6 prepared in Example 6.

[0041] Figure 7 The HRMS spectrum of the organotin complex A7 prepared in Example 7.

[0042] Figure 8 The HRMS spectrum of the organotin complex A8 prepared in Example 8.

[0043] Figure 9 The crystal structure diagram of the organotin complex A1 prepared in Example 1.

[0044] Figure 10 The crystal structure diagram of the organotin complex A3 prepared in Example 3.

[0045] Figure 11 The crystal structure diagram of the organotin complex A4 prepared in Example 4.

[0046] Figure 12 The crystal structure diagram of the organotin complex A5 prepared in Example 5.

[0047] Figure 13 The crystal structure diagram of the organotin complex A6 prepared in Example 6.

[0048] Figure 14 The crystal structure diagram of the organotin complex A7 prepared in Example 7.

[0049] Figure 15 The crystal structure diagram of the organotin complex A8 prepared in Example 8. Detailed implementation manners

[0050] The following examples are further detailed descriptions of the present invention.

[0051] Example 1 Preparation of dibutyltin complex A1 of 9,10-anthraquinone-(3-hydroxysalicylaldehyde) Schiff base

[0052] Add 1 mmol of 2-amino-3-hydroxy-9,10-anthraquinone, 1 mmol of salicylaldehyde, 1 mmol of dibutyltin oxide and 30 mL of anhydrous methanol as the solvent into a 50 mL round-bottom flask, heat under reflux for 8 h, cool, filter, and control the solvent evaporation and crystallization at room temperature to obtain a brownish-red transparent crystal, which is the dibutyltin complex A1 of 9,10-anthraquinone-(3-hydroxysalicylaldehyde) Schiff base. Yield: 82%.

[0053] The results of nuclear magnetic resonance spectroscopy, high-resolution mass spectrometry, and X-ray single crystal diffraction structure analysis are as follows:

[0054] 1 H NMR(500MHz,CDCl3)δ9.04 - 8.80(m,1H),8.43 - 8.16(m,3H),7.83 - 7.69(m,2H),7.59(s,1H),7.47(t,J=7.5Hz,1H),7.36(d,J=7.8Hz,1H),6.93 - 6.67(m,2H),1.78 - 1.47(m,8H),1.43 - 1.20(m,4H),0.86(t,J=7.3Hz,6H).

[0055] 13 C NMR(126MHz,CDCl3)δ183.12,181.87,170.79,165.07,165.01,138.45,136.83,136.10,135.04,134.06,133.92,133.83,133.47,127.06,127.01,123.02,122.84,117.74,117.69,116.15,114.66,26.92,26.59,22.56,13.56.

[0056] 119 Sn NMR(187MHz,CDCl3)δ - 178.09.

[0057] HRMS(ESI)m / z calcd for C 29 H 30 NO4Sn + [M + H] + 576.1197,found 576.1199.

[0058] Crystallographic data: Triclinic system, space group P - 1, α=68.446(3)°,β=85.290(3)°,γ=85.264(3)°,Z=6, Dc=1.501Mg·m -3 , F(000)=1752.0; The tin atom in the molecule has a pentacoordinate trigonal bipyramidal configuration.

[0059] Example 2 Preparation of 9,10 - anthraquinone - (3 - hydroxy salicylaldehyde) Schiff base dibutyltin complex A2

[0060] Add 1 mmol of 2-amino-3-hydroxy-9,10-anthraquinone, 1 mmol of 3-hydroxy salicylaldehyde, 1 mmol of dibutyltin oxide and 30 mL of anhydrous methanol as the solvent into a 50 mL round-bottom flask. Heat under reflux for 8 h, cool, filter, and control the solvent evaporation and crystallization at room temperature to obtain a brownish-red transparent crystal, which is the dibutyltin complex A2 of 9,10-anthraquinone-(3-hydroxy salicylaldehyde) Schiff base. Yield: 85%.

[0061] The results of nuclear magnetic resonance spectrum and high-resolution mass spectrometry structure analysis are as follows:

[0062] 1 H NMR(500MHz,CDCl3)δ8.99-8.89(m,1H),8.32-8.23(m,3H),7.78-7.72(m,2H),7.60(s,1H),7.12(d,J=7.5Hz,1H),6.94(d,J=8.0Hz,1H),6.74(t,J=7.8Hz,1H),6.32(s,1H),1.68-1.51(m,8H),1.38-1.30(m,4H),0.86(t,J=7.3Hz,6H).

