Preparation method and application of tris (2-methyl-2-phenylpropyl) tin 5-bromosalicylate complex

Abstract

The invention discloses a preparation method and application of a tris (2-methyl-2-phenylpropyl) tin 5-bromosalicylate complex. The tris (2-methyl-2-phenylpropyl) tin 5-bromosalicylate complex is a complex # imgabs0 # with the following structural formula (I). The invention also discloses a preparation method of the tris (2-methyl-2-phenylpropyl) tin 5-bromosalicylate complex and an application of the tris (2-methyl-2-phenylpropyl) tin 5-bromosalicylate complex in preparation of antitumor drugs.

Description

Technical Field

[0001] The present invention relates to a tris(2-methyl-2-phenylpropyl)tin 5-bromosalicylate complex, a preparation method thereof, and an application of the complex in the preparation of anti-tumor drugs. Background Art

[0002] Organotin carboxylates have high biological activities and have broad application prospects in the fields of sterilization, insecticidal, and anti-cancer drug preparation. Therefore, the research on the synthesis, structure, and biological activities of organotin carboxylate complexes has received extensive attention from scientists. Existing research shows that the hydrocarbon group R in organotin carboxylates is the main factor determining the anti-cancer activity of the compound. For example, cyclohexyl, n-butyl, and phenyltin compounds have relatively strong anti-cancer activities, ethyl is the second, and methyl has almost no anti-cancer activity. However, since known organotin compounds generally have strong toxicity, their applications are subject to certain limitations. Adjusting the balance between their toxicity and biological activities is an important research direction at present. One of the currently effective methods is to greatly change the coordination mode of tin atoms by functionalizing the hydrocarbon group or ligand, thereby affecting the biological activities of organotin complexes. Research shows that the toxicity of organotin compounds is related to their relative molecular masses. The smaller the relative molecular mass, the greater the toxicity, and the relatively large molecular mass of large steric hindrance hydrocarbon group tin. Therefore, synthesizing novel large steric hindrance hydrocarbon group tin carboxylate complexes and studying their structures and biological activities have important research significance.

[0003] The bis[tris(2-methyl-2-phenylpropyl)tin] carboxylate disclosed in European Patent EP0177785B1 has stronger biological activities than bis[tris(2-methyl-2-phenylpropyl)tin] oxide.

[0004] Chinese Patent CN 106279256 B discloses the application of bis[tris(2-methyl-2-phenyl)propyltin] 2,2'-biphenyldicarboxylate complex in the preparation of drugs for treating lung cancer, breast cancer, and liver cancer.

[0005] Chinese Patent CN 106279253 B discloses the application of bis[tris(2-methyl-2-phenyl)propyltin] 5-nitroisophthalate complex in the preparation of drugs for treating lung cancer, breast cancer, and liver cancer.

[0006] Salicylic acid is a fat-soluble organic carboxylic acid and has long been used as a main raw material for synthesizing antipyretic and analgesic drugs (aspirin). The latest research shows that salicylic acid has an effect on the treatment of type I diabetic patients with existing heart diseases and is recommended as a drug for preventing complications. Some salicylic acid ligands also have good drug activities. For example, 5-aminosalicylic acid, also known as mesalazine, is a new drug for treating ulcerative colitis. Therefore, it is very necessary to combine bioactive large steric hindrance hydrocarbyltin compounds with drug-active salicylic acid ligands to synthesize novel large steric hindrance hydrocarbyltin carboxylate compounds and study their biological activities.

[0007] Based on the fact that bis[tris(2-methyl-2-phenylpropyl)]tin oxide is a substance proven to have good biological activity through experiments, and 2-methyl-2-phenylpropyl has characteristics such as large steric hindrance and large molecular weight, the present invention selects bis[tris(2-methyl-2-phenylpropyl)]tin oxide and reacts with the salicylic acid ligand 5-bromosalicylic acid under certain conditions to synthesize a complex with strong inhibitory activities against A549 (human lung cancer cells), Hela (human cervical cancer cells), and HGC-27 (human gastric cancer cells), providing a new way for the development of anticancer drugs. Summary of the Invention

[0008] Aiming at the problems existing in the above-mentioned prior art, the first object of the present invention is to provide a tris(2-methyl-2-phenylpropyl)tin 5-bromosalicylate complex.

