CN113368113B - Anti-tumor application of benzothiadiazoloquinazolinone compound - Google Patents
Anti-tumor application of benzothiadiazoloquinazolinone compound Download PDFInfo
- Publication number
- CN113368113B CN113368113B CN202010159877.0A CN202010159877A CN113368113B CN 113368113 B CN113368113 B CN 113368113B CN 202010159877 A CN202010159877 A CN 202010159877A CN 113368113 B CN113368113 B CN 113368113B
- Authority
- CN
- China
- Prior art keywords
- compound
- formula
- colorectal cancer
- benzothiadiazoloquinazolinone
- tumor
- 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.)
- Expired - Fee Related
Links
- 230000000259 anti-tumor effect Effects 0.000 title abstract description 11
- -1 benzothiadiazoloquinazolinone compound Chemical class 0.000 title description 5
- 150000001875 compounds Chemical class 0.000 claims abstract description 19
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 12
- 239000003814 drug Substances 0.000 claims abstract description 10
- 206010006187 Breast cancer Diseases 0.000 claims abstract description 8
- 208000026310 Breast neoplasm Diseases 0.000 claims abstract description 8
- 150000003839 salts Chemical class 0.000 claims description 2
- 206010052360 Colorectal adenocarcinoma Diseases 0.000 claims 1
- 206010009944 Colon cancer Diseases 0.000 abstract description 15
- 208000001333 Colorectal Neoplasms Diseases 0.000 abstract description 15
- 230000012010 growth Effects 0.000 abstract description 4
- 230000002401 inhibitory effect Effects 0.000 abstract description 4
- OAVCWZUKQIEFGG-UHFFFAOYSA-O 2-(5-methyl-2H-tetrazol-1-ium-1-yl)-1,3-thiazole Chemical compound CC1=NN=N[NH+]1C1=NC=CS1 OAVCWZUKQIEFGG-UHFFFAOYSA-O 0.000 abstract 1
- 230000000118 anti-neoplastic effect Effects 0.000 abstract 1
- 238000011156 evaluation Methods 0.000 abstract 1
- 238000000338 in vitro Methods 0.000 abstract 1
- 210000004027 cell Anatomy 0.000 description 22
- 230000000694 effects Effects 0.000 description 11
- 239000002246 antineoplastic agent Substances 0.000 description 7
- 229940041181 antineoplastic drug Drugs 0.000 description 7
- 201000011510 cancer Diseases 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- 230000005764 inhibitory process Effects 0.000 description 6
- 210000004881 tumor cell Anatomy 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
- MKGXBJZWDOJJLD-UHFFFAOYSA-N O=S1N=NC2=C1C=CC1=C2C=CC2=C1N=CN=C2 Chemical group O=S1N=NC2=C1C=CC1=C2C=CC2=C1N=CN=C2 MKGXBJZWDOJJLD-UHFFFAOYSA-N 0.000 description 3
- 102000054896 human PML Human genes 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 238000002835 absorbance Methods 0.000 description 2
- 230000034994 death Effects 0.000 description 2
- 231100000517 death Toxicity 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000012827 research and development Methods 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 230000001133 acceleration Effects 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 230000003698 anagen phase Effects 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 239000000824 cytostatic agent Substances 0.000 description 1
- 230000001085 cytostatic effect Effects 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000012091 fetal bovine serum Substances 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
- 231100000053 low toxicity Toxicity 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
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
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with 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
Abstract
The invention relates to the technical field of antitumor medicine. In particular, the invention relates to the application of the compound with the structure of formula I in antitumor activity. According to the invention, the compound shown in the structure of the formula I is found to have a remarkable inhibiting effect on the growth of human colorectal cancer HCT116 and human breast cancer cell MCF-7 through in vitro MTT (methyl thiazolyl tetrazolium) antitumor activity evaluation. The compound with the structure shown in the formula I is disclosed for the first time in antineoplastic activity, can be used for preparing medicaments for resisting colorectal cancer and other tumors, and has good development and application prospects. Formula I
Description
Technical Field
The invention relates to a compound with an anti-tumor effect and anti-tumor activity thereof, belonging to the field of anti-tumor related medicines.
Background
Cancer is one of the diseases which have the greatest harm to human life health, according to statistics, the total number of cancer deaths in the world reaches 700 million people every year, more than 100 million people who die from tumors in China every year, the tumor morbidity and mortality also rise with the increase of population number and the acceleration of population aging, and the research and development of anti-cancer drugs are the first cause of death of urban population.
