CN107235947A - The ketone new compound of one class 5,7 pairs hydroxyl 6,8 pairs (1 methyl piperazine) 4H chromenes 4 and its anticancer usage - Google Patents
The ketone new compound of one class 5,7 pairs hydroxyl 6,8 pairs (1 methyl piperazine) 4H chromenes 4 and its anticancer usage Download PDFInfo
- Publication number
- CN107235947A CN107235947A CN201710541722.1A CN201710541722A CN107235947A CN 107235947 A CN107235947 A CN 107235947A CN 201710541722 A CN201710541722 A CN 201710541722A CN 107235947 A CN107235947 A CN 107235947A
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- China
- Prior art keywords
- pairs
- class
- compound
- hydroxyl
- chromenes
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 18
- 125000002887 hydroxy group Chemical group [H]O* 0.000 title claims abstract description 7
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 title claims abstract description 6
- JCIDEANDDNSHQC-UHFFFAOYSA-N 4H-chromene Chemical class C1=CC=C2CC=COC2=C1 JCIDEANDDNSHQC-UHFFFAOYSA-N 0.000 title abstract 2
- 230000001093 anti-cancer Effects 0.000 title description 2
- 150000002576 ketones Chemical class 0.000 title 1
- 230000000118 anti-neoplastic effect Effects 0.000 claims abstract description 4
- -1 ketone compounds Chemical class 0.000 claims abstract 4
- 125000003282 alkyl amino group Chemical group 0.000 claims 2
- 125000000217 alkyl group Chemical group 0.000 claims 2
- 125000003118 aryl group Chemical group 0.000 claims 2
- 125000000753 cycloalkyl group Chemical group 0.000 claims 2
- 125000001188 haloalkyl group Chemical group 0.000 claims 2
- 229910052736 halogen Inorganic materials 0.000 claims 2
- 150000002367 halogens Chemical class 0.000 claims 2
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 2
- 125000001424 substituent group Chemical group 0.000 claims 2
- 125000003107 substituted aryl group Chemical group 0.000 claims 2
- 125000005346 substituted cycloalkyl group Chemical group 0.000 claims 2
- 125000006528 (C2-C6) alkyl group Chemical group 0.000 claims 1
- 125000003342 alkenyl group Chemical group 0.000 claims 1
- 125000003545 alkoxy group Chemical group 0.000 claims 1
- 206010017758 gastric cancer Diseases 0.000 abstract description 14
- 208000005718 Stomach Neoplasms Diseases 0.000 abstract description 13
- 201000011549 stomach cancer Diseases 0.000 abstract description 13
- 238000000338 in vitro Methods 0.000 abstract description 10
- 230000002401 inhibitory effect Effects 0.000 abstract description 4
- 238000012216 screening Methods 0.000 abstract description 4
- 230000001629 suppression Effects 0.000 abstract description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 230000005757 colony formation Effects 0.000 description 3
- 230000012010 growth Effects 0.000 description 3
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 230000029087 digestion Effects 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 150000002611 lead compounds Chemical class 0.000 description 2
- 238000002965 ELISA Methods 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 230000001464 adherent effect Effects 0.000 description 1
- 125000000609 carbazolyl group Chemical class C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000001332 colony forming effect Effects 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 208000010749 gastric carcinoma Diseases 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 230000031700 light absorption Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 201000000498 stomach carcinoma Diseases 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/22—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4
- C07D311/26—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3
- C07D311/28—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3 with aromatic rings attached in position 2 only
- C07D311/30—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3 with aromatic rings attached in position 2 only not hydrogenated in the hetero ring, e.g. flavones
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/22—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4
Abstract
One class 5 of new discovery of the present invention, 7 pairs of hydroxyls 6,8 pairs of ketone compounds of (1 methyl piperazine) 4H chromenes 4, in-vitro screening shows that such compound has stronger inhibitory action to a variety of stomach cancer cells (BGC 823, MGC 803), and subsequent Cell suppression test proves that such compound can suppress stomach cancer cell (BGC 823, MGC 803) in-vitro multiplication.Such new compound is applicable as antineoplastic.
Description
Technical field
Present invention discover that a class 5, double (1- the methyl piperazines) -4H- chromene -4- ketone new compounds of the double hydroxyls -6,8- of 7-,
Such compound can suppress the in-vitro multiplication of stomach cancer cell.Present invention discover that such compound answering in antineoplastic is prepared
With belonging to pharmaceutical technology field.