[0063] 13 C NMR(126MHz,CDCl3)δ183.04,181.84,165.40,164.78,157.43,148.16,136.69,135.18,134.01,133.90,133.88,133.56,127.09,127.05,126.02,123.21,119.23,117.96,116.31,116.23,114.88,26.89,26.64,22.93,13.52.

[0064] 119 Sn NMR(187MHz,CDCl3)δ-170.93.

[0065] HRMS(ESI)m / z calcd for C 29 H 29 NO5NaSn + [M+Na] + 614.0965,found 614.0970. Example 3 Preparation of dibutyltin complex A3 of 9,10-anthraquinone-(3-methyl salicylaldehyde) Schiff base

[0066] Add 1 mmol of 2-amino-3-hydroxy-9,10-anthraquinone, 1 mmol of 3-methylsalicylaldehyde, 1 mmol of dibutyltin oxide and 30 mL of anhydrous methanol as the solvent into a 50 mL round-bottom flask. Heat under reflux for 8 h, cool, filter, and control the evaporation of the solvent at room temperature to crystallize, obtaining a brownish-red transparent crystal, which is the dibutyltin complex A3 of 9,10-anthraquinone-(3-methylsalicylaldehyde) Schiff base. Yield: 87%.

[0067] The results of nuclear magnetic resonance spectroscopy, high-resolution mass spectrometry, and X-ray single crystal diffraction structure analysis are as follows:

[0068] 1 H NMR (500 MHz, CDCl3) δ 8.93 - 8.84 (m, 1H), 8.30 - 8.21 (m, 3H), 7.81 - 7.70 (m, 2H), 7.58 (s, 1H), 7.37 (d, J = 6.9 Hz, 1H), 7.21 (d, J = 7.8 Hz, 1H), 6.71 (t, J = 7.5 Hz, 1H), 2.17 (s, 3H), 1.72 - 1.48 (m, 8H), 1.40 - 1.31 (m, 4H), 0.87 (t, J = 7.3 Hz, 6H).

[0069] 13 C NMR (126 MHz, CDCl3) δ 183.12, 181.89, 169.42, 165.05, 164.90, 138.33, 136.95, 134.87, 134.07, 133.92, 133.78, 133.42, 131.27, 127.03, 126.99, 123.01, 117.29, 116.79, 116.06, 114.51, 26.87, 26.59, 22.45, 16.01, 13.57.

[0070] 119 Sn NMR (187 MHz, CDCl3) δ -177.25.

[0071] HRMS (ESI) m / z calcd for C 30 H 31 NO4NaSn + [M + Na] + 612.1173, found 612.1177.

[0072] Crystallographic data: Monoclinic system, space group P21 / c, α = 90(3)°, β = 94.540(2)°, γ = 90°, Z = 4, Dc=1.502Mg·m -3 , F(000)=1200.0; the tin atom in the molecule has a penta-coordinated trigonal bipyramidal configuration.

[0073] Example 4 Preparation of 9,10-anthraquinone-(3-tert-butylsalicylaldehyde) Schiff base dibutyltin complex A4

[0074] To a 50 mL round-bottom flask, add 1 mmol of 2-amino-3-hydroxy-9,10-anthraquinone, 1 mmol of 3-tert-butyl salicylaldehyde, 1 mmol of dibutyltin oxide, and 30 mL of anhydrous methanol. Heat under reflux for 8 hours, cool, filter, and allow the solvent to evaporate and crystallize at room temperature to obtain brownish-red transparent crystals, namely, 9,10-anthraquinone-(3-tert-butyl salicylaldehyde) Schiff base dibutyltin complex A4. Yield: 78%.

[0075] The results of nuclear magnetic resonance spectroscopy, high-resolution mass spectrometry, and X-ray single crystal diffraction structure analysis are as follows:

[0076] 1 H NMR (500MHz, CDCl3) δ8.96-8.83(m,1H),8.31-8.19(m,3H),7.79-7.70(m,2H),7.60(s,1H),7.50(d,J=7.4Hz,1H),7.23(d,J=7. 8Hz,1H),6.75(t,J=7.6Hz,1H),1.63(dq,J=16.2,7.8Hz,8H),1.41(s,9H),1.33(dt,J=13.5,6.8Hz,4H),0.85(t,J=7.3Hz,6H).

