CN101434622B - Antimony triphenyl complexes, as well as preparation method and application thereof - Google Patents

Abstract

The invention discloses a triphenylantimony composition with a structural formula as follow. The preparation method of the triphenylantimony composition comprises the steps that: 0.2mmol to 0.8mmol of bis(triphenylantimony catecholate) oxide and 0.4mmol to 2mmol of sodium methoxide are added into a reaction vessel and stirred for 0.5h to 1h; then 10mL to 20mL of methanol is added into the mixture, stirred for 20h to 30h under normal temperature and then filtered in vacuum to obtain a solid matter; the solid matter is re-crystallized by dichloromethane-petroleum ether to obtain a colorless crystal which is the triphenylantimony composition; the yield of the reaction is 72 percent to 82 percent. The triphenylantimony composition has high anti-cancer activity and can be used as raw materials for preparing medicaments treating stomach cancer, nasopharyngeal cancer, liver cancer or leucocythemia. Compared with the existing platinum-based anti-cancer compounds, the triphenylantimony composition has the advantages of high anti-cancer activity, good lipid solubility, low cost and simple preparation method and the like, thus providing new ways for developing anti-cancer medicaments.

Description

A kind of triphenyl antimony complex and its preparation method and application

technical field

The invention relates to a triphenyl antimony complex, a preparation method thereof, and an application of the compound in the preparation of anticancer drugs.

Background technique

Organometallic compounds refer to compounds containing one or more metal-carbon bonds (M-C bonds), which are widely used in synthesis, catalysis, antifouling, pharmaceuticals, PVC stabilizers, etc. focus on. As early as the mid-19th century, people began to study organic antimony complexes. As drugs, until the 1980s, there were more researches on organic antimony complexes. Potassium antimony tartrate (sodium) became one of the important drugs included in the national pharmacopoeia. 1. It can treat schistosomiasis and kala-azar. Triphenyl antimony has been studied by the National Cancer Institute of the United States for its anticancer activity. P.Raj et al. synthesized and determined the biological activity of a tetraphenyl antimonide, which has bactericidal and insecticidal properties. and anticholinesterase activity.

The successful application of many traditional characterization methods such as infrared spectroscopy, nuclear magnetic resonance spectroscopy, and mass spectrometry in organic antimony complexes provides an important guarantee for its research; and the development and application of X-ray diffraction technology provides an intuitive and accurate structural information.

Because organoantimony complexes have certain pharmacological and physiological activities, and because they contain multiple coordination possibilities, and the steric hindrance between ligands is not large, they are easy to form dinuclear complexes. people's research objects. It is an urgent desire to develop an organoantimony complex with good pharmacological and physiological activities.

Contents of the invention

Aiming at the above-mentioned prior art, the present invention provides a new triphenylantimony complex, and provides a preparation method and application of the compound.

A triphenyl antimony complex, the structural formula is as follows:

A preparation method of a triphenylantimony complex, the steps are as follows: add 0.2 to 0.8 mmol of triphenylantimony (v) dichloride and 0.4 to 2 mmol of sodium methoxide into a reaction vessel, and stir 0.5~1h, then add 10~20mL of methanol, stir at room temperature for 20~30h, vacuum filter to obtain a solid, and then recrystallize with dichloromethane-petroleum ether with a volume ratio of 1:1~1:2 to obtain colorless The crystal is triphenyl antimony complex, and the yield is 72-82%.

Application of the triphenyl antimony complex in the preparation of medicines for treating gastric cancer, nasopharyngeal cancer, human liver cancer or leukemia.

The molecular formula of the triphenylantimony complex of the present invention is: C ₃₈ H ₃₆ O ₃ Sb ₂ , the melting point is 197°C, it has high anticancer activity, and it can be used as a raw material to prepare and treat gastric cancer, nasopharyngeal cancer, human liver cancer or leukemia Drug. Compared with platinum-based anti-cancer commonly used at present, the organotin coordination compound of the present invention has the characteristics of high anti-cancer activity, good fat solubility, low cost, simple preparation method, etc., and provides a new way for the development of anti-cancer drugs.

Detailed ways

The present invention will be further described below in conjunction with embodiment:

Example 1: Preparation of triphenylantimony complex: Add 0.0848g (0.2mmol) of bistriphenylantimony chloride oxide and 0.4mmol of sodium methoxide to the flask, stir for 0.5h, then add 10mL of methanol, and set at room temperature Stir for 24 hours, and vacuum filter to obtain a solid, which is then recrystallized with dichloromethane-petroleum ether (V:V=1:1). After 74 hours, a colorless crystal is obtained, which is a triphenylantimony complex with a melting point of 197 °C, yield 72%.

