Use of a quinoline sulfonamide compound

Abstract

The application discloses application of a quinoline sulfonamide compound. The application of the quinoline sulfonamide compound in preparation of a medicine for preventing and / or treating cancer is disclosed. The structure of the quinoline sulfonamide compound is as follows: The inventor of the application firstly finds that the quinoline sulfonamide compound has excellent activity on various types of human tumors through activity screening on a small molecule skeleton, and provides an optional scheme for a broad-spectrum anticancer medicine.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical technology, specifically relating to the application of a quinoline sulfonamide compound. Background Technology

[0002] Cancer is currently one of the leading causes of death worldwide, posing a serious threat to human health. Over the past three decades, significant progress has been made in the research and development of anti-tumor drugs. Treatment strategies have gradually shifted from traditional chemotherapy to molecularly targeted therapy and immunotherapy, forming a new treatment landscape with multiple mechanisms. Statistics show that small molecule drugs account for approximately 78% of the 174 widely used anti-tumor drugs globally. Therefore, developing a product that can solve the aforementioned technical challenges is essential. Summary of the Invention

[0003] The purpose of this invention is to provide an application of a quinoline sulfonamide compound.

[0004] The objective of this invention is achieved through the use of the quinoline sulfonamide compound in the preparation of drugs for the prevention and / or treatment of cancer, wherein the structure of the quinoline sulfonamide compound is as follows:

[0005] .

[0006] The quinoline sulfonamide compounds described are sulfonamide derivatives based on the quinoline ring, primarily containing a quinoline-2-one skeleton. These compounds are commonly found in various bioactive molecules (such as antibacterial quinolones) and possess DNA topoisomerase inhibition potential, potentially interfering with cancer cell DNA replication. Furthermore, the integration of sulfonamide and thiophene units suggests multi-target activity. Although studies have reported the wide application of these compounds in the pharmaceutical field, their comprehensive chemical composition and antitumor mechanisms remain relatively scarce.

[0007] The quinoline sulfonamide compound N-butyl-2-oxo-N-(thiophene-2-ylmethyl)-1,2-dihydroquinoline-6-sulfonamide described in this invention has the following English name: N -butyl-2-oxo- N -(thiophen-2-ylmethyl)-1,2-dihydroquinoline-6-sulfonamide.

[0008] This invention has revealed that N-butyl-2-oxo-N-(thiophene-2-ylmethyl)-1,2-dihydroquinoline-6-sulfonamide exhibits strong inhibitory activity against tumor cells. Cell activity experiments according to this invention have shown that the quinoline sulfonamide compound described herein displays clear and differential activity against human liver cancer cells, human lung cancer cells, and human osteosarcoma cells in vitro.

[0009] The inventors of this invention, through activity screening of small molecule skeletons, discovered for the first time that the quinoline sulfonamide compound exhibits excellent activity against a variety of different types of human tumors, providing an option for broad-spectrum anticancer drugs. Attached Figure Description

[0010] Figure 1 The graph shows the inhibition curves of the quinoline sulfonamide compound on the activity of three types of human tumor cells. Detailed Implementation

[0011] The present invention will be further described below with reference to embodiments, but this is not intended to limit the present invention in any way. Any modifications or substitutions made based on the teachings of the present invention shall fall within the protection scope of the present invention.

[0012] The application of the quinoline sulfonamide compound of the present invention in the preparation of drugs for the prevention and / or treatment of cancer, wherein the structure of the quinoline sulfonamide compound is as follows:

[0013] It originates from a drug-like compound library containing 5000 compounds developed by Shanghai Taoshu Biotechnology Co., Ltd. The quinoline sulfonamide compound has the Library ID G852-0385, Plate layout PHD198946, CAS Number 1115430-99-3, and chemical formula C. 18 H 20 N2O3S2 has a relative molecular mass of 376.49. The quinoline sulfonamide compounds used in Examples 1-3 were purchased from Shanghai Taoshu Biotechnology Co., Ltd.

[0014] The cancer mentioned is liver cancer, bone cancer, or lung cancer.

[0015] The human liver cancer cells described in the following examples are human liver cancer cells LM3, the human lung cancer cells are human lung cancer cells A549, and the human osteosarcoma cells are human osteosarcoma cells MG63. All the conventional cancer cells used above were obtained from Kunming Medical University.

[0016] Unless otherwise specified, all reagents used in the embodiments of this invention are commercially available. RPMI 1640 medium, DMEM medium, and fetal bovine serum were purchased from Biological Industries; phosphate-buffered saline (PBS) and 0.25% trypsin (containing EDTA) were purchased from Gibco.

