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

Abstract

The invention discloses a preparation method and application of a tris (2-methyl-2-phenylpropyl) stann-5-methyl salicylate complex. The tris (2-methyl-2-phenylpropyl) stann-5-methyl salicylate 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-methyl salicylate complex and an application of the tris (2-methyl-2-phenylpropyl) tin-5-methyl salicylate complex in preparation of antitumor drugs.

Description

Technical Field

[0001] The invention relates to a tris(2-methyl-2-phenylpropyl)tin-5-methylsalicylate complex, a preparation method thereof, and application of the complex in preparing antitumor drugs. Background Art

[0002] Organotin carboxylates have high biological activity and have broad application prospects in the fields of sterilization, insecticide, and preparation of anticancer drugs. Therefore, the synthesis, structure, and biological activity of organotin carboxylates have attracted extensive attention from scientists. Existing studies have shown that the hydrocarbon group R in organotin carboxylates is the main factor determining the anticancer activity of the compound. For example, cyclohexyl, n-butyl, and phenyltin compounds have strong anticancer activity, followed by ethyl, and methyl has almost no anticancer activity. However, since the known organotin compounds are generally highly toxic, their application is subject to certain restrictions. Adjusting the balance between toxicity and biological activity is an important research direction. Functionalizing the hydrocarbon group or ligand can greatly change the coordination mode of the tin atom, thereby affecting the biological activity of the organotin complex, which is one of the effective methods currently available. Studies have shown that the toxicity of organotin compounds is related to their relative molecular mass. The smaller the relative molecular mass, the greater the toxicity, and the larger the relative molecular mass of the large sterically hindered hydrocarbon tin. Therefore, it is of great research significance to synthesize new large sterically hindered hydrocarbon tin carboxylates and study their structure and biological activity.

[0003] European Patent EP0177785B1 discloses that bis[tri(2-methyl-2-phenylpropyl)tin]carboxylate has stronger biological activity than bis[tri(2-methyl-2-phenylpropyl)tin]oxide.

[0004] Chinese patent CN 106279256 B discloses the use of bis[tri(2-methyl-2-phenyl)propyltin]2,2'-biphenyl dicarboxylate complexes in the preparation of drugs for treating lung cancer, breast cancer and liver cancer.

[0005] Chinese patent CN 106279253 B discloses the use of bis[tri(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, which has long been used as a main raw material for the synthesis of antipyretic analgesics (aspirin). The latest studies have shown that salicylic acid is effective in the treatment of type I diabetic patients who already have heart disease, and is recommended as a drug to prevent complications. Some salicylic acid ligands also have good drug activity, such as 5-aminosalicylic acid, also known as masalazone, which is a new drug for the treatment of ulcerative colitis. Therefore, it is very necessary to combine biologically active bulky sterically hindered alkyltin compounds with pharmaceutically active salicylic acid ligands to synthesize new bulky sterically hindered alkyltin carboxylate compounds and study their biological activity.

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

[0008] In view of the problems existing in the prior art, the first object of the present invention is to provide a tri(2-methyl-2-phenylpropyl)tin-5-methylsalicylate complex.

[0009] The second object of the present invention is to provide a method for preparing the above tri(2-methyl-2-phenylpropyl)tin-5-methylsalicylate complex.

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

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

[0012] The tri(2-methyl-2-phenylpropyl)tin-5-methylsalicylate complex of the present invention was subjected to elemental analysis, infrared spectrum analysis, nuclear magnetic resonance spectrum and X-ray single crystal structure analysis, and the results are as follows: Elemental analysis (C 38 H 46 O3Sn): Theoretical value: C, 68.17; H, 6.93. Found: C, 68.22; H, 6.95.

