CN111087419A - Preparation method and application of tri (2-methyl-2-phenylpropyl) tin p-chlorobenzoate complex - Google Patents
Preparation method and application of tri (2-methyl-2-phenylpropyl) tin p-chlorobenzoate complex Download PDFInfo
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Abstract
The invention discloses a preparation method and application of a tri (2-methyl-2-phenylpropyl) tin p-chlorobenzoate complex, which is a complex with the following structural formula (I)
Description
Technical Field
The invention relates to a tri (2-methyl-2-phenylpropyl) tin p-chlorobenzoate complex, a preparation method thereof and application of the complex in preparing anti-tumor drugs.
Background
The organic tin carboxylate has high bioactivity and wide application prospect in the fields of sterilization, insecticide, anti-cancer drug preparation and the like, so that research on synthesis, structure and bioactivity of organic tin carboxylate complexes is widely concerned by scientists. The existing research shows that the alkyl R in the organotin carboxylate is the main factor for determining the anticancer activity of the compound, for example, cyclohexyl, n-butyl and phenyl tin compounds have stronger anticancer activity, and ethyl has almost no anticancer activity, and the known organotin compounds generally have stronger toxicity, so the application is limited. Regulating the balance between toxicity and biological activity is an important direction of research. The functional activation of alkyl or ligand can greatly change the coordination mode of tin atom, and further influence the bioactivity of organic tin complex. Research shows that the toxicity of the organic tin compound is related to the relative molecular mass of the organic tin compound, the smaller the relative molecular mass is, the greater the toxicity is, and the larger the relative molecular mass of the large steric hindrance alkyl tin. Therefore, the novel large steric hindrance alkyl tin carboxylate complex is synthesized, and the structure and the biological activity of the complex are researched, so that the complex has important research significance.
The bis [ tris (2-methyl-2-phenylpropyl) tin ] carboxylate disclosed in european patent EP0177785B1 has stronger biological activity than bis [ tris (2-methyl-2-phenylpropyl) tin ] oxide.
Chinese patent CN 106279256B discloses the application of bis [ tris (2-methyl-2-phenyl) propyl tin ]2, 2' -biphenyl diformate complex in the preparation of drugs for treating lung cancer, breast cancer and liver cancer.
Chinese patent CN 106279253B discloses the application of bis [ tris (2-methyl-2-phenyl) propyl tin ] 5-nitroisophthalate complex in the preparation of drugs for treating lung cancer, breast cancer and liver cancer.
Based on that the bis [ tri (2-methyl-2-phenylpropyl) ] tin oxide is a substance with better biological activity proved by experiments, and the 2-methyl-2-phenylpropyl has the characteristics of larger steric hindrance, larger molecular weight and the like, the invention selects the bis [ tri (2-methyl-2-phenylpropyl) ] tin oxide to react with ligand p-chlorobenzoic acid under certain conditions to synthesize the complex with stronger inhibitory activity to A549 (human lung cancer cells), Hela (human cervical cancer cells) and HGC-27 (human gastric cancer cells), thereby providing a new way for developing anticancer drugs.
Disclosure of Invention
In view of the problems of the prior art, the first object of the present invention is to provide a tris (2-methyl-2-phenylpropyl) tin p-chlorobenzoate complex.
The second object of the present invention is to provide a process for producing the above tris (2-methyl-2-phenylpropyl) tin p-chlorobenzoate complex.
The third purpose of the invention is to provide the application of the tri (2-methyl-2-phenylpropyl) tin p-chlorobenzoate complex in preparing anti-cancer drugs.
A tris (2-methyl-2-phenylpropyl) tin p-chlorobenzoate complex of the first aspect of the present invention has the following structural formula (I):
(I)。
the tris (2-methyl-2-phenylpropyl) tin p-chlorobenzoate complex of the invention has the following results after elemental analysis, infrared spectroscopic analysis and nuclear magnetic resonance spectroscopy:
elemental analysis (C)37H43ClO2Sn): theoretical value: c, 65.94; h, 6.43. Measurement value: c, 65.92; h, 6.48.
