CN112237581B - Application of ligustrazine derivative in preparation of medicine for treating breast cancer - Google Patents
Application of ligustrazine derivative in preparation of medicine for treating breast cancer Download PDFInfo
- Publication number
- CN112237581B CN112237581B CN202011234669.9A CN202011234669A CN112237581B CN 112237581 B CN112237581 B CN 112237581B CN 202011234669 A CN202011234669 A CN 202011234669A CN 112237581 B CN112237581 B CN 112237581B
- Authority
- CN
- China
- Prior art keywords
- ligustrazine
- breast cancer
- medicine
- derivative
- treating breast
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/4965—Non-condensed pyrazines
- A61K31/497—Non-condensed pyrazines containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Landscapes
- Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses an application of a ligustrazine derivative in preparing a medicine for treating breast cancer. The research of the invention finds that the inhibitory activity of the ligustrazine derivative 4- (3-sulfo-3H-1, 2-dithiol-5-yl) phenyl-3, 5, 6-trimethyl pyrazine-2-hexahydrophthalic acid ester on breast cancer MCF-7 cells is obviously better than that of ligustrazine, and the ligustrazine derivative has a prospect of being developed into a medicine for treating breast cancer.
Description
Technical Field
The invention belongs to the field of medicines, and particularly relates to application of a ligustrazine derivative in preparation of a medicine for treating breast cancer.
Background
Ligustrazine (Ligustrazine) is a pharmaceutical compound, has effects of resisting platelet aggregation, dilating arteriole, improving microcirculation and cerebral blood flow, and can be used for treating occlusive vascular diseases, cerebral thrombosis, angiitis, coronary heart disease, angina pectoris, etc.
The chemical structural formula of ligustrazine is as follows.
Studies have shown that ligustrazine also has a variety of pharmacological activities, such as anti-tumor activity. The whole-taking research of the von chuanxiongzine shows that the chuanxiongzine has a therapeutic effect on various cancers such as liver cancer, breast cancer and the like (a doctor academic paper of Nanjing university of traditional Chinese medicine, 2015). Wangzhiting et al found that ligustrazine has effects of inhibiting proliferation and inducing apoptosis on leukemia U937 cells, and the mechanism of ligustrazine may be to influence cell cycle distribution, to down-regulate Bcl-2 expression, to finally activate Caspase-3, to initiate apoptosis pathway, to induce apoptosis (Wangzhiting et al, research on the effects and mechanism of ligustrazine on proliferation and apoptosis of leukemia U937 cells, J.Med. 2015 6 months). However, ligustrazine has good inhibitory activity only on few tumors, and has a general inhibitory effect on most tumors.
The abundant chemical derivatives provide a huge compound library for drug screening and development. 4- (3-thio-3H-1, 2-dithiol-5-yl) phenyl-3, 5, 6-trimethylpyrazine-2-phthalate (compound I-2) and 4- (3-thio-3H-1, 2-dithiol-5-yl) phenyl-3, 5, 6-trimethylpyrazine-2-hexahydrophthalate (compound I-4) are 2 kinds of ligustrazine derivatives disclosed in the literature (Chinese patent, publication No. CN111825664A), and no report on antitumor activity thereof has been found at present.
The structural formulas of the compound I-2 and the compound I-4 are shown as follows.
Disclosure of Invention
The invention aims to improve the prior art and provides the application of the ligustrazine derivative in preparing the medicine for treating breast cancer.
The technical scheme is as follows:
the application of ligustrazine derivative in preparing medicine for treating breast cancer is 4- (3-sulfo-3H-1, 2-dithiole-5-yl) phenyl-3, 5, 6-trimethyl pyrazine-2-hexahydro phthalate and has the following chemical structural formula.
A medicinal preparation for treating breast cancer contains ligustrazine derivative as active ingredient.
The technical effects are as follows:
according to the invention, through experimental research, the inhibition activity of the ligustrazine derivative 4- (3-sulfo-3H-1, 2-dithiol-5-yl) phenyl-3, 5, 6-trimethyl pyrazine-2-hexahydrophthalic acid ester on breast cancer MCF-7 cells is obviously superior to that of ligustrazine, and the ligustrazine derivative has a prospect of being developed into a medicine for treating breast cancer.
Drawings
FIG. 1 shows the half inhibitory concentration (. mu.g/mL) of each drug against leukemia cells.
