CN111138482A - Tris (2-methyl-2-phenyl propyl) tin 5-bromo-2-furoate complex and preparation method and application thereof - Google Patents
Tris (2-methyl-2-phenyl propyl) tin 5-bromo-2-furoate complex and preparation method and application thereof Download PDFInfo
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- XIXRBBYUNBUHHQ-UHFFFAOYSA-M tris(2-methyl-2-phenylpropyl)stannyl 5-bromofuran-2-carboxylate Chemical compound CC(C)(C[Sn](CC(C)(C)C1=CC=CC=C1)(CC(C)(C)C2=CC=CC=C2)OC(=O)C3=CC=C(O3)Br)C4=CC=CC=C4 XIXRBBYUNBUHHQ-UHFFFAOYSA-M 0.000 title claims abstract description 44
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- FIDXVVHZWRFINX-UHFFFAOYSA-N tris(2-methyl-2-phenylpropyl)tin Chemical compound C=1C=CC=CC=1C(C)(C)C[Sn](CC(C)(C)C=1C=CC=CC=1)CC(C)(C)C1=CC=CC=C1 FIDXVVHZWRFINX-UHFFFAOYSA-N 0.000 claims description 15
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- YVTQHZDUDUCGRD-UHFFFAOYSA-N 5-bromofuran-2-carboxylic acid Chemical compound OC(=O)C1=CC=C(Br)O1 YVTQHZDUDUCGRD-UHFFFAOYSA-N 0.000 claims description 12
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- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical group [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 6
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- VMGAPWLDMVPYIA-HIDZBRGKSA-N n'-amino-n-iminomethanimidamide Chemical compound N\N=C\N=N VMGAPWLDMVPYIA-HIDZBRGKSA-N 0.000 description 4
- BOLDJAUMGUJJKM-LSDHHAIUSA-N renifolin D Natural products CC(=C)[C@@H]1Cc2c(O)c(O)ccc2[C@H]1CC(=O)c3ccc(O)cc3O BOLDJAUMGUJJKM-LSDHHAIUSA-N 0.000 description 4
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- AYOHIQLKSOJJQH-UHFFFAOYSA-N dibutyltin Chemical compound CCCC[Sn]CCCC AYOHIQLKSOJJQH-UHFFFAOYSA-N 0.000 description 1
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- 229910052757 nitrogen Inorganic materials 0.000 description 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
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- 239000000575 pesticide Substances 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
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- LOAUVZALPPNFOQ-UHFFFAOYSA-N quinaldic acid Chemical compound C1=CC=CC2=NC(C(=O)O)=CC=C21 LOAUVZALPPNFOQ-UHFFFAOYSA-N 0.000 description 1
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- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/22—Tin compounds
- C07F7/2224—Compounds having one or more tin-oxygen linkages
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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Abstract
The invention discloses a tri (2-methyl-2-phenylpropyl) tin 5-bromo-2-furoate complex, a preparation method and an application thereof, and the complex is a complex with a structural formula (I)
Description
Technical Field
The invention relates to a tri (2-methyl-2-phenylpropyl) tin 5-bromo-2-furoate complex, a preparation method thereof and application of the complex in preparing an anti-tumor medicament.
Background
Since Brown first discovered that organotin carboxylates (CH3CO2SnPh3) have bioactivity in inhibiting mouse tumors, research on the synthesis, structure and bioactivity of organotin carboxylate complexes has received much attention from scientists. However, the known organotin compounds are generally highly toxic and thus have limited applications. Research has shown that the structure, reactivity and biological activity of organotin compounds are related both to the structure of the hydrocarbon group directly attached to the tin atom and to the nature of the ligand. The optimization of the structure of the organic tin complex through molecular design so as to adjust the balance between the toxicity and the biological activity of the organic tin complex is an important direction of research of people at present. 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 alkyl tin complex with large steric hindrance is synthesized, and the structure and the biological activity of the complex are researched, so that the method has important research significance.
