Preparation method and application of tricyclohexyltin-5-methyl salicylate complex

Abstract

The invention discloses a preparation method and application of a tricyclohexyltin-5-methyl salicylate complex. The tricyclohexyltin-5-methyl salicylate complex is a complex # imgabs0 # with a structural formula (I) as shown in the specification. The invention also discloses a preparation method of the tricyclohexyltin-5-methyl salicylate complex and an application of the tricyclohexyltin-5-methyl salicylate complex in preparation of antitumor drugs.

Description

Technical Field

[0001] The present invention relates to a tricyclohexyltin-5-methylsalicylate 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, anti-cancer drug preparation, etc. 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 compounds. For example, cyclohexyl, n-butyl and phenyltin compounds have 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 hydrocarbon groups or ligands, 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 relative molecular mass of large steric hindrance hydrocarbon tin is relatively large. Therefore, synthesizing novel large steric hindrance hydrocarbon tin complexes and studying their structures and biological activities have important research significance.

[0003] Chinese Patent CN 106188128B discloses the application of tricyclohexyltin 2-naphthoate in the preparation of drugs for treating lung cancer, breast cancer and liver cancer.

[0004] Chinese Patent CN 103396437B discloses the application of tricyclohexyltin acid ester in the preparation of drugs for treating cervical cancer, breast cancer, liver cancer, colon cancer and lung cancer.

[0005] Chinese Patent CN 103087325B discloses the application of a ferrocene-based tricyclohexyltin acid ester complex in the preparation of drugs for treating liver cancer, nasopharyngeal cancer, breast cancer, colon cancer and lung cancer.

[0006] Salicylic acid is a fat-soluble organic carboxylic acid and has long been used as a main raw material for synthesizing antipyretic analgesics (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 called mesalazine, is a new drug for treating ulcerative colitis. Therefore, it is very necessary to combine large steric hindrance hydrocarbon tin compounds with biological activities and salicylic acid ligands with drug activities to synthesize novel large steric hindrance hydrocarbon tin carboxylate compounds and study their biological activities.

[0007] Based on the fact that tricyclohexyltin hydroxide is a substance proven to have good biological activity through experiments, and cyclohexyl has characteristics such as large steric hindrance and large molecular weight, the present invention selects tricyclohexyltin hydroxide and reacts with the ligand 5-methylsalicylic acid under certain conditions to synthesize a complex with strong inhibitory activity against A549 (human lung cancer cells), Hela (human cervical cancer cells), and HGC-27 (human gastric cancer cells), providing a new approach for the development of anti-cancer drugs. Summary of the Invention

[0008] In view of the problems existing in the above-mentioned prior art, the first object of the present invention is to provide a tricyclohexyltin-5-methylsalicylate complex.

[0009] The second object of the present invention is to provide a preparation method of the above-mentioned tricyclohexyltin-5-methylsalicylate complex.

[0010] The third object of the present invention is to provide the application of the above-mentioned tricyclohexyltin-5-methylsalicylate complex in the preparation of anti-cancer drugs.

[0011] As a tricyclohexyltin-5-methylsalicylate complex according to the first aspect of the present invention, its structural formula (I) is as follows: (I).

[0012] The tricyclohexyltin-5-methylsalicylate complex of the present invention is subjected to elemental analysis, infrared spectroscopy analysis, nuclear magnetic resonance spectroscopy, and X-ray single crystal structure analysis, and the results are as follows: Elemental analysis (C 26 H 40 O 3 Sn): Theoretical values: C, 60.13; H, 7.76. Measured values: C, 60.12; H, 7.71.

[0013] IR (KBr, v / cm -1 ): 2920.23 (s), 2845.00 (s), 1631.78 (m), 1575.84 (m), 1442.75 (s), 1384.89 (s), 1342.46 (s), 1244.09 (s), 1172.72 (m), 1083.99 (w), 1039.63 (w), 991.41 (m), 904.61 (w), 875.68 (m), 813.96 (m), 763.81 (m), 727.16 (m), 638.44 (w), 561.29 (w), 499.56 (m), 437.84 (m).