[0013] IR(KBr, v / cm-1 ): 3055.24 (m), 3028.24 (m), 2960.73 (s), 2895.15 (m),2864.29 (m), 1639.49 (m), 1581.63 (s), 1490.97 (s), 1442.75 (m), 1388.75 (s),1350.17(s), 1292.31 (m), 1240.23 (s), 1205.51 (m), 1076.28 (m), 1031.92 (w),999.13 (w), 813.96 (m), 769.60 (s), 744.52 (m), 702.09 (s), 680.87 (m),611.43 (m),555.50 (m), 534.28 (w), 480.28 (w), 459,06 (w), 426.27 (w)。

[0014] 1 H NMR (CDCl3, 500 MHz) d (ppm): 11.54 (s, 1H), 7.55(d, J = 1.5Hz, 1H),7.32 - 7.29 ( m, 6H), 7.24 - 7.21 (m, 4H), 7.12 - 7.10, (m, 6H), 6.87 (d, J = 8Hz, 1H), 2.31 (s, 3H), 1.28 (s, 6H), 1.25 (s, 18H)。

[0015] 13 C NMR(CDCl3, 125 MHz), δ(ppm): 173.72, 159.45, 150.71, 135.39,130.86, 128.41, 127.49, 125.39, 125.24, 116.68,114.68, 37.83, 37.70 (t, J =9.95 Hz), 32.83 (t, J = 22.43 Hz), 20.47。

[0016] 119 Sn NMR (CDCl3, 186 MHz) d (ppm):106.29。

[0017] The tri(2-methyl-2-phenylpropyl)tin-5-methylsalicylate complex of the present invention is a crystal structure, and its crystallographic data: the crystal belongs to the triclinic system, and the space group P -1, a =0.94079(6) nm, b =1.15405(8) nm, c =1.71945(12)nm, α =99°, β =103°, c =102°, Z =2,V=1.7427(2)nm 3 , D c=1.276 Mg·m -3 , m (MoKa) = 0.766 mm -1 , F (000) = 696, 2.29° < i <27.58°, crystal size: 0.25×0.20×0.22 mm, R =0.0266, wR =0.0660.

[0018] The structural feature of the tri(2-methyl-2-phenylpropyl)tin-5-methylsalicylate complex of the present invention is that the central tin in the molecule forms a distorted tetrahedral configuration with the coordination atom.

[0019] As a preparation method of a tri(2-methyl-2-phenylpropyl)tin-5-methylsalicylate complex according to the second aspect of the present invention, bis(tri(2-methyl-2-phenylpropyl)]tin oxide, 5-methylsalicylic acid and anhydrous methanol as solvent are sequentially added to a microwave reaction tank, and microwave reaction is carried out at a radiation power of 800 W and a temperature of 100° C. under an air atmosphere for 60 to 120 min. After the reaction is completed, the reaction is naturally cooled and filtered, and the solvent is naturally evaporated and crystallized at room temperature to obtain white crystals, which are tri(2-methyl-2-phenylpropyl)tin-5-methylsalicylate complex.

[0020] In a preferred embodiment of the present invention, the molar ratio of the bis[tri(2-methyl-2-phenylpropyl)]tin oxide to 5-methylsalicylic acid is 1.0:(2.0-2.1).

[0021] In a preferred embodiment of the present invention, the amount of the solvent anhydrous methanol is 10-15 ml per mmol of bis[tri(2-methyl-2-phenylpropyl)]tin oxide.

[0022] As the third aspect of the present invention, a tri(2-methyl-2-phenylpropyl)tin-5-methylsalicylate complex is used in the preparation of anticancer drugs.

[0023] The applicant conducted an in vitro anti-tumor activity confirmation study on the above-mentioned complex and confirmed that the complex has certain anti-tumor biological activity, that is, the use of the above-mentioned complex is in the preparation of anti-tumor drugs, specifically in the preparation of anti-human lung cancer drugs, human cervical cancer drugs, and human gastric cancer drugs.

[0024] The tris(2-methyl-2-phenylpropyl)tin-5-methylsalicylate complex of the present invention shows good anticancer activity against human lung cancer cells, human cervical cancer cells, human gastric cancer cells and the like, and can be used as a raw material to prepare anti-lung cancer, anti-cervical cancer and anti-gastric cancer drugs. Compared with the currently commonly used platinum anticancer drugs, the tris(2-methyl-2-phenylpropyl)tin-5-methylsalicylate complex of the present invention has the characteristics of high anticancer activity, low cost, simple preparation method and the like, and provides a new approach for the development of anticancer drugs. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] Figure 1 This is a crystal molecular structure diagram of tri(2-methyl-2-phenylpropyl)tin-5-methylsalicylate complex.

[0026] Figure 2 This is the IR spectrum of tri(2-methyl-2-phenylpropyl)tin-5-methylsalicylate complex.