As is well known, nitrogen heterocycles are important and common structural units of medicines, pesticides, functional materials and the like, and most of them are closely related to life systems, so that the research on the structure of organotin derivatives of such ligands can not only provide useful information for the revealed anticancer mechanism, but also provide a possible molecular design scheme for the development of novel drugs. Nitrogen-containing heteroatom carboxylic acid is an important carboxylic acid ligand, and the synthesis of novel nitrogen-containing heterocyclic organic tin carboxylate compounds and the research on the biological activity of the nitrogen-containing heterocyclic organic tin carboxylate compounds are very necessary. For example, Chinese patent CN101402650B discloses the application of a dibutyltin and quinolinecarboxylic acid complex in preparing medicines for treating gastric cancer, nasopharyngeal carcinoma, human liver cancer or leukemia.
Based on that the bis [ tris (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 [ tris (2-methyl-2-phenylpropyl) ] tin oxide to react with heterocyclic carboxylic acid ligand 5-bromo-2-furoic 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 5-bromo-2-furoate complex.
It is a second object of the present invention to provide a process for preparing the above tris (2-methyl-2-phenylpropyl) tin 5-bromo-2-furoate complex.
The third purpose of the invention is to provide the application of the tris (2-methyl-2-phenylpropyl) tin 5-bromo-2-furoate complex in preparing an anti-cancer drug.
A tris (2-methyl-2-phenylpropyl) tin 5-bromo-2-furoate complex as a first aspect of the present invention is a complex of the following structural formula (I):
(I)。
the tris (2-methyl-2-phenylpropyl) tin 5-bromo-2-furoate complex of the present invention has the following results by elemental analysis, infrared spectroscopic analysis and nuclear magnetic resonance spectroscopy:
elemental analysis (C)35H41BrO3Sn): theoretical value: c, 59.35; h, 5.83. Measurement value: c, 59.31; h, 5.85.
IR(KBr, v/cm-1): 3053.31 (w), 3020.52 (w), 2960.73 (s), 2897.08 (m),2860.43(m), 1641.42 (m), 1631.78 (m), 1583.56 (s), 1494.83 (m), 1469.76 (s),1442.75 (m), 1382.96 (m), 1342.45 (m), 1278.80 (m), 1205.51 (m), 1168.86 (m),1076.28 (m), 1020.34 (m), 950.90 (m), 921.97 (w), 769.60 (s),742.59 (m),700.16 (s), 621.08 (m), 586.36 (m), 555.50 (m), 503.42 (m), 445.55 (w)。
1H NMR(CDCl3, 500 MHz),δ(ppm): 7.30-7.26 (m, 6H), 7.20 (t,J= 7 Hz,3H), 7.10 (d,J= 7.5 Hz, 6H), 6.90 (d,J= 3.5 Hz, 1H), 6.39 (d,J= 3.5 Hz,1H), 1.22 (s, 24H)。
13C NMR(CDCl3, 125 MHz),δ(ppm): 161.35, 150.77, 149.01, 128.40,125.90, 125.29, 118.26, 113.40, 37.71, 37.60, 32.75。
119Sn NMR(CDCl3, 186 MHz), δ(ppm):106.56。
The tri (2-methyl-2-phenylpropyl) tin 5-bromo-2-furoate complex has the structural characteristics that: the central tin in the molecule forms a distorted tetrahedral configuration with the coordinating atoms.
In the second aspect of the invention, the preparation method of the tris (2-methyl-2-phenylpropyl) tin 5-bromo-2-furoate complex comprises the steps of sequentially oxidizing bis [ tris (2-methyl-2-phenylpropyl) ] tin, 5-bromo-2-furoic acid and a solvent toluene in a 250 mL round-bottomed flask, installing a Dean-Stark water separator, and carrying out heating reflux reaction at 112-120 ℃ for 6-12 hours. After the reaction is finished, filtering the solution while the solution is hot, removing the solvent from the filtrate by using a rotary evaporator to obtain a white solid, and recrystallizing the white solid by using ethanol to obtain the tris (2-methyl-2-phenylpropyl) tin 5-bromo-2-furoate complex.
In a preferred embodiment of the invention, the mass ratio of the bis [ tris (2-methyl-2-phenylpropyl) ] tin oxide to the 5-bromo-2-furoic acid is 1.0 (2.0-2.2).
In a preferred embodiment of the invention, the solvent toluene is added in an amount of 25 to 35 ml per mmol of bis [ tris (2-methyl-2-phenylpropyl) ] tin oxide.