[0014] 1 1H NMR (CDCl 3 , 500 MHz) δ (ppm): 11.35 (s, 1H), 7.68 (d, J J = 1.5 Hz, 1H),7.21 (dd, J J = 8.5 Hz, J J = 2.5 Hz, 1H), 6.86 (d, J J = 8.5 Hz, 1H), 2.29 (s, 3H), 2.03 - 1.37 (m, 33H).

[0015] 13 13C NMR (CDCl 3 , 125 MHz) δ (ppm): 174.04, 159.28, 135.62, 131.07,127.70, 116.75, 114.10, 34.34, 31.07 (t, J J = 7.38 Hz), 28.91 (t, J J = 31.88 Hz),26.85, 20.39。

[0016] 119 119Sn NMR (CDCl 3 , 186 MHz) δ (ppm): 31.16。

[0017] The tricyclohexyltin-5-methylsalicylate complex of the present invention is in crystal structure, and its crystallographic data: The crystal belongs to the monoclinic system, space group C2 / c, a a = 2.5202(4) nm, b b = 1.5333(2) nm, c c = 1.6575(3) nm, α α = 90°, β β = 125°, γ γ = 90°, Z Z = 8, V = 5.2206(13) nm 3 , D ρc = 1.321 Mg·m -3 , μ μ(MoKa) = 1.001 mm -1 , F F(000) = 2160, 1.66° < θ θ < 27.46°, Crystal size: 0.23 × 0.21 × 0.20 mm,R = 0.0319, wR = 0.1151.

[0018] The structural feature of the tricyclohexyltin-5-methylsalicylate complex of the present invention is that the central tin in the molecule forms a distorted tetrahedral configuration with the coordinating atoms.

[0019] As a preparation method of the tricyclohexyltin-5-methylsalicylate complex according to the second aspect of the present invention, tricyclohexyltin hydroxide, 5-methylsalicylic acid and anhydrous methanol as the solvent 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 naturally volatilized and crystallized at room temperature to obtain white crystals, which are the tricyclohexyltin-5-methylsalicylate complex.

[0020] In a preferred embodiment of the present invention, the molar ratio of the tricyclohexyltin hydroxide to the 5-methylsalicylic acid is 1:(1 - 1.05).

[0021] In a preferred embodiment of the present invention, the amount of the anhydrous methanol used as the solvent is 10 - 15 mL per millimole of the tricyclohexyltin hydroxide.

[0022] As an application of the tricyclohexyltin-5-methylsalicylate complex according to the third aspect of the present invention in the preparation of anti-cancer drugs.

[0023] The applicant has carried out research on the confirmation of the in vitro anti-tumor activity of the above complex, and confirmed that the complex has certain anti-tumor biological activity. That is to say, the use of the above complex is in the application of the preparation of anti-tumor drugs. Specifically, it is in the application of the preparation of anti-human lung cancer drugs, anti-human cervical cancer drugs, and anti-human gastric cancer drugs.

[0024] The tricyclohexyltin-5-methylsalicylate complex of the present invention shows good anti-cancer activity against human lung cancer cells, human cervical cancer cells, human gastric cancer cells, etc. Anti-lung cancer, anti-cervical cancer, and anti-gastric cancer drugs can be prepared with it as the raw material. Compared with the commonly used platinum-based anti-cancer drugs at present, the tricyclohexyltin-5-methylsalicylate complex of the present invention has the characteristics of high anti-cancer activity, low cost, and simple preparation method, providing a new way for the development of anti-cancer drugs. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] Figure 1 It is the crystal molecular structure diagram of the tricyclohexyltin-5-methylsalicylate complex.

[0026] Figure 2 It is the IR spectrum diagram of the tricyclohexyltin-5-methylsalicylate complex.