[0017] Cell lines were cultured in DMEM or RPMI 1640 medium containing 10% fetal bovine serum at 37°C, 5% CO2 and 90% humidity.

[0018] Example 1

[0019] The CCK-8 assay was used to detect cell growth inhibition. The CCK-8 assay, short for Cell Counting Kit-8, is a commonly used method for detecting cell proliferation and cytotoxicity. The principle of the CCK-8 assay is based on the compound WST-8 (2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfonic acid phenyl)-2H-tetrazole monosodium salt). In the presence of the electron carrier 1-Methoxy PMS (menaquinone phosphate), WST-8 can be reduced by intracellular mitochondrial dehydrogenases to produce a highly water-soluble orange-yellow formazan product. The amount of formazan produced is directly proportional to the number of viable cells, and the color intensity reflects cellular metabolic activity. The number of viable cells can be indirectly reflected by measuring the absorbance at 450 nm using a microplate reader. Therefore, CCK-8 can be used to assess cell proliferation, cytotoxicity, or the cellular effects of drugs.

[0020] N-Butyl-2-oxo-N-(thiophene-2-ylmethyl)-1,2-dihydroquinoline-6-sulfonamide was dissolved in DMSO (dimethyl sulfoxide), and then solutions with compound concentrations of 10 μM, 5 μM, 1 μM, 0.5 μM and 0.1 μM were prepared using DMSO. The above concentration solutions were used as the test solutions.

[0021] Human lung cancer cells A549 (4×10) 3 Cells were seeded in 96-well plates with 99 μL of culture medium per well and incubated at 37°C with 5% CO2 for 24 h. Then, 1 μL of the test solution was added to each well. For the control group, only 1 μL of DMSO was added to the cell culture, and the plates were incubated for 72 h. Then, 10 μL of CCK8 solution was added to each well, and the mixture was gently mixed to avoid air bubbles. The plates were incubated for another 1 h, and the absorbance of each well was measured at 450 nm using a microplate reader. The average OD value of each well was calculated, and the results were compared with the control group (untreated cells) to analyze changes in cell proliferation or toxicity. The percentage of absorbance in the experimental group relative to the absorbance in the control group represents the cell viability or proliferation level; the control group is assumed to be 100%.

[0022] The results are shown in Table 1 and Figure 1 As shown:

[0023] Table 1. Inhibitory effects of quinoline sulfonamide compounds on human lung cancer cell line A549.

[0024]

[0025] According to Table 1 and Figure 1The results showed that the quinoline sulfonamide compound (CAS number 1115430-99-3) exhibited cancer cell toxicity against the human lung cancer cell line A549.

[0026] Example 2

[0027] The human lung cancer cell line A549 from Example 1 was replaced with the human osteosarcoma cell line MG63. Other procedures were the same as in Example 1. Results are shown in Table 2. Figure 1 As shown.

[0028] Table 2. Inhibition results of quinoline sulfonamide compounds on human osteosarcoma cell line MG63.

[0029]

[0030] According to Table 2 and Figure 1 The results showed that the quinoline sulfonamide compound (CAS number 1115430-99-3) exhibited cancer cell toxicity against the human osteosarcoma cell line MG63.

[0031] Example 3

[0032] The human lung cancer cell line A549 was replaced with human liver cancer cell line LM3. Other procedures were the same as in Example 1. Results are shown in Table 3. Figure 1 As shown.

[0033] Table 3. Inhibitory effects of quinoline sulfonamide compounds on human hepatocellular carcinoma cell line LM3.

[0034]

[0035] According to Table 3 and Figure 1 The results showed that the quinoline sulfonamide compound (CAS No. 1115430-99-3) exhibited cancer cell toxicity against the human liver cancer cell line LM3.

[0036] In summary: as shown in Tables 1-3 and Figure 1 As shown, N-butyl-2-oxo-N-(thiophene-2-ylmethyl)-1,2-dihydroquinoline-6-sulfonamide exhibited significant dose-dependent inhibitory activity against human osteosarcoma cells, human liver cancer cells, and human lung cancer cells. Cell activity decreased with increasing drug concentration, indicating that the quinoline sulfonamide compound possesses a clear anti-proliferative effect.

[0037] The above are merely embodiments of the present invention and do not limit the scope of the patent. Any equivalent modifications made based on the content of this specification, or direct or indirect applications in other related technical fields, are similarly included within the scope of patent protection of the present invention.

Claims

1. The application of a quinoline sulfonamide compound, characterized in that, The quinoline sulfonamide compound is used in the preparation of drugs for the prevention and / or treatment of liver cancer, osteosarcoma, or lung cancer. The structure of the quinoline sulfonamide compound is as follows: 。

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