The application of the tri (2-methyl-2-phenylpropyl) tin 5-bromo-2-furoate complex serving as the third aspect of the invention in preparing an anti-cancer drug.
The applicant carries out in-vitro antitumor activity confirmation research on the complex, confirms that the complex has certain antitumor biological activity, namely the application of the complex in preparing antitumor drugs, in particular to the application in preparing anti-human lung cancer drugs, human cervical cancer drugs and human gastric cancer drugs
The tri (2-methyl-2-phenylpropyl) tin 5-bromo-2-furoate 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 5-bromo-2-furoate 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 5-bromo-2-furoate complex.
FIG. 2 is a drawing of a tris (2-methyl-2-phenylpropyl) tin 5-bromo-2-furoate complex1H NMR spectrum.
FIG. 3 is a drawing of a tris (2-methyl-2-phenylpropyl) tin 5-bromo-2-furoate complex13C NMR spectrum.
FIG. 4 is a drawing of a tris (2-methyl-2-phenylpropyl) tin 5-bromo-2-furoate 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 5-bromo-2-furoate complex:
in a 250 mL round-bottom flask, 1.0533 g (1.0mmol) of bis [ tris (2-methyl-2-phenylpropyl) ] tin oxide, 0.3822 g (2.0mmol) of 5-bromo-2-furoic acid and 25 mL of toluene solvent are sequentially added, a Dean-Stark water separator is arranged, and the mixture is heated and refluxed at 120 ℃ for 6 hours. After the reaction is finished, filtering the solution while the solution is hot, removing the solvent from the filtrate by using a rotary evaporator to obtain a white solid, and recrystallizing the white solid by using ethanol to obtain the tris (2-methyl-2-phenylpropyl) tin 5-bromo-2-furoate complex. Yield: 81%, melting point: 169-172 ℃.
Elemental analysis (C)35H41BrO3Sn): theoretical value: c, 59.35; h, 5.83. Measurement value: c, 59.31; h, 5.85. IR (KBr, v/cm)-1): 3053.31 (w), 3020.52 (w), 2960.73 (s), 2897.08 (m), 2860.43(m),1641.42 (m), 1631.78 (m), 1583.56 (s), 1494.83 (m), 1469.76 (s), 1442.75 (m),1382.96 (m), 1342.45 (m), 1278.80 (m), 1205.51 (m), 1168.86 (m), 1076.28 (m),1020.34 (m), 950.90 (m), 921.97 (w), 769.60 (s),742.59 (m), 700.16 (s),621.08 (m), 586.36 (m), 555.50 (m), 503.42 (m), 445.55 (w)。
1H NMR(CDCl3, 500 MHz),δ(ppm): 7.30-7.26 (m, 6H), 7.20 (t,J= 7 Hz,3H), 7.10 (d,J= 7.5 Hz, 6H), 6.90 (d,J= 3.5 Hz, 1H), 6.39 (d,J= 3.5 Hz,1H), 1.22 (s, 24H)。
13C NMR(CDCl3, 125 MHz),δ(ppm): 161.35, 150.77, 149.01, 128.40,125.90, 125.29, 118.26, 113.40, 37.71, 37.60, 32.75。
119Sn NMR(CDCl3, 186 MHz), δ(ppm):106.56。
Example 2:
preparation of tris (2-methyl-2-phenylpropyl) tin 5-bromo-2-furoate complex:
in a 250 mL round-bottom flask, 1.0536 g (1.0mmol) of bis [ tris (2-methyl-2-phenylpropyl) ] tin oxide, 0.4206 g (2.2 mmol) of 5-bromo-2-furoic acid and 25 mL of solvent toluene are sequentially added, a Dean-Stark water separator is installed, and the reaction is heated at 120 ℃ and refluxed for 8 hours. After the reaction is finished, filtering the solution while the solution is hot, removing the solvent from the filtrate by using a rotary evaporator to obtain a white solid, and recrystallizing the white solid by using ethanol to obtain the tris (2-methyl-2-phenylpropyl) tin 5-bromo-2-furoate complex. Yield: 80%, melting point: 169-172 ℃.
Elemental analysis (C)35H41BrO3Sn): theoretical value: c, 59.35; h, 5.83. Measurement value: c, 59.31; h, 5.85.