At present, for most cancer patients, clinically existing antitumor drugs have certain curative effect but have high cytotoxicity, and can inhibit the growth of normal cells of normal organisms to generate side effects while inhibiting cancer cells, and some side effects are even stronger than the curative effect. In addition, medical technology only improves the treatment effect of early cancer in recent years, and no ideal treatment medicine is available for the advanced cancer. Therefore, the research and development of high-efficiency low-toxicity high-targeting antitumor drugs is a problem to be solved urgently at present. The invention discloses the antitumor activity of a compound, and the compound can inhibit colorectal cancer cells (HCT116) and human breast cancer cells MCF-7 for the first time, but is not limited to the two tumor cells, the inhibition on HCT116 is most obvious, and the compound has great significance for developing novel antitumor drugs and tumor treatment.
Disclosure of Invention
The invention relates to an application of a benzothiadiazoloquinazolinone compound in preparation of an anti-tumor drug.
The invention aims to provide a compound with a benzothiadiazoloquinazolinone structure. The compound can effectively inhibit colorectal cancer tumor cells HCT116 and human breast cancer cells MCF-7, but is not limited to the two cells.
The invention also aims to provide the antitumor and antitumor application of the pharmaceutically acceptable salt of the compound with the benzothiadiazoloquinazolinone structure.
The above object of the present invention is achieved by the following technical solutions:
the invention provides a compound with a benzothiadiazoloquinazolinone structure, which has the following structure shown in 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 compound in inhibiting colorectal cancer cells and breast cancer cells, but not limited to colorectal cancer tumor cells, is disclosed for the first time, and has a remarkable inhibiting effect on colorectal cancer (HCT116), so that a new choice is provided 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 of different tumor cell lines with compound (30. mu.M).
Detailed Description
The MTT method is adopted to evaluate the growth inhibition of the benzothiadiazoloquinazolinone compound human colorectal cancer cell strain provided by the invention.
Methods cells in logarithmic growth phase, human colorectal cancer cell line HCT116, human breast cancer cell MCF7 and human promyelocytic leukemia cell (HL60) (ATCC, Manassas, Va., USA) at 1.5X 105The concentrations were plated in 96-well plates. The original culture is sucked off after the cell culture is carried out for 24 hours and the wall is attachedAnd (5) nutrient base. 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 culture medium containing a test compound at a drug concentration of 30. mu.M. After 48h incubation, MTT was added at a concentration of 5mg/mL and CO was added2The culture was incubated for 4 hours in an incubator, 100. mu.L of the supernatant was aspirated along the upper part of the culture, 100. mu.L of DMSO was added, the culture was left in the dark for 10 min, absorbance (wavelength 490nmHCT116 and MCF7, 570nmHL60) was measured using a microplate reader (product of Sunrise), and cell survival was calculated from the absorbance, and 6 replicate wells were provided for each treatment. Cytostatic (%) = (1-AOD drug treatment/AOD blank) × 100.
The result shows that the benzothiadiazoloquinazolinone compound provided by the invention has different degrees of inhibition effects on the growth of human colorectal cancer cell strain HCT116, breast cancer cell MCF7 and human promyelocytic leukemia cell (HL60), and the inhibition rates at 30 mu M are respectively 44.25%, 58.96% and 22.80%. The human colorectal cancer cell strain HCT116 is most remarkably inhibited.