IR(KBr, v/cm-1): 3055.24 (w), 2956.87 (s), 2920.23 (m), 2858.51 (m),1651.07 (s), 1618..28 (w), 1593.20 (m), 1575.84 (w), 1494.83 (s), 1471.69(w), 1442.75 (m), 1396.46 (m), 1382.69 (m), 1363.67 (m), 1325.10 (s), 1305.81(m), 1276.88 (m), 1238.30 (w), 1188.15 (w), 1165.00 (w), 1124.50 (m), 1085.92(m), 1072.42 (m), 1029.99 (w), 1012.63 (m), 948.98 (w), 929.69 (w), 906.54(w), 846.75 (m), 765.74 (s), 750.31 (m), 732.95 (m), 700.16 (s), 615.29 (w),594.08 (m), 555.50 (m), 522.71 (w), 472.56 (w), 453.27 (w), 412.77 (w)。
1H NMR (CDCl3, 500 MHz)δ(ppm): 7.88 (d,J= 8 Hz, 2H), 7.36 (d,J= 8Hz, 2H), 7.29-7.28 (m,5H), 7.24 (s, 1H), 7.21-7.18 (m, 3H), 7.11 (d,J= 7.5Hz, 6H) 1.26-1.23(m, 24H)。
13C NMR (CDCl3, 125MHz)δ(ppm): 169.61, 150.80, 138.01, 131.60,131.40, 128.36, 128.24, 125.87, 125.26,37,74, 37.45, 32.79。
119Sn NMR (CDCl3, 186 MHz), δ (ppm): 95.49。
The tri (2-methyl-2-phenyl propyl) tin p-chlorobenzoate complex has the structural characteristics that: the central tin in the molecule forms a distorted tetrahedral configuration with the coordinating atoms.
In the preparation method of the tris (2-methyl-2-phenylpropyl) tin p-chlorobenzoate complex of the second aspect of the present invention, bis [ tris (2-methyl-2-phenylpropyl) ] tin oxide, p-chlorobenzoic acid and solvent anhydrous methanol are sequentially added into a microwave reaction tank in sequence, and microwave reaction is performed at an irradiation power of 800W and a temperature of 100 ℃ for a duration of 60 to 120 min under an air atmosphere. After the reaction is finished, naturally cooling, filtering, and naturally volatilizing the solvent at room temperature to crystallize to obtain a light yellow crystal, namely the tri (2-methyl-2-phenyl propyl) tin p-chlorobenzoate complex.
In a preferred embodiment of the invention, the mass ratio of the bis [ tris (2-methyl-2-phenylpropyl) ] tin oxide to the p-chlorobenzoic acid is 1 (2-2.1).
In a preferred embodiment of the present invention, the solvent is anhydrous methanol in an amount of 10 to 15 ml per mmol of bis [ tris (2-methyl-2-phenylpropyl) ] tin oxide.
The application of the tri (2-methyl-2-phenylpropyl) tin p-chlorobenzoate complex as the third aspect of the invention in the preparation of anti-cancer drugs.
The applicant carries out in-vitro antitumor activity confirmation research on the complex, and confirms that the complex has certain antitumor biological activity, namely the application of the complex in preparing antitumor drugs, in particular in preparing anti-human lung cancer drugs, human cervical cancer drugs and human gastric cancer drugs.
The tris (2-methyl-2-phenylpropyl) tin p-chlorobenzoate complex shows good anticancer activity on human lung cancer cells, human cervical cancer cells, human gastric cancer cells and the like, and can be used as a raw material for preparing anti-lung cancer, anti-cervical cancer and anti-gastric cancer medicines. Compared with the currently commonly used platinum anticancer drugs, the tris (2-methyl-2-phenylpropyl) tin p-chlorobenzoate complex has the characteristics of high anticancer activity, low cost, simple preparation method and the like, and provides a new way for developing anticancer drugs.