FIG. 2 shows the half inhibitory concentration (. mu.g/mL) of each drug against breast cancer cells.
Detailed Description
The following description and drawings are included to describe the general nature of the invention, and are not intended to limit the scope of the invention.
First, test materials
Leukemia U937 cells and breast cancer MCF-7 cells were purchased from ATCC.
Fetal bovine serum, RPMI 1640 medium was purchased from Thermo Fisher Scientific.
CCK-8 reagent was purchased from Homophilus Japan.
The purities of the ligustrazine, the 4- (3-sulfo-3H-1, 2-dithiol-5-yl) phenyl-3, 5, 6-trimethyl pyrazine-2-phthalic acid ester (compound I-2) and the 4- (3-sulfo-3H-1, 2-dithiol-5-yl) phenyl-3, 5, 6-trimethyl pyrazine-2-hexahydrophthalic acid ester (compound I-4) are not less than 98%.
Second, test method
1. Cell culture
Leukemia U937 cells and breast cancer MCF-7 cells were cultured in RPMI 1640 containing 10% fetal bovine serum at 37 deg.C and 5% CO 2 Culturing under saturated humidity condition. Cells in the logarithmic growth phase were taken for the experiment.
2. CCK-8 method for measuring tumor cell proliferation
Taking tumor cells in logarithmic growth phase, digesting with pancreatin, and preparing with total culture medium to obtain the final product with concentration of 5 × 10 4 Cell suspension per mL, seeded in 96-well plates at 100 μ L per well. The test is divided into a drug group, a negative control group and a positive control group, and each group (or each drug concentration) is provided with 3 multiple wells. After 24h of culture, the drug groups replaced the original culture medium with 100. mu.L of culture medium containing compound I-2 or compound I-4 at different concentrations, the positive control group replaced the original culture medium with 100. mu.L of culture medium containing ligustrazine at different concentrations, and the negative control group replaced the original culture medium with 100. mu.L of fresh complete culture medium. Continuing culturing for 48h, adding 10 μ L of CCK-8 reagent into each well, continuing incubating for 3h, measuring absorbance (OD value) of each well at 450nm wavelength with microplate reader, calculating inhibition rate of drug with different concentrations on tumor cells according to formula, and calculating half Inhibition Concentration (IC) with Graphpad Prism 6.0 software 50 ). Inhibition rate (1-drug group or positive control OD value/negative control OD value) × 100%.
3. Statistical method
Data are expressed in x + -s, and the comparison among groups is carried out by adopting one-way anova, and P is less than 0.05, thus having statistical significance.
Third, test results
The results are shown in Table 1 and figures 1 and 2, the inhibitory activity of the compound I-2 on leukemia U937 cells is obviously better than that of ligustrazine, but the inhibitory activity on breast cancer MCF-7 cells is weaker; the compound I-4 has obviously better inhibitory activity on breast cancer MCF-7 cells than ligustrazine, but has weaker inhibitory activity on leukemia U937 cells.
TABLE 1 half inhibitory concentration (μ g/mL) of each drug on tumor cells
Therefore, 4- (3-thio-3H-1, 2-dithiolan-5-yl) phenyl-3, 5, 6-trimethylpyrazine-2-phthalate (compound I-2) has a prospect of being developed into an anti-leukemia drug, and 4- (3-thio-3H-1, 2-dithiolan-5-yl) phenyl-3, 5, 6-trimethylpyrazine-2-hexahydrophthalate (compound I-4) has a prospect of being developed into an anti-breast cancer drug.
The above-mentioned embodiments and the accompanying drawings are used to specifically describe the material of the present invention, but should not be construed as limiting the scope of the present invention.