[0009] The second object of the present invention is to provide a preparation method of the above-mentioned tris(2-methyl-2-phenylpropyl)tin 5-bromosalicylate complex.

[0010] The third object of the present invention is to provide the application of the above-mentioned tris(2-methyl-2-phenylpropyl)tin 5-bromosalicylate complex in the preparation of anticancer drugs.

[0011] As a tris(2-methyl-2-phenylpropyl)tin 5-bromosalicylate complex according to the first aspect of the present invention, its structural formula (I) is as follows: (I).

[0012] The tris(2-methyl-2-phenylpropyl)tin 5-bromosalicylate complex of the present invention is analyzed by elemental analysis, infrared spectroscopy, and nuclear magnetic resonance spectroscopy, and the results are as follows: Elemental analysis (C 37 H 43 BrO 3 Sn): Theoretical values: C, 60.52; H, 5.90. Measured values: C, 60.56; H, 5.95.

[0013] IR (KBr, v / cm -1): 3051.39 (w), 3020.53 (w), 2960.73 (s), 2920.23 (m), 1631.78 (m), 1593.20 (m), 1492.90 (m), 1465.90 (m), 1440.83 (m), 1381.03 (s), 1344.38 (m), 1290.38 (m), 1246.02 (m), 1076.28 (m), 1029.99 (w), 825.53 (m), 810.10 (m), 767.67 (m), 742.59 (m), 721.38 (m), 700.16 (s), 626.87 (w), 603.72 (m), 555.50 (m), 528.50 (w), 462.92 (m).

[0014] 1 H NMR (CDCl 3 , 500 MHz) δ (ppm): 11.75 (s, 1H), 7.80 (d, J =2 Hz, 1H), 7.48 - 7.46 (m, 1H), 7.31 (t, J =7.5 Hz, 6H), 7.23 (t, J =7 Hz, 3H), 7.10 (d, J =7.5 Hz, 6H), 6.85 (d, J =9 Hz, 6H), 1.29 (s, 6H), 1.24 (s, 18H).

[0015] 13 C NMR(CDCl 3 , 125 MHz) δ (ppm): 172.59, 160.72, 150.57, 137.14, 133.31, 128.48, 126.04, 125.23, 118.93, 116.80, 110.07, 38.15, 37.74, 32.89 (t, J =22.9 Hz).

[0016] 119 Sn NMR(CDCl 3 , 186 MHz), δ(ppm): 115.43.

[0017] The structural feature of the tris(2-methyl-2-phenylpropyl)tin 5-bromosalicylate complex of the present invention is that the central tin in the molecule forms a distorted tetrahedral configuration with the coordinating atoms.

[0018] As a preparation method of the tris(2-methyl-2-phenylpropyl)tin 5-bromosalicylate complex according to the second aspect of the present invention, bis[tris(2-methyl-2-phenylpropyl)]tin oxide, 5-bromosalicylic acid and the solvent anhydrous methanol are sequentially added into a microwave reaction vessel. Under an air atmosphere, microwave reaction is carried out at a radiation power of 800 W and a temperature of 100 °C for 60 - 120 min. After the reaction is completed, it is naturally cooled, filtered, and the solvent is allowed to naturally volatilize and crystallize at room temperature to obtain white crystals, which are the tris(2-methyl-2-phenylpropyl)tin 5-bromosalicylate complex.

[0019] In a preferred embodiment of the present invention, the molar ratio of bis[tris(2-methyl-2-phenylpropyl)]tin oxide to 5-bromosalicylic acid is 1:(2 - 2.1).