Drawings
FIG. 1 is an IR spectrum of tris (2-methyl-2-phenylpropyl) tin p-chlorobenzoate complex.
FIG. 2 is a diagram of tris (2-methyl-2-phenylpropyl) tin p-chlorobenzoate complex1H NMR spectrum.
FIG. 3 is a drawing showing a tris (2-methyl-2-phenylpropyl) tin p-chlorobenzoate complex13C NMR spectrum.
FIG. 4 is a drawing showing a tris (2-methyl-2-phenylpropyl) tin p-chlorobenzoate complex119Sn NMR spectrum.
Detailed Description
The present invention is further illustrated in detail by the following examples, but it should be noted that the scope of the present invention is not limited by these examples at all.
Example 1:
preparation of tris (2-methyl-2-phenylpropyl) tin p-chlorobenzoate complex:
the method comprises the steps of sequentially adding 1.0535 g (1mmol) of bis [ tri (2-methyl-2-phenylpropyl) ] tin oxide, 0.13136 g (2 mmol) of p-chlorobenzoic acid and 10 mL of solvent anhydrous methanol into a microwave reaction tank, and carrying out microwave reaction at 100 ℃ for 60 min under the air atmosphere at the radiation power of 800W. After the reaction is finished, naturally cooling, filtering, and naturally volatilizing the solvent at room temperature to crystallize to obtain a light yellow crystal, namely the tri (2-methyl-2-phenyl propyl) tin p-chlorobenzoate complex. Yield: 71%, melting point: 101-103 ℃.
Elemental analysis (C)37H43ClO2Sn): theoretical value: c, 65.94; h, 6.43. Measurement value: c, 65.92; h, 6.48.
IR(KBr, v/cm-1): 3055.24 (w), 2956.87 (s), 2920.23 (m), 2858.51 (m),1651.07 (s), 1618..28 (w), 1593.20 (m), 1575.84 (w), 1494.83 (s), 1471.69(w), 1442.75 (m), 1396.46 (m), 1382.69 (m), 1363.67 (m), 1325.10 (s), 1305.81(m), 1276.88 (m), 1238.30 (w), 1188.15 (w), 1165.00 (w), 1124.50 (m), 1085.92(m), 1072.42 (m), 1029.99 (w), 1012.63 (m), 948.98 (w), 929.69 (w), 906.54(w), 846.75 (m), 765.74 (s), 750.31 (m), 732.95 (m), 700.16 (s), 615.29 (w),594.08 (m), 555.50 (m), 522.71 (w), 472.56 (w), 453.27 (w), 412.77 (w)。
1H NMR (CDCl3, 500 MHz)δ(ppm): 7.88 (d,J= 8 Hz, 2H), 7.36 (d,J= 8Hz, 2H), 7.29-7.28 (m,5H), 7.24 (s, 1H), 7.21-7.18 (m, 3H), 7.11 (d,J= 7.5Hz, 6H) 1.26-1.23(m, 24H)。
13C NMR (CDCl3, 125MHz)δ(ppm): 169.61, 150.80, 138.01, 131.60,131.40, 128.36, 128.24, 125.87, 125.26,37,74, 37.45, 32.79。
119Sn NMR (CDCl3, 186 MHz), δ (ppm): 95.49。
Example 2:
preparation of tris (2-methyl-2-phenylpropyl) tin p-chlorobenzoate complex:
the method comprises the steps of sequentially adding 1.0534 g (1.0mmol) of bis [ tri (2-methyl-2-phenylpropyl) ] tin oxide, 0.3290 g (2.1 mmol) of p-chlorobenzoic acid and 15 mL of solvent anhydrous methanol into a microwave reaction tank, and carrying out microwave reaction at the radiation power of 800W and the temperature of 100 ℃ for 60 min under the air atmosphere. After the reaction is finished, naturally cooling, filtering, and naturally volatilizing the solvent at room temperature to crystallize to obtain a light yellow crystal, namely the tri (2-methyl-2-phenyl propyl) tin p-chlorobenzoate complex. Yield: 70%, melting point: 101-103 ℃.