IR(KBr, v/cm-1): 3053.31 (w), 3020.52 (w), 2960.73 (s), 2897.08 (m),2860.43(m), 1641.42 (m), 1631.78 (m), 1583.56 (s), 1494.83 (m), 1469.76 (s),1442.75 (m), 1382.96 (m), 1342.45 (m), 1278.80 (m), 1205.51 (m), 1168.86 (m),1076.28 (m), 1020.34 (m), 950.90 (m), 921.97 (w), 769.60 (s),742.59 (m),700.16 (s), 621.08 (m), 586.36 (m), 555.50 (m), 503.42 (m), 445.55 (w)。
1H NMR(CDCl3, 500 MHz),δ(ppm): 7.30-7.26 (m, 6H), 7.20 (t,J= 7 Hz,3H), 7.10 (d,J= 7.5 Hz, 6H), 6.90 (d,J= 3.5 Hz, 1H), 6.39 (d,J= 3.5 Hz,1H), 1.22 (s, 24H)。
13C NMR(CDCl3, 125 MHz),δ(ppm): 161.35, 150.77, 149.01, 128.40,125.90, 125.29, 118.26, 113.40, 37.71, 37.60, 32.75。
119Sn NMR(CDCl3, 186 MHz), δ(ppm):106.56。
Example 3:
preparation of tris (2-methyl-2-phenylpropyl) tin 5-bromo-2-furoate complex:
in a 250 mL round-bottom flask, 1.0534 g (1.0mmol) of bis [ tris (2-methyl-2-phenylpropyl) ] tin oxide, 0.4212 g (2.2 mmol) of 5-bromo-2-furoic acid and 35 mL of solvent toluene are sequentially added, a Dean-Stark water separator is installed, and the reaction is heated at 120 ℃ and refluxed for 8 hours. After the reaction is finished, filtering the solution while the solution is hot, removing the solvent from the filtrate by using a rotary evaporator to obtain a white solid, and recrystallizing the white solid by using ethanol to obtain the tris (2-methyl-2-phenylpropyl) tin 5-bromo-2-furoate complex. Yield: 81%, melting point: 169-172 ℃.
Elemental analysis (C)35H41BrO3Sn): theoretical value: c, 59.35; h, 5.83. Measurement value: c, 59.31; h, 5.85.
IR(KBr, v/cm-1): 3053.31 (w), 3020.52 (w), 2960.73 (s), 2897.08 (m),2860.43(m), 1641.42 (m), 1631.78 (m), 1583.56 (s), 1494.83 (m), 1469.76 (s),1442.75 (m), 1382.96 (m), 1342.45 (m), 1278.80 (m), 1205.51 (m), 1168.86 (m),1076.28 (m), 1020.34 (m), 950.90 (m), 921.97 (w), 769.60 (s),742.59 (m),700.16 (s), 621.08 (m), 586.36 (m), 555.50 (m), 503.42 (m), 445.55 (w)。
1H NMR(CDCl3, 500 MHz),δ(ppm): 7.30-7.26 (m, 6H), 7.20 (t,J= 7 Hz,3H), 7.10 (d,J= 7.5 Hz, 6H), 6.90 (d,J= 3.5 Hz, 1H), 6.39 (d,J= 3.5 Hz,1H), 1.22 (s, 24H)。
13C NMR(CDCl3, 125 MHz),δ(ppm): 161.35, 150.77, 149.01, 128.40,125.90, 125.29, 118.26, 113.40, 37.71, 37.60, 32.75。
119Sn NMR(CDCl3, 186 MHz), δ(ppm):106.56。
Example 4:
preparation of tris (2-methyl-2-phenylpropyl) tin 5-bromo-2-furoate complex:
in a 250 mL round-bottom flask, 2.1065 g (2.0mmol) of bis [ tris (2-methyl-2-phenylpropyl) ] tin oxide, 0.8025 g (4.2 mmol) of 5-bromo-2-furoic acid and 50 mL of solvent toluene are sequentially added, a Dean-Stark water separator is installed, and the reaction is heated at 120 ℃ and refluxed for 8 hours. After the reaction is finished, filtering the solution while the solution is hot, removing the solvent from the filtrate by using a rotary evaporator to obtain a white solid, and recrystallizing the white solid by using ethanol to obtain the tris (2-methyl-2-phenylpropyl) tin 5-bromo-2-furoate complex. Yield: 83%, melting point: 169-172 ℃.