[0027] Figure 3 It is a complex of tri(2-methyl-2-phenylpropyl)tin-5-methylsalicylate 1 H NMR spectrum.

[0028] Figure 4 It is a complex of tri(2-methyl-2-phenylpropyl)tin-5-methylsalicylate 13 C NMR spectrum.

[0029] Figure 5 It is a complex of tri(2-methyl-2-phenylpropyl)tin-5-methylsalicylate 119 Sn NMR spectrum.

[0030] Figure 6 This is the TG-DTG curve of tri(2-methyl-2-phenylpropyl)tin-5-methylsalicylate complex. DETAILED DESCRIPTION

[0031] The present invention is further described in detail by the following examples, but it should be noted that the scope of the present invention is not limited by these examples.

[0032] Embodiment 1: Preparation of tri(2-methyl-2-phenylpropyl)tin-5-methylsalicylate complex: Add 1.0537 g (1.0 mmol) of bis(tri(2-methyl-2-phenylpropyl))tin oxide, 0.3054 g (2.0 mmol) of 5-methylsalicylic acid, and 10 mL of anhydrous methanol to a microwave reaction tank in order. Perform microwave reaction at a radiation power of 800 W and a temperature of 100 °C under air atmosphere for 60 min. After the reaction is completed, cool naturally, filter, and the solvent evaporates and crystallizes naturally at room temperature to obtain white crystals, which are tri(2-methyl-2-phenylpropyl)tin-5-methylsalicylate complexes. Yield: 62%, melting point: 63 – 65 °C.

[0033] Elemental analysis (C 38 H 46 O3Sn): Theoretical value: C, 68.17; H, 6.93. Found: C, 68.22; H, 6.95.

[0034] IR(KBr, v / cm -1 ): 3055.24 (m), 3028.24 (m), 2960.73 (s), 2895.15 (m), 2864.29 (m), 1639.49 (m), 1581.63 (s), 1490.97 (s), 1442.75 (m), 1388.75 (s),1350.17(s), 1292.31 (m), 1240.23 (s), 1205.51 (m), 1076.28 (m), 1031.92 (w),999.13 (w), 813.96 (m), 769.60 (s), 744.52 (m), 702.09 (s), 680.87 (m), 611.43 (m),555.50 (m), 534.28 (w), 480.28 (w), 459,06 (w), 426.27 (w).

[0035] 1 H NMR (CDCl3, 500 MHz) d (ppm): 11.54 (s, 1H), 7.55(d, J = 1.5Hz, 1H),7.32 - 7.29 (m, 6H), 7.24 - 7.21 (m, 4H), 7.12 - 7.10, (m, 6H), 6.87 (d, J= 8Hz, 1H), 2.31 (s, 3H), 1.28 (s, 6H), 1.25 (s, 18H).

[0036] 13 C NMR (CDCl3, 125 MHz), δ (ppm): 173.72, 159.45, 150.71, 135.39,130.86, 128.41, 127.49, 125.39, 125.24, 116.68,114.68, 37.83, 37.70 (t, J =9.95 Hz), 32.83 (t, J = 22.43 Hz), 20.47.

[0037] 119 Sn NMR (CDCl3, 186 MHz) d (ppm):106.29.

[0038] Its crystallographic data: The crystal belongs to the triclinic system, space group P -1, a =0.94079(6) nm, b =1.15405(8)nm, c =1.71945(12) nm, α =99°, β =103°, c =102°, Z =2,V=1.7427(2)nm 3 , D c=1.276 Mg·m -3 , m (MoKa) = 0.766 mm -1 , F (000) = 696, 2.29° < i <27.58°, crystal size: 0.25×0.20×0.22 mm, R =0.0266, wR =0.0660.

[0039] Embodiment 2: Preparation of tri(2-methyl-2-phenylpropyl)tin-5-methylsalicylate complex: Add 1.0541 g (1 mmol) of bis(tri(2-methyl-2-phenylpropyl))tin oxide, 0.3198 g (2.1 mmol) of 5-methylsalicylic acid, and 15 mL of anhydrous methanol to a microwave reaction tank in sequence. Perform microwave reaction at a radiation power of 800 W and a temperature of 100 °C under air atmosphere for 60 min. After the reaction is completed, cool naturally, filter, and the solvent evaporates and crystallizes naturally at room temperature to obtain white crystals, which are tri(2-methyl-2-phenylpropyl)tin-5-methylsalicylate complexes. Yield: 63%, melting point: 63 – 65 °C.

