Application of oxamide compound in preparation of anti-hepatoma drugs

Abstract

The invention discloses an application of an oxamide compound in preparation of an anti-liver cancer drug, the oxamide compound is N-(4, 5, 6, 7-tetrahydro-1H-indazole-5-)-N '-(4-(p-tolyl) phenyl) oxamide, the molecular formula is C22H22N4O3, the molecular weight is 390.44, and the structural formula is as shown in formula (I). By investigating the influence of N-(4, 5, 6, 7-tetrahydro-1H-indazole-5-)-N '-(4-(p-tolyl) phenyl) oxamide on hepatoma cell proliferation, the obtained experimental result shows that N-(4, 5, 6, 7-tetrahydro-1H-indazole-5-)-N'-(4-(p-tolyl) phenyl) oxamide shows remarkable proliferation inhibition activity on human hepatoma cells (Hep G2, Hep 3B, PLC / PRF / 5 and Huh7), and the N-(4, 5, 6, 7-tetrahydro-1H-indazole-5-)-N '-(4-(p-tolyl) phenyl) oxamide can be used for preparing the liver cancer cell proliferation inhibitor. Meanwhile, the toxicity to human normal liver cells LX-2 is relatively low, which indicates that the compound has relatively strong anti-hepatoma activity and good cell selectivity. Therefore, the compound is expected to be applied to preparation of anti-hepatoma drugs.

Description

Technical Field

[0001] The invention belongs to the field of medical technology, and particularly relates to the application of an oxalamide compound in the preparation of an anti-liver cancer drug. Background Art

[0002] Liver cancer is a major disease that endangers human health. The treatment of liver cancer faces challenges because it is difficult to completely remove the tumor through surgery, and many liver cancer patients have no obvious symptoms in the early stage, and are already in the late stage of liver cancer when diagnosed, so it is necessary to develop liver cancer drugs. At present, researchers have developed a variety of therapeutic targeted drugs for liver cancer treatment, including: sorafenib, lenvatinib, donafenib, etc. However, the efficacy of existing liver cancer drugs cannot fully meet actual needs, and there are also toxic side effects, so it is necessary to develop new anti-liver cancer drugs.

[0003] So far, there has been no literature report on the anti-liver cancer activity of oxalamide compounds, specifically N-(4,5,6,7-tetrahydro-1H-indazole-5-)-N'-(4-(p-tolyl)phenyl)oxalamide. Summary of the invention

[0004] In view of the technical problems existing in the background technology, the purpose of the present invention is to provide an application of oxalamide compounds in the preparation of anti-liver cancer drugs.

[0005] In order to achieve the above object, the present invention adopts the following technical solution:

[0006] The first aspect of the present invention provides an application of an oxalamide compound in the preparation of an anti-liver cancer drug, wherein the oxalamide compound is specifically N-(4,5,6,7-tetrahydro-1H-indazole-5-)-N'-(4-(p-tolyl)phenyl)oxalamide, with a molecular formula of C 22 H 22 N4O3, molecular weight is 390.44, structural formula is shown in formula (I):

[0007]

[0008] Preferably, the drug is a pharmaceutical composition comprising the above-mentioned oxamide compound as an active ingredient and pharmaceutically acceptable excipients.

[0009] The present invention has the following beneficial effects:

[0010] The present invention investigates the effect of an oxalamide compound, specifically N-(4,5,6,7-tetrahydro-1H-indazole-5-)-N'-(4-(p-methylphenyl)phenyl)oxalamide, on the proliferation of liver cancer cells (Hep G2, Hep3B, PLC / PRF / 5, Huh7), and obtains experimental results showing that N-(4,5,6,7-tetrahydro-1H-indazole-5-)-N'-(4-(p-methylphenyl)phenyl)oxalamide not only exhibits significant proliferation inhibition activity on four cell lines of human liver cancer cells Hep G2, Hep 3B, PLC / PRF / 5, and Huh7, but also has low toxicity to normal human liver cells LX-2, which indicates that it has strong anti-liver cancer activity and good cell selectivity. Therefore, it is expected to be applied to the preparation of anti-liver cancer drugs. BRIEF DESCRIPTION OF THE DRAWINGS

[0011] In order to more clearly illustrate the technical solutions in the embodiments of the present invention, the following briefly introduces the drawings required for use in the embodiments. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without creative work.