[0077] 13 C NMR (126MHz, CDCl3) δ183.14,181.91,170.66,165.37,164.93,142.08,136.95,135.27,134.83,134.71,134.08,133.9 3,133.78,133.43,127.03,126.99,123.04,118.10,117.27,116.03,114.40,35.06,29.32,26.86,26.64,22.51,13.50.

[0078] 119 Sn NMR(187MHz, CDCl3)δ-177.29.

[0079] HRMS(ESI)m / z calcd for C33 H 37 NO4NaSn + [M+Na] + 654.1642, found 654.1647.

[0080] Crystallographic data: orthorhombic system, space group Pbcn, α = 90°, β = 90°, γ = 90°, Z = 8, Dc = 1.457 Mg·m -3 , F(000) = 2592.0; The tin atom in the molecule has a trigonal bipyramidal configuration with five - coordinate.

[0081] Example 5 Preparation of 9,10 - anthraquinone - (3 - methoxysalicylaldehyde) Schiff base dibutyltin complex A5

[0082] Add 1 mmol of 2 - amino - 3 - hydroxy - 9,10 - anthraquinone, 1 mmol of 3 - methoxysalicylaldehyde, 1 mmol of dibutyltin oxide and 30 mL of anhydrous methanol as the solvent into a 50 mL round - bottom flask. Heat under reflux for 8 h, cool, filter, and control the solvent evaporation and crystallization at room temperature to obtain a brown - red transparent crystal, which is 9,10 - anthraquinone - (3 - methoxysalicylaldehyde) Schiff base dibutyltin complex A5. Yield: 87%.

[0083] The results of nuclear magnetic resonance spectroscopy, high - resolution mass spectrometry, and X - ray single - crystal diffraction structure analysis are as follows:

[0084] 1 H NMR(500 MHz, CDCl3) δ 8.96 - 8.85(m, 1H), 8.32 - 8.23(m, 3H), 7.77 - 7.70(m, 2H), 7.59(s, 1H), 6.99(t, J = 8.3 Hz, 2H), 6.73(t, J = 7.9 Hz, 1H), 3.87(s, 3H), 1.70 - 1.52(m, 8H), 1.37 - 1.29(m, 4H), 0.84(t, J = 7.3 Hz, 6H).

[0085] 1313C NMR(126MHz,CDCl3)δ183.14,181.85,165.28,165.12,161.81,151.81,137.01,135.03,134.06,133.91,133.81,133.44,127.22,127.04,127.00,123.03,117.70,117.57,116.85,116.12,114.73,56.27,26.90,26.57,22.96,13.55.

[0086] 119 119Sn NMR(187MHz,CDCl3)δ -176.03.

[0087] HRMS(ESI)m / z calcd for C 30 H 31 NO5NaSn + [M + Na] + 628.1122, found 628.1124.

[0088] Crystallographic data: Triclinic system, space group P - 1, α = 105.4590(10)°, β = 103.8170(10)°, γ = 97.4450(10)°, Z = 2, Dc = 1.523 Mg·m -3 , F(000) = 616.0; The tin atom in the molecule has a pentacoordinate trigonal bipyramidal configuration.

[0089] Example 6 Preparation of 9,10 - anthraquinone - (3 - fluorosalicylaldehyde) Schiff base dibutyltin complex A6

[0090] Add 1 mmol of 2 - amino - 3 - hydroxy - 9,10 - anthraquinone, 1 mmol of 3 - fluorosalicylaldehyde, 1 mmol of dibutyltin oxide and 30 mL of anhydrous methanol as the solvent into a 50 mL round - bottom flask. Heat under reflux for 8 h, cool, filter, and control the solvent evaporation and crystallization at room temperature to obtain a brown - red transparent crystal, which is 9,10 - anthraquinone - (3 - fluorosalicylaldehyde) Schiff base dibutyltin complex A6. Yield: 85%.