[0040] Elemental analysis (C 38 H 46 O3Sn): Theoretical value: C, 68.17; H, 6.93. Found: C, 68.22; H, 6.95.

[0041] IR(KBr, v / cm -1 ): 3055.24 (m), 3028.24 (m), 2960.73 (s), 2895.15 (m), 2864.29 (m), 1639.49 (m), 1581.63 (s), 1490.97 (s), 1442.75 (m), 1388.75 (s),1350.17(s), 1292.31 (m), 1240.23 (s), 1205.51 (m), 1076.28 (m), 1031.92 (w),999.13 (w), 813.96 (m), 769.60 (s), 744.52 (m), 702.09 (s), 680.87 (m), 611.43 (m),555.50 (m), 534.28 (w), 480.28 (w), 459,06 (w), 426.27 (w).

[0042] 1 H NMR (CDCl3, 500 MHz) d (ppm): 11.54 (s, 1H), 7.55(d, J = 1.5Hz, 1H),7.32 - 7.29 (m, 6H), 7.24 - 7.21 (m, 4H), 7.12 - 7.10, (m, 6H), 6.87 (d, J = 8Hz, 1H), 2.31 (s, 3H), 1.28 (s, 6H), 1.25 (s, 18H).

[0043] 13 C NMR (CDCl3, 125 MHz), δ (ppm): 173.72, 159.45, 150.71, 135.39,130.86, 128.41, 127.49, 125.39, 125.24, 116.68,114.68, 37.83, 37.70 (t, J =9.95 Hz), 32.83 (t, J = 22.43 Hz), 20.47.

[0044] 119 Sn NMR (CDCl3, 186 MHz) d (ppm):106.29.

[0045] Its crystallographic data: The crystal belongs to the triclinic system, space group P -1, a =0.94079(6) nm, b =1.15405(8)nm, c =1.71945(12) nm, α =99°, β =103°, c =102°, Z =2,V=1.7427(2)nm 3 , D c=1.276 Mg·m -3 , m (MoKa) = 0.766 mm -1 , F (000) = 696, 2.29° < i <27.58°, crystal size: 0.25×0.20×0.22 mm, R =0.0266, wR =0.0660.

[0046] Embodiment 3: Preparation of tri(2-methyl-2-phenylpropyl)tin-5-methylsalicylate complex: Add 1.0534 g (1.0 mmol) of bis(tri(2-methyl-2-phenylpropyl))tin oxide, 0.3050 g (2.0 mmol) of 5-methylsalicylic acid, and 12 mL of anhydrous methanol solvent to a microwave reaction tank in order. Perform microwave reaction at a radiation power of 800 W and a temperature of 100 °C under air atmosphere for 120 min. After the reaction is completed, cool naturally, filter, and the solvent evaporates and crystallizes naturally at room temperature to obtain white crystals, which are tri(2-methyl-2-phenylpropyl)tin-5-methylsalicylate complexes. Yield: 64%, melting point: 63 – 65 °C.

[0047] Elemental analysis (C 38 H 46 O3Sn): Theoretical value: C, 68.17; H, 6.93. Found: C, 68.22; H, 6.95.

[0048] IR(KBr, v / cm -1 ): 3055.24 (m), 3028.24 (m), 2960.73 (s), 2895.15 (m), 2864.29 (m), 1639.49 (m), 1581.63 (s), 1490.97 (s), 1442.75 (m), 1388.75 (s),1350.17(s), 1292.31 (m), 1240.23 (s), 1205.51 (m), 1076.28 (m), 1031.92 (w),999.13 (w), 813.96 (m), 769.60 (s), 744.52 (m), 702.09 (s), 680.87 (m), 611.43 (m),555.50 (m), 534.28 (w), 480.28 (w), 459,06 (w), 426.27 (w).

