Preparation method and application of tricyclohexyltin 2-hydroxy-1-naphthoic acid ester complex

Abstract

The invention discloses a preparation method and application of a tricyclohexyltin 2-hydroxy-1-naphthoic acid ester complex. The tricyclohexyltin 2-hydroxy-1-naphthoic acid ester complex is a complex # imgabs0 # with the following structural formula (I). The invention further discloses a preparation method of the tricyclohexyltin 2-hydroxy-1-naphthoic acid ester complex and application of the tricyclohexyltin 2-hydroxy-1-naphthoic acid ester complex in preparation of antitumor drugs.

Description

Technical Field

[0001] The invention relates to a tricyclohexyltin 2-hydroxy-1-naphthoate 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 that determines 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 complexes and study their structure and biological activity.

[0003] Chinese patent CN 106188128B discloses the use 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 use of tricyclohexyl stannate 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 use of a ferrocenyl tricyclohexyl stannate 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, 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 tricyclohexyltin hydroxide is a substance proved to have good biological activity by experiments, and the cyclohexyl group has the characteristics of large steric hindrance and large molecular weight, the present invention selects tricyclohexyltin hydroxide and reacts it with salicylic acid ligand 2-hydroxy-1-naphthoic 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), providing a new way to develop anticancer 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 2-hydroxy-1-naphthoate complex.

[0009] The second object of the present invention is to provide a method for preparing the above tricyclohexyltin 2-hydroxy-1-naphthoate complex.

[0010] The third object of the present invention is to provide the use of the above tricyclohexyltin 2-hydroxy-1-naphthoate complex in the preparation of anticancer drugs.

[0011] As a tricyclohexyltin 2-hydroxy-1-naphthoate complex of the first aspect of the present invention, its structural formula (I) is as follows: (I).

[0012] The tricyclohexyltin 2-hydroxy-1-naphthoate 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 29 H 40 O3Sn): Theoretical value: C, 62.72; H, 7.26. Found: C, 62.82; H, 7.15.

[0013] IR(KBr, v / cm -1): 2920.23 (s), 2846.93 (s), 1624.06 (m), 1602.85 (s), 1562.34 (s), 1508.33 (m), 1489.76 (m), 1444.88 (m), 1382.96 (s), 1346.31 (m),1280.73(s), 1257.59(s), 1207.44 (m), 1170.79 (m), 1147.65 (m), 1083.99 (m),991.41 (m), 875.68 (w), 823.60 (m), 740.67 (m), 651.94 (m), 601.79 (m), 532.35 (w), 495.71 (m), 418.55 (m).

[0014] 1 H NMR(CDCl3, 500 MHz), δ(ppm): 13.18 (s, 1H), 9.13 (d, J = 9 Hz, 1H), 7.85 (d, J = 9 Hz, 1H), 7.73 (d, J = 7.5Hz, 1H), 7.53 (t, J = 8 Hz, 1H), 7.33(t, J = 7.5 Hz, 1H), 7.17(d, J = 9 Hz, 1H), 2.08-2.01 (m, 9H), 1.82-1.67 (m,15H), 1.41-1.34 (m, 9H).

[0015] 13 C NMR (CDCl3, 125 MHz), δ (ppm): 175.96, 163.94, 135.658, 133.19,128.67, 127.83, 125.86, 123.05, 119.33,105.96, 34.49, 31.15, 28.95, 26.88.

[0016] 119 Sn NMR (CDCl3, 186 MHz), δ (ppm): 35.32.

[0017] The tricyclohexyltin 2-hydroxy-1-naphthoate complex of the present invention is a crystal structure, and its crystallographic data: the crystal belongs to the monoclinic system, the space group P 2 1 / c , a =1.7817(3) nm, b=1.5165(2) nm, c =2.0866(3) nm, α =90°, β =106°, γ =90°, Z =8,V=5.4171(14) nm 3 , D c=1.362 Mg·m -3 , μ (MoKa)=0.970mm -1 , F (000) = 2304, 2.22°< θ <25.01°, crystal size: 0.23×0.19×0.24 mm, R =0.0740, wxya =0.1798.

[0018] The structural feature of the tricyclohexyltin 2-hydroxy-1-naphthoate complex of the present invention is that the central tin in the molecule forms a distorted tetrahedral configuration with the coordination atoms.