[0027] Figure 3 of tricyclohexyltin-5-methylsalicylate complex 1 H NMR spectrum

[0028] Figure 4 of tricyclohexyltin-5-methylsalicylate complex 13 C NMR spectrum

[0029] Figure 5 of tricyclohexyltin-5-methylsalicylate complex 119 Sn NMR spectrum

[0030] Figure 6 TG-DTG curve of tricyclohexyltin-5-methylsalicylate complex Detailed implementation mode

[0031] 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.

[0032] Example 1: Preparation of tricyclohexyltin-5-methylsalicylate complex: 0.3847 g (1 mmol) of tricyclohexyltin hydroxide, 0.1524 g (1 mmol) of 5-methylsalicylic acid, and 10 mL of anhydrous methanol as the 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 tricyclohexyltin-5-methylsalicylate complex. Yield: 73%, melting point: 103 - 105 °C.

[0033] Elemental analysis (C 26 H 40 O 3 Sn): Theoretical values: C, 60.13; H, 7.76. Measured values: C, 60.12; H, 7.71.

[0034] IR (KBr, v / cm -1): 2920.23 (s), 2845.00 (s), 1631.78 (m), 1575.84 (m), 1442.75 (s), 1384.89 (s), 1342.46 (s), 1244.09 (s), 1172.72 (m), 1083.99 (w), 1039.63 (w), 991.41 (m), 904.61 (w), 875.68 (m), 813.96 (m), 763.81 (m), 727.16 (m), 638.44 (w), 561.29 (w), 499.56 (m), 437.84 (m).

[0035] 1 H NMR (CDCl 3 , 500 MHz) δ (ppm): 11.35 (s, 1H), 7.68 (d, J = 1.5 Hz, 1H), 7.21 (dd, J = 8.5 Hz, J = 2.5 Hz, 1H), 6.86 (d, J = 8.5 Hz, 1H), 2.29 (s, 3H), 2.03 - 1.37 (m, 33H).

[0036] 13 C NMR (CDCl 3 , 125 MHz) δ (ppm): 174.04, 159.28, 135.62, 131.07, 127.70, 116.75, 114.10, 34.34, 31.07 (t, J = 7.38 Hz), 28.91 (t, J = 31.88 Hz), 26.85, 20.39.

[0037] 119 Sn NMR (CDCl 3 , 186 MHz) δ (ppm): 31.16.

[0038] Its crystallographic data: The crystal belongs to the monoclinic system, space group C2 / c, a = 2.5202(4) nm, b = 1.5333(2) nm, c = 1.6575(3) nm,α = 90°, β = 125°, γ = 90°, Z = 8, V = 5.2206(13) nm 3 , D c = 1.321 Mg·m -3 , μ (MoKa) = 1.001 mm -1 , F (000) = 2160, 1.66° < θ < 27.46°, crystal size: 0.23 × 0.21 × 0.20 mm, R = 0.0319, wR = 0.1151.

[0039] Example 2: Preparation of tricyclohexyltin-5-methylsalicylate complex: 0.3851 g (1 mmol) of tricyclohexyltin hydroxide, 0.1591 g (1.05 mmol) of 5-methylsalicylic acid, and 15 mL of anhydrous methanol as the 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 tricyclohexyltin-5-methylsalicylate complex. Yield: 74%, melting point: 103 - 105 °C.

[0040] Elemental analysis (C 26 H 40 O 3 Sn): Theoretical values: C, 60.13; H, 7.76. Measured values: C, 60.12; H, 7.71.

[0041] IR (KBr, v / cm -1 ): 2920.23 (s), 2845.00 (s), 1631.78 (m), 1575.84 (m), 1442.75 (s), 1384.89 (s), 1342.46 (s), 1244.09 (s), 1172.72 (m), 1083.99 (w), 1039.63 (w), 991.41 (m), 904.61 (w), 875.68 (m), 813.96 (m), 763.81 (m), 727.16 (m), 638.44 (w), 561.29 (w), 499.56 (m), 437.84 (m).