[0020] In a preferred embodiment of the present invention, the amount of the solvent anhydrous methanol used is 10 - 15 mL per millimole of bis[tris(2-methyl-2-phenylpropyl)]tin oxide.

[0021] Use of the tris(2-methyl-2-phenylpropyl)tin 5-bromosalicylate complex according to the third aspect of the present invention in the preparation of anticancer drugs.

[0022] The applicant has conducted research on the confirmation of the in vitro antitumor activity of the above complex, and confirmed that the complex has certain antitumor biological activity. That is to say, the use of the above complex is in the preparation of antitumor drugs, specifically in the preparation of drugs for treating human lung cancer, human cervical cancer, and human gastric cancer.

[0023] The tris(2-methyl-2-phenylpropyl)tin 5-bromosalicylate complex of the present invention shows good anticancer activity against human lung cancer cells, human cervical cancer cells, human gastric cancer cells, etc., and anti-lung cancer, anti-cervical cancer, and anti-gastric cancer drugs can be prepared from it. Compared with the commonly used platinum-based anticancer drugs at present, the tris(2-methyl-2-phenylpropyl)tin 5-bromosalicylate complex of the present invention has the characteristics of high anticancer activity, low cost, simple preparation method, etc., providing a new way for the development of anticancer drugs. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] Figure 1 It is the IR spectrum of the tris(2-methyl-2-phenylpropyl)tin 5-bromosalicylate complex.

[0025] Figure 21H NMR spectrum of tris(2-methyl-2-phenylpropyl)tin 5-bromosalicylate complex 1 1H NMR spectrum

[0026] Figure 3 13C NMR spectrum of tris(2-methyl-2-phenylpropyl)tin 5-bromosalicylate complex 13 13C NMR spectrum

[0027] Figure 4 119Sn NMR spectrum of tris(2-methyl-2-phenylpropyl)tin 5-bromosalicylate complex 119 119Sn NMR spectrum

[0028] The present invention will be further described in detail by the following examples, but it should be noted that the scope of the present invention is not limited by any of these examples.

[0029] Example 1 Preparation of tris(2-methyl-2-phenylpropyl)tin 5-bromosalicylate complex 1.0533 g (1.0 mmol) of bis[tris(2-methyl-2-phenylpropyl)]tin oxide, 0.4342 g (2.0 mmol) of 5-bromosalicylic acid and 10 mL of anhydrous methanol as solvent were sequentially added to a microwave reaction vessel. Under an air atmosphere, microwave reaction was carried out at a radiation power of 800 W and a temperature of 100 °C for 60 min. After the reaction, it was naturally cooled, filtered, and the solvent was allowed to naturally volatilize and crystallize at room temperature to obtain white crystals, which were tris(2-methyl-2-phenylpropyl)tin 5-bromosalicylate complex. Yield: 86%, melting point: 75 - 77 °C.

[0030] Elemental analysis (C 37 H 43 BrO 3 Sn): Theoretical values: C, 60.52; H, 5.90. Measured values: C, 60.56; H, 5.95.

[0031] IR (KBr, v / cm -1): 3051.39 (w), 3020.53 (w), 2960.73 (s), 2920.23 (m), 1631.78 (m), 1593.20 (m), 1492.90 (m), 1465.90 (m), 1440.83 (m), 1381.03 (s), 1344.38 (m), 1290.38 (m), 1246.02 (m), 1076.28 (m), 1029.99 (w), 825.53 (m), 810.10 (m), 767.67 (m), 742.59 (m), 721.38 (m), 700.16 (s), 626.87 (w), 603.72 (m), 555.50 (m), 528.50 (w), 462.92 (m).

[0032] 1 H NMR (CDCl 3 , 500 MHz) δ (ppm): 11.75 (s, 1H), 7.80 (d, J =2 Hz, 1H), 7.48 - 7.46 (m, 1H), 7.31 (t, J =7.5 Hz, 6H), 7.23 (t, J =7 Hz, 3H), 7.10 (d, J =7.5 Hz, 6H), 6.85 (d, J =9 Hz, 6H), 1.29 (s, 6H), 1.24 (s, 18H).

