CN107043345A - Preparation, structure and the purposes of the diketone Schiff base of 4-acetylbiphenyl hydrazone indoline 2,3 - Google Patents

Abstract

The invention relates to the structure, preparation method and partial properties of a Schiff base compound. The appearance of the compound is yellow powdery solid, melting point 235.8-236.3°C, molecular formula C ₂₂ H ₁₇ N ₃ O, chemical name: (E)-3-((E)-(1-(biphenyl-4-yl) Ethylene)-hydrazino)indoline-2-one, the structure is as follows: The preparation method of the compound is simple, and the IC50 (half inhibitory concentration of the drug ₎ against A549 lung cancer cells, 4T1 breast cancer cells and CT‑26 colon cancer cells are 40.5 μM, 47.0 μM and 38.5 μM, respectively, which shows that the compound has the effect on these three It has a certain inhibitory effect on cancer cells.

Description

Preparation, structure and application of diphenone hydrazone-indoline-2,3-dione Schiff base

technical field

The invention relates to the fields of organic synthesis and medicinal chemistry, and uses relatively simple raw materials and methods to synthesize target products in one step.

Background technique

Schiff base is a compound with a relatively special structure, and different types of Schiff bases can be synthesized according to the different groups introduced. Schiff bases have important applications in the fields of medicine, catalysis, analytical chemistry, corrosion and photochromism. For example, in the medical field, Schiff base has antibacterial, bactericidal, antitumor, and antiviral biological activities; in the field of optical materials, due to its electron-rich and rigid plane characteristics, it has good fluorescence properties and nonlinear optical properties. nature.

There are few reports on the use of biphenyl ketone hydrazone Schiff bases in drugs, but drug molecules containing biphenyl ring structures are very common; in the field of drug design, biphenyl ring systems stabilize the aromatic-hydrophobic interactions of drug molecules, so they are often Used in the construction of drug molecules.

Contents of the invention

The content of the present invention is to synthesize a biphenylphenone hydrazone-indoline-2,3-dione Schiff base compound, which is a yellow powdery solid with a melting point of 235.8-236.3°C and a molecular formula of C ₂₂ H ₁₇ N ₃ O, chemical name: (E)-3-((E)-(1-(biphenyl-4-yl)ethylidene)-hydrazinide)indoline-2-one, [English system name It is: (E)-3-((E)-(1-(biphenyl-4-yl)ethylene)hydrazono)indolin-2-one], abbreviated as 3-BEHIO; the structure is as follows.

1. Structural identification.

Elemental analysis shows that the percentages of C, H and N are 77.91%, 5.11% and 12.42% respectively (theoretical values based on the molecular formula C ₂₂ H ₁₇ N ₃ O are 77.86%, 5.05% and 12.38%) respectively. See Figure 1 for the ¹ HNMR spectrum.

2. Synthesis method.

The synthesis method of the compound is characterized in that: using diphenone hydrazone and indoline-2,3-dione as raw materials, the solution synthesis or solid phase synthesis is adopted. Proceed as follows:

1) Dissolve biphenylphenone hydrazone and indoline-2,3-dione in suitable organic solvents respectively, then mix them in a certain molar ratio, stir and react at a certain temperature for a certain period of time; Solvent, directly mix the two reactants, grind the reaction.

2) During the liquid phase reaction, remove most of the solvent from the obtained solution by a certain method to obtain a yellow powdery solid, which is the target product; during the solid phase reaction, grind for a certain period of time to obtain the target product.

3) The target product can be recrystallized in a suitable organic solvent to purify the product.

Preferably, the above-mentioned reaction solvent or organic solvent for recrystallization is selected from: methanol, ethyl acetate, dichloromethane, ethanol, acetonitrile, acetone, chloroform, tetrahydrofuran.

Preferably, the reaction molar ratio of diphenone hydrazone and indoline-2,3-dione is 1:4 to 4:1.

Preferably, the reaction temperature is from room temperature to heating to reflux.

Preferably, the reaction time is 0.5-12 hours.

Preferably, the method for removing the solvent is natural volatilization or atmospheric/vacuum distillation.

The beneficial effect of the invention is that relatively complex functional molecular materials can be synthesized in one step with relatively simple steps and reactants, and the separation method is simple.

3. Antitumor activity in vitro:

A549 lung cancer cells, 4T1 breast cancer cells and CT _- 26 colon cancer cells in the logarithmic phase were digested with 0.25% trypsin to make them single cells, and F12K culture medium containing 10% fetal bovine serum A single-cell suspension with a concentration of 1.25×10 ⁷ cells/L was prepared, and the cells were seeded in a 96-well culture plate at 200 μL per well (2.5×10 ³ cells per well). The 96-well cell culture plate was placed in a CO ₂ incubator at 37°C and 5% CO ₂ for 48 hours.