[0049] 1 H NMR (CDCl3, 500 MHz) d (ppm): 11.54 (s, 1H), 7.55(d, J = 1.5Hz, 1H),7.32 - 7.29 (m, 6H), 7.24 - 7.21 (m, 4H), 7.12 - 7.10, (m, 6H), 6.87 (d, J = 8Hz, 1H), 2.31 (s, 3H), 1.28 (s, 6H), 1.25 (s, 18H).

[0050] 13 C NMR (CDCl3, 125 MHz), δ (ppm): 173.72, 159.45, 150.71, 135.39,130.86, 128.41, 127.49, 125.39, 125.24, 116.68,114.68, 37.83, 37.70 (t, J =9.95 Hz), 32.83 (t, J = 22.43 Hz), 20.47.

[0051] 119 Sn NMR (CDCl3, 186 MHz) d (ppm):106.29.

[0052] Its crystallographic data: The crystal belongs to the triclinic system, space group P -1, a =0.94079(6) nm, b =1.15405(8)nm, c =1.71945(12) nm, α =99°, β =103°, c =102°, Z =2,V=1.7427(2)nm 3 , D c=1.276 Mg·m -3 , m (MoKa) = 0.766 mm -1 , F (000) = 696, 2.29° < i <27.58°, crystal size: 0.25×0.20×0.22 mm, R =0.0266, wR =0.0660.

[0053] Embodiment 4: Preparation of tri(2-methyl-2-phenylpropyl)tin-5-methylsalicylate complex: Add 2.1073 g (2.0 mmol) of bis(tri(2-methyl-2-phenylpropyl))tin oxide, 0.6092 g (4.0 mmol) of 5-methylsalicylic acid, and 25 mL of anhydrous methanol solvent to a microwave reaction tank in order. Perform microwave reaction at a radiation power of 800 W and a temperature of 100 °C under air atmosphere for 60 min. After the reaction is completed, cool naturally, filter, and the solvent evaporates and crystallizes naturally at room temperature to obtain white crystals, which are tri(2-methyl-2-phenylpropyl)tin-5-methylsalicylate complexes. Yield: 63%, melting point: 63 – 65 °C.

[0054] Elemental analysis (C 38 H 46 O3Sn): Theoretical value: C, 68.17; H, 6.93. Found: C, 68.22; H, 6.95.

[0055] IR(KBr, v / cm -1 ): 3055.24 (m), 3028.24 (m), 2960.73 (s), 2895.15 (m), 2864.29 (m), 1639.49 (m), 1581.63 (s), 1490.97 (s), 1442.75 (m), 1388.75 (s),1350.17(s), 1292.31 (m), 1240.23 (s), 1205.51 (m), 1076.28 (m), 1031.92 (w),999.13 (w), 813.96 (m), 769.60 (s), 744.52 (m), 702.09 (s), 680.87 (m), 611.43 (m),555.50 (m), 534.28 (w), 480.28 (w), 459,06 (w), 426.27 (w).

[0056] 1 H NMR (CDCl3, 500 MHz) d (ppm): 11.54 (s, 1H), 7.55(d, J = 1.5Hz, 1H),7.32 - 7.29 (m, 6H), 7.24 - 7.21 (m, 4H), 7.12 - 7.10, (m, 6H), 6.87 (d, J = 8Hz, 1H), 2.31 (s, 3H), 1.28 (s, 6H), 1.25 (s, 18H).

[0057] 13 C NMR (CDCl3, 125 MHz), δ (ppm): 173.72, 159.45, 150.71, 135.39,130.86, 128.41, 127.49, 125.39, 125.24, 116.68,114.68, 37.83, 37.70 (t, J =9.95 Hz), 32.83 (t, J = 22.43 Hz), 20.47.

[0058] 119 Sn NMR (CDCl3, 186 MHz) d (ppm):106.29.

[0059] Its crystallographic data: The crystal belongs to the triclinic system, space group P -1, a =0.94079(6) nm, b =1.15405(8)nm, c =1.71945(12) nm, α =99°, β =103°, c =102°, Z =2,V=1.7427(2)nm 3 , D c=1.276 Mg·m -3 , m (MoKa) = 0.766 mm -1 , F (000) = 696, 2.29° < i <27.58°, crystal size: 0.25×0.20×0.22 mm, R =0.0266, wR =0.0660.