Elemental analysis (C)37H43ClO2Sn): theoretical value: c, 65.94; h, 6.43. Measurement value: c, 65.92; h, 6.48.
IR(KBr, v/cm-1): 3055.24 (w), 2956.87 (s), 2920.23 (m), 2858.51 (m),1651.07 (s), 1618..28 (w), 1593.20 (m), 1575.84 (w), 1494.83 (s), 1471.69(w), 1442.75 (m), 1396.46 (m), 1382.69 (m), 1363.67 (m), 1325.10 (s), 1305.81(m), 1276.88 (m), 1238.30 (w), 1188.15 (w), 1165.00 (w), 1124.50 (m), 1085.92(m), 1072.42 (m), 1029.99 (w), 1012.63 (m), 948.98 (w), 929.69 (w), 906.54(w), 846.75 (m), 765.74 (s), 750.31 (m), 732.95 (m), 700.16 (s), 615.29 (w),594.08 (m), 555.50 (m), 522.71 (w), 472.56 (w), 453.27 (w), 412.77 (w)。
1H NMR (CDCl3, 500 MHz)δ(ppm): 7.88 (d,J= 8 Hz, 2H), 7.36 (d,J= 8Hz, 2H), 7.29-7.28 (m,5H), 7.24 (s, 1H), 7.21-7.18 (m, 3H), 7.11 (d,J= 7.5Hz, 6H) 1.26-1.23(m, 24H)。
13C NMR (CDCl3, 125MHz)δ(ppm): 169.61, 150.80, 138.01, 131.60,131.40, 128.36, 128.24, 125.87, 125.26,37,74, 37.45, 32.79。
119Sn NMR (CDCl3, 186 MHz), δ (ppm): 95.49。
Example 3:
preparation of tris (2-methyl-2-phenylpropyl) tin p-chlorobenzoate complex:
the method comprises the steps of sequentially adding 0.3857 g (1mmol) of bis [ tri (2-methyl-2-phenylpropyl) ] tin oxide, 0.3139 g (2 mmol) of p-chlorobenzoic acid and 12 mL of solvent anhydrous methanol into a microwave reaction tank, and carrying out microwave reaction at 100 ℃ for 120 min under the air atmosphere at the radiation power of 800W. After the reaction is finished, naturally cooling, filtering, and naturally volatilizing the solvent at room temperature to crystallize to obtain a light yellow crystal, namely the tri (2-methyl-2-phenyl propyl) tin p-chlorobenzoate complex. Yield: 69%, melting point: 101-103 ℃.
Elemental analysis (C)37H43ClO2Sn): theoretical value: c, 65.94; h, 6.43. Measurement value: c, 65.92; h, 6.48.
