Application of a pyrrole dione compound

Abstract

This invention discloses the application of a pyrrole dione compound. Specifically, it describes the application of this pyrrole dione compound in the preparation of drugs for the prevention and / or treatment of cancer. The structure of the pyrrole dione compound is as follows: The inventors of this invention, through activity screening of small molecule skeletons, have for the first time discovered that the pyrrole dione compound exhibits excellent activity against various types of human tumors, providing an option for broad-spectrum anticancer drugs.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical technology, specifically relating to the application of a pyrroledione 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 pyrroledione compound.

[0004] The object of this invention is achieved by the use of the pyrrole dione compound in the preparation of drugs for the prevention and / or treatment of cancer, wherein the structure of the pyrrole dione compound is as follows:

[0005] .

[0006] The pyrrole dione compound described is (S)-7-chloro-2-(3-(dimethylamino)propyl)-1-(pyridin-3-yl)-1,2-dihydrochromeno[2,3-c]pyrrole-3,9-dione, a well-designed and structurally complex candidate drug molecule. Its structural features strongly suggest an anticancer mechanism targeting DNA or topoisomerases, while also possessing the potential to be developed as a kinase inhibitor, making it a highly promising lead compound for anticancer applications. Although studies have reported the wide application of this type of compound in the pharmaceutical field, its comprehensive chemical composition and antitumor mechanism are still relatively scarce.

[0007] The pyrrole dione compound described in this invention is (S)-7-chloro-2-(3-(dimethylamino)propyl)-1-(pyridin-3-yl)-1,2-dihydrochromeno[2,3-c]pyrrole-3,9-dione, with the English name (S)-7-chloro-2-(3-(dimethylamino)propyl)-1-(pyridin-3-yl)-1,2-dihydrochromeno[2,3-c]pyrrole-3,9-dione.

[0008] The inventors of this invention have discovered that (S)-7-chloro-2-(3-(dimethylamino)propyl)-1-(pyridin-3-yl)-1,2-dihydrochromeno[2,3-c]pyrrole-3,9-dione exhibits strong inhibitory activity against tumor cells. According to cell activity experiments based on this invention, the pyrrole dione compound described herein shows clear and differential anti-human lung cancer cell activity in vitro.

[0009] The inventors of this invention, through activity screening of small molecule skeletons, discovered for the first time that the pyrrole dione 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 curve of the pyrrole dione compound on the viability of one type 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 pyrrole dione compound of the present invention in the preparation of drugs for the prevention and / or treatment of cancer, wherein the structure of the pyrrole dione compound is as follows:

[0013] It originates from a drug-like compound library containing 5000 compounds developed by Shanghai Taoshu Biotechnology Co., Ltd. Compound I has the Library ID G856-6184, Plate layout PHD198946, CAS Number 874397-34-9, and chemical formula C. 21 H 20 ClN3O3 has a relative molecular mass of 397.86. The pyrrole dione compound used in Example 1 was purchased from Shanghai Taoshu Biotechnology Co., Ltd.

[0014] The cancer mentioned is lung cancer.

[0015] The human lung cancer cells described in the following examples are human lung cancer cells A549. 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 and fetal bovine serum were purchased from Biological Industries; phosphate-buffered saline (PBS) and 0.25% trypsin (containing EDTA) were purchased from Gibco.

[0017] The cell lines were cultured in 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] (S)-7-chloro-2-(3-(dimethylamino)propyl)-1-(pyridin-3-yl)-1,2-dihydrochromeno[2,3-c]pyrrole-3,9-dione 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. These solutions were used as 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 pyrrolodione compounds on human lung cancer cell line A549.

[0024]

[0025] According to Table 1 and Figure 1 The results showed that the pyrrole dione compound (CAS number 874397-34-9) exhibited cancer cell toxicity against the human lung cancer cell line A549.

[0026] In summary: as shown in Table 1 and Figure 1 As shown, (S)-7-chloro-2-(3-(dimethylamino)propyl)-1-(pyridin-3-yl)-1,2-dihydrochromeno[2,3-c]pyrrole-3,9-dione exhibits significant dose-dependent inhibitory activity against human lung cancer cells. Cell viability decreases with increasing drug concentration, indicating that the pyrrole dione compound described in this invention has a clear anti-proliferative effect.

[0027] 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 pyrrole dione compound, characterized in that, The pyrrole dione compound is used in the preparation of drugs for the prevention and / or treatment of lung cancer, and the structure of the pyrrole dione compound is as follows: 。

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