Through infrared spectrum analysis and NMR analysis, the results are as follows:

IR (KBr, cm-1): 732-768cm-1 (Sb-O-Sb), 3640cm-1 (OH)

H ¹ NMR: 7.32ppm (m-ph), 7.71ppm (p-ph), 8.21ppm (o-ph), 3.12ppm (CH3), 10.3ppm (OH)

C ¹³ NMR: 131.8 (m-ph), 133.9 (p-ph), 135.6 (o-ph), 140.1 (C-Sb), 170.0 (C=O), 37.42 (CH3)

Example 2: Preparation of triphenylantimony complex: add 0.1696g (0.4mmol) of bistriphenylantimony chloride oxide, 1.0mmol of sodium methoxide to the flask, stir for 1h, then add 15mL of methanol, and stir at room temperature After 20 hours, vacuum filtration to obtain a solid, which was then recrystallized with dichloromethane-petroleum ether (V:V=1:2). After 74 hours, a colorless crystal was obtained, which was a triphenylantimony complex, with a melting point of 197°C , yield 80%.

Example 3: Preparation of triphenylantimony complex: Add 0.3392g (0.8mmol) of bistriphenylantimony chloride oxide and 2.0mmol of sodium methoxide to the flask, stir for 1h, then add 20mL of methanol, and stir at room temperature After 30 hours, vacuum filtration to obtain a solid, and then recrystallized with dichloromethane-petroleum ether (V:V=1:2), and after 74 hours, a colorless crystal was obtained, which is a triphenylantimony complex, with a melting point of 197°C , yield 82%.

Example 4: Preparation of triphenylantimony complex: add 0.2544g (0.6mmol) of bistriphenylantimony chloride oxide, 1.5mmol of sodium methoxide to the flask, stir for 45min, then add 18mL of methanol, and stir at room temperature 28h, vacuum filtration to obtain a solid, and then recrystallized with dichloromethane-petroleum ether (V:V=1:1.5), after 74h, a colorless crystal was obtained, namely

It is a triphenyl antimony complex with a melting point of 197°C and a yield of 76%.

Test example: the triphenyl antimony complex of the present invention, its in vitro anticancer activity measurement is realized by two experimental methods of MTT and SRB, and its principle is:

MTT analysis method: Based on the metabolic reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl terrazolium bromide, there is a dehydrogenase related to NADP in the mitochondria of living cells, which can reduce yellow MTT to Insoluble blue-purple Formazan, dead cells do not have this enzyme, and MTT is not reduced. After dissolving Formazan with DMSO, the optical density of the characteristic wavelength can be measured with a microplate reader, and the relevant data can be processed to draw a conclusion.

SRB analysis method: Sulforhodamine B is a pink protein-binding dye that is soluble in water and can be combined with basic amino acids in biological macromolecules. Its OD reading at 515nm has a good linear relationship with the number of cells and can be quantitatively calculated Data on drug dosage and related cell numbers were obtained.

The human liver cancer Bel-7402 cell line, the human gastric cancer BGC-823 cell line, and the human nasopharyngeal carcinoma KB cell line were analyzed by SRB assay, and the human leukemia HL-60 cell line was analyzed by MTT assay to determine the IC ₅₀ values, the results are shown in Table 1, and the conclusion is: as can be seen from the data in the table, the anticancer drug of the present invention has certain anticancer activity against human liver cancer and leukemia, and has a relatively large anticancer activity against human nasopharyngeal carcinoma, and can be used as an anticancer drug. Drug candidate compounds.

Table 1 In vitro activity test data of anticancer drugs of triphenylantimony complexes

cell line Concentration (μM/L) Inhibition rate(%) human liver cancer 1.252.551020 -0.094.223.148.547.91 human leukemia 1.252.551020 8.583.582.90-0.320.97 human nasopharyngeal carcinoma 1.252.551020 -1.5714.489.1718.3221.25 human stomach cancer 1.252.551020 -13.94-4.91-2.40-7.534.37

Claims (2)

1. A triphenyl antimony complex, characterized in that: the complex is prepared by the following method: adding 0.2 to 0.8 mmol of bis-triphenyl antimony chloride oxide, 0.4 to 2 mmol of Sodium methoxide, stirred for 0.5~1h, then added 10~20mL of methanol, stirred at room temperature for 20~30h, vacuum filtered to obtain a solid, and then recrystallized with dichloromethane-petroleum ether with a volume ratio of 1:1~1:2 , to obtain colorless crystals, which are triphenyl antimony complexes. 2. The application of a triphenylantimony complex according to claim 1 in the preparation of medicines for treating gastric cancer, nasopharyngeal cancer, human liver cancer or leukemia.