IR(KBr, v/cm-1): 3055.24 (w), 2956.87 (s), 2920.23 (m), 2858.51 (m),1651.07 (s), 1618..28 (w), 1593.20 (m), 1575.84 (w), 1494.83 (s), 1471.69(w), 1442.75 (m), 1396.46 (m), 1382.69 (m), 1363.67 (m), 1325.10 (s), 1305.81(m), 1276.88 (m), 1238.30 (w), 1188.15 (w), 1165.00 (w), 1124.50 (m), 1085.92(m), 1072.42 (m), 1029.99 (w), 1012.63 (m), 948.98 (w), 929.69 (w), 906.54(w), 846.75 (m), 765.74 (s), 750.31 (m), 732.95 (m), 700.16 (s), 615.29 (w),594.08 (m), 555.50 (m), 522.71 (w), 472.56 (w), 453.27 (w), 412.77 (w)。
1H NMR (CDCl3, 500 MHz)δ(ppm): 7.88 (d,J= 8 Hz, 2H), 7.36 (d,J= 8Hz, 2H), 7.29-7.28 (m,5H), 7.24 (s, 1H), 7.21-7.18 (m, 3H), 7.11 (d,J= 7.5Hz, 6H) 1.26-1.23(m, 24H)。
13C NMR (CDCl3, 125MHz)δ(ppm): 169.61,150.80, 138.01, 131.60,131.40, 128.36, 128.24, 125.87, 125.26,37,74, 37.45, 32.79。
119Sn NMR (CDCl3, 186 MHz), δ (ppm): 95.49。
Example 4:
preparation of tris (2-methyl-2-phenylpropyl) tin p-chlorobenzoate complex:
0.7702 g (2.0mmol) of bis [ tris (2-methyl-2-phenylpropyl) ] tin oxide, 0.6260 g (4 mmol) of p-chlorobenzoic acid and 25mL of solvent anhydrous methanol are sequentially added into a microwave reaction tank, and microwave reaction is carried out at the radiation power of 800W and the temperature of 100 ℃ for 60 min under the air atmosphere. After the reaction is finished, naturally cooling, filtering, and naturally volatilizing the solvent at room temperature to crystallize to obtain a light yellow crystal, namely the tri (2-methyl-2-phenyl propyl) tin p-chlorobenzoate complex. Yield: 70%, melting point: 101-103 ℃.
Elemental analysis (C)37H43ClO2Sn): theoretical value: c, 65.94; h, 6.43. Measurement value: c, 65.92; h, 6.48.
IR(KBr, v/cm-1): 3055.24 (w), 2956.87 (s), 2920.23 (m), 2858.51 (m),1651.07 (s), 1618..28 (w), 1593.20 (m), 1575.84 (w), 1494.83 (s), 1471.69(w), 1442.75 (m), 1396.46 (m), 1382.69 (m), 1363.67 (m), 1325.10 (s), 1305.81(m), 1276.88 (m), 1238.30 (w), 1188.15 (w), 1165.00 (w), 1124.50 (m), 1085.92(m), 1072.42 (m), 1029.99 (w), 1012.63 (m), 948.98 (w), 929.69 (w), 906.54(w), 846.75 (m), 765.74 (s), 750.31 (m), 732.95 (m), 700.16 (s), 615.29 (w),594.08 (m), 555.50 (m), 522.71 (w), 472.56 (w), 453.27 (w), 412.77 (w)。
1H NMR (CDCl3, 500 MHz)δ(ppm): 7.88 (d,J= 8 Hz, 2H), 7.36 (d,J= 8Hz, 2H), 7.29-7.28 (m,5H), 7.24 (s, 1H), 7.21-7.18 (m, 3H), 7.11 (d,J= 7.5Hz, 6H) 1.26-1.23(m, 24H)。
13C NMR (CDCl3, 125MHz)δ(ppm): 169.61, 150.80, 138.01, 131.60,131.40, 128.36, 128.24, 125.87, 125.26,37,74, 37.45, 32.79。
119Sn NMR (CDCl3, 186 MHz), δ (ppm): 95.49。
Example 5:
preparation of tris (2-methyl-2-phenylpropyl) tin p-chlorobenzoate complex:
0.7706 g (2.0mmol) of bis [ tri (2-methyl-2-phenylpropyl) ] tin oxide, 0.6428 g (4.1 mmol) of p-chlorobenzoic acid and 25mL of solvent anhydrous methanol are sequentially added into a microwave reaction tank, and microwave reaction is carried out at the radiation power of 800W and the temperature of 100 ℃ for 90 min under the air atmosphere. After the reaction is finished, naturally cooling, filtering, and naturally volatilizing the solvent at room temperature to crystallize to obtain a light yellow crystal, namely the tri (2-methyl-2-phenyl propyl) tin p-chlorobenzoate complex. Yield: 72%, melting point: 101-103 ℃.
Elemental analysis (C)37H43ClO2Sn): theoretical value: c, 65.94; h, 6.43. Measurement value: c, 65.92; h, 6.48.
