CN113368111A - Anti-tumor effect of phenazine carboxylic acid compounds - Google Patents
Anti-tumor effect of phenazine carboxylic acid compounds Download PDFInfo
- Publication number
- CN113368111A CN113368111A CN202010159876.6A CN202010159876A CN113368111A CN 113368111 A CN113368111 A CN 113368111A CN 202010159876 A CN202010159876 A CN 202010159876A CN 113368111 A CN113368111 A CN 113368111A
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- Prior art keywords
- compound
- carboxylic acid
- cells
- tumor
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- 230000000259 anti-tumor effect Effects 0.000 title claims abstract description 9
- JGCSKOVQDXEQHI-UHFFFAOYSA-N phenazine-1-carboxylic acid Chemical class C1=CC=C2N=C3C(C(=O)O)=CC=CC3=NC2=C1 JGCSKOVQDXEQHI-UHFFFAOYSA-N 0.000 title description 13
- 210000004027 cell Anatomy 0.000 claims abstract description 22
- 241000282414 Homo sapiens Species 0.000 claims abstract description 18
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 13
- 150000001875 compounds Chemical class 0.000 claims abstract description 13
- 239000003814 drug Substances 0.000 claims abstract description 12
- 230000005764 inhibitory process Effects 0.000 claims abstract description 8
- 206010006187 Breast cancer Diseases 0.000 claims abstract description 7
- 208000026310 Breast neoplasm Diseases 0.000 claims abstract description 7
- 210000004881 tumor cell Anatomy 0.000 claims abstract description 7
- 229940079593 drug Drugs 0.000 claims description 7
- 150000003839 salts Chemical class 0.000 claims description 2
- 206010052360 Colorectal adenocarcinoma Diseases 0.000 claims 2
- 239000003937 drug carrier Substances 0.000 claims 1
- 239000000203 mixture Substances 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 206010009944 Colon cancer Diseases 0.000 abstract description 14
- 208000001333 Colorectal Neoplasms Diseases 0.000 abstract description 14
- 230000000694 effects Effects 0.000 abstract description 9
- 238000000034 method Methods 0.000 abstract description 5
- 239000002246 antineoplastic agent Substances 0.000 abstract description 4
- 229940041181 antineoplastic drug Drugs 0.000 abstract description 4
- 230000035755 proliferation Effects 0.000 abstract description 2
- 230000001093 anti-cancer Effects 0.000 abstract 1
- -1 phenazine carboxylic acid compound Chemical class 0.000 description 7
- 230000002401 inhibitory effect Effects 0.000 description 5
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 101000573199 Homo sapiens Protein PML Proteins 0.000 description 3
- 201000011510 cancer Diseases 0.000 description 3
- 102000054896 human PML Human genes 0.000 description 3
- 238000002835 absorbance Methods 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 230000003698 anagen phase Effects 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 239000000824 cytostatic agent Substances 0.000 description 1
- 230000001085 cytostatic effect Effects 0.000 description 1
- 239000012091 fetal bovine serum Substances 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 230000009036 growth inhibition Effects 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 229940126585 therapeutic drug Drugs 0.000 description 1
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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
- A61K31/498—Pyrazines or piperazines ortho- and peri-condensed with carbocyclic ring systems, e.g. quinoxaline, phenazine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Hematology (AREA)
- Oncology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention belongs to the technical field of antitumor medicine, and particularly relates to an application of an antitumor compound shown as a formula I, namely dibenzo [ a, c ]]Application of phenazine-11-carboxylic acid in antitumor drugs. The MTT method is adopted to test the inhibition effect of the compound on human colorectal cancer cells HCT-115 and human breast cancer cells MCF-7. Experiments prove that the compound of the invention has obvious proliferation inhibition effect on the two tumor cells, thereby providing a new choice for treating related tumors. The compound has simple structure and good activity, can be used as a leading compound of an anti-cancer medicament, and has good application prospect. Formula I
Description
Technical Field
The invention relates to the field of anti-tumor related medicaments. In particular to a phenazine carboxylic acid compound and application thereof in preparing an anti-tumor medicament, which provide a basis for developing medicaments for preventing and treating tumors.
