CN106146336A - A kind of compound with anti-breast cancer activity and application thereof - Google Patents

Abstract

The invention discloses a compound with anti-breast cancer activity, its name is methyl2-(4-fluoro-2-hydroxybenzamido)benzoate, and its structural formula is as I. The compound is obtained by screening the tumor cells cultured in vitro in a small molecule chemical library, and further evaluated with a tumor nude mouse xenograft model. In vivo and in vitro tests have shown that the compound has a strong inhibitory effect on the growth and proliferation of breast cancer cells, and can kill tumor cells at a lower concentration, but has no effect on the growth and survival of normal breast cells. 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 has a good application prospect.

Description

A compound with anti-breast cancer activity and application thereof

technical field

The invention relates to compounds and applications thereof, in particular to a compound with anti-breast cancer activity and applications thereof, which belongs to the field of biomedicine.

Background technique

Breast cancer is a major malignant tumor that endangers women's health. It is the type of cancer with the highest incidence rate in Chinese women. Its incidence rate has been increasing year by year in recent years, and the trend of younger age is obvious. It is estimated that by 2030, the incidence of female breast cancer in my country will reach 234,000, and the growth rate of new incidence is twice the world average. The average age of onset is 10-15 years earlier than that of Western countries, and the 5-year survival rate is only 50. %-60%. According to molecular subtype and immunohistochemical characteristics, breast cancer can be divided into 4 types clinically: Luminal A type (ER+/PR+, HER-2-), Luminal B type (ER+/PR+, HER-2+), HER -2+ type (ER-/PR-/HER-2+) and Basal-like type (ER-/PR-/HER-2-). The clinical treatment response and survival period of different molecular subtypes of breast cancer are different, which has attracted more and more clinical attention. At present, the methods used to treat breast cancer mainly include surgery, radiotherapy, and chemotherapy. Among them, surgical treatment has high risks and great trauma to the human body, which reduces the patient's immunity and resistance to disease, and is only suitable for early-stage patients. Radiation therapy has a poor local control effect on tumors, which will kill normal tissues in the irradiated area, and can also cause systemic adverse reactions such as fatigue and nausea, or iatrogenic injuries such as radiation myelitis. Chemotherapy is the most extensive means of treating breast cancer, but there are many thorny problems in traditional anti-breast cancer chemotherapy drugs: 1. Inhibit tumor growth is not significant or can not kill tumor cells; 2. In the inhibition of tumor cell growth or While killing cancer cells, it also has different degrees of toxic and side effects on various types of cells that normally reproduce in the body, and is likely to cause damage to the immune system; 3. It is resistant to certain breast cancer patients; 4. A single drug cannot kill cancer cells at the same time. Dead breast cancer cells of different molecular subtypes. Therefore, it is very urgent to find a new chemotherapeutic 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 with anti-breast cancer activity screened by the present invention is called methyl 2-(4-fluoro-2-hydroxybenzamido)benzoate, and its molecular formula is shown in I. The compound can significantly inhibit the growth and survival of various molecular subtypes of breast cancer cells, and can effectively inhibit the proliferation of tumors in mice, suggesting that it has important development and application value in the clinical treatment of breast cancer, and can be prepared as an anti-mammary gland Drugs for cancer 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 growth and survival inhibitory effect of the compound on human normal breast cell line MCF-10A and breast cancer cell lines of various molecular subtypes.

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

detailed description

1) The compound inhibits the growth and survival of breast cancer cell lines of each molecular subtype.

The normal breast cell line MCF10A and the molecular subtype breast cancer cell lines MDA231, MCF7, T47D and SKBR3 were inoculated into 96-well plates at 10,000 cells per well. The next day, the compound with a concentration of 1 μM and the same volume of PBS (control group) were added, and after 48 hours, the AQ _ueous single solution cell proliferation detection kit (Promega company) quantitatively measures the proliferation of cells in each treatment group; The luminescent cell viability assay kit (Promega) was used to quantify the number of viable cells in each treatment group. Both methods add a single reagent directly to cultured cells containing serum without washing the cells, removing media, or performing multiple loading steps. a) In the cell proliferation assay experiment, add 20μl of medium to each well of 100ul After AQueous One Solution Reagent, incubate at 37°C, 5% CO2 for 4 hours, and then read the absorbance value at 490nm. b) In a cell survival assay, in a 96-well plate, add After the reagents are mixed, they are detected by a luminescence detector within 10 minutes.

The results showed that the compound had no effect on the growth and survival of human normal breast cell line MCF-10A, but had a significant inhibitory effect on the growth and survival of breast cancer cell lines of various molecular subtypes (Figure 1). Wherein Fig. 1A is the detection of the growth inhibitory effect of this compound on human normal breast cell line MCF-10A and each molecular subtype breast cancer cell line; Fig. 1B is the detection of this compound on human normal breast cell line MCF-10A and each molecular subtype breast cancer cell line Detection of the inhibitory effect on the survival of cancer cell lines.

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 inoculated subcutaneously with 1 million MDA231 human breast cancer cells in the right axilla. After 10 days, when the tumor grew to about 200mm ³ , they were randomly divided into 3 groups with 20 rats in each group. The first group was the control group, and 100 μl of PBS was injected intraperitoneally every other day; the second group was injected with 100 μl of the compound at a concentration of 5 mg/kg body weight every other day; the third group was injected with 100 μl of the compound at a concentration of 10 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 sacrificed, 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)-in the tumor 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 tumors in mice at two doses of 5 mg/kg body weight and 10 mg/kg body weight, and the dose-effect relationship is obvious ( FIG. 2 ).

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 equivalent technologies thereof, 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. An anti-breast cancer compound, 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.