IR(KBr, v/cm-1): 3055.24 (w), 2956.87 (s), 2920.23 (m), 2858.51 (m),1651.07 (s), 1618..28 (w), 1593.20 (m), 1575.84 (w), 1494.83 (s), 1471.69(w), 1442.75 (m), 1396.46 (m), 1382.69 (m), 1363.67 (m), 1325.10 (s), 1305.81(m), 1276.88 (m), 1238.30 (w), 1188.15 (w), 1165.00 (w), 1124.50 (m), 1085.92(m), 1072.42 (m), 1029.99 (w), 1012.63 (m), 948.98 (w), 929.69 (w), 906.54(w), 846.75 (m), 765.74 (s), 750.31 (m), 732.95 (m), 700.16 (s), 615.29 (w),594.08 (m), 555.50 (m), 522.71 (w), 472.56 (w), 453.27 (w), 412.77 (w)。
1H NMR (CDCl3, 500 MHz)δ(ppm): 7.88 (d,J= 8 Hz, 2H), 7.36 (d,J= 8Hz, 2H), 7.29-7.28 (m,5H), 7.24 (s, 1H),7.21-7.18 (m, 3H), 7.11 (d,J= 7.5Hz, 6H) 1.26-1.23(m, 24H)。
13C NMR (CDCl3, 125MHz)δ(ppm): 169.61, 150.80, 138.01, 131.60,131.40, 128.36, 128.24, 125.87, 125.26,37,74, 37.45, 32.79。
119Sn NMR (CDCl3, 186 MHz), δ (ppm): 95.49。
Example 6:
preparation of tris (2-methyl-2-phenylpropyl) tin p-chlorobenzoate complex:
the method comprises the steps of sequentially adding 1.1557 g (3.0mmol) of bis [ tri (2-methyl-2-phenylpropyl) ] tin oxide, 0.9393 g (6.0 mmol) of p-chlorobenzoic acid and 30 mL of solvent anhydrous methanol into a microwave reaction tank, and carrying out microwave reaction at the radiation power of 800W and the temperature of 100 ℃ for 120 min under the air atmosphere. After the reaction is finished, naturally cooling, filtering, and naturally volatilizing the solvent at room temperature to crystallize to obtain a light yellow crystal, namely the tri (2-methyl-2-phenyl propyl) tin p-chlorobenzoate complex. Yield: 70%, melting point: 101-103 ℃.
Elemental analysis (C)37H43ClO2Sn): theoretical value: c, 65.94; h, 6.43. Measurement value: c, 65.92; h, 6.48.
IR(KBr, v/cm-1): 3055.24 (w), 2956.87 (s), 2920.23 (m), 2858.51 (m),1651.07 (s), 1618..28 (w), 1593.20 (m), 1575.84 (w), 1494.83 (s), 1471.69(w), 1442.75 (m), 1396.46 (m), 1382.69 (m), 1363.67 (m), 1325.10 (s), 1305.81(m), 1276.88 (m), 1238.30 (w), 1188.15 (w), 1165.00 (w), 1124.50 (m), 1085.92(m), 1072.42 (m), 1029.99 (w), 1012.63 (m), 948.98 (w), 929.69 (w), 906.54(w), 846.75 (m), 765.74 (s), 750.31 (m), 732.95 (m), 700.16 (s), 615.29 (w),594.08 (m), 555.50 (m), 522.71 (w), 472.56 (w), 453.27 (w), 412.77 (w)。
1H NMR (CDCl3, 500 MHz)δ(ppm): 7.88 (d,J= 8 Hz, 2H), 7.36 (d,J= 8Hz, 2H), 7.29-7.28 (m,5H), 7.24 (s, 1H), 7.21-7.18 (m, 3H), 7.11 (d,J= 7.5Hz, 6H) 1.26-1.23(m, 24H)。
13C NMR (CDCl3, 125MHz)δ(ppm): 169.61, 150.80, 138.01, 131.60,131.40, 128.36, 128.24, 125.87, 125.26,37,74, 37.45, 32.79。
119Sn NMR (CDCl3, 186 MHz), δ (ppm): 95.49。
Test example:
the determination of the in vitro anticancer activity of the tri (2-methyl-2-phenylpropyl) tin p-chlorobenzoate complex is realized by an MTT experimental method.