[0033] 13 C NMR(CDCl 3 , 125 MHz) δ (ppm): 172.59, 160.72, 150.57, 137.14, 133.31, 128.48, 126.04, 125.23, 118.93, 116.80, 110.07, 38.15, 37.74, 32.89 (t, J =22.9 Hz).

[0034] 119 Sn NMR(CDCl 3 , 186 MHz), δ(ppm): 115.43.

[0035] Example 2: Preparation of tris(2-methyl-2-phenylpropyl)tin 5-bromosalicylate complex: 1.0537 g (1.0 mmol) of bis[tris(2-methyl-2-phenylpropyl)]tin oxide, 0.4559 g (2.1 mmol) of 5-bromosalicylic acid and 15 mL of anhydrous methanol as the solvent were successively added to a microwave reaction vessel. Under an air atmosphere, microwave reaction was carried out at a radiation power of 800 W and a temperature of 100 °C for 60 min. After the reaction, it was naturally cooled, filtered, and the solvent was allowed to naturally volatilize and crystallize at room temperature to obtain white crystals, which were tris(2-methyl-2-phenylpropyl)tin 5-bromosalicylate complex. Yield: 87%, melting point: 75 - 77 °C.

[0036] Elemental analysis (C 37 H 43 BrO 3 Sn): Theoretical values: C, 60.52; H, 5.90. Measured values: C, 60.56; H, 5.95.

[0037] IR (KBr, v / cm -1 ): 3051.39 (w), 3020.53 (w), 2960.73 (s), 2920.23 (m), 1631.78 (m), 1593.20 (m), 1492.90 (m), 1465.90 (m), 1440.83 (m), 1381.03 (s), 1344.38 (m), 1290.38 (m), 1246.02 (m), 1076.28 (m), 1029.99 (w), 825.53 (m), 810.10 (m), 767.67 (m), 742.59 (m), 721.38 (m), 700.16 (s), 626.87 (w), 603.72 (m), 555.50 (m), 528.50 (w), 462.92 (m).

[0038] 1 H NMR (CDCl 3 , 500 MHz) δ (ppm): 11.75 (s, 1H), 7.80 (d, J = 2 Hz, 1H), 7.48 - 7.46 (m, 1H), 7.31 (t, J = 7.5 Hz, 6H), 7.23 (t, J = 7 Hz, 3H), 7.10 (d, J= 7.5 Hz, 6H), 6.85 (d, J = 9 Hz, 6H), 1.29 (s, 6H), 1.24 (s, 18H).

[0039] 13 C NMR(CDCl 3 , 125 MHz) δ (ppm): 172.59, 160.72, 150.57, 137.14, 133.31, 128.48, 126.04, 125.23, 118.93, 116.80, 110.07, 38.15, 37.74, 32.89 (t, J = 22.9 Hz).

[0040] 119 Sn NMR(CDCl 3 , 186 MHz), δ (ppm): 115.43.

[0041] Example 3: Preparation of tris(2-methyl-2-phenylpropyl)tin 5-bromosalicylate complex: 1.0535 g (1.0 mmol) of bis[tris(2-methyl-2-phenylpropyl)]tin oxide, 0.4352 g (2.0 mmol) of 5-bromosalicylic acid and 12 mL of anhydrous methanol as the solvent were successively added to a microwave reaction vessel. Under an air atmosphere, microwave reaction was carried out at a radiation power of 800 W and a temperature of 100 °C for 120 min. After the reaction, it was naturally cooled, filtered, and the solvent was allowed to naturally volatilize and crystallize at room temperature to obtain white crystals, which were tris(2-methyl-2-phenylpropyl)tin 5-bromosalicylate complex. Yield: 86%, melting point: 75 - 77 °C.

[0042] Elemental analysis (C 37 H 43 BrO 3 Sn): Theoretical values: C, 60.52; H, 5.90. Measured values: C, 60.56; H, 5.95.