Elemental analysis (C)35H41BrO3Sn): theoretical value: c, 59.35; h, 5.83. Measurement value: c, 59.31; h, 5.85.
IR(KBr, v/cm-1): 3053.31 (w), 3020.52 (w), 2960.73 (s), 2897.08 (m),2860.43(m), 1641.42 (m), 1631.78 (m), 1583.56 (s), 1494.83 (m), 1469.76 (s),1442.75 (m), 1382.96 (m), 1342.45 (m), 1278.80 (m), 1205.51 (m), 1168.86 (m),1076.28 (m), 1020.34 (m), 950.90 (m), 921.97 (w), 769.60 (s),742.59 (m),700.16 (s), 621.08 (m), 586.36 (m), 555.50 (m), 503.42 (m), 445.55 (w)。
1H NMR(CDCl3, 500 MHz),δ(ppm): 7.30-7.26 (m, 6H), 7.20 (t,J= 7 Hz,3H), 7.10 (d,J= 7.5 Hz, 6H), 6.90 (d,J= 3.5 Hz, 1H), 6.39 (d,J= 3.5 Hz,1H), 1.22 (s, 24H)。
13C NMR(CDCl3, 125 MHz),δ(ppm): 161.35, 150.77, 149.01, 128.40,125.90, 125.29, 118.26, 113.40, 37.71, 37.60, 32.75。
119Sn NMR(CDCl3, 186 MHz), δ(ppm):106.56。
Example 5:
preparation of tris (2-methyl-2-phenylpropyl) tin 5-bromo-2-furoate complex:
in a 250 mL round-bottom flask, 2.1064 g (2.0mmol) of bis [ tris (2-methyl-2-phenylpropyl) ] tin oxide, 0.7645g (4.0 mmol) of 5-bromo-2-furoic acid and 60 mL of solvent toluene are sequentially added, a Dean-Stark water separator is installed, and the mixture is heated and refluxed at 120 ℃ for 12 hours. After the reaction is finished, filtering the solution while the solution is hot, removing the solvent from the filtrate by using a rotary evaporator to obtain a white solid, and recrystallizing the white solid by using ethanol to obtain the tris (2-methyl-2-phenylpropyl) tin 5-bromo-2-furoate complex. Yield: 82%, melting point: 169-172 ℃.
Elemental analysis (C)35H41BrO3Sn): theoretical value: c, 59.35; h, 5.83. Measurement value: c, 59.31; h, 5.85.
IR(KBr, v/cm-1): 3053.31 (w), 3020.52 (w), 2960.73 (s), 2897.08 (m),2860.43(m), 1641.42 (m), 1631.78 (m), 1583.56 (s), 1494.83 (m), 1469.76 (s),1442.75 (m), 1382.96 (m), 1342.45 (m), 1278.80 (m), 1205.51 (m), 1168.86 (m),1076.28 (m), 1020.34 (m), 950.90 (m), 921.97 (w), 769.60 (s),742.59 (m),700.16 (s), 621.08 (m), 586.36 (m), 555.50 (m), 503.42 (m), 445.55 (w)。
1H NMR(CDCl3, 500 MHz),δ(ppm): 7.30-7.26 (m, 6H), 7.20 (t,J= 7 Hz,3H), 7.10 (d,J= 7.5 Hz, 6H), 6.90 (d,J= 3.5 Hz, 1H), 6.39 (d,J= 3.5 Hz,1H), 1.22 (s, 24H)。
13C NMR(CDCl3, 125 MHz),δ(ppm): 161.35, 150.77, 149.01, 128.40,125.90, 125.29, 118.26, 113.40, 37.71, 37.60, 32.75。
119Sn NMR(CDCl3, 186 MHz), δ(ppm):106.56。
Example 6:
preparation of tris (2-methyl-2-phenylpropyl) tin 5-bromo-2-furoate complex:
in a 250 mL round-bottom flask, 3.1594 g (3.0 mmol) of bis [ tris (2-methyl-2-phenylpropyl) ] tin oxide, 1.1465 g (6.0 mmol) of 5-bromo-2-furoic acid and 75 mL of solvent toluene are sequentially added, a Dean-Stark water separator is installed, and the mixture is heated and refluxed at 120 ℃ for 12 hours. After the reaction is finished, filtering the solution while the solution is hot, removing the solvent from the filtrate by using a rotary evaporator to obtain a white yellow solid, and recrystallizing the white yellow solid by using ethanol to obtain the tris (2-methyl-2-phenylpropyl) tin 5-bromo-2-furoate complex. Yield: 81%, melting point: 169-172 ℃.