[0060] Embodiment 5: Preparation of tri(2-methyl-2-phenylpropyl)tin-5-methylsalicylate complex: Add 2.1073 g (2.0 mmol) of bis(tri(2-methyl-2-phenylpropyl))tin oxide, 0.6231 g (4.1 mmol) of 5-methylsalicylic acid, and 25 mL of anhydrous methanol solvent to a microwave reaction tank in order. Perform microwave reaction at a radiation power of 800 W and a temperature of 100 °C under air atmosphere for 90 min. After the reaction is completed, cool naturally, filter, and the solvent evaporates and crystallizes naturally at room temperature to obtain white crystals, which are tri(2-methyl-2-phenylpropyl)tin-5-methylsalicylate complexes. Yield: 64%, melting point: 63 – 65 °C.

[0061] Elemental analysis (C 38 H 46 O3Sn): Theoretical value: C, 68.17; H, 6.93. Found: C, 68.22; H, 6.95.

[0062] IR(KBr, v / cm -1 ): 3055.24 (m), 3028.24 (m), 2960.73 (s), 2895.15 (m), 2864.29 (m), 1639.49 (m), 1581.63 (s), 1490.97 (s), 1442.75 (m), 1388.75 (s),1350.17 (s),1292.31 (m), 1240.23 (s), 1205.51 (m), 1076.28 (m), 1031.92 (w),999.13 (w), 813.96 (m), 769.60 (s), 744.52 (m), 702.09 (s), 680.87 (m), 611.43 (m), 555.50(m), 534.28(w), 480.28(w), 459.06(w), 426.27(w).

[0063] 1 H NMR (CDCl3, 500 MHz) d (ppm): 11.54 (s, 1H), 7.55(d, J = 1.5Hz, 1H),7.32 - 7.29 (m, 6H), 7.24 - 7.21 (m, 4H), 7.12 - 7.10, (m, 6H), 6.87 (d, J = 8Hz, 1H), 2.31 (s, 3H), 1.28 (s, 6H), 1.25 (s, 18H).

[0064] 13 C NMR (CDCl3, 125 MHz), δ (ppm): 173.72, 159.45, 150.71, 135.39,130.86, 128.41, 127.49, 125.39, 125.24, 116.68,114.68, 37.83, 37.70 (t, J =9.95 Hz), 32.83 (t, J = 22.43 Hz), 20.47.

[0065] 119 Sn NMR (CDCl3, 186 MHz) d (ppm):106.29.

[0066] Its crystallographic data: The crystal belongs to the triclinic system, space group P -1, a =0.94079(6) nm, b =1.15405(8)nm, c =1.71945(12) nm, α =99°, β =103°, c =102°, Z =2,V=1.7427(2)nm 3 , D c=1.276 Mg·m -3 , m (MoKa) = 0.766 mm -1 , F (000) = 696, 2.29° < i <27.58°, crystal size: 0.25×0.20×0.22 mm, R =0.0266, wR =0.0660.

[0067] Embodiment 6: Preparation of tri(2-methyl-2-phenylpropyl)tin-5-methylsalicylate complex: Add 3.1594 g (3.0 mmol) of bis(tri(2-methyl-2-phenylpropyl))tin oxide, 0.9132 g (6.0 mmol) of 5-methylsalicylic acid, and 30 mL of anhydrous methanol solvent to a microwave reaction tank in order. Perform microwave reaction at a radiation power of 800 W and a temperature of 100 °C under air atmosphere for 120 min. After the reaction is completed, cool naturally, filter, and the solvent evaporates and crystallizes naturally at room temperature to obtain white crystals, which are tri(2-methyl-2-phenylpropyl)tin-5-methylsalicylate complexes. Yield: 65%, melting point: 63 – 65 °C.

[0068] Elemental analysis (C 38 H 46 O3Sn): Theoretical value: C, 68.17; H, 6.93. Found: C, 68.22; H, 6.95.

[0069] IR(KBr, v / cm -1 ): 3055.24 (m), 3028.24 (m), 2960.73 (s), 2895.15 (m), 2864.29 (m), 1639.49 (m), 1581.63 (s), 1490.97 (s), 1442.75 (m), 1388.75 (s),1350.17(s), 1292.31 (m), 1240.23 (s), 1205.51 (m), 1076.28 (m), 1031.92 (w),999.13 (w), 813.96 (m), 769.60 (s), 744.52 (m), 702.09 (s), 680.87 (m), 611.43 (m), 555.50(m), 534.28(w), 480.28(w), 459.06(w), 426.27(w).