[0043] IR (KBr, v / cm -1): 3051.39 (w), 3020.53 (w), 2960.73 (s), 2920.23 (m), 1631.78 (m), 1593.20 (m), 1492.90 (m), 1465.90 (m), 1440.83 (m), 1381.03 (s), 1344.38 (m), 1290.38 (m), 1246.02 (m), 1076.28 (m), 1029.99 (w), 825.53 (m), 810.10 (m), 767.67 (m), 742.59 (m), 721.38 (m), 700.16 (s), 626.87 (w), 603.72 (m), 555.50 (m), 528.50 (w), 462.92 (m).

[0044] 1 1H NMR (CDCl 3 , 500 MHz) δ (ppm): 11.75 (s, 1H), 7.80 (d, J =2 Hz, 1H), 7.48 - 7.46 (m, 1H), 7.31 (t, J =7.5 Hz, 6H), 7.23 (t, J =7 Hz, 3H), 7.10 (d, J =7.5 Hz, 6H), 6.85 (d, J =9 Hz, 6H), 1.29 (s, 6H), 1.24 (s, 18H).

[0045] 13 13C NMR(CDCl 3 , 125 MHz) δ (ppm): 172.59, 160.72, 150.57, 137.14, 133.31, 128.48, 126.04, 125.23, 118.93, 116.80, 110.07, 38.15, 37.74, 32.89 (t, J =22.9 Hz).

[0046] 119 119Sn NMR(CDCl 3 , 186 MHz), δ (ppm): 115.43.

[0047] Example 4: Preparation of tris(2-methyl-2-phenylpropyl)tin 5-bromosalicylate complex: Add 2.1064 g (2.0 mmol) of bis[tris(2-methyl-2-phenylpropyl)]tin oxide, 0.8685 g (4.0 mmol) of 5-bromosalicylic acid, and 25 mL of anhydrous methanol as the solvent into the microwave reaction vessel in sequence. Under an air atmosphere, carry out microwave reaction at a radiation power of 800 W and a temperature of 100 °C for 60 min. After the reaction is completed, cool naturally, filter, and let the solvent volatilize and crystallize naturally at room temperature to obtain white crystals, which are tris(2-methyl-2-phenylpropyl)tin 5-bromosalicylate complex. Yield: 89%, melting point: 75 - 77 °C.

[0048] Elemental analysis (C 37 H 43 BrO 3 Sn): Theoretical values: C, 60.52; H, 5.90. Measured values: C, 60.56; H, 5.95.

[0049] IR (KBr, v / cm -1 ): 3051.39 (w), 3020.53 (w), 2960.73 (s), 2920.23 (m), 1631.78 (m), 1593.20 (m), 1492.90 (m), 1465.90 (m), 1440.83 (m), 1381.03 (s), 1344.38 (m), 1290.38 (m), 1246.02 (m), 1076.28 (m), 1029.99 (w), 825.53 (m), 810.10 (m), 767.67 (m), 742.59 (m), 721.38 (m), 700.16 (s), 626.87 (w), 603.72 (m), 555.50 (m), 528.50 (w), 462.92 (m).

[0050] 1 H NMR (CDCl 3 , 500 MHz) δ (ppm): 11.75 (s, 1H), 7.80 (d, J =2 Hz, 1H), 7.48 - 7.46 (m, 1H), 7.31 (t, J =7.5 Hz, 6H), 7.23 (t, J =7 Hz, 3H), 7.10 (d, J= 7.5 Hz, 6H), 6.85 (d, J = 9 Hz, 6H), 1.29 (s, 6H), 1.24 (s, 18H).

[0051] 13 C NMR(CDCl 3 , 125 MHz) δ (ppm): 172.59, 160.72, 150.57, 137.14, 133.31, 128.48, 126.04, 125.23, 118.93, 116.80, 110.07, 38.15, 37.74, 32.89 (t, J = 22.9 Hz).