[0042] 1 H NMR (CDCl 3 , 500 MHz) δ (ppm): 11.35 (s, 1H), 7.68 (d, J J = 1.5 Hz, 1H),7.21 (dd, J J = 8.5 Hz, J J = 2.5 Hz, 1H), 6.86 (d, J J = 8.5 Hz, 1H), 2.29 (s, 3H), 2.03 - 1.37 (m, 33H).

[0043] 13 C NMR (CDCl 3 , 125 MHz) δ (ppm): 174.04, 159.28, 135.62, 131.07,127.70, 116.75, 114.10, 34.34, 31.07 (t, J J = 7.38 Hz), 28.91 (t, J J = 31.88 Hz),26.85, 20.39。

[0044] 119 Sn NMR (CDCl 3 , 186 MHz) δ (ppm): 31.16。

[0045] Its crystallographic data: The crystal belongs to the monoclinic system, space group C2 / c, a a = 2.5202(4) nm, b b = 1.5333(2) nm, c c = 1.6575(3) nm, α α = 90°, β β = 125°, γ γ = 90°, Z Z = 8, V = 5.2206(13) nm 3 , D ρc = 1.321 Mg·m -3 , μ μ(MoKα) = 1.001 mm -1 , F (000) = 2160, 1.66° < θ θ < 27.46°, Crystal size: 0.23 × 0.21 × 0.20 mm,R = 0.0319, wR = 0.1151.

[0046] Example 3: Preparation of tricyclohexyltin-5-methylsalicylate complex: 0.3854 g (1 mmol) of tricyclohexyltin hydroxide, 0.1526 g (1 mmol) of 5-methylsalicylic acid, and 12 mL of anhydrous methanol as the 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 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 tricyclohexyltin-5-methylsalicylate complex. Yield: 74%, melting point: 103 - 105 °C.

[0047] Elemental analysis (C 26 H 40 O 3 Sn): Theoretical values: C, 60.13; H, 7.76. Measured values: C, 60.12; H, 7.71.

[0048] IR (KBr, v / cm -1 ): 2920.23 (s), 2845.00 (s), 1631.78 (m), 1575.84 (m), 1442.75 (s), 1384.89 (s), 1342.46 (s), 1244.09 (s), 1172.72 (m), 1083.99 (w), 1039.63 (w), 991.41 (m), 904.61 (w), 875.68 (m), 813.96 (m), 763.81 (m), 727.16 (m), 638.44 (w), 561.29 (w), 499.56 (m), 437.84 (m).

[0049] 1 H NMR (CDCl 3 , 500 MHz) δ (ppm): 11.35 (s, 1H), 7.68 (d, J = 1.5 Hz, 1H), 7.21 (dd, J = 8.5 Hz, J = 2.5 Hz, 1H), 6.86 (d, J= 8.5 Hz, 1H), 2.29 (s, 3H), 2.03- 1.37 (m, 33H).

[0050] 13 C NMR (CDCl 3 , 125 MHz) δ (ppm): 174.04, 159.28, 135.62, 131.07,127.70, 116.75, 114.10, 34.34, 31.07 (t, J = 7.38 Hz), 28.91 (t, J = 31.88 Hz),26.85, 20.39。

[0051] 119 Sn NMR (CDCl 3 , 186 MHz) δ (ppm): 31.16。

[0052] Its crystallographic data: The crystal belongs to the monoclinic system, space group C2 / c, a =2.5202(4) nm, b =1.5333(2) nm, c =1.6575(3) nm, α =90°, β =125°, γ =90°, Z =8, V=5.2206(13) nm 3 , D c=1.321 Mg·m -3 , μ (MoKa)=1.001 mm -1 , F (000)=2160, 1.66°< θ <27.46°, Crystal size: 0.23×0.21×0.20 mm, R =0.0319, wR =0.1151。

[0053] Example 4: Preparation of tricyclohexyltin-5-methylsalicylate complex: 0.7704 g (2.0 mmol) of tricyclohexyltin hydroxide, 0.3045 g (2 mmol) of 5-methylsalicylic acid, and 25 mL of anhydrous methanol as the solvent were sequentially added to a microwave reaction vessel. Under an air atmosphere, a 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 evaporate and crystallize at room temperature to obtain white crystals, which were the tricyclohexyltin-5-methylsalicylate complex. Yield: 73%, melting point: 103 - 105 °C.