[0091] The results of nuclear magnetic resonance spectroscopy, high - resolution mass spectrometry, and X - ray single - crystal diffraction structure analysis are as follows:

[0092] 11H NMR (500 MHz, CDCl3) δ 9.07–8.88 (m, 1H), 8.28 (dd, J = 20.1, 11.8 Hz, 3H), 7.91–7.72 (m, 2H), 7.61 (s, 1H), 7.27 (t, J = 9.2 Hz, 1H), 7.17 (d, J = 8.0 Hz, 1H), 6.72 (td, J = 7.9, 4.2 Hz, 1H), 1.79–1.53 (m, 8H), 1.44–1.21 (m, 4H), 0.86 (t, J = 7.3 Hz, 6H).

[0093] 13 13C NMR (126 MHz, CDCl3) δ 183.04, 181.82, 165.09, 164.84 (d, J F-C = 2.7 Hz), 159.09 (d, J F-C = 14.2 Hz), 154.32 (d, J F-C = 246.1 Hz), 136.56, 135.36, 134.02, 133.90, 133.56, 130.89 (d, J F-C = 3.5 Hz), 127.11, 127.04, 123.12, 122.35 (d, J F-C = 18.6 Hz), 119.45 (d, J F-C = 4.5 Hz), 116.44, 116.34 (d, J F-C = 6.7 Hz), 114.92, 26.85, 26.57, 22.99, 13.52.

[0094] 119 119Sn NMR (187 MHz, CDCl3) δ -175.96.

[0095] 19 19F NMR (471 MHz, CDCl3) δ -134.70.

[0096] HRMS (ESI) m / z calcd for C 29 H 28 FNO4NaSn + [M+Na] + 616.0922, found 616.0927.

[0097] Crystallographic data: Monoclinic system, space group P21 / c, α = 90°, β = 110.0830(10)°, γ = 90°, Z = 4, Dc = 1.540 Mg·m -3 , F(000) = 1200.0; The tin atom in the molecule has a trigonal bipyramidal configuration with five coordination sites.

[0098] Example 7 Preparation of 9,10-anthraquinone-(3-chlorosalicylaldehyde) Schiff base dibutyltin complex A7

[0099] Add 1 mmol of 2-amino-3-hydroxy-9,10-anthraquinone, 1 mmol of 3-chlorosalicylaldehyde, 1 mmol of dibutyltin oxide and 30 mL of anhydrous methanol as the solvent to a 50 mL round-bottom flask. Heat under reflux for 8 h, cool, filter, and control the solvent evaporation and crystallization at room temperature to obtain a brownish-red transparent crystal, which is 9,10-anthraquinone-(3-chlorosalicylaldehyde) Schiff base dibutyltin complex A7. Yield: 86%.

[0100] The results of nuclear magnetic resonance spectroscopy, high-resolution mass spectrometry, and X-ray single crystal diffraction structure analysis are as follows:

[0101] 1 H NMR(500 MHz, CDCl3) δ 9.00 - 8.84(m, 1H), 8.39 - 8.19(m, 3H), 7.83 - 7.71(m, 2H), 7.66 - 7.53(m, 2H), 7.30(d, J = 7.9 Hz, 1H), 6.75(t, J = 7.8 Hz, 1H), 1.79 - 1.53(m, 8H), 1.46 - 1.29(m, 4H), 0.87(t, J = 7.3 Hz, 6H).

[0102] 13 C NMR(126 MHz, CDCl3) δ 183.03, 181.83, 165.05, 164.90, 164.78, 137.32, 136.49, 135.33, 134.55, 134.02, 133.90, 133.56, 127.12, 127.04, 126.86, 123.15, 118.43, 117.38, 116.45, 114.92, 26.77, 26.59, 22.91, 13.56.

[0103] 119 Sn NMR(187 MHz, CDCl3) δ -174.82.

[0104] HRMS(ESI) m / z calcd for C 29 H 28 ClNO4NaSn + [M + Na] +632.0627, found 632.0629.

[0105] Crystallographic data: Monoclinic system, space group α = 90°, β = 113.160(2)°, γ = 90°, Z = 4, Dc = 1.525 Mg·m -3 , F(000) = 1232.0; The tin atom in the molecule has a pentacoordinate trigonal bipyramidal configuration.