Claims (1)
1. The application of a ligustrazine derivative in preparing a medicine for treating breast cancer is disclosed, wherein the ligustrazine derivative is 4- (3-sulfo-3H-1, 2-dithiole-5-yl) phenyl-3, 5, 6-trimethyl pyrazine-2-hexahydrophthalic acid ester, and the chemical structural formula is as follows:
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011234669.9A CN112237581B (en) | 2020-11-07 | 2020-11-07 | Application of ligustrazine derivative in preparation of medicine for treating breast cancer |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011234669.9A CN112237581B (en) | 2020-11-07 | 2020-11-07 | Application of ligustrazine derivative in preparation of medicine for treating breast cancer |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN112237581A CN112237581A (en) | 2021-01-19 |
| CN112237581B true CN112237581B (en) | 2022-08-09 |
Family
ID=74170070
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202011234669.9A Active CN112237581B (en) | 2020-11-07 | 2020-11-07 | Application of ligustrazine derivative in preparation of medicine for treating breast cancer |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN112237581B (en) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111825664A (en) * | 2020-08-01 | 2020-10-27 | 泰州学院 | Ligustrazine derivative, preparation method and medical application |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110483419B (en) * | 2019-09-11 | 2022-11-29 | 泰州学院 | Ligustrazine/azonium dialkoxide derivative, preparation method and application thereof |
-
2020
- 2020-11-07 CN CN202011234669.9A patent/CN112237581B/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111825664A (en) * | 2020-08-01 | 2020-10-27 | 泰州学院 | Ligustrazine derivative, preparation method and medical application |
Non-Patent Citations (1)
| Title |
|---|
| 石斛对乳腺癌抑制作用的研究进展及临床应用;郑喆文等;《安徽医科大学学报》;20171016;第52卷(第12期);第1893-1896页，尤其是第1893页右栏第1行、第1894页左栏1.4 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN112237581A (en) | 2021-01-19 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Wei et al. | Marine compounds targeting the PI3K/Akt signaling pathway in cancer therapy | |
| CN102234259B (en) | Sphaelactone derivatives, their pharmaceutical compositions, preparation method thereof and application thereof | |
| CN108358973B (en) | Naphthalimide tetravalent platinum compound, preparation method and application thereof in preparation of antitumor drugs | |
| CN104151391B (en) | A kind of oleanolic acid derivate with antitumor action and its production and use | |
| CN104367584A (en) | Application of doxycycline in preparation of antitumor drugs | |
| CN112237581B (en) | Application of ligustrazine derivative in preparation of medicine for treating breast cancer | |
| Baguley | Tumor stem cell niches: a new functional framework for the action of anticancer drugs | |
| CN112190584B (en) | Application of ligustrazine derivative in preparation of anti-leukemia drugs | |
| CN110882238A (en) | Application of morin N in preparation of antitumor drugs | |
| CN102531875B (en) | 3-Oxo-1,2-naphthoquinone analogues, preparation method and application thereof | |
| CN112245425B (en) | Application of isoindolinone compounds in preparation of antitumor drugs | |
| EP1686122B1 (en) | Antitumor agent | |
| CN106674323B (en) | Pentacyclic triterpenoid and application thereof with ACC1 protein regulation effect | |
| CN114805470A (en) | Pennogenin-arginine derivative, preparation method thereof and application thereof in preparing non-small cell lung cancer resistant medicine | |
| CN107412736B (en) | Anti-tumor combined medicine and application thereof in preparing anti-cancer medicine | |
| CN115634224B (en) | Application of TERPESTACIN derivative in preparation of medicine for treating brain glioma | |
| CN113788822B (en) | Novel naringenin pyrimidine hydrazone derivative and preparation method and application thereof | |
| CN109498624B (en) | Anticancer medical application of thiazoline derivative | |
| CN115252611B (en) | Amide compound, application thereof and anti-tumor pharmaceutical composition | |
| CN109432095B (en) | Medical application of thiazoline derivative | |
| CN113582863B (en) | Aminoethyl biphenyl compound and preparation method and application thereof | |
| CN115957204B (en) | Application of diphenyl sulfide compound in preparation of antitumor drugs | |
| CN110218174B (en) | Compound and preparation method and application thereof | |
| CN113929669B (en) | Novel hesperetin pyrimidine hydrazone derivative as well as preparation method and application thereof | |
| CN113797191B (en) | Application of compound in treating vascular proliferation related diseases and resisting tumors |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| TA01 | Transfer of patent application right |
Effective date of registration: 20220714 Address after: 311202 room 3201, unit 1, building 12, Biyun Tianyuan, Hubin garden, Beigan street, Xiaoshan District, Hangzhou, Zhejiang Province Applicant after: Han Huijing Address before: 223001 Huai'an Medical Industrial Park, 128 Meigao West Road, Qingpu Industrial Park, Huai'an City, Jiangsu Province Applicant before: Huaian taikairui Pharmaceutical Technology Co.,Ltd. |
|
| TA01 | Transfer of patent application right | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |