CN106146509A - A kind of compound suppressing breast carcinoma to breed and application thereof - Google Patents

Abstract

The invention discloses a compound for inhibiting the proliferation of breast cancer, which is named 6-(4-amino-1-tert-butyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-3-chloro- 5-hydroxycycl ohexa-2, 4-dienone, the structural formula is the following formula I. The compound is obtained from a small molecule chemical library by screening tumor cells cultured in vitro, and is further evaluated by an immunodeficiency mouse xenograft tumor model. Experimental results show that the compound can not only significantly inhibit the proliferation of breast cancer cell lines cultured in vitro, but also effectively inhibit the growth of transplanted tumors in mice. Because of its safe, efficient and ideal anticancer effect, it can be tried to be developed as a new type of therapeutic drug against breast cancer, and will have a good application prospect.

Description

A compound for inhibiting proliferation of breast cancer and application thereof

technical field

The invention relates to compounds and applications thereof, in particular to a compound for inhibiting breast cancer proliferation and applications thereof, belonging to the field of biomedicine.

Background technique

Breast cancer is a malignant tumor occurring in the glandular epithelial tissue of the mammary gland, which seriously endangers women's health. The incidence of breast cancer has been increasing year by year in recent years, and the trend of rejuvenation is significant. At present, breast cancer is the cancer with the highest incidence rate in Chinese women. Globally, China accounts for 12.2% of newly diagnosed breast cancer cases and 9.6% of breast cancer deaths. The cause of cancer death ranks sixth. Adjuvant chemotherapy for breast cancer is popular in China, and about 81.4% of all invasive breast cancer patients received adjuvant chemotherapy. Chemotherapy refers to the methods and means of using drugs to treat diseases. Surgery and radiation kill cancer cells in specific areas, while chemotherapy works on the whole body of the body. Chemotherapy kills cancer cells that have spread to other parts of the body. At present, there are as many as thousands of chemotherapeutic drugs under research and on the market, and more than 100 kinds have been used for the treatment of various cancers. These chemotherapy drugs vary in their chemical makeup, how they are used, how well they work against certain cancers, and their side effects. At present, the anti-breast cancer chemotherapeutic drugs that are mainly used clinically have various problems in the treatment process, mainly focusing on: 1. Inhibit the growth of tumors, but the dose used is large, which is likely to cause toxic side effects on the body; 2. For some breast cancers Patients develop drug resistance; 3. The drug has a long cycle of action, and the short-term tumor suppression effect is not good. There are many difficulties in the development of new anti-tumor drugs, and its overall development is facing great challenges. High knock-out rates and drug-resistant suppression are limiting factors for the development of anti-breast cancer drugs. Therefore, it is very urgent to quickly find a new chemotherapy drug, which will have important practical significance for the treatment of breast cancer.

Contents of the invention

In view of this, in order to solve the above problems, a compound that can significantly inhibit the proliferation of breast cancer screened by the present invention is named 6-(4-amino-1-tert-butyl-1H-pyrazolo[3,4-d ]pyrimidin-3-yl)-3-chloro-5-hydroxycycl ohexa-2,4-dienone, the molecular formula is shown in formula I below. The compound can not only inhibit the proliferation of breast cancer cell lines cultured in vitro, but also inhibit the growth of xenograft tumors in mice, suggesting that it has important development and application value in the clinical treatment of breast cancer, and it can be tried to be prepared as an anti-breast cancer cell line. Drugs for treatment.

Description of drawings

In order to make the purpose, technical solutions and advantages of the present invention clearer, the present invention will be described in further detail below in conjunction with the accompanying drawings , wherein:

Figure 1. Detection of the inhibitory effect of the compound on the proliferation of human breast cancer cell lines.

Figure 2. Detection of the compound's inhibitory effect on the growth of transplanted tumor in mice.

detailed description

1) The compound inhibits the proliferation of breast cancer cell lines.

Breast cancer cell lines such as BT20, HS587T, MDA231, T47D and SKBR3 were inoculated into 96-well plates at a density of 10,000 cells per well. After 24 hours, the compounds at concentrations of 1 μM and 5 μM were added respectively, and the same volume of DMSO (the diluent of the compound) was added to the control group, and each treatment group had 16 replicate wells. After 48 hours of treatment, use AQ _ueous single solution cell proliferation detection kit (Promega Company) was used to quantitatively measure the proliferation of cells in each treatment group. This method is simple and easy to operate, and a single reagent can be directly added to the cultured cells containing serum without washing the cells, removing the medium, or performing multiple loading steps. In the cell proliferation assay experiment, add 20μl of medium to each well of 100ul A _Queous One Solution Reagent was then incubated at 37°C in a 5% CO2 cell culture incubator for 4 hours, and then read the absorbance value at 490nm with a microwell plate reader. The experimental results show that the compound can inhibit the proliferation of all breast cancer cell lines detected at a lower concentration (1 μM) ( see Figure 1 , where ** represents p<0.01, representing the results of three independent repeated experiments) .

2) The compound inhibits the growth of human breast cancer cells in mice.

Sixty severe combined immunodeficiency (SCID) female mice weighing 20±2 g were fed for 6-8 weeks. Each mouse was orthotopically inoculated with 1 million SKBR3 human breast cancer cells. After 12 days, when the tumors grew to be visible to the naked eye (about 200mm ³ ), they were randomly divided into 3 groups, 20 in each group. The first group is the control group, and 100 μl of PBS is injected intraperitoneally every other day; the second group is intraperitoneally injected with 100 μl of the compound with a concentration of 2.5 mg/kg body weight every other day; the third group is injected with 100 μl of the compound with a concentration of 5 mg/kg body weight every other day . The injection was continued for 4 weeks according to this method, and the tumor size was measured every 3 days. Four weeks later, the tumor-bearing mice were killed, and the subcutaneous tumor mass was dissected, and the tumor weight was weighed, and the tumor inhibition rate was calculated according to the following formula: tumor inhibition rate (IR) = [tumor weight of the control group (g) - tumor mass of the medication group (g) ]/Tumor weight of the control group (g)×100%. The results show that the compound can significantly inhibit the growth of mouse tumors at two doses of 2.5 mg/kg body weight and 5 mg/kg body weight, and the dose-effect relationship is obvious ( Fig. 2 , A is the tumor of each treatment group). Growth curve; B is the average tumor weight of each treatment group, where * represents 0.01<p<0.05, ** represents p<0.01).

The above descriptions are only preferred embodiments of the present invention, and are not intended to limit the present invention. Obviously, those skilled in the art can make various changes and modifications to the present invention without departing from the spirit and scope of the present invention. Thus, if these modifications and variations of the present invention fall within the scope of the claims of the present invention and their equivalent technologies, the present invention also intends to include these modifications and variations.

Claims (3)

1. have the compound of structure shown in formula I: 2. Use of the compound shown in claim 1 in the preparation of anti-breast cancer drugs. 3. A compound for anti-proliferation of breast cancer, characterized in that: the anti-breast cancer drug is a preparation prepared by adding the compound of claim 1 as an active ingredient and adding a pharmaceutical carrier.