[0070] 1 H NMR (CDCl3, 500 MHz) d (ppm): 11.54 (s, 1H), 7.55(d, J = 1.5Hz, 1H),7.32 - 7.29 (m, 6H), 7.24 - 7.21 (m, 4H), 7.12 - 7.10, (m, 6H), 6.87 (d, J = 8Hz, 1H), 2.31 (s, 3H), 1.28 (s, 6H), 1.25 (s, 18H).

[0071] 13 C NMR (CDCl3, 125 MHz), δ (ppm): 173.72, 159.45, 150.71, 135.39,130.86, 128.41, 127.49, 125.39, 125.24, 116.68,114.68, 37.83, 37.70 (t, J =9.95 Hz), 32.83 (t, J = 22.43 Hz), 20.47.

[0072] 119 Sn NMR (CDCl3, 186 MHz) d (ppm):106.29.

[0073] Its crystallographic data: The crystal belongs to the triclinic system, space group P -1, a =0.94079(6) nm, b =1.15405(8)nm, c =1.71945(12) nm, α =99°, β =103°, c =102°, Z =2,V=1.7427(2)nm 3 , D c=1.276 Mg·m -3 , m (MoKa) = 0.766 mm -1 , F (000) = 696, 2.29° < i <27.58°, crystal size: 0.25×0.20×0.22 mm, R =0.0266, wR =0.0660.

[0074] Test example: The in vitro anticancer activity determination of the tri(2-methyl-2-phenylpropyl)tin-5-methylsalicylate complex of the invention is achieved through the MTT experimental method.

[0075] MTT assay: Based on the metabolic reduction of 3-(4,5-Dimethylthiazol-2-yl)-2,5-diArenyltetrazoliumbromide. The succinate dehydrogenase in the mitochondria of living cells can reduce exogenous MTT to water-insoluble blue-purple 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 of the characteristic wavelength is measured by a microplate reader, which can indirectly reflect the number of living cells.

[0076] The MTT method was used to determine the inhibitory activity of the tri(2-methyl-2-phenylpropyl)tin-5-methylsalicylate complex prepared in Example 1 on lung cancer cells (A549), human cervical cancer cells (Hela), and human gastric cancer cells (HGC-27).

[0077] Cell lines and culture system: A549, Hela and HGC-27 cell lines were obtained from the American Tissue Culture Collection (ATCC). They were cultured in vitro in a 5% (volume fraction) CO2, 37°C saturated humidity incubator using RPMI1640 (GIBICO) culture medium containing 10% fetal bovine serum.

[0078] Test process: The test solution (0.0625μmol / L~0.5μmol / L) was added to 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 (adding different concentrations of test drugs), a control group (adding only culture medium and cells, without test drugs) and a blank group (adding only culture medium, without cells and test drugs). The well plate after drug addition was placed in a 37℃, 5% CO2 incubator for 24h. The activity of the control drug was determined according to the method of the test sample. In the well plate after 48h of culture, 20uL of MTT (prepared with PBS solution to 5g / L) was added to each well. After being placed at 37℃ for 4h, the supernatant was removed. 150uL DMSO was added to each well and shaken for 10min to dissolve the Formazan crystals. Finally, the absorbance value of each well was measured at a wavelength of 570nm using a BioTek multifunctional microplate reader.

[0079] Data processing: Data were processed using GraAr Pad Prism version 5.0. 50 The results were obtained by fitting a nonlinear regression model with a sigmoidal dose response in the program.

[0080] Human lung cancer cell (A549) cell line, human cervical cancer cell (Hela) cell line, and human gastric cancer cell (HGC-27) cell line were analyzed by MTT assay to determine their IC 50The results are shown in Table 1. The conclusion is: It can be seen from the data in the table that the tri(2-methyl-2-phenylpropyl)tin-5-methylsalicylate complex of the present invention has high anticancer activity against human lung cancer, human cervical cancer and human gastric cancer as an anticancer drug, and can be used as a candidate complex for anticancer drugs.