Elemental analysis (C)35H41BrO3Sn): theoretical value: c, 59.35; h, 5.83. Measurement value: c, 59.31; h, 5.85.
IR(KBr, v/cm-1): 3053.31 (w), 3020.52 (w), 2960.73 (s), 2897.08 (m),2860.43(m), 1641.42 (m), 1631.78 (m), 1583.56 (s), 1494.83 (m), 1469.76 (s),1442.75 (m), 1382.96 (m), 1342.45 (m), 1278.80 (m), 1205.51 (m), 1168.86 (m),1076.28 (m), 1020.34 (m), 950.90 (m), 921.97 (w), 769.60 (s),742.59 (m),700.16 (s), 621.08 (m), 586.36 (m), 555.50 (m), 503.42 (m), 445.55 (w)。
1H NMR(CDCl3, 500 MHz),δ(ppm): 7.30-7.26 (m, 6H), 7.20 (t,J= 7 Hz,3H), 7.10 (d,J= 7.5 Hz, 6H), 6.90 (d,J= 3.5 Hz, 1H), 6.39 (d,J= 3.5 Hz,1H), 1.22 (s, 24H)。
13C NMR(CDCl3, 125 MHz),δ(ppm): 161.35, 150.77, 149.01, 128.40,125.90, 125.29, 118.26, 113.40, 37.71, 37.60, 32.75。
119Sn NMR(CDCl3, 186 MHz), δ(ppm):106.56。
Example 7:
preparation of tris (2-methyl-2-phenylpropyl) tin 5-bromo-2-furoate complex:
in a 250 mL round-bottom flask, 3.1593 g (3.0 mmol) of bis [ tris (2-methyl-2-phenylpropyl) ] tin oxide, 1.2614 g (6.6 mmol) of 5-bromo-2-furoic acid and 90 mL of solvent toluene are sequentially added, a Dean-Stark water separator is installed, and the mixture is heated at 120 ℃ for reflux reaction for 6 hours. After the reaction is finished, filtering the solution while the solution is hot, removing the solvent from the filtrate by using a rotary evaporator to obtain a white solid, and recrystallizing the white solid by using ethanol to obtain the tris (2-methyl-2-phenylpropyl) tin 5-bromo-2-furoate complex. Yield: 81%, melting point: 169-172 ℃.
Elemental analysis (C)35H41BrO3Sn): theoretical value: c, 59.35; h, 5.83. Measurement value: c, 59.31; h, 5.85.
IR(KBr, v/cm-1): 3053.31 (w), 3020.52 (w), 2960.73 (s), 2897.08 (m),2860.43(m), 1641.42 (m), 1631.78 (m), 1583.56 (s), 1494.83 (m), 1469.76 (s),1442.75 (m), 1382.96 (m), 1342.45 (m), 1278.80 (m), 1205.51 (m), 1168.86 (m),1076.28 (m), 1020.34 (m), 950.90 (m), 921.97 (w), 769.60 (s),742.59 (m),700.16 (s), 621.08 (m), 586.36 (m), 555.50 (m), 503.42 (m), 445.55 (w)。
1H NMR(CDCl3, 500 MHz),δ(ppm): 7.30-7.26 (m, 6H), 7.20 (t,J= 7 Hz,3H), 7.10 (d,J= 7.5 Hz, 6H), 6.90 (d,J= 3.5 Hz, 1H), 6.39 (d,J= 3.5 Hz,1H), 1.22 (s, 24H)。
13C NMR(CDCl3, 125 MHz),δ(ppm): 161.35, 150.77, 149.01, 128.40,125.90, 125.29, 118.26, 113.40, 37.71, 37.60, 32.75。
119Sn NMR(CDCl3, 186 MHz), δ(ppm):106.56。
Test example:
the in vitro anticancer activity of the tri (2-methyl-2-phenylpropyl) tin 5-bromo-2-furoate complex is determined 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 5-bromo-2-furoate 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.