[0012] Figure 1 It is the structural formula of N-(4,5,6,7-tetrahydro-1H-indazole-5-)-N'-(4-(p-tolyl)phenyl)oxalamide. DETAILED DESCRIPTION

[0013] In the following description, for the purpose of illustration rather than limitation, specific details such as specific system structures and technologies are provided to provide a thorough understanding of the embodiments of the present invention. However, it should be clear to those skilled in the art that the present invention may also be implemented in other embodiments without these specific details.

[0014] Example 1

[0015] 1. Cell experiments

[0016] 1. Solution preparation

[0017] The oxalamide compound, specifically N-(4,5,6,7-tetrahydro-1H-indazole-5-)-N'-(4-(p-tolyl)phenyl)oxalamide (commercially available), was dissolved in DMSO to prepare a sample stock solution with a concentration of 10mM, and then diluted to five concentration gradients with NGM culture medium, namely 62.5μM, 12.5μM, 2.5μM, 0.5μM, and 0.1μM, wherein the final concentration of DMSO was ≤1%. The degree of inhibition of the proliferation of various tumor cells by the target product at different gradient concentrations was tested respectively, and the half inhibition concentration, i.e., IC 50 value.

[0018] 2. Cell growth inhibition assay (MTT method)

[0019] (1) Take hepatocellular carcinoma cells (Hep G2, Hep 3B, PLC / PRF / 5, Huh7) and normal human liver cells LX-2 in the logarithmic growth phase, digest them with trypsin, and prepare a cell suspension with a concentration of 5000 cells / mL in RPM11640 culture medium containing 10% calf serum. Inoculate 190 μL per well in a 96-well culture plate to a cell density of 1000 to 10000 cells / well (the edge wells are filled with sterile PBS); incubate at 37°C, 5% CO2 for 24 h until the cell monolayer covers the bottom of the well;

[0020] Add 10 μL of oxalamide compound solution with a certain concentration gradient to each well, set 4 replicate wells for each concentration gradient, incubate at 5% CO2, 37°C for 48 hours, and observe under an inverted microscope; add 10 μL of MTT solution (5 mg / mL PBS, i.e. 0.5% MTT) to each well, and continue to culture for 4 hours; terminate the culture, carefully remove the culture solution in the well, add 150 μL of DMSO to each well to fully dissolve the formazan precipitate, mix on an oscillator, and measure the optical density (OD value) of each well on a microplate reader with a wavelength of 570 nm and a reference wavelength of 450 nm;

[0021] (2) Set up zero wells (culture medium, MTT, DMSO) and control wells (cells, drug dissolution medium of the same concentration, culture medium, MTT, DMSO).

[0022] (3) The number of living cells is determined based on the measured optical density (OD value). The larger the OD value, the stronger the cell activity. Calculate the IC value of oxalamide compounds on tumor cell growth 50 Value (μM), specific test results are shown in Table 1.

[0023] Table 1 IC values ​​of oxalamide compounds on the growth of various cell lines 50 Value (μM).

[0024]

[0025] From the in vitro anti-tumor activity test results in Table 1, it can be seen that the oxamide compounds showed significant proliferation inhibition activity on four cell lines of human liver cancer cells Hep G2, Hep 3B, PLC / PRF / 5, and Huh7, among which the activity on Hep G2 cells was the highest. In addition, the oxamide compounds had low toxicity to normal human liver cells LX-2, indicating that they had good cell selectivity. Therefore, it is expected that N-(4,5,6,7-tetrahydro-1H-indazole-5-)-N'-(4-(p-tolyl)phenyl)oxamide can be used in the preparation of anti-liver cancer drugs.

[0026] The present invention is not limited to the above-mentioned specific implementation modes. Various changes made by ordinary technicians in this field based on the above-mentioned concepts without creative work are all within the protection scope of the present invention.

Claims

1. An application of an oxalamide compound in the preparation of an anti-liver cancer drug, characterized in that: The oxalamide compound is specifically N-(4,5,6,7-tetrahydro-1H-indazole-5-)-N'-(4-(p-tolyl)phenyl)oxalamide, with a molecular formula of C 22 H 22 N4O3, molecular weight is 390.44, structural formula is shown in formula (I):

2. The use of the oxalamide compound according to claim 1 in the preparation of an anti-liver cancer drug, characterized in that: The medicine is a pharmaceutical composition comprising the oxamide compound described in claim 1 as an active ingredient and pharmaceutically acceptable excipients.

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