[0054] Elemental analysis (C 26 H 40 O 3 Sn): Theoretical values: C, 60.13; H, 7.76. Measured values: C, 60.12; H, 7.71.

[0055] IR (KBr, v / cm -1 ): 2920.23 (s), 2845.00 (s), 1631.78 (m), 1575.84 (m), 1442.75 (s), 1384.89 (s), 1342.46 (s), 1244.09 (s), 1172.72 (m), 1083.99 (w), 1039.63 (w), 991.41 (m), 904.61 (w), 875.68 (m), 813.96 (m), 763.81 (m), 727.16 (m), 638.44 (w), 561.29 (w), 499.56 (m), 437.84 (m).

[0056] 1 H NMR (CDCl 3 , 500 MHz) δ (ppm): 11.35 (s, 1H), 7.68 (d, J = 1.5 Hz, 1H), 7.21 (dd, J = 8.5 Hz, J = 2.5 Hz, 1H), 6.86 (d, J = 8.5 Hz, 1H), 2.29 (s, 3H), 2.03 - 1.37 (m, 33H).

[0057] 13 C NMR (CDCl 3 , 125 MHz) δ(ppm): 174.04, 159.28, 135.62, 131.07, 127.70, 116.75, 114.10, 34.34, 31.07 (t, J = 7.38 Hz), 28.91 (t, J = 31.88 Hz), 26.85, 20.39。

[0058] 119 Sn NMR (CDCl 3 , 186 MHz) δ (ppm): 31.16。

[0059] Its crystallographic data: The crystal belongs to the monoclinic system, space group C2 / c, a = 2.5202(4) nm, b = 1.5333(2) nm, c = 1.6575(3) nm, α = 90°, β = 125°, γ = 90°, Z = 8, V = 5.2206(13) nm 3 , D c = 1.321 Mg·m -3 , μ (MoKa) = 1.001 mm -1 , F (000) = 2160, 1.66° < θ <27.46°, Crystal size: 0.23 × 0.21 × 0.20 mm, R = 0.0319, wR = 0.1151。

[0060] Example 5: Preparation of tricyclohexyltin-5-methylsalicylate complex: Add 0.7706 g (2.0 mmol) of tricyclohexyltin hydroxide, 0.3119 g (2.05 mmol) of 5-methylsalicylic acid, and 25 mL of anhydrous methanol as the solvent to 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 90 min. After the reaction, cool naturally, filter, and let the solvent evaporate and crystallize naturally at room temperature to obtain white crystals, which are tricyclohexyltin-5-methylsalicylate complex. Yield: 74%, Melting point: 103 - 105 °C.

[0061] Elemental analysis (C 26 H40 O 3 Sn): Theoretical values: C, 60.13; H, 7.76. Measured values: C, 60.12; H, 7.71.

[0062] IR (KBr, v / cm -1 ): 2920.23 (s), 2845.00 (s), 1631.78 (m), 1575.84 (m), 1442.75 (s), 1384.89 (s), 1342.46 (s), 1244.09 (s), 1172.72 (m), 1083.99 (w), 1039.63 (w), 991.41 (m), 904.61 (w), 875.68 (m), 813.96 (m), 763.81 (m), 727.16 (m), 638.44 (w), 561.29 (w), 499.56 (m), 437.84 (m).