TestingThe process is as follows: 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 culture medium only, without cells and test drug 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 5-bromo-2-furoate complex provided by the invention is used as an anticancer drug, has high anticancer activity on human lung cancer, human cervical cancer and human gastric cancer, and can be used as a candidate complex of the anticancer drug.
Table 1 tris (2-methyl-2-phenylpropyl) tin 5-bromo-2-furoate complex anticancer drug in vitro activity test data.
| Human lung cancer cell | Human cervical cancer cell | Human gastric cancer cell | |
| Cell line | A549 | Hela | HGC-27 |
| IC50μM | 0.6383 | 0.5808 | 0.677 |
The tris (2-methyl-2-phenylpropyl) tin 5-bromo-2-furoate 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 experimental example, and the test results were substantially the same as in table 1.
Claims (7)
1. A tris (2-methyl-2-phenylpropyl) tin 5-bromo-2-furoate complex, which is a complex of the following structural formula (I):
(I)。
2. the tris (2-methyl-2-phenylpropyl) tin 5-bromo-2-furoate complex as claimed in claim 1 having an infrared spectrum of: FT-IR (KBr, v/cm)-1): 3053.31 (w), 3020.52 (w), 2960.73 (s),2897.08 (m), 2860.43(m), 1641.42 (m), 1631.78 (m), 1583.56 (s), 1494.83 (m),1469.76 (s), 1442.75 (m), 1382.96 (m), 1342.45 (m), 1278.80 (m), 1205.51 (m),1168.86 (m), 1076.28 (m), 1020.34 (m), 950.90 (m), 921.97 (w), 769.60 (s),742.59 (m), 700.16 (s), 621.08 (m), 586.36 (m), 555.50 (m), 503.42 (m),445.55 (w), nuclear magnetic spectrum data:1H NMR (CDCl3, 500 MHz)δ(ppm): 7.30-7.26 (m, 6H),7.20 (t,J= 7 Hz, 3H), 7.10 (d,J= 7.5 Hz, 6H), 6.90 (d,J= 3.5 Hz, 1H),6.39 (d,J= 3.5 Hz, 1H), 1.22 (s, 24H);13C NMR (CDCl3, 125MHz)δ(ppm):161.35, 150.77, 149.01, 128.40, 125.90, 125.29, 118.26, 113.40, 37.71, 37.60,32.75;119Sn NMR (CDCl3，186 MHz),δ(ppm):106.56。
3. the preparation method of the tris (2-methyl-2-phenylpropyl) tin 5-bromo-2-furoate complex according to claim 1, wherein bis [ tris (2-methyl-2-phenylpropyl) ] tin oxide, 5-bromo-2-furoic acid and the solvent toluene are sequentially added into a 250 mL round bottom flask, a Dean-Stark water separator is arranged, and the mixture is heated and refluxed at 112-120 ℃ for 6-12 hours; after the reaction is finished, filtering the solution while the solution is hot, removing the solvent from the filtrate by using a rotary evaporator to obtain a white solid, and recrystallizing the white solid by using ethanol to obtain the tris (2-methyl-2-phenylpropyl) tin 5-bromo-2-furoate complex.
4. The method according to claim 3, wherein the mass ratio of bis [ tris (2-methyl-2-phenylpropyl) ] tin oxide to 5-bromo-2-furoic acid is 1.0 (2.0-2.2).
5. The method according to claim 3, wherein the solvent toluene is used in an amount of 25 to 35 ml per mmol of bis [ tris (2-methyl-2-phenylpropyl) ] tin oxide.
6. Use of the tris (2-methyl-2-phenylpropyl) tin 5-bromo-2-furoate complex of claim 1 for the preparation of an anticancer drug.
7. The use of claim 6, wherein the cancer cell is lung cancer, cervical cancer, gastric cancer.
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| 庾江喜等，: "两个三环己基锡芳香羧酸酯的合成、结构、热稳定性及体外抗癌活性研究", 《无机化学学报》 * |
| 田来进等，: "双( 三有机锡)2 , 3 - 吡啶二甲酸酯的合成、表征和体外抗癌活性", 《无机化学学报》 * |
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