[0106] Example 8 Preparation of 9,10-anthraquinone-(3-bromosalicylaldehyde) Schiff base dibutyltin complex A8

[0107] Add 1 mmol of 2-amino-3-hydroxy-9,10-anthraquinone, 1 mmol of 3-bromosalicylaldehyde, 1 mmol of dibutyltin oxide and 30 mL of anhydrous methanol as the solvent to a 50 mL round-bottom flask, heat under reflux for 8 h, cool, filter, and control the solvent evaporation and crystallization at room temperature to obtain a brownish-red transparent crystal, which is 9,10-anthraquinone-(3-bromosalicylaldehyde) Schiff base dibutyltin complex A8. Yield: 81%.

[0108] The results of nuclear magnetic resonance spectroscopy, high-resolution mass spectrometry, and X-ray single crystal diffraction structure analysis are as follows:

[0109] 1 H NMR(500 MHz, CDCl3) δ 8.98 - 8.85(m, 1H), 8.38 - 8.21(m, 3H), 7.76(ddd, J = 9.2, 6.5, 4.6 Hz, 3H), 7.66 - 7.53(m, 1H), 7.35(d, J = 7.8 Hz, 1H), 6.70(t, J = 7.7 Hz, 1H), 1.83 - 1.53(m, 8H), 1.45 - 1.25(m, 4H), 0.88(t, J = 7.3 Hz, 6H).

[0110] 13 C NMR(126 MHz, CDCl3) δ 183.02, 181.84, 165.48, 165.04, 164.70, 140.61, 136.44, 135.42, 135.33, 134.02, 133.90, 133.57, 127.12, 127.05, 123.16, 118.18, 118.04, 117.34, 116.46, 114.94, 26.75, 26.61, 22.90, 13.58.

[0111] 119 Sn NMR (187 MHz, CDCl3) δ -174.56.

[0112] HRMS (ESI) m / z calcd for C 29 H 28 BrNO4NaSn + [M + Na] + 676.0121, found 676.0114.

[0113] Crystallographic data: Triclinic system, space group P - 1, α = 76.1480(10)°, β = 79.2200(10)°, γ = 87.9860(10)°, Z = 4, Dc = 1.660 Mg·m -3 , F(000) = 1304.0; The tin atom in the molecule has a pentacoordinate trigonal bipyramidal configuration.

[0114] Application example: MTT method for detecting the proliferation effect of compounds on tumor cells

[0115] Take human lung cancer (A549), human liver cancer (HepG2), human breast cancer (MDA - MB - 231) and human oral cancer (CAL - 27) cells in the logarithmic growth phase, and inoculate them into 96 - well culture plates at a density of 3 - 5×10 3 cells / well. After the cells adhere for 24 h, carefully discard the original medium. Add 100 μL of medium to the negative control group, add 100 μL of compound solutions with different concentrations to the experimental groups respectively, and add 100 μL of drug solutions with different concentrations to the positive control groups respectively. Set 3 parallel replicate wells for each concentration, place them in an incubator at 37 °C and 5% CO2 for continued culture for 48 h. Add 20 μL of 5 mg·L -1 MTT solution to each well, continue to incubate for 4 h, carefully discard the supernatant, add 100 μL of DMSO to each well to dissolve, shake at low speed for 10 min, and measure the absorbance value (OD value) of each well at a wavelength of 490 nm on a full - automatic microplate reader. Calculate the inhibition rate of cell growth according to the following formula.

[0116] Cell growth inhibition rate % = [1 - (OD value of the drug - added group / OD value of the blank group)] × 100%.

[0117] The results are shown in Table 1, and the conclusion is as follows: As can be seen from the data in the table, when the 9,10-anthraquinone-(3-substituted salicylaldehyde) Schiff base dibutyltin complex of the present invention is used as an anticancer drug, it has certain efficacy against human lung cancer (A549), human liver cancer (HepG2), human breast cancer (MDA-MB-231) and human oral cancer (CAL-27) cells. The anticancer activity of most complexes is superior to that of the positive control drug cisplatin. Therefore, it can be used as a candidate compound for anticancer drugs and has potential application value.

[0118] Table 1 Effects of different complexes on the in vitro proliferation of different cancer cells

[0119]

[0120]

Claims

1. A dibutyltin complex of 9,10-anthraquinone-(3-substituted salicylaldehyde) Schiff base, characterized in that A compound of the following structural formula (I): Wherein, R is -H, -OH, -CH3, -C(CH3)3, -OCH3, -F, -Cl, -Br.