[0063] 1 1H NMR (CDCl 3 , 500 MHz) δ (ppm): 11.35 (s, 1H), 7.68 (d, J J = 1.5 Hz, 1H), 7.21 (dd, J J = 8.5 Hz, J J = 2.5 Hz, 1H), 6.86 (d, J J = 8.5 Hz, 1H), 2.29 (s, 3H), 2.03 - 1.37 (m, 33H).

[0064] 13 13C NMR (CDCl 3 , 125 MHz) δ (ppm): 174.04, 159.28, 135.62, 131.07, 127.70, 116.75, 114.10, 34.34, 31.07 (t, J J = 7.38 Hz), 28.91 (t, J J = 31.88 Hz), 26.85, 20.39.

[0065] 119 119Sn NMR (CDCl 3 , 186 MHz) δ (ppm): 31.16.

[0066] Its crystallographic data: The crystal belongs to the monoclinic system, space group C2 / c, a a = 2.5202(4) nm, b b = 1.5333(2) nm, c c = 1.6575(3) nm, α α = 90°, β β = 125°, γ γ = 90°, Z Z = 8, V = 5.2206(13) nm 3 , D ρc = 1.321 Mg·m -3 , μ μ(MoKα) = 1.001 mm -1 , F F(000) = 2160, 1.66° < θ θ < 27.46°, Crystal size: 0.23 × 0.21 × 0.20 mm, R R1 = 0.0319, wR wR2 = 0.1151.

[0067] Example 6: Preparation of tricyclohexyltin-5-methylsalicylate complex: 1.1554 g (3.0 mmol) of tricyclohexyltin hydroxide, 0.4562 g (3 mmol) of 5-methylsalicylic acid and 30 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 evaporate and crystallize naturally at room temperature to obtain white crystals, which were tricyclohexyltin-5-methylsalicylate complex. Yield: 75%, Melting point: 103 - 105 °C.

[0068] Elemental analysis (C 26 H 40 O 3 Sn): Theoretical values: C, 60.13; H, 7.76. Measured values: C, 60.12; H, 7.71.

[0069] IR (KBr, ν / cm -1): 2920.23 (s), 2845.00 (s), 1631.78 (m), 1575.84 (m), 1442.75 (s), 1384.89 (s), 1342.46 (s), 1244.09 (s), 1172.72 (m), 1083.99 (w), 1039.63 (w), 991.41 (m), 904.61 (w), 875.68 (m), 813.96 (m), 763.81 (m), 727.16 (m), 638.44 (w), 561.29 (w), 499.56 (m), 437.84 (m).

[0070] 1 H NMR (CDCl 3 , 500 MHz) δ (ppm): 11.35 (s, 1H), 7.68 (d, J = 1.5 Hz, 1H), 7.21 (dd, J = 8.5 Hz, J = 2.5 Hz, 1H), 6.86 (d, J = 8.5 Hz, 1H), 2.29 (s, 3H), 2.03 - 1.37 (m, 33H).

[0071] 13 C NMR (CDCl 3 , 125 MHz) δ (ppm): 174.04, 159.28, 135.62, 131.07, 127.70, 116.75, 114.10, 34.34, 31.07 (t, J = 7.38 Hz), 28.91 (t, J = 31.88 Hz), 26.85, 20.39.

[0072] 119 Sn NMR (CDCl 3 , 186 MHz) δ (ppm): 31.16.

[0073] Its crystallographic data: The crystal belongs to the monoclinic system, space group C2 / c, a = 2.5202(4) nm, b = 1.5333(2) nm, c = 1.6575(3) nm,α = 90°, β = 125°, γ = 90°, Z = 8, V = 5.2206(13) nm 3 , D c = 1.321 Mg·m -3 , μ (MoKa) = 1.001 mm -1 , F (000) = 2160, 1.66° < θ < 27.46°, crystal size: 0.23 × 0.21 × 0.20 mm, R = 0.0319, wR = 0.1151.

[0074] Test Example: For the tricyclohexyltin-5-methylsalicylate complex of the present invention, its in vitro anticancer activity was determined by the MTT assay method.