MTT assay:
based on the metabolic reduction of 3- (4, 5-dimethylthiozol-2-yl) -2, 5-diaryltetrazolium bromide. Succinate dehydrogenase in mitochondria of living cells can reduce exogenous MTT to water-insoluble blue-purple crystalline Formazan (Formazan) and deposit in cells, while dead cells do not have this function. Dimethyl sulfoxide (DMSO) can dissolve formazan in cells, and the optical density of characteristic wavelength is measured by enzyme labeling instrument, which can indirectly reflect the number of living cells.
The inhibitory activity of the tris (2-methyl-2-phenylpropyl) tin p-chlorobenzoate complex prepared in example 1 on human lung cancer cells (a 549), human cervical cancer cells (Hela), and human gastric cancer cells (HGC-27) was determined by the MTT method.
Cell line and culture System: the A549, Hela and HGC-27 cell lines were obtained from the American tissue culture Bank (ATCC). Using RPMI1640 medium (GIBICO) containing 10% fetal bovine serum at 5% (volume fraction) CO2And culturing in vitro in a 37 ℃ saturated humidity incubator.
The testing process comprises the following steps: and respectively adding the test liquid medicine (0.0625-0.5 mu mol/L) into each hole according to the concentration gradient of the concentration, wherein each concentration is provided with 3 parallel holes. The experiment was divided into drug test group (with different concentrations of test drug added), control group (with culture medium and cells only, without test drug added) and blank group (with test drug only)Culture medium was added, cells and test agent were not added). Placing the medicated hole plate at 37 deg.C and 5% CO2Culturing in an incubator for 24 h. The activity of the control drug was determined as per the method of the test sample. In the well plate after 48 hours of incubation, 20uL of MTT (5 g/L in PBS) was added to each well. After standing at 37 ℃ for 4h, the supernatant was removed. Add 150uL DMSO to each well, shake for 10min to dissolve the Formazan crystals. Finally, the absorbance of each well was measured at a wavelength of 570nm using a BioTek multifunctional microplate reader.
Data processing: data processing Using GraAr Pad Prism version5.0 program, Complex IC50Fitting was done by a non-linear regression model with sigmoidal dose response in the program.
Analyzing human lung cancer cell (A549) cell line, human cervical cancer cell (Hela) cell line and human gastric cancer cell (HGC-27) cell line by MTT analysis method, and determining IC50The results are shown in table 1, with the conclusion that: as can be seen from the data in the table, the tris (2-methyl-2-phenylpropyl) tin p-chlorobenzoate complex has high anticancer activity on human lung cancer, human cervical cancer and human gastric cancer as an anticancer drug, and can be used as a candidate complex of the anticancer drug.
Table 1 data of in vitro activity test of tris (2-methyl-2-phenylpropyl) tin p-chlorobenzoate complex anticancer drugs.
| Human lung cancer cell | Human cervical cancer cell | Human gastric cancer cell | |
| Cell line | A549 | Hela | HGC-27 |
| IC50 μM | 0.8517 | 0.7958 | 0.4737 |
The tris (2-methyl-2-phenylpropyl) tin p-chlorobenzoate complex prepared in the remaining examples was tested for anticancer activity against human lung cancer cells (a 549), human cervical cancer cells (Hela) and human gastric cancer cells (HGC-27) by MTT method in the same test example, and the test results were substantially the same as in table 1.