[0052] 119 Sn NMR(CDCl 3 , 186 MHz), δ (ppm): 115.43.

[0053] Example 5: Preparation of tris(2-methyl-2-phenylpropyl)tin 5-bromosalicylate complex: Add 2.1069 g (2.0 mmol) of bis[tris(2-methyl-2-phenylpropyl)]tin oxide, 0.8905 g (4.1 mmol) of 5-bromosalicylic acid, and 25 mL of anhydrous methanol as the solvent to the microwave reaction vessel in sequence. Under an air atmosphere, perform microwave reaction at a radiation power of 800 W and a temperature of 100 °C for 90 min. After the reaction is completed, cool naturally, filter, and let the solvent volatilize and crystallize naturally at room temperature to obtain white crystals, which are tris(2-methyl-2-phenylpropyl)tin 5-bromosalicylate complex. Yield: 88%, melting point: 75 - 77 °C.

[0054] Elemental analysis (C 37 H 43 BrO 3 Sn): Theoretical values: C, 60.52; H, 5.90. Measured values: C, 60.56; H, 5.95.

[0055] IR(KBr, v / cm -1): 3051.39 (w), 3020.53 (w), 2960.73 (s), 2920.23 (m), 1631.78 (m), 1593.20 (m), 1492.90 (m), 1465.90 (m), 1440.83 (m), 1381.03 (s), 1344.38 (m), 1290.38 (m), 1246.02 (m), 1076.28 (m), 1029.99 (w), 825.53 (m), 810.10 (m), 767.67 (m), 742.59 (m), 721.38 (m), 700.16 (s), 626.87 (w), 603.72 (m), 555.50 (m), 528.50 (w), 462.92 (m).

[0056] 1 1H NMR (CDCl 3 , 500 MHz) δ (ppm): 11.75 (s, 1H), 7.80 (d, J J = 2 Hz, 1H), 7.48 - 7.46 (m, 1H), 7.31 (t, J J = 7.5 Hz, 6H), 7.23 (t, J J = 7 Hz, 3H), 7.10 (d, J J = 7.5 Hz, 6H), 6.85 (d, J J = 9 Hz, 6H), 1.29 (s, 6H), 1.24 (s, 18H).

[0057] 13 13C NMR(CDCl 3 , 125 MHz) δ (ppm): 172.59, 160.72, 150.57, 137.14, 133.31, 128.48, 126.04, 125.23, 118.93, 116.80, 110.07, 38.15, 37.74, 32.89 (t, J J = 22.9 Hz).

[0058] 119 119Sn NMR(CDCl 3 , 186 MHz), δ (ppm): 115.43.

[0059] Example 6: Preparation of tris(2-methyl-2-phenylpropyl)tin 5-bromosalicylate complex: Add 3.1596 g (3.0 mmol) of bis[tris(2-methyl-2-phenylpropyl)]tin oxide, 1.3025 g (6.0 mmol) of 5-bromosalicylic acid, and 30 mL of anhydrous methanol as the solvent into the microwave reaction vessel in sequence. Under an air atmosphere, carry out microwave reaction at a radiation power of 800 W and a temperature of 100 °C for 120 min. After the reaction is completed, cool naturally, filter, and let the solvent volatilize and crystallize naturally at room temperature to obtain white crystals, which are tris(2-methyl-2-phenylpropyl)tin 5-bromosalicylate complex. Yield: 88%, melting point: 75 - 77 °C.

[0060] Elemental analysis (C 37 H 43 BrO 3 Sn): Theoretical values: C, 60.52; H, 5.90. Measured values: C, 60.56; H, 5.95.

[0061] IR (KBr, v / cm -1 ): 3051.39 (w), 3020.53 (w), 2960.73 (s), 2920.23 (m), 1631.78 (m), 1593.20 (m), 1492.90 (m), 1465.90 (m), 1440.83 (m), 1381.03 (s), 1344.38 (m), 1290.38 (m), 1246.02 (m), 1076.28 (m), 1029.99 (w), 825.53 (m), 810.10 (m), 767.67 (m), 742.59 (m), 721.38 (m), 700.16 (s), 626.87 (w), 603.72 (m), 555.50 (m), 528.50 (w), 462.92 (m).