The examples show that the compound has good inhibition effect on the growth of human colorectal cancer cell strain HCT 116. Therefore, the compound disclosed by the invention 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 (1)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202010159877.0A CN113368113B (en) | 2020-03-10 | 2020-03-10 | Anti-tumor application of benzothiadiazoloquinazolinone compound |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202010159877.0A CN113368113B (en) | 2020-03-10 | 2020-03-10 | Anti-tumor application of benzothiadiazoloquinazolinone compound |
Publications (2)
Publication Number | Publication Date |
---|---|
CN113368113A CN113368113A (en) | 2021-09-10 |
CN113368113B true CN113368113B (en) | 2022-04-22 |
Family
ID=77568644
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202010159877.0A Expired - Fee Related CN113368113B (en) | 2020-03-10 | 2020-03-10 | Anti-tumor application of benzothiadiazoloquinazolinone compound |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN113368113B (en) |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN103127091A (en) * | 2012-10-25 | 2013-06-05 | 吴俊华 | Application of Aphanamixoid A in medicines curing colorectal cancer |
WO2013123071A1 (en) * | 2012-02-13 | 2013-08-22 | Cleave Biosciences, Inc. | Methods and compositions for jamm protease inhibition |
CN103405424A (en) * | 2013-08-29 | 2013-11-27 | 南京大学 | Application of Chukrasone B in medicine for treating colorectal cancer |
CN103405418A (en) * | 2013-08-29 | 2013-11-27 | 南京大学 | Application of Chukrasone B in medicine for treating breast cancer |
CN103463046A (en) * | 2013-09-23 | 2013-12-25 | 南京广康协生物医药技术有限公司 | Application of Lycojaponicumin A in drugs for treating colorectal cancer |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1763345A2 (en) * | 2004-06-18 | 2007-03-21 | GPC Biotech Inc. | Kinase inhibitors for treating cancers |
-
2020
- 2020-03-10 CN CN202010159877.0A patent/CN113368113B/en not_active Expired - Fee Related
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2013123071A1 (en) * | 2012-02-13 | 2013-08-22 | Cleave Biosciences, Inc. | Methods and compositions for jamm protease inhibition |
CN103127091A (en) * | 2012-10-25 | 2013-06-05 | 吴俊华 | Application of Aphanamixoid A in medicines curing colorectal cancer |
CN103405424A (en) * | 2013-08-29 | 2013-11-27 | 南京大学 | Application of Chukrasone B in medicine for treating colorectal cancer |
CN103405418A (en) * | 2013-08-29 | 2013-11-27 | 南京大学 | Application of Chukrasone B in medicine for treating breast cancer |
CN103463046A (en) * | 2013-09-23 | 2013-12-25 | 南京广康协生物医药技术有限公司 | Application of Lycojaponicumin A in drugs for treating colorectal cancer |
Also Published As
Publication number | Publication date |
---|---|
CN113368113A (en) | 2021-09-10 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN113368113B (en) | Anti-tumor application of benzothiadiazoloquinazolinone compound | |
CN113368111B (en) | Anti-tumor effect of phenazine carboxylic acid compounds | |
CN113368114B (en) | Antitumor application of morpholine pyrimidine compounds | |
CN115531380A (en) | Application of fluoropyridoxine in preparation of anti-cancer drugs | |
CN113735909B (en) | Lindqvist-type tungsten vanadate trimethylolethane derivative and preparation method and application thereof | |
CN111329855B (en) | Application of 12 alpha-methoxy-germacrane-triene-12, 6 alpha-acetal in resisting human breast cancer | |
CN102885806B (en) | Application of Aphanamixoid A in preparation of drug for treating laryngeal cancers | |
CN104230997A (en) | Platinum (II) complex, and preparation method, medicament composition and applications of platinum (II) complex | |
CN102872111B (en) | Application of Houttuynoid C in medicament for treating pancreatic cancer | |
CN102885843B (en) | Application of Houttuynoid B in medicament for treating breast cancer | |
CN102861079B (en) | Application of Houttuynoid B in medicine for treating skin cancer | |
CN116726001A (en) | Application of ophiopogon japonicus homoisoflavone A in preparing antitumor drugs and chemotherapeutic drug sensitizers | |
CN103463046A (en) | Application of Lycojaponicumin A in drugs for treating colorectal cancer | |
CN112704683A (en) | Novel camptothecin derivative and application thereof in preparing antitumor drugs | |
CN105596334A (en) | Application of Leuconoxine in preparation of medicine for treating breast cancer | |
CN103463065A (en) | Application of Lycojaponicumin C in preparation of medicines for treating skin cancer | |
CN106389423A (en) | Application of Ternatusine A in preparing medicines for treating endometrial cancer | |
CN103463044A (en) | Application of Lycojaponicumin A in drugs for treating skin cancer | |
CN103393645A (en) | Application of Sarcaboside B to medicament for treatment of skin cancer | |
CN103393653A (en) | Application of Sarcaboside B to medicament for treatment of carcinoma of bile duct | |
CN103463050A (en) | Application of Lycojaponicumin A in medicine for treating gastric cancer | |
CN103479630A (en) | Application of Lycojaponicumin A in preparation of drugs for treating breast cancer | |
CN103393644A (en) | Application of Sarcaboside A to preparation of medicament for treatment of ileocecum cancer | |
CN103462969A (en) | Application of Incarviatone A in medicaments for treating breast cancer | |
CN103446128A (en) | Application of Lycojaponicumin B in skin cancer treatment drug |
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 | ||
GR01 | Patent grant | ||
GR01 | Patent grant | ||
CF01 | Termination of patent right due to non-payment of annual fee | ||
CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20220422 |