[0081] Table 1 In vitro activity test data of anticancer drugs of tri(2-methyl-2-phenylpropyl)tin-5-methylsalicylate complex.

[0082] human lung cells cervical cancer cells human stomach cells cell line A549 Hello HGC-27 <![CDATA[IC 50 μM]]> 0.512 0.4756 0.4533

[0083] The anticancer activity test method of tri(2-methyl-2-phenylpropyl)tin-5-methylsalicylate complex prepared in other examples on human lung cancer cells (A549), human cervical cancer cells (Hela) and human gastric cancer cells (HGC-27) by MTT method is the same as that of the test example, and the test results are basically the same as those in Table 1.

Claims

1. A tri(2-methyl-2-phenylpropyl)tin-5-methylsalicylate complex, which is a complex of the following structural formula (I): (I)。 2. The tri(2-methyl-2-phenylpropyl)tin-5-methylsalicylate complex as claimed in claim 1, wherein the infrared spectrum data are as follows: FT-IR (KBr, v / cm -1 ): 3055.24 (m), 3028.24 (m), 2960.73 (s), 2895.15 (m), 2864.29 (m), 1639.49 (m), 1581.63 (s), 1490.97 (s), 1442.75 (m), 1388.75 (s), 1350.17 (s), 1292.31 (m), 1240.23 (s), 1205.51 (m), 1076.28 (m), 1031.92 (w), 999.13 (w), 813.96 (m), 769.60 (s), 744.52 (m), 702.09 (s), 680.87 (m), 611.43 (m), 555.50 (m), 534.28 (w), 480.28 (w), 459,06 (w),426.27 (w); Its NMR spectrum data: 1 H NMR (CDCl3, 500 MHz) δ (ppm): 11.54 (s, 1H), 7.55(d, J = 1.5Hz, 1H), 7.32 - 7.29 (m, 6H), 7.24 - 7.21 (m, 4H), 7.12 - 7.10, (m, 6H), 6.87 (d, J = 8 Hz, 1H), 2.31 (s, 3H), 1.28 (s, 6H), 1.25 (s, 18H); 13 C NMR (CDCl3, 125 MHz) δ (ppm): 173.72, 159.45, 150.71, 135.39, 130.86,128.41, 127.49, 125.39, 125.24, 116.68, 114.68, 37.83, 37.70 (t, J = 9.95Hz), 32.83 (t, J = 22.43 Hz), 20.47; 119 Sn NMR (CDCl3, 186 MHz) δ (ppm):106.

29.

3. The tris(2-methyl-2-phenylpropyl)tin-5-methylsalicylate complex according to claim 1, wherein The tri(2-methyl-2-phenylpropyl)tin-5-methylsalicylate complex is a crystal structure, and its crystallographic data are as follows: triclinic system, space group P -1, a =0.94079(6) nm, b =1.15405(8) nm, c =1.71945(12) nm, α =99°, β =103°, γ =102°, Z =2,V=1.7427(2)nm 3 ; The central tin in the molecule and the coordinating atoms form a distorted tetrahedral configuration.

4. The method for preparing the tri(2-methyl-2-phenylpropyl)tin-5-methylsalicylate complex according to claim 1, characterized in that: In a microwave reaction tank, bis(tri(2-methyl-2-phenylpropyl))tin oxide, 5-methylsalicylic acid and anhydrous methanol as solvent were added in sequence. The microwave reaction was carried out at a radiation power of 800 W and a temperature of 100 °C under air atmosphere for 60 to 120 min. After the reaction was completed, the mixture was naturally cooled and filtered. The solvent evaporated and crystallized naturally at room temperature to obtain white crystals, which were tri(2-methyl-2-phenylpropyl)tin-5-methylsalicylate complex.

5. The preparation method according to claim 4, characterized in that: The molar ratio of the bis[tri(2-methyl-2-phenylpropyl)]tin oxide to 5-methylsalicylic acid is 1.0:(2.0-2.1).

6. The preparation method according to claim 4, 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.

7. The tri(2-methyl-2-phenylpropyl)tin-5-methylsalicylate complex of claim 1 has a certain thermal stability range and can stably exist below 240°C.

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

9. The use according to claim 8, wherein the cancer cells are lung cancer, cervical cancer, or gastric cancer.

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