[0062] 1 H NMR (CDCl 3 , 500 MHz) δ (ppm): 11.75 (s, 1H), 7.80 (d, J = 2 Hz, 1H), 7.48 - 7.46 (m, 1H), 7.31 (t, J = 7.5 Hz, 6H), 7.23 (t, J = 7 Hz, 3H), 7.10 (d, J= 7.5 Hz, 6H), 6.85 (d, J = 9 Hz, 6H), 1.29 (s, 6H), 1.24 (s, 18H).

[0063] 13 C NMR(CDCl 3 , 125 MHz) δ (ppm): 172.59, 160.72, 150.57, 137.14, 133.31, 128.48, 126.04, 125.23, 118.93, 116.80, 110.07, 38.15, 37.74, 32.89 (t, J = 22.9 Hz).

[0064] 119 Sn NMR(CDCl 3 , 186 MHz), δ (ppm): 115.43.

[0065] Test Example: For the tris(2-methyl-2-phenylpropyl)tin 5-bromosalicylate complex of the present invention, its in vitro anti-cancer activity was determined by the MTT assay method.

[0066] MTT Analysis Method: Based on the metabolic reduction of 3-(4,5-Dimethylthiazol-2-yl)-2,5-diArenyltetrazoliumbromide. Succinate dehydrogenase in the mitochondria of living cells can reduce exogenous MTT to water-insoluble blue-violet crystalline formazan and deposit it in the cells, while dead cells do not have this function. Dimethyl sulfoxide (DMSO) can dissolve the formazan in the cells, and the optical density at a characteristic wavelength is measured with an enzyme-linked immunosorbent assay (ELISA) reader, which can indirectly reflect the number of living cells.

[0067] The MTT method was used to determine the inhibitory activities of the tris(2-methyl-2-phenylpropyl)tin 5-bromosalicylate complex prepared in Example 1 against human lung cancer cells (A549), human cervical cancer cells (Hela), and human gastric cancer cells (HGC-27).

[0068] Cell Lines and Culture Systems: The A549, Hela, and HGC-27 cell lines were obtained from the American Type Culture Collection (ATCC). They were cultured in vitro in RPMI 1640 (GIBICO) medium containing 10% fetal bovine serum in a 5% (volume fraction) CO 2 , 37 °C saturated humidity incubator.

[0069] Test procedure: Test liquid medicine (0.0625 μmol / L - 0.5 μmol / L) was added into each well according to the concentration gradient, and 3 parallel wells were set for each concentration. The experiment was divided into a drug test group (different concentrations of the test drug were added respectively), a control group (only culture medium and cells were added, without the test drug), and a blank group (only culture medium was added, without cells and the test drug). The microplate after adding the drug was placed in an incubator at 37 °C and 5% CO 2 and cultured for 24 h. The activity of the control drug was determined according to the method of the test sample. In the microplate after culturing for 48 h, 20 μL of MTT (prepared into 5 g / L with PBS solution) was added to each well. After placing at 37 °C for 4 h, the supernatant was removed. 150 μL of DMSO was added to each well and shaken for 10 min to dissolve the Formazan crystals. Finally, the absorbance value of each well was measured at a wavelength of 570 nm using a BioTek multi-functional microplate reader.

[0070] Data processing: Data processing was performed using the GraAr Pad Prism version 5.0 program, and the IC 50 of the complex was obtained by fitting through the non-linear regression model with S-shaped dose response in the program.

[0071] The human lung cancer cell line (A549), human cervical cancer cell line (Hela), and human gastric cancer cell line (HGC-27) were analyzed by the MTT assay to measure their IC 50 values. The results are shown in Table 1. The conclusion is: As can be seen from the data in the table, the tris(2-methyl-2-phenylpropyl)tin 5-bromosalicylate complex of the present invention has relatively high anti-cancer activity against human lung cancer, human cervical cancer, and human gastric cancer, and can be used as a candidate complex for anti-cancer drugs.