Background
Cancer is the second leading factor of human death in China, is second to cardiovascular diseases, although the average life of human beings is prolonged, the threat of malignant tumor to human beings is increasingly prominent, and with the change of disease spectrum, tumor becomes one of the common causes of death at present. The morbidity and mortality of tumors in China are in a remarkable rising trend, the mortality of cancers is increased at present, and if the mortality is not controlled, the psychological burden of life of people is increased, and a layer of shadow is formed in the beautiful life. Small molecule chemical drugs are one of the most important methods for treating tumors. In order to overcome diseases such as cancer, which seriously harm human health, people continuously develop new therapeutic drugs.
The invention discloses a phenazine carboxylic acid compound for the first time, which can be used for inhibiting colorectal cancer cells (HCT116) and human breast cancer cells MCF-7 in a targeted manner, particularly has the most obvious inhibition effect on HCT116, and has great significance for developing novel antitumor drugs and tumor treatment.
Disclosure of Invention
The invention relates to an anti-tumor application of a novel phenazine carboxylic acid compound.
An object of the present invention is to provide phenazine carboxylic acids having a tumor-inhibiting effect, which are effective in inhibiting HCT116 colorectal cancer tumor cells and MCF-7 cells, but not limited to the above tumor cells.
The invention also aims to provide the anti-tumor application of the phenazine carboxylic acid compounds in pharmaceutically acceptable salts.
The above object of the present invention is achieved by the following technical solutions:
the invention provides a phenazine carboxylic acid compound, which has a structure shown in the following formula (I):
formula I
。
Experiments prove that the MTT method is adopted to test the inhibition effect of the compound on human colorectal cancer cells HCT-116, human breast cancer cells MCF-7 and human promyelocytic leukemia cells (HL60), and the experiments prove that the compound has the proliferation inhibition effect on the three tumor cells. Compared with other anti-tumor drugs reported in literatures, the anti-tumor drug has the advantages of simplicity, easy obtainment and obvious activity.
The application of the novel compound in inhibiting colorectal cancer cells, but not limited to colorectal cancer tumor cells, is disclosed for the first time, and because the skeleton type belongs to a brand new skeleton type, the possibility that other compounds give any revelation does not exist, the novel compound has prominent substantive characteristics, and the novel compound has obvious inhibition on colorectal cancer (HCT116), thereby providing a new choice for treating related tumors.
The present invention will be described in further detail with reference to the following examples, but the scope of the present invention is not limited to the specific examples, but is defined by the claims.
Drawings
FIG. 1 survival rates of different tumor cell lines in phenazine carboxylates (30. mu.M).
Detailed Description
The growth inhibition of the phenazine carboxylic acid compound human colorectal cancer cell line provided by the invention is evaluated by adopting an MTT method.
Method for the growth of cells in logarithmic growth phase, human colorectal cancer cell line HCT116 and human breast cancer cell MCF7 human promyelocytic leukemia cell (HL60) (ATCC, Manassas, Va., USA) at a rate of 1.5X 105One was inoculated in a 96-well plate. The original culture medium is aspirated after 24 h of cell culture adherence. The test is divided into a blank control group and a drug treatment group. The blank group was replaced with 1640 culture containing 10% fetal bovine serum, and the drug treatment group was replaced with 30. mu.M drug concentration. After 48h incubation, MTT was added at a concentration of 5mg/mL and CO was added2The culture was incubated in an incubator for 4 hours, 100 uL of the supernatant was aspirated along the upper part of the culture, 100 uL of DMSO was added, the culture was left in the dark for 10 min, absorbance values (wavelengths 490nm HCT116 and MCF7, 570nm HL60) were measured using a microplate reader (product of Sunrise), and cell survival was calculated from the absorbance values, and 6 replicate wells were provided for each treatment. Cytostatic (%) = (1-AOD drug treatment/AOD white control) × 100.