[0019] As a preparation method of a tricyclohexyltin 2-hydroxy-1-naphthoate complex according to the second aspect of the present invention, tricyclohexyltin hydroxide, 2-hydroxy-1-naphthoic acid and solvent anhydrous methanol 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 air atmosphere for 60 to 120 min. After the reaction is completed, it is naturally cooled and filtered, and the solvent is naturally evaporated and crystallized at room temperature to obtain white crystals, which are tricyclohexyltin 2-hydroxy-1-naphthoate complexes.

[0020] In a preferred embodiment of the present invention, the molar ratio of tricyclohexyltin hydroxide to 2-hydroxy-1-naphthoic acid is 1:(1-1.05).

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

[0022] As the third aspect of the present invention, a tricyclohexyltin 2-hydroxy-1-naphthoate 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 tricyclohexyltin 2-hydroxy-1-naphthoate 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 tricyclohexyltin 2-hydroxy-1-naphthoate 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 the crystal molecular structure diagram of tricyclohexyltin 2-hydroxy-1-naphthoate complex.

[0026] Figure 2 This is the IR spectrum of tricyclohexyltin 2-hydroxy-1-naphthoate complex.

[0027] Figure 3 It is a complex of tricyclohexyltin 2-hydroxy-1-naphthoate 1 H NMR spectrum.

[0028] Figure 4 It is a complex of tricyclohexyltin 2-hydroxy-1-naphthoate 13 C NMR spectrum.

[0029] Figure 5 It is a complex of tricyclohexyltin 2-hydroxy-1-naphthoate 119 Sn NMR spectrum. DETAILED DESCRIPTION

[0030] 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.

[0031] Embodiment 1: Preparation of tricyclohexyltin 2-hydroxy-1-naphthoate complex: Add 0.385 g (1 mmol) of tricyclohexyltin hydroxide, 0.1882 g (1 mmol) of 2-hydroxy-1-naphthoic acid, and 10 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 tricyclohexyltin 2-hydroxy-1-naphthoate complexes. Yield: 85%, melting point: 94-96 °C.

[0032] Elemental analysis (C 29 H 40O3Sn): Theoretical value: C, 62.72; H, 7.26. Found: C, 62.82; H, 7.15.

[0033] IR (KBr, v / cm -1 ): 2920.23 (s), 2846.93 (s), 1624.06 (m), 1602.85 (s), 1562.34 (s), 1508.33 (m), 1489.76 (m), 1444.88 (m), 1382.96 (s), 1346.31 (m),1280.73 (s), 1257.59(s), 1207.44 (m), 1170.79 (m), 1147.65 (m), 1083.99 (m),991.41 (m), 875.68 (w), 823.60 (m), 740.67 (m), 651.94 (m), 601.79 (m), 532.35 (w), 495.71 (m), 418.55 (m).

[0034] 1 H NMR (CDCl3, 500 MHz), δ (ppm): 13.18 (s, 1H), 9.13 (d, J = 9 Hz,1H), 7.85 (d, J = 9 Hz, 1H), 7.73 (d, J = 7.5 Hz,1H), 7.53 (t, J = 8 Hz, 1H),7.33 (t, J = 7.5 Hz, 1H), 7.17(d, J = 9 Hz, 1H), 2.08-2.01 (m, 9H), 1.82-1.67(m, 15H), 1.41-1.34 (m, 9H).

[0035] 13 C NMR (CDCl3, 125 MHz), δ (ppm): 175.96, 163.94, 135.658, 133.19,128.67, 127.83, 125.86, 123.05, 119.33, 105.96, 34.49,31.15, 28.95, 26.88.

[0036] 119 Sn NMR (CDCl3, 186 MHz), δ (ppm): 35.32.

[0037] Its crystallographic data: the crystal belongs to the monoclinic system, the space groupP 2 1 / c , a =1.7817(3) nm, b =1.5165(2)nm, c =2.0866(3) nm, α =90°, β =106°, γ =90°, Z =8,V=5.4171(14) nm 3 , D c=1.362 Mg·m -3 , μ (MoKa) = 0.970 mm -1 , F (000) = 2304, 2.22°< θ <25.01°, crystal size: 0.23×0.19×0.24 mm, R =0.0740, wxya =0.1798.

[0038] Embodiment 2: Preparation of tricyclohexyltin 2-hydroxy-1-naphthoate complex: Add 0.385 g (1.0 mmol) of tricyclohexyltin hydroxide, 0.1975 g (1.05 mmol) of 2-hydroxy-1-naphthoic acid, and 15 mL of anhydrous methanol as solvent 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 tricyclohexyltin 2-hydroxy-1-naphthoate complexes. Yield: 84%, melting point: 94-96 °C.

[0039] Elemental analysis (C 29 H 40 O3Sn): Theoretical value: C, 62.72; H, 7.26. Found: C, 62.82; H, 7.15.

[0040] IR (KBr, v / cm -1): 2920.23 (s), 2846.93 (s), 1624.06 (m), 1602.85 (s), 1562.34 (s), 1508.33 (m), 1489.76 (m), 1444.88 (m), 1382.96 (s), 1346.31 (m),1280.73 (s), 1257.59(s), 1207.44 (m), 1170.79 (m), 1147.65 (m), 1083.99 (m),991.41 (m), 875.68 (w), 823.60 (m), 740.67 (m), 651.94 (m), 601.79 (m), 532.35 (w), 495.71 (m), 418.55 (m).

[0041] 1 H NMR (CDCl3, 500 MHz), δ (ppm): 13.18 (s, 1H), 9.13 (d, J = 9 Hz,1H), 7.85 (d, J = 9 Hz, 1H), 7.73 (d, J = 7.5 Hz,1H), 7.53 (t, J = 8 Hz, 1H),7.33 (t, J = 7.5 Hz, 1H), 7.17(d, J = 9 Hz, 1H), 2.08-2.01 (m, 9H), 1.82-1.67(m, 15H), 1.41-1.34 (m, 9H).

[0042] 13 C NMR (CDCl3, 125 MHz), δ (ppm): 175.96, 163.94, 135.658, 133.19,128.67, 127.83, 125.86, 123.05, 119.33, 105.96, 34.49,31.15, 28.95, 26.88.

[0043] 119 Sn NMR (CDCl3, 186 MHz), δ (ppm): 35.32.

[0044] Its crystallographic data: the crystal belongs to the monoclinic system, the space group P 2 1 / c , a =1.7817(3) nm, b =1.5165(2)nm,c =2.0866(3) nm, α =90°, β =106°, γ =90°, Z =8,V=5.4171(14) nm 3 , D c=1.362 Mg·m -3 , μ (MoKa) = 0.970 mm -1 , F (000) = 2304, 2.22°< θ <25.01°, crystal size: 0.23×0.19×0.24 mm, R =0.0740, wxya =0.1798.

[0045] Embodiment 3: Preparation of tricyclohexyltin 2-hydroxy-1-naphthoate complex: Add 0.385 g (1 mmol) of tricyclohexyltin hydroxide, 0.188 g (1 mmol) of 2-hydroxy-1-naphthoic acid, and 12 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 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 tricyclohexyltin 2-hydroxy-1-naphthoate complexes. Yield: 87%, melting point: 94-96 °C.

[0046] Elemental analysis (C 29 H 40 O3Sn): Theoretical value: C, 62.72; H, 7.26. Found: C, 62.82; H, 7.15.

[0047] IR (KBr, v / cm -1): 2920.23 (s), 2846.93 (s), 1624.06 (m), 1602.85 (s), 1562.34 (s), 1508.33 (m), 1489.76 (m), 1444.88 (m), 1382.96 (s), 1346.31 (m),1280.73 (s), 1257.59(s), 1207.44 (m), 1170.79 (m), 1147.65 (m), 1083.99 (m),991.41 (m), 875.68 (w), 823.60 (m), 740.67 (m), 651.94 (m), 601.79 (m), 532.35 (w), 495.71 (m), 418.55 (m).

[0048] 1 H NMR (CDCl3, 500 MHz), δ (ppm): 13.18 (s, 1H), 9.13 (d, J = 9 Hz,1H), 7.85 (d, J = 9 Hz, 1H), 7.73 (d, J = 7.5 Hz,1H), 7.53 (t, J = 8 Hz, 1H),7.33 (t, J = 7.5 Hz, 1H), 7.17(d, J = 9 Hz, 1H), 2.08-2.01 (m, 9H), 1.82-1.67(m, 15H), 1.41-1.34 (m, 9H).

[0049] 13 C NMR (CDCl3, 125 MHz), δ (ppm): 175.96, 163.94, 135.658, 133.19,128.67, 127.83, 125.86, 123.05, 119.33, 105.96, 34.49,31.15, 28.95, 26.88.

[0050] 119 Sn NMR (CDCl3, 186 MHz), δ (ppm): 35.32.

[0051] Its crystallographic data: the crystal belongs to the monoclinic system, the space group P 2 1 / c , a =1.7817(3) nm, b =1.5165(2)nm,c =2.0866(3) nm, α =90°, β =106°, γ =90°, Z =8,V=5.4171(14) nm 3 , D c=1.362 Mg·m -3 , μ (MoKa) = 0.970 mm -1 , F (000) = 2304, 2.22°< θ <25.01°, crystal size: 0.23×0.19×0.24 mm, R =0.0740, wxya =0.1798.

[0052] Embodiment 4: Preparation of tricyclohexyltin 2-hydroxy-1-naphthoate complex: Tricyclohexyltin hydroxide 0.7705 g (2.0 mmol), 2-hydroxy-1-naphthoic acid 0.3764 g (2 mmol), and solvent anhydrous methanol 25 mL were added to the 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 min. After the reaction was completed, it was cooled naturally and filtered. The solvent evaporated and crystallized naturally at room temperature to obtain white crystals, which were tricyclohexyltin 2-hydroxy-1-naphthoate complexes. Yield: 83%, melting point: 94-96 °C.

[0053] Elemental analysis (C 29 H 40 O3Sn): Theoretical value: C, 62.72; H, 7.26. Found: C, 62.82; H, 7.15.

[0054] IR (KBr, v / cm -1): 2920.23 (s), 2846.93 (s), 1624.06 (m), 1602.85 (s), 1562.34 (s), 1508.33 (m), 1489.76 (m), 1444.88 (m), 1382.96 (s), 1346.31 (m),1280.73 (s), 1257.59(s), 1207.44 (m), 1170.79 (m), 1147.65 (m), 1083.99 (m),991.41 (m), 875.68 (w), 823.60 (m), 740.67 (m), 651.94 (m), 601.79 (m), 532.35 (w), 495.71 (m), 418.55 (m).

[0055] 1 H NMR (CDCl3, 500 MHz), δ (ppm): 13.18 (s, 1H), 9.13 (d, J = 9 Hz,1H), 7.85 (d, J = 9 Hz, 1H), 7.73 (d, J = 7.5 Hz,1H), 7.53 (t, J = 8 Hz, 1H),7.33 (t, J = 7.5 Hz, 1H), 7.17(d, J = 9 Hz, 1H), 2.08-2.01 (m, 9H), 1.82-1.67(m, 15H), 1.41-1.34 (m, 9H).

[0056] 13 C NMR (CDCl3, 125 MHz), δ (ppm): 175.96, 163.94, 135.658, 133.19,128.67, 127.83, 125.86, 123.05, 119.33, 105.96, 34.49,31.15, 28.95, 26.88.

[0057] 119 Sn NMR (CDCl3, 186 MHz), δ (ppm): 35.32.

[0058] Its crystallographic data: the crystal belongs to the monoclinic system, the space group P 2 1 / c , a =1.7817(3) nm, b =1.5165(2)nm,c =2.0866(3) nm, α =90°, β =106°, γ =90°, Z =8,V=5.4171(14) nm 3 , D c=1.362 Mg·m -3 , μ (MoKa) = 0.970 mm -1 , F (000) = 2304, 2.22°< θ <25.01°, crystal size: 0.23×0.19×0.24 mm, R =0.0740, wxya =0.1798.

[0059] Embodiment 5: Preparation of tricyclohexyltin 2-hydroxy-1-naphthoate complex: Tricyclohexyltin hydroxide 0.7706 g (2.0 mmol), 2-hydroxy-1-naphthoic acid 0.3856 g (2.05 mmol), and solvent anhydrous methanol 25 mL were added to the 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 90 min. After the reaction was completed, it was cooled naturally and filtered. The solvent evaporated and crystallized naturally at room temperature to obtain white crystals, which were tricyclohexyltin 2-hydroxy-1-naphthoate complexes. Yield: 86%, melting point: 94-96 ° C.

[0060] Meta-element analysis (C 29 H 40 O3Sn): Theoretical value: C, 62.72; H, 7.26. Found: C, 62.82; H, 7.15.

[0061] IR (KBr, v / cm -1): 2920.23 (s), 2846.93 (s), 1624.06 (m), 1602.85 (s), 1562.34 (s), 1508.33 (m), 1489.76 (m), 1444.88 (m), 1382.96 (s), 1346.31 (m),1280.73 (s), 1257.59(s), 1207.44 (m), 1170.79 (m), 1147.65 (m), 1083.99 (m),991.41 (m), 875.68 (w), 823.60 (m), 740.67 (m), 651.94 (m), 601.79 (m), 532.35 (w), 495.71 (m), 418.55 (m).

[0062] 1 H NMR (CDCl3, 500 MHz), δ (ppm): 13.18 (s, 1H), 9.13 (d, J = 9 Hz,1H), 7.85 (d, J = 9 Hz, 1H), 7.73 (d, J = 7.5 Hz,1H), 7.53 (t, J = 8 Hz, 1H),7.33 (t, J = 7.5 Hz, 1H), 7.17(d, J = 9 Hz, 1H), 2.08-2.01 (m, 9H), 1.82-1.67(m, 15H), 1.41-1.34 (m, 9H).

[0063] 13 C NMR (CDCl3, 125 MHz), δ (ppm): 175.96, 163.94, 135.658, 133.19,128.67, 127.83, 125.86, 123.05, 119.33, 105.96, 34.49,31.15, 28.95, 26.88.

[0064] 119 Sn NMR (CDCl3, 186 MHz), δ (ppm): 35.32.

[0065] Its crystallographic data: the crystal belongs to the monoclinic system, the space group P 2 1 / c , a =1.7817(3) nm, b =1.5165(2)nm,c =2.0866(3) nm, α =90°, β =106°, γ =90°, Z =8,V=5.4171(14) nm 3 , D c=1.362 Mg·m -3 , μ (MoKa) = 0.970 mm -1 , F (000) = 2304, 2.22°< θ <25.01°, crystal size: 0.23×0.19×0.24 mm, R =0.0740, wxya =0.1798.

[0066] Embodiment 6: Preparation of tricyclohexyltin 2-hydroxy-1-naphthoate complex: Add 1.1551 g (3.0 mmol) of tricyclohexyltin hydroxide, 0.5648 g (3 mmol) of 2-hydroxy-1-naphthoic acid, and 30 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 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 tricyclohexyltin 2-hydroxy-1-naphthoate complexes. Yield: 84%, melting point: 94-96 °C.

[0067] Elemental analysis (C 29 H 40 O3Sn): Theoretical value: C, 62.72; H, 7.26. Found: C, 62.82; H, 7.15.

[0068] IR (KBr, v / cm -1): 2920.23 (s), 2846.93 (s), 1624.06 (m), 1602.85 (s), 1562.34 (s), 1508.33 (m), 1489.76 (m), 1444.88 (m), 1382.96 (s), 1346.31 (m),1280.73 (s), 1257.59(s), 1207.44 (m), 1170.79 (m), 1147.65 (m), 1083.99 (m),991.41 (m), 875.68 (w), 823.60 (m), 740.67 (m), 651.94 (m), 601.79 (m), 532.35 (w), 495.71 (m), 418.55 (m).

[0069] 1 H NMR (CDCl3, 500 MHz), δ (ppm): 13.18 (s, 1H), 9.13 (d, J = 9 Hz,1H), 7.85 (d, J = 9 Hz, 1H), 7.73 (d, J = 7.5 Hz,1H), 7.53 (t, J = 8 Hz, 1H),7.33 (t, J = 7.5 Hz, 1H), 7.17(d, J = 9 Hz, 1H), 2.08-2.01 (m, 9H), 1.82-1.67(m, 15H), 1.41-1.34 (m, 9H).

[0070] 13 C NMR (CDCl3, 125 MHz), δ (ppm): 175.96, 163.94, 135.658, 133.19,128.67, 127.83, 125.86, 123.05, 119.33, 105.96, 34.49,31.15, 28.95, 26.88.

[0071] 119 Sn NMR (CDCl3, 186 MHz), δ (ppm): 35.32.

[0072] Its crystallographic data: the crystal belongs to the monoclinic system, the space group P 2 1 / c , a =1.7817(3) nm, b =1.5165(2)nm,c =2.0866(3) nm, α =90°, β =106°, γ =90°, Z =8,V=5.4171(14) nm 3 , D c=1.362 Mg·m -3 , μ (MoKa) = 0.970 mm -1 , F (000) = 2304, 2.22°< θ <25.01°, crystal size: 0.23×0.19×0.24 mm, R =0.0740, wxya =0.1798.

[0073] Test example: The in vitro anticancer activity determination of the tricyclohexyltin 2-hydroxy-1-naphthoate complex of the invention is achieved through the MTT experimental method.

[0074] 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.