Background technology
The present invention passes through the screening to compound library, it was found that a class 5, and the double hydroxyls -6,8- of 7- double (1- methyl piperazines) -
4H- chromene -4- ketone new compounds, such compound can significantly inhibit the in-vitro multiplication of stomach cancer cell.
The content of the invention
Lead compound is found on cellular level in vitro of the invention, it was found that a class 5, double (the 1- first of the double hydroxyls -6,8- of 7-
Base piperazine) the novel compound of -4H- chromene -4- ketones structure, and cytologic experiment confirms that such compound can suppress tumour
The in-vitro multiplication of cell.The present invention can provide lead compound for the exploitation of antineoplastic.
The technical scheme is that：Carry out primary dcreening operation, secondary screening on a cellular level first, it is found that a class can suppress swollen in vitro
The compound of oncocyte；Then, its effect for suppressing proliferation of human gastric cancer cell is confirmed with MTT experiment and colony formation.
Brief description of the drawings
Fig. 1：No. 1 sample suppresses the block diagram (n=3) of two kinds of stomach cancer cell growth in vitro；
Fig. 2：No. 1 sample suppresses the colony formation (representative graph) of two kinds of stomach cancer cells；
Fig. 3：The statistical chart (n=3) of No. 1 Sample clones formation experiment.
Embodiment：
Below in conjunction with brief description of the drawings
1.MTT is tested
(1) take in exponential phase of growth one bottle of gastric carcinoma cells in good condition, counted after digestion, take 180 μ l cells to hang
Liquid is inoculated on 96 orifice plates, 2-4 × 103Individual/hole, puts constant temperature CO2Cultivated 24 hours in incubator.
The fresh nutrient solution of change in (2) second days (containing 10% serum), adds the given the test agent of various concentrations, continues to cultivate
72 hours.
(3) MTT reagents are added in 96 orifice plates, 20 μ l/ holes, reacted 4 hours in incubator.
(4) supernatant is sucked, adds on DMSO, 150 μ l/ holes, plate shaker and shakes 5 minutes.Use enzyme-linked immunosorbent assay instrument
It is that the light absorption value per hole is determined at 570nm in wavelength, and calculates Carbazole alkaloid.
2. colony formation
Take the logarithm the stomach cancer cell in growth period, 1000 are counted after digestion, is added in 3.5cm Tissue Culture Dish, adherent mistake
Night；Fresh culture 2ml is changed within second day, the test medicine of various concentrations is added, is put into constant temperature CO2Incubator is continuously cultivated 7 days.
Ji's nurse Sa is dyed, and is counted under disecting microscope containing colonies more than 50 cells.
Experimental result
1. it is as follows to screen such obtained compound structure formula：
| Compound | R1 | R2 | R3 |
| 1 | F | A | A |
| 2 | F | B | B |
| 3 | F | C | C |
| 4 | F | D | D |
| 5 | F | E | E |
| 6 | F | F | F |
| 7 | F | K | K |
| 8 | F | L | L |
| 9 | E | A | A |
| 10 | G | A | A |
| 11 | H | A | A |
| 12 | I | A | A |
| 13 | I | B | B |
| 14 | J | A | A |
| 15 | K | A | A |
| 16 | L | A | A |
Wherein,
A：-H；
B：-CH2-CH3；
C：-O-CH3；
D：-CH2OH；
2.10 μ g/ml sample is as follows to the inhibiting rate (72h, %) of stomach cancer cell：
3. suppression and IC of the sample to stomach cancer cell50It is worth (72h)
According to primary dcreening operation result, No. 1 best sample of Selection effect carries out secondary screening, makes sample and suppresses Growth of Gastric
Block diagram (Fig. 1).IC of No. 1 sample to stomach cancer BGC-823 and MGC-803 cell50Value is respectively 11.27 ± 0.67 μM and 7.31
±0.53μM。
4. sample suppresses the in-vitro multiplication of stomach cancer cell
Study inhibitory action of No. 1 sample to two kinds of cell proliferation in vitro of BGC-823 and MGC-803.Height (5 μ are set respectively
M (3 μM), low (1 μM) three groups of dosage, give BGC-823 and MGC-803 cells, constant temperature CO in),2Incubator continuously culture 7
My god.Experiment is dyed after terminating with Ji's nurse Sa, and the formation situation of cell colony is observed under disecting microscope.As a result Fig. 2, statistics knot are seen
Fruit sees Fig. 3.It can be seen that, No. 1 sample is respectively provided with obvious inhibitory action to the Colony forming of two kinds of stomach cancer cells, and is presented significant
Dose dependent.