When the cells in the wells are overgrown (90% full), add different doses of Bencifer base solution (200 μL/well) according to the experimental grouping, so that the final concentrations of the compounds to be tested are 5 μM, 10 μM, 30 μM, 50 μM, 100μM, each group set up 3 replicate wells, cultured for 96h.

20 μL of MTT at a concentration of 0.5 g/L was added to each well, and the culture was continued for 4 hours to reduce MTT to formazan. After aspirating all the supernatant, add 200 μL of DMSO to each well and shake for 15 min to fully dissolve formazan, then measure the absorbance (OD value) at 490 nm with an enzyme-linked immunosorbent assay. Then calculate according to the following formula:

Cell inhibition rate%=(OD value of control group-OD value of experimental group)/OD value of control group×100%

The test results show that the IC50 (half inhibitory concentration of the drug) of the Schiff base _on A549 lung cancer cells, 4T1 breast cancer cells and CT-26 colon cancer cells is 40.5 μM, 47.0 μM and 38.5 μM respectively, which shows that the compound has These three cancer cells have a certain inhibitory effect.

detailed description

In order to better understand the content of the present invention, the technical solution of the present invention is further described below through two specific examples:

Example 1.

Weigh 0.20 g (0.95 mmol) of biphenylphenone hydrazone and dissolve it in 30 mL of anhydrous methanol, heat and stir until completely dissolved, add 0.14 g (0.95 mmol) of indoline-2,3-dione, heat and reflux and stir for 6 hours , then filter to obtain the filtrate, put it in a beaker and let it stand for volatilization, a large amount of powdery precipitate can be obtained, the obtained precipitate is filtered to obtain the initial product (yield is about 79%), and this initial product can be recrystallized with ethanol to obtain a yellow powder The solid is 3-BEHIO Schiff base.

Example 2.

Weigh 0.40 g (1.9 mmol) of biphenylphenone hydrazone and put it into a mortar, add 0.28 g (1.9 mmol) of indoline-2,3-dione, and grind for 3 hours to obtain the crude product of the target product; Recrystallized with ethanol to obtain a yellow powdery solid, namely 3-BEHIO Schiff base.

Description of drawings

Accompanying drawing 1 is the ¹ H NMR spectrogram of benzophenone hydrazone-indoline-2,3-dione Schiff base.

Claims (4)

1. A compound whose appearance is yellow powdery solid, melting point 235.8-236.3°C, molecular formula C ₂₂ H ₁₇ N ₃ O, chemical name: (E)-3-((E)-(1-(biphenyl- 4-yl)ethylidene)-hydrazino)indolin-2-one, the structure is as follows. 2. The preparation method of the compound as claimed in claim 1 is characterized in that: taking diphenone hydrazone and indoline-2,3-dione as raw materials, adopting a solution synthesis method, the steps are as follows: 1) Dissolve benzophenone hydrazone and indoline-2,3-dione in organic solvents such as methanol, ethyl acetate, dichloromethane, ethanol, acetonitrile, acetone, chloroform or tetrahydrofuran, respectively, and then press 1:4 Mix to 4:1 molar ratio, stir and react at room temperature to reflux temperature for 0.5-12 hours; 2) Remove most of the solvent from the obtained solution by natural volatilization or atmospheric/vacuum distillation to obtain a yellow powder, which is the target product; 3) The target product can be recrystallized in organic solvents such as methanol, ethyl acetate, dichloromethane, ethanol, acetonitrile, acetone, chloroform or tetrahydrofuran to purify the product. 3. The preparation method of the compound as claimed in claim 1, characterized in that: using diphenone hydrazone and indoline-2,3-dione as raw materials, adopting solid-phase synthesis, the steps are as follows: 1) Mix biphenylphenone hydrazone and indoline-2,3-dione at a molar ratio of 1:4 to 4:1, grind and react at room temperature for 0.5-12 hours, and the obtained powder is the primary product of the target product; 2) The initial target product can be recrystallized in organic solvents such as methanol, ethyl acetate, dichloromethane, ethanol, acetonitrile, acetone, chloroform or tetrahydrofuran to purify the product. 4. The use of the compound or a pharmaceutically acceptable salt thereof as claimed in claim 1 in the preparation of a drug for the prevention and/or treatment of tumors, characterized in that: the tumor is lung cancer, breast cancer or colon cancer.