As a result, the IC50 of the phenazine carboxylic acid compound provided by the invention at 30 mu M for human breast cancer cells MCF-7 and human promyelocytic leukemia cells (HL60) human colorectal cancer cell strain HCT116 is 22.52%, 14.04% and 63.24% respectively. Of these, the inhibitory effect on colorectal cancer cells is most pronounced.
The examples show that the phenazine carboxylic acid compounds have good inhibition effect on the growth of human colorectal cancer cell strain HCT 116. Therefore, the phenazine carboxylic acid compound has the anti-colorectal cancer activity and can be used for preparing anti-colorectal cancer medicines.
The present invention is further described in detail by the examples, but the scope of the present invention is not limited by the examples, but is defined by the claims.
Claims (4)
1. The compound with the structural formula shown as formula 1 or pharmaceutically acceptable salt thereof and a preparation formed by the compound are characterized by application in preparing a product for treating tumors
Formula I
。
2. Use according to claim 1, characterized in that: the tumor comprises human colorectal adenocarcinoma cells and breast cancer cells, but is not limited to the tumor cells.
3. The use of claim 1, wherein the composition is a pharmaceutical composition for clinical use in combination with other related drugs and combinations, or a combination with a pharmaceutically acceptable carrier.
4. Use according to claim 1, characterized in that: has certain antitumor activity, and the inhibition rate of human breast cancer MCF-7 and human colorectal adenocarcinoma HCT116 cells reaches a significant level (p < 0.05).
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010159876.6A CN113368111B (en) | 2020-03-10 | 2020-03-10 | Anti-tumor effect of phenazine carboxylic acid compounds |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010159876.6A CN113368111B (en) | 2020-03-10 | 2020-03-10 | Anti-tumor effect of phenazine carboxylic acid compounds |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN113368111A true CN113368111A (en) | 2021-09-10 |
| CN113368111B CN113368111B (en) | 2022-04-22 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202010159876.6A Expired - Fee Related CN113368111B (en) | 2020-03-10 | 2020-03-10 | Anti-tumor effect of phenazine carboxylic acid compounds |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN113368111B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114558013A (en) * | 2022-03-28 | 2022-05-31 | 中国药科大学 | Application of phenazine derivative in preparation of medicine for weakening mammary cancer stem cell dryness by triggering iron death specificity |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008083346A1 (en) * | 2006-12-28 | 2008-07-10 | Ambrx, Inc. | Phenazine and quinoxaline substituted amino acids and polypeptides |
| US20140080824A1 (en) * | 2010-10-21 | 2014-03-20 | New York University | Structure-guided identification of binding interactions of human laminin receptor precursor with laminin and identification of compounds that affect binding |
-
2020
- 2020-03-10 CN CN202010159876.6A patent/CN113368111B/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008083346A1 (en) * | 2006-12-28 | 2008-07-10 | Ambrx, Inc. | Phenazine and quinoxaline substituted amino acids and polypeptides |
| US20140080824A1 (en) * | 2010-10-21 | 2014-03-20 | New York University | Structure-guided identification of binding interactions of human laminin receptor precursor with laminin and identification of compounds that affect binding |
Non-Patent Citations (2)
| Title |
|---|
| DERYA AKAR等: "Syntheis and Antitumor activity of some 6-chloro-and 6,7-dichloro-2,3-sisubsitituted-quinoxaline derivatives", 《TURKISH JOURNAL OF PHARMACEUTICAL SCIENCES》 * |
| HABIBA GU EDOUAR等: "Synthesis and characterization of phenanthrene derivatives with anticancer property against human colon and epithelial cancer cell lines", 《COMPTES RENDUS CHIMIE》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114558013A (en) * | 2022-03-28 | 2022-05-31 | 中国药科大学 | Application of phenazine derivative in preparation of medicine for weakening mammary cancer stem cell dryness by triggering iron death specificity |
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| Publication number | Publication date |
|---|---|
| CN113368111B (en) | 2022-04-22 |
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Granted publication date: 20220422 |