Claims (7)
1. A tris (2-methyl-2-phenylpropyl) tin p-chlorobenzoate complex is a complex of the following structural formula (I):
(I)。
2. the tris (2-methyl-2-phenylpropyl) tin p-chlorobenzoate complex as claimed in claim 1, having infrared spectral data of: FT-IR (KBr, v/cm)-1) 3055.24 (w), 2956.87(s), 2920.23 (m), 2858.51(m), 1651.07(s), 1618..28 (w), 1593.20 (m), 1575.84 (w), 1494.83(s), 1471.69 (w), 1442.75 (m), 1396.46 (m), 1382.69 (m), 1363.67 (m), 1325.10(s), 1305.81 (m), 1276.88 (m), 1238.30 (w), 1188.15 (w), 1165.00 (w), 1124.50 (m),1085.92 (m), 1072.42 (m), 1029.99 (w), 1012.63 (m), 948.98 (w), 929.69 (w),906.54 (w), 846.75 (m), 765.74(s), 750.31 (m), 732.95 (m), 700.16(s), 615.29 (w), 594.08 (m), 555.50 (m), 522.71 (w), 472.56 (w), 453.27 (w),412.77 (w), and nuclear magnetic spectrum data:1H NMR (CDCl3, 500 MHz)δ(ppm): 7.88 (d,J= 8 Hz,2H), 7.36 (d,J= 8 Hz, 2H), 7.29-7.28 (m,5H), 7.24 (s, 1H), 7.21-7.18 (m,3H), 7.11 (d,J= 7.5 Hz, 6H) 1.26-1.23(m, 24H);13C NMR (CDCl3, 125MHz)δ(ppm): 169.61, 150.80, 138.01, 131.60, 131.40, 128.36, 128.24, 125.87,125.26,37,74, 37.45, 32.79;119Sn NMR (CDCl3, 186 MHz), δ (ppm): 95.49。
3. the preparation method of tris (2-methyl-2-phenylpropyl) tin-p-chlorobenzoate complex as claimed in claim 1, characterized in that bis [ tris (2-methyl-2-phenylpropyl) ] tin oxide, p-chlorobenzoic acid and anhydrous methanol as solvent are sequentially added into a microwave reaction tank in sequence, and microwave reaction is carried out at a radiation power of 800W and a temperature of 100 ℃ for a period of 60-120 min under an air atmosphere; after the reaction is finished, naturally cooling, filtering, and naturally volatilizing the solvent at room temperature to crystallize to obtain a light yellow crystal, namely the tri (2-methyl-2-phenyl propyl) tin p-chlorobenzoate complex.
4. The method according to claim 3, wherein the amount ratio of bis [ tris (2-methyl-2-phenylpropyl) ] tin oxide to p-chlorobenzoic acid is 1 (2-2.1).
5. The method according to claim 3, wherein the solvent is 10 to 15 ml of anhydrous methanol per mmol of bis [ tris (2-methyl-2-phenylpropyl) ] tin oxide.
6. Use of the tris (2-methyl-2-phenylpropyl) tin p-chlorobenzoate complex of claim 1 in the preparation of an anti-cancer medicament.
7. The use of claim 6, wherein the cancer cell is lung cancer, cervical cancer, gastric cancer.
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| CN103554170A (en) * | 2013-11-10 | 2014-02-05 | 衡阳师范学院 | Aryl organic acid ester-containing tricyclohexyltin compounds, and preparation methods and application thereof |
| CN106279259A (en) * | 2016-08-21 | 2017-01-04 | 衡阳师范学院 | A kind of three (2 methyl 2 phenyl propyl) stannum 3,5 dinitrobenzoic acid ester coordination compound and preparation method and application |
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| CN103554170A (en) * | 2013-11-10 | 2014-02-05 | 衡阳师范学院 | Aryl organic acid ester-containing tricyclohexyltin compounds, and preparation methods and application thereof |
| CN106279259A (en) * | 2016-08-21 | 2017-01-04 | 衡阳师范学院 | A kind of three (2 methyl 2 phenyl propyl) stannum 3,5 dinitrobenzoic acid ester coordination compound and preparation method and application |
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| MIN YANG: "(4-Chlorobenzoato)tris(2-methyl-2-phenylpropyl)tin(IV)", 《ACTA CRYSTALLOGRAPHIC A SECTION E》 * |
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