2. The anthraquinone dibutyltin complex according to claim 1, characterized in that: When R is -H, the complex is A1, and its crystal is triclinic system, space group P-1, α = 68.446(3)°, β = 85.290(3)°, γ = 85.264(3)°, Z = 6, Dc = 1.501 Mg·m -3 , F(000) = 1752.0; the tin atom in the molecule has a five-coordinate trigonal bipyramidal configuration; When R is -CH3, the complex is A3, and its crystal is monoclinic system, space group P21 / c, α = 90(3)°, β = 94.540(2)°, γ = 90°, Z = 4, Dc = 1.502 Mg·m -3 , F(000) = 1200.0; the tin atom in the molecule has a pentacoordinated trigonal bipyramidal configuration; When R is -C(CH3)3, the complex is A4, and its crystal is orthorhombic system, space group Pbcn, α = 90°, β = 90°, γ = 90°, Z = 8, Dc = 1.457 Mg·m -3 , F(000) = 2592.0; the tin atom in the molecule has a pentacoordinate trigonal bipyramidal configuration; When R is -OCH3, the complex is A5, and its crystal is triclinic system with space group P-1. α = 105.4590(10)°, β = 103.8170(10)°. γ = 97.4450(10)°, Z = 2, Dc = 1.523 Mg·m -3 , F(000) = 616.0; the tin atom in the molecule has a trigonal bipyramidal configuration with five coordination sites; When R is -F, the complex is A6, and its crystal is monoclinic system, space group P21 / c, α = 90°, β = 110.0830(10)°, γ = 90°, Z = 4, Dc = 1.540 Mg·m -3 , F(000) = 1200.0; the tin atom in the molecule has a pentacoordinated trigonal bipyramidal configuration; When R is -Cl, the complex is A7, and its crystal is monoclinic system, space group P21 / c, α = 90°, β = 113.160(2)°, γ = 90°, Z = 4, Dc = 1.525 Mg·m -3 , F(000) = 1232.0; the tin atom in the molecule has a five - coordinate trigonal bipyramidal configuration; When R is -Br, the complex is A8, and its crystal is triclinic system, space group P-1, α = 76.1480(10)°, β = 79.2200(10)°, γ = 87.9860(10)°, Z = 4, Dc = 1.660 Mg·m -3 , F(000) = 1304.0; In the molecule The tin atom has a trigonal bipyramidal configuration with five coordination sites.

3. Use of the anthraquinone dibutyltin complex according to claim 1 in the preparation of anti-tumor drugs.

4. The application according to claim 3, characterized in that: The tumors are lung cancer, liver cancer, breast cancer or oral cancer.

5. The application according to claim 4, wherein: The lung cancer, liver cancer, breast cancer, and oral cancer are derived from human lung cancer cell line A549, human liver cancer cell line HepG2, human breast cancer cell line MDA-MB-231, and human oral cancer cell line CAL-27, respectively.

6. The preparation method of the anthraquinone dibutyltin complex according to claim 1, characterized in that: Using 2-amino-3-hydroxyanthraquinone, 3-substituted salicylaldehyde and dibutyltin oxide as raw materials, and anhydrous methanol as the solvent, the reaction is completed under the condition of heating and refluxing.

7. The preparation method according to claim 6, characterized in that: The 3-substituted salicylaldehyde is salicylaldehyde, 3-hydroxysalicylaldehyde, 3-methylsalicylaldehyde, 3-tert-butylsalicylaldehyde, 3-methoxysalicylaldehyde, 3-fluorosalicylaldehyde, 3-chlorosalicylaldehyde, or 3-bromosalicylaldehyde.

8. The preparation method according to claim 6, characterized in that: The molar ratio of 2-amino-3-hydroxyanthraquinone, 3-substituted salicylaldehyde and dibutyltin oxide is 1:1:

1.

9. The preparation method according to claim 8, characterized in that: Add 1 mmol of 2-amino-3-hydroxyanthraquinone, 1 mmol of 3-substituted salicylaldehyde, 1 mmol of dibutyltin oxide and 30 ml of anhydrous methanol as the solvent into a flask, react under the condition of heating and refluxing for 8 h, cool, filter, and control the solvent evaporation and crystallization at room temperature to obtain the product.

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