Claims (2)
1. a class 5, double (1- the methyl piperazines) -4H- chromene -4- ketone new compounds of the double hydroxyls -6,8- of 7-, its structure such as formula
(I) shown in：
Wherein：
R1 represents C4-C7 cycloalkyl, substituted cycloalkyl, aryl or substituted aryl, and the substituent is alkyl, alkenyl, alkane
Epoxide, haloalkyl, halogen, nitro, hydroxyl, hydroxyalkyl, amino, alkylamino.
R2, R3 represent C2-C6 alkyl, alkoxy, haloalkyl, cycloalkyl, substituted cycloalkyl, aryl or substituted aryl, institute
Substituent is stated for alkyl, halogen, nitro, hydroxyl, hydroxyalkyl, amino, alkylamino.
2. application of the compound described in claim 1 in antineoplastic.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710541722.1A CN107235947B (en) | 2017-06-29 | 2017-06-29 | Novel 5, 7-dihydroxy-6, 8-bis (1-methylpiperazine) -4H-chromen-4-one compounds and antitumor application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710541722.1A CN107235947B (en) | 2017-06-29 | 2017-06-29 | Novel 5, 7-dihydroxy-6, 8-bis (1-methylpiperazine) -4H-chromen-4-one compounds and antitumor application thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN107235947A true CN107235947A (en) | 2017-10-10 |
| CN107235947B CN107235947B (en) | 2023-10-31 |
Family
ID=59990267
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201710541722.1A Active CN107235947B (en) | 2017-06-29 | 2017-06-29 | Novel 5, 7-dihydroxy-6, 8-bis (1-methylpiperazine) -4H-chromen-4-one compounds and antitumor application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN107235947B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113549044A (en) * | 2021-07-23 | 2021-10-26 | 中国药科大学 | 8-azacyclo-substituted chromone derivative and preparation method and pharmaceutical application thereof |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1997042949A1 (en) * | 1996-05-10 | 1997-11-20 | Bristol-Myers Squibb Company | 2-thio or 2-oxo flavopiridol analogs |
-
2017
- 2017-06-29 CN CN201710541722.1A patent/CN107235947B/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1997042949A1 (en) * | 1996-05-10 | 1997-11-20 | Bristol-Myers Squibb Company | 2-thio or 2-oxo flavopiridol analogs |
Non-Patent Citations (5)
| Title |
|---|
| S. P. BONDARENKO ET AL.: ""SYNTHESIS OF AMINOMETHYL DERIVATIVES OF CHRYSIN"", 《CHEMISTRY OF NATURAL COMPOUNDS》 * |
| SHIXUAN ZHANG ET AL.: ""Nitrogen-containing flavonoid analogues as CDK1/cyclin B inhibitors: Synthesis,SAR analysis, and biological activity"", 《BIOORGANIC & MEDICINAL CHEMISTRY》 * |
| TAO LIU ET AL.: ""Nitrogen-containing flavonoids as CDK1/Cyclin B inhibitors: Design, synthesis, and biological evaluation"", 《BIOORGANIC & MEDICINAL CHEMISTRY LETTERS》 * |
| VAN-SON NGUYEN ET AL.: ""Synthesis of kaempferide Mannich base derivatives and their antiproliferative activity on three human cancer cell lines"", 《ACTA BIOCHIMICA POLONICA》 * |
| 余元勋: "《中国分子胃癌学》", 30 April 2016, 安徽科学技术出版社 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113549044A (en) * | 2021-07-23 | 2021-10-26 | 中国药科大学 | 8-azacyclo-substituted chromone derivative and preparation method and pharmaceutical application thereof |
| CN113549044B (en) * | 2021-07-23 | 2024-01-23 | 中国药科大学 | 8-azacyclo-substituted chromone derivative and preparation method and pharmaceutical application thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN107235947B (en) | 2023-10-31 |
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