Application of an oxamide compound in the preparation of anti-liver cancer drugs

Abstract

The present invention discloses an application of an oxamide compound in the 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, and the molecular formula is C 22 H 22 N4O3, with a molecular weight of 390.44 and a structural formula as shown in Formula (I), investigated the effect of N-(4,5,6,7-tetrahydro-1H-indazole-5-)-N'-(4-(p-tolyl)phenyl)oxalamide on the proliferation of liver cancer cells. The results showed that N-(4,5,6,7-tetrahydro-1H-indazole-5-)-N'-(4-(p-tolyl)phenyl)oxalamide exhibited significant anti-proliferation activity against human liver cancer cells (Hep G2, Hep 3B, PLC / PRF / 5, and Huh7), while exhibiting low toxicity against normal human liver cells (LX-2). This suggests that it possesses strong anti-liver cancer activity and excellent cell selectivity. Therefore, it is expected to be used in the preparation of anti-liver cancer drugs.

Description

Technical Field

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

[0002] Liver cancer is a serious health hazard. Its treatment presents challenges, as complete tumor removal through surgery is difficult. Furthermore, many patients experience no obvious symptoms in the early stages of the disease, often progressing to advanced stages by the time they are diagnosed. Therefore, the development of liver cancer drugs is crucial. Currently, researchers have developed a variety of targeted drugs for liver cancer treatment, including sorafenib, lenvatinib, and donafenib. However, existing liver cancer drugs are ineffective and often have toxic side effects, necessitating the development of novel anti-liver cancer drugs.

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

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

[0006] The first aspect of the present invention provides an application of an oxamide compound in the preparation of an anti-liver cancer drug, wherein the oxamide compound is specifically N-(4,5,6,7-tetrahydro-1H-indazole-5-)-N'-(4-(p-tolyl)phenyl)oxamide, with a molecular formula of C 22 H 22 N4O3, molecular weight is 390.44, and the 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 oxamide compound, specifically N-(4,5,6,7-tetrahydro-1H-indazole-5-)-N'-(4-(p-tolyl)phenyl)oxamide, on the proliferation of liver cancer cells (Hep G2, Hep 3B, PLC / PRF / 5, and Huh 7). Experimental results show that N-(4,5,6,7-tetrahydro-1H-indazole-5-)-N'-(4-(p-tolyl)phenyl)oxamide exhibits significant proliferation inhibition activity against all four human liver cancer cell lines: Hep G2, Hep 3B, PLC / PRF / 5, and Huh 7. Furthermore, the compound exhibits low toxicity against normal human liver cells: LX-2. This demonstrates its strong anti-liver cancer activity and excellent cell selectivity. Therefore, it is expected to be used in 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 paying any creative work.

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

[0013] In the following description, specific details such as specific system structures and technologies are provided for the purpose of illustration rather than limitation to facilitate 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 oxamide compound, specifically N-(4,5,6,7-tetrahydro-1H-indazole-5-)-N'-(4-(p-tolyl)phenyl)oxamide (commercially available), was dissolved in DMSO to prepare a 10mM sample stock solution. The sample was then diluted to five concentration gradients using NGM culture medium: 62.5μM, 12.5μM, 2.5μM, 0.5μM, and 0.1μM, with a final DMSO concentration of ≤1%. The inhibitory effect of the target product on the proliferation of various tumor cells at different concentration gradients was tested and used to calculate the half-maximal inhibitory concentration (IC50). 50 value.

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

[0019] (1) Hepatocellular carcinoma cells (Hep G2, Hep 3B, PLC / PRF / 5, Huh7) and normal human liver cells LX-2 were obtained and digested with trypsin. A cell suspension at a concentration of 5000 cells / mL was prepared using RPM11640 culture medium containing 10% calf serum. 190 μL of the suspension was seeded into each well of a 96-well culture plate to a cell density of 1000 to 10000 cells / well (the edge wells were filled with sterile PBS). The cells were incubated at 37°C, 5% CO2 for 24 h until the cell monolayer covered the bottom of the well.

[0020] Add 10 μL of a concentration gradient of oxalamide compound solution to each well, with four replicate wells for each concentration gradient. Incubate at 37°C with 5% CO2 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 incubation for 4 hours. Terminate the incubation, carefully aspirate the culture medium, add 150 μL of DMSO to each well to fully dissolve the formazan precipitate, mix on an oscillator, and measure the optical density (OD) of each well on a microplate reader at a wavelength of 570 nm and a reference wavelength of 450 nm.

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

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

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

[0024]

[0025] As shown in the in vitro antitumor activity test results in Table 1, these oxamide compounds exhibited significant anti-proliferation activity against four human liver cancer cell lines: Hep G2, Hep 3B, PLC / PRF / 5, and Huh7. The highest activity was observed against Hep G2 cells. Furthermore, these oxamide compounds exhibited low toxicity against normal human liver LX-2 cells, demonstrating their excellent cell selectivity. Therefore, N-(4,5,6,7-tetrahydro-1H-indazole-5-)-N'-(4-(p-tolyl)phenyl)oxamide is expected to be used in the preparation of anti-liver cancer drugs.

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

Claims

1. Use of an oxamide compound in the preparation of an anti-liver cancer drug, characterized in that: The oxamide compound is specifically N-(4,5,6,7-tetrahydro-1H-indazole-5-)-N'-(4-(p-tolyl)phenoxy)oxamide, with a molecular formula of C 22 H 22 N4O3, molecular weight is 390.44, and the structural formula is shown in formula (I): 。 2. Use of the oxamide 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 according to claim 1 as an active ingredient and pharmaceutically acceptable excipients.

Images