[0075] MTT Assay: 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.

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

[0077] 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 RPMI1640 (GIBICO) medium containing 10% fetal bovine serum in a 5% (volume fraction) CO 2 , 37 °C saturated humidity incubator.

[0078] Test procedure: Test liquid medicine (0.0625 μmol / L - 0.5 μmol / L) was added to each well according to the concentration gradient of the concentration. Three 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 the culture medium and cells were added, without the test drug), and a blank group (only the culture medium was added, without cells and the test drug). The well plate 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 well plate after 48 h of culture, 20 μL of MTT (prepared into 5 g / L with PBS solution) was added to each well. After being placed 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 values of each well were measured at a wavelength of 570 nm using a BioTek multi-functional microplate reader.

[0079] 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 an S-shaped dose response in the program.

[0080] 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 tricyclohexyltin-5-methylsalicylate complex of the present invention has 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.

[0081] Table 1 In vitro activity test data of the tricyclohexyltin-5-methylsalicylate 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]]> 0.1854 0.1539 0.2468

[0082] The test method for the anti-cancer activity of the tricyclohexyltin-5-methylsalicylate complex prepared in the remaining examples 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 tricyclohexyltin-5-methylsalicylate complex, which is a complex of the following structural formula (I): (I)。 2. The tricyclohexyltin-5-methyl salicylate complex as claimed in claim 1, wherein the infrared spectrum data is: FT-IR (KBr, v / cm -1 ): 2920.23 (s), 2845.00 (s), 1631.78 (m), 1575.84 (m),1442.75 (s), 1384.89 (s), 1342.46 (s), 1244.09 (s), 1172.72 (m), 1083.99 (w),1039.63 (w), 991.41 (m), 904.61 (w), 875.68 (m), 813.96 (m), 763.81 (m),727.16 (m), 638.44 (w), 561.29 (w), 499.56 (m), 437.84 (m); Its NMR spectrum data: 1 HNMR (CDCl3, 500 MHz) δ (ppm): 11.35 (s, 1H), 7.68 (d, J = 1.5 Hz, 1H), 7.21(dd, J = 8.5 Hz, J = 2.5 Hz, 1H), 6.86 (d, J = 8.5 Hz, 1H), 2.29 (s, 3H), 2.03 - 1.37 (m, 33H); 13 C NMR (CDCl3, 125 MHz) δ (ppm): 174.04, 159.28,135.62, 131.07, 127.70, 116.75, 114.10, 34.34, 31.07 (t, J = 7.38 Hz), 28.91(t, J = 31.88 Hz), 26.85, 20.39; 119 Sn NMR (CDCl3, 186 MHz) δ (ppm): 31.

16.

3. The tricyclohexyltin-5-methylsalicylate complex according to claim 1, wherein The tricyclohexyltin-5-methylsalicylate complex is a crystal structure, and its crystallographic data are as follows: monoclinic system, space group C2 / c, a =2.5202(4) nm, b =1.5333(2) nm, c =1.6575(3) nm, α =90°, β =125°, γ =90°, Z =8, V = 5.2206(13)nm 3 ; The central tin in the molecule and the coordinating atoms form a distorted tetrahedral configuration.

4. The method for preparing the tricyclohexyltin-5-methylsalicylate complex according to claim 1, characterized in that: Tricyclohexyltin hydroxide, 5-methylsalicylic acid and anhydrous methanol were added to a microwave reaction tank 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 tricyclohexyltin-5-methylsalicylate complex.

5. The preparation method according to claim 4, characterized in that: The molar ratio of the tricyclohexyltin hydroxide and 5-methylsalicylic acid is 1:(1-1.05).

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 tricyclohexyltin hydroxide.

7. The tricyclohexyltin-5-methyl salicylate complex of claim 1 has a certain thermal stability range and can stably exist below 190°C.

8. Use of the tricyclohexyltin-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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