CN112999221A

CN112999221A - Application of triazole compound in preparation of antitumor drugs

Info

Publication number: CN112999221A
Application number: CN202110301156.3A
Authority: CN
Inventors: 李环球; 汪维鹏; 吕依昕; 朱一凡
Original assignee: Suzhou University
Current assignee: Suzhou University
Priority date: 2021-03-22
Filing date: 2021-03-22
Publication date: 2021-06-22
Anticipated expiration: 2041-03-22
Also published as: CN112999221B; WO2022198777A1

Abstract

The invention provides an application of a triazole compound or a pharmaceutically acceptable salt thereof in preparing an anti-tumor medicament. The invention discovers for the first time that the triazole compound N- (5-benzothiazole-2-thiomethyl) -4H-1, 2,4 triazole-3-benzamide has anti-tumor activity, has good inhibition effect on multiple primary and transformed tumor cells, and can be used for preparing anti-tumor medicaments.

Description

Application of triazole compound in preparation of antitumor drugs

Technical Field

The invention belongs to the field of antitumor drugs, and particularly relates to an application of a triazole compound in preparation of an antitumor drug.

Background

Malignant tumors are the second lethal disease in global ranking, and the leaders in lung cancer, prostate cancer, colorectal cancer and breast cancer are the first, and the morbidity and mortality of the cancers are in a continuous rising state in the last ten years. The conventional treatment methods include various operations, chemotherapy, radiotherapy and the like. However, most of the traditional treatment methods can not achieve the curative effect, and particularly, the mortality rate of patients with middle and late malignant tumors is high. The micromolecule targeted antitumor drug has the advantages of high curative effect, low toxic and side effect and high specificity, and is gradually a hot project for developing innovative drugs at home and abroad. Different from the traditional medicine, the micromolecule medicine can be specifically combined with a human target, can effectively play an inhibiting role aiming at the primary tumor, and has the advantages of low toxicity, high bioavailability, wide bioactivity, good biocompatibility and curative effect. Many outstanding results indicate that the small molecule compounds have wide potential application as medicinal drugs and diagnostic agents. Especially clinical anticancer, antitumor, etc., a large number of small molecular compounds have been successfully developed, sold and widely applied to the prevention and treatment of various diseases. Is widely applied in chemical, medical, biological and material science fields.

The chemical small molecules can penetrate through cell membranes to influence the expression and the function of targets in cells, and the application range is very wide; in addition, the chemical micromolecules have good oral bioavailability after being chemically modified, and the compliance of patients after taking the chemical micromolecules is better; the research of chemical small molecule drugs is more mature than biological drugs regardless of the selling price or the administration mode of dosage forms, and in contrast, the chemical small molecule drugs have good potential and market competitiveness. Therefore, the search for the anti-tumor drugs with new structural types has important significance.

Disclosure of Invention

The invention aims to provide the application of a triazole compound in preparing an anti-tumor medicament, and the small molecular compound has good inhibitory activity on multiple primary and transformed tumor cells.

The triazole compound is N- (5-benzothiazole-2-thiomethyl) -4H-1, 2,4 triazole-3-benzamide, and has a structure shown in a formula I:

in the invention, the pharmaceutically acceptable salt is one or more of hydrochloride, phosphate, sulfate, acetate, maleate, citrate, benzene sulfonate, methyl benzene sulfonate, fumarate and tartrate.

The tumor is selected from colon cancer, gastric cancer or lung cancer.

The invention also provides application of the triazole compound or the pharmaceutically acceptable salt thereof in preparing a medicament for inhibiting tumor cells.

The tumor cell is colon cancer cell SW480, drug-resistant colon cancer cell SW620, gastric cancer cell SGC7901 or lung cancer cell A549.

Drawings

In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the embodiments or the prior art will be briefly described below, it is obvious that the drawings in the following description are only embodiments of the present invention, and for those skilled in the art, other drawings can be obtained according to the provided drawings without creative efforts.

FIG. 1 shows the SW480 inhibitory activity of test compounds against colon cancer cells in vitro;

FIG. 2 is a graph of the inhibitory activity of test compounds against drug-resistant colon cancer cells SW620 in vitro.

Detailed Description

In the invention, the N- (5-benzothiazole-2-thiomethyl) -4-hydrogen-1, 2,4 triazole-3-benzamide compound is prepared according to the following process:

specifically, the N- (5-benzothiazole-2-thiomethyl) -4-hydrogen-1, 2,4 triazole-3-benzamide compound used in the invention is prepared according to the document Shostakov, A.S.; gusakova, n.v.; verezhnikov, v.n.; shikhaliev, Kh.S. Synthesis of triazine from cyanamides and hydrazides IZvestiya Vyshikh Uchebykh Zaveediii, Khimiya i Khimichushaya Tekkechnology iya (2005),48(6), 126-.

1. Determination of antitumor Activity of Compounds

The selected tumor cells comprise colon cancer cells SW480, drug-resistant colon cancer cells SW620, stomach cancer cells SGC7901 and lung cancer cells A549, the cells in logarithmic growth phase are taken, digested and counted, the cell state is adjusted, and then the plate paving operation is carried out. The cells were seeded at 3000/well cell density in 96-well plates and placed overnight in an incubator. (note: the outer ring of PBS is filled up.) the administration operation is carried out after 18-24 h. The cell culture medium was aspirated and a culture medium containing a drug at a certain concentration was added. Blank group (solvent control group) and experimental group are set in the experiment. The concentrations of the drugs in the experimental groups were 1. mu.M, 5. mu.M, 20. mu.M, 50. mu.M, 100. mu.M, and 200. mu.M, respectively. Each set of experiments was equipped with 3 secondary wells, the positive control was pentafluorouracil, and the procedure was the same as for the test compounds.

After 72h dosing, 10. mu.L of MTT solution was added to each well and placed in a cell incubator for further 2h incubation. The absorbance of each well at a wavelength of 492nm was measured with a microplate reader.

The viability of the cells in each well was calculated from the absorbance values, and the IC50 value of the drug was calculated. The results are shown in Table 1.

TABLE 1 screening of test Compounds for anti-tumor Activity in vitro

As can be seen from Table 1, the tested compound N- (5-benzothiazole-2-thiomethyl) -4H-1, 2,4 triazole-3-benzamide has anti-tumor activity, has good inhibition effect on multiple primary and transformed tumor cells, and can be used for preparing anti-tumor drugs.

The foregoing is only a preferred embodiment of the present invention, and it should be noted that, for those skilled in the art, various modifications and decorations can be made without departing from the principle of the present invention, and these modifications and decorations should also be regarded as the protection scope of the present invention.

Claims

1. The application of the triazole compound or the pharmaceutically acceptable salt thereof in preparing the antitumor drug;

the triazole compound has a structure shown in formula I:

2. the use according to claim 1, wherein the pharmaceutically acceptable salt is one or more of hydrochloride, phosphate, sulfate, acetate, maleate, citrate, benzenesulfonate, methylbenzenesulfonate, fumarate and tartrate.

3. The use of claim 1, wherein the tumor comprises colon, gastric, or lung cancer.

4. The use of claim 1, wherein the anti-tumor is inhibition of proliferation of tumor cells.

5. The use of claim 4, wherein the tumor cell is a colon cancer cell SW480, a drug-resistant colon cancer cell SW620, a gastric cancer cell SGC7901, or a lung cancer cell A549.