[0072] Table 1 In vitro activity test data of the tris(2-methyl-2-phenylpropyl)tin 5-bromosalicylate complex as an anti-cancer drug. Human lung cancer cells Human cervical cancer cells Human gastric cancer cells Cell line A549 Hela HGC-27 <![CDATA[IC 50 μM]]> 0.5026 0.4929 0.4693

[0073] For the tris(2-methyl-2-phenylpropyl)tin 5-bromosalicylate complex prepared in the remaining examples, the test method for the anti-cancer activity against human lung cancer cells (A549), human cervical cancer cells (Hela), and human gastric cancer cells (HGC-27) by the MTT method was the same as that in the test example, and the test results were basically the same as those in Table 1.

Claims

1. A tri(2-methyl-2-phenylpropyl)tin 5-bromosalicylate complex having the following structural formula (I): (I)。 2. The tri(2-methyl-2-phenylpropyl)tin 5-bromosalicylate complex as claimed in claim 1, wherein the infrared spectrum data are as follows: FT-IR (KBr, v / cm -1 ): 3051.39 (w), 3020.53 (w), 2960.73 (s), 2920.23(m), 1631.78 (m), 1593.20 (m), 1492.90 (m), 1465.90 (m), 1440.83 (m), 1381.03(s), 1344.38 (m), 1290.38 (m), 1246.02 (m), 1076.28 (m), 1029.99 (w), 825.53(m), 810.10 (m), 767.67 (m), 742.59 (m), 721.38 (m), 700.16 (s), 626.87 (w), 603.72 (m), 555.50 (m), 528.50 (w), 462.92 (m); Its NMR spectrum data: 1 H NMR (CDCl3, 500MHz) δ (ppm): 11.75 (s, 1H), 7.80 (d, J =2 Hz, 1H), 7.48-7.46 (m, 1H), 7.31(t, J =7.5 Hz, 6H), 7.23 (t, J =7 Hz, 3H), 7.10 (d, J =7.5 Hz, 6H), 6.85 (d, J =9 Hz, 6H), 1.29 (s, 6H), 1.24(s, 18H); 13 CNMR(CDCl3, 125MHz) δ (ppm):172.59, 160.72, 150.57, 137.14, 133.31, 128.48, 126.04, 125.23, 118.93,116.80, 110.07, 38.15, 37.74, 32.89 (t, J =22.9 Hz); 119 Sn NMR (CDCl3, 186MHz), δ (ppm): 115.

43.

3. The method for preparing the tri(2-methyl-2-phenylpropyl)tin 5-bromosalicylate complex according to claim 1, characterized in that: Add bis(tri(2-methyl-2-phenylpropyl)]tin oxide, 5-bromosalicylic acid and solvent anhydrous methanol into a microwave reaction tank in sequence, and carry out microwave reaction at a radiation power of 800 W and a temperature of 100 °C under air atmosphere for 60-120 min. After the reaction is completed, cool naturally, filter, and allow the solvent to evaporate and crystallize naturally at room temperature to obtain white crystals, which are tri(2-methyl-2-phenylpropyl)tin 5-bromosalicylate complex.

4. The preparation method according to claim 3, characterized in that: The molar ratio of the bis[tri(2-methyl-2-phenylpropyl)]tin oxide to 5-bromosalicylic acid is 1:(2-2.1).

5. The preparation method according to claim 3, characterized in that: The amount of the solvent anhydrous methanol is 10-15 ml per millimole of bis[tri(2-methyl-2-phenylpropyl)]tin oxide.

6. Use of the tri(2-methyl-2-phenylpropyl)tin 5-bromosalicylate complex of claim 1 in the preparation of anticancer drugs.

7. The use according to claim 6, wherein the cancer cells are lung cancer, cervical cancer, or gastric cancer.

Images