[0075] The MTT method was used to determine the inhibitory activity of the tricyclohexyltin 2-hydroxy-1-naphthoate complex prepared in Example 1 on human lung cancer cells (A549), human cervical cancer cells (Hela), and human gastric cancer cells (HGC-27).

[0076] 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.

[0077] 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.

[0078] 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.

[0079] The human lung cancer cell line (A549), human cervical cancer cell line (Hela), and human gastric cancer cell line (HGC-27) were analyzed by MTT assay to determine their IC 50 The results are shown in Table 1. The conclusion is: It can be seen from the data in the table that the tricyclohexyltin 2-hydroxy-1-naphthoate 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.

[0080] Table 1 In vitro activity test data of anticancer drugs of tricyclohexyltin 2-hydroxy-1-naphthoate complex. Human lung cancer cells Human cervical cancer cells Human gastric cancer cells Cell lines A549 Hela HGC-27 <![CDATA[IC 50 μM]]> 0.2425 0.2237 0.1383

[0081] The anticancer activity test method of the tricyclohexyltin 2-hydroxy-1-naphthoate complex prepared in the remaining examples on human lung cancer cells (A549), human cervical cancer cells (Hela) and human gastric cancer cells (HGC-27) using the MTT method is the same as that of the experimental example, and the test results are basically the same as those in Table 1.

Claims

1. A tricyclohexyltin 2-hydroxy-1-naphthoate complex, which is a complex of the following structural formula (I): (I)。 2. The tricyclohexyltin 2-hydroxy-1-naphthoate complex as claimed in claim 1, wherein the infrared spectrum data are as follows: FT-IR (KBr, v / cm -1 ): 2920.23 (s), 2846.93 (s), 1624.06 (m), 1602.85 (s), 1562.34 (s), 1508.33 (m), 1489.76 (m), 1444.88 (m), 1382.96 (s), 1346.31 (m),1280.73 (s), 1257.59(s), 1207.44 (m), 1170.79 (m), 1147.65 (m), 1083.99 (m),991.41 (m), 875.68 (w), 823.60 (m), 740.67 (m), 651.94 (m), 601.79 (m), 532.35 (w), 495.71 (m), 418.55 (m); Its NMR spectrum data: 1 H NMR (CDCl3, 500 MHz) δ (ppm): 13.18 (s, 1H), 9.13 (d, J = 9 Hz, 1H), 7.85 (d, J = 9 Hz, 1H), 7.73(d, J = 7.5 Hz, 1H), 7.53 (t, J = 8 Hz, 1H), 7.33 (t, J = 7.5 Hz, 1H), 7.17(d, J = 9 Hz, 1H), 2.08-2.01 (m, 9H), 1.82-1.67 (m, 15H), 1.41-1.34 (m, 9H); 13 CNMR (CDCl3, 125MHz) δ (ppm): 175.96, 163.94, 135.658, 133.19, 128.67,127.83, 125.86, 123.05, 119.33, 105.96, 34.49, 31.15, 28.95, 26.88; 119 Sn NMR (CDCl3, 186 MHz), δ (ppm):35.

32.

3. The tricyclohexyltin 2-hydroxy-1-naphthoate complex according to claim 1, wherein The tricyclohexyltin 2-hydroxy-1-naphthoate complex is a crystal structure, and its crystallographic data are as follows: monoclinic system, space group P 2 1 / c , a =1.7817(3) nm, b =1.5165(2) nm, c =2.0866(3) nm, α =90°, β =106°, γ =90°, Z =8,V=5.4171(14) nm 3 ; The central tin in the molecule and the coordinating atoms form a distorted tetrahedral configuration.

4. The method for preparing the tricyclohexyltin 2-hydroxy-1-naphthoate complex according to claim 1, characterized in that: Tricyclohexyltin hydroxide, 2-hydroxy-1-naphthoic acid and solvent anhydrous methanol were added to a microwave reaction tank in sequence, and microwave reaction was carried out at a radiation power of 800 W and a temperature of 100 °C under air atmosphere for 60-120 min. After the reaction was completed, the mixture was naturally cooled and filtered, and the solvent was naturally evaporated and crystallized at room temperature to obtain white crystals, which were tricyclohexyltin 2-hydroxy-1-naphthoate complex.

5. The preparation method according to claim 4, characterized in that: The molar ratio of the tricyclohexyltin hydroxide and 2-hydroxy-1-naphthoic 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. Use of the tricyclohexyltin 2-hydroxy-1-naphthoate complex of claim 1 in the preparation of anticancer drugs.

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

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