CN105523948A - 1,4-dihydroxy anthraquinone bisbenzyl quaternary ammonium salt having water solubility and anticancer activity - Google Patents
1,4-dihydroxy anthraquinone bisbenzyl quaternary ammonium salt having water solubility and anticancer activity Download PDFInfo
- Publication number
- CN105523948A CN105523948A CN201510966462.3A CN201510966462A CN105523948A CN 105523948 A CN105523948 A CN 105523948A CN 201510966462 A CN201510966462 A CN 201510966462A CN 105523948 A CN105523948 A CN 105523948A
- Authority
- CN
- China
- Prior art keywords
- ammonium salt
- quaternary ammonium
- anthraquinone
- dihydroxyanthraquinone
- nitrae
- 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.)
- Granted
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
- C07C213/04—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton by reaction of ammonia or amines with olefin oxides or halohydrins
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C217/00—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton
- C07C217/02—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton
- C07C217/48—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being unsaturated and containing rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C46/00—Preparation of quinones
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Abstract
The invention discloses 1,4-dihydroxy anthraquinone bisbenzyl quaternary ammonium salt having water solubility and anticancer activity and preparation thereof. Particularly, the preparation comprises the steps: 1,4-dihydroxy anthraquinone is subjected to a reaction with excessive p-dibenzyl bromide to obtain anthraquinone dibenzyl bromide; the anthraquinone dibenzyl bromide is subjected to a reaction with N-methyldi-n-octylamine to obtain anthraquinone benzyl bromide quaternary ammonium salt; then the anthraquinone benzyl bromide quaternary ammonium salt is subjected to a reaction with triethanolamine to obtain the corresponding hydroxy anthraquinone bisquaternary ammonium salt. The anthraquinone bisquaternary ammonium salt has relatively good inhibition ability to a variety of cancer cells while maintaining water solubility. The compound which has both water solubility and anticancer activity is expected to be developed as an anticancer drug and has good application prospects.
Description
Technical field
The invention belongs to the preparation field of quaternary ammonium salt cancer therapy drug, be specifically related to a kind of two benzyl quaternary ammonium salt of Isosorbide-5-Nitrae-dihydroxyanthraquinone and the preparation thereof with water-soluble and antitumour activity.
Background technology
Quaternary ammonium salt cancer therapy drug has the mitochondrial function of target cancer cell, because the mitochondrial membrane potential of cancer cells is generally higher than normal cell, so positively charged quaternary ammonium salt cancer therapy drug is easily enriched in the mitochondrial matrix of cancer cells.Plastosome is the main cell device performing apoptosis program, but mitochondrial inner membrance is fat-soluble comparatively strong, and water-soluble strong medicine is difficult to play cancer cell specific induction of apoptosis function through mitochondrial inner membrane usually.Drug molecule is because enhance water-soluble and example that is that lose antitumour activity can be found everywhere.
Summary of the invention
The object of the present invention is to provide a kind of two benzyl quaternary ammonium salt of Isosorbide-5-Nitrae-dihydroxyanthraquinone with water-soluble and antitumour activity and preparation method thereof.The present invention introduces the short carbon chain quaternary ammonium salt that has very strong water-soluble again in containing the molecule of long carbon chain quaternary ammonium salt, obtains bi-quaternary ammonium salt.Wherein short carbon chain quaternary ammonium salt plays hydrophile function, long carbon chain quaternary ammonium salt plays and carries the function of anthraquinone through mitochondrial inner membrane, make this bi-quaternary ammonium salt keeping water miscible while, cancer cells mitochondrial inner membrane can be passed through smoothly and enter matrix, thus keep the ability of good anticancer activity.
For achieving the above object, the present invention adopts following technical scheme:
Have the two benzyl quaternary ammonium salt of Isosorbide-5-Nitrae-dihydroxyanthraquinone that is water-soluble and antitumour activity, its molecular structural formula is:
。
A kind of method preparing the two benzyl quaternary ammonium salt of the Isosorbide-5-Nitrae-dihydroxyanthraquinone as mentioned above with water-soluble and antitumour activity: first obtained anthraquinone dibenzyl bromine:
, more obtained anthraquinone benzyl bromine quaternary ammonium salt:
, the finally two benzyl quaternary ammonium salt of obtained Isosorbide-5-Nitrae-dihydroxyanthraquinone:
.
The described preparation method with the two benzyl quaternary ammonium salt of Isosorbide-5-Nitrae-dihydroxyanthraquinone that is water-soluble and antitumour activity, concrete steps are:
1) synthesis of anthraquinone dibenzyl bromine: first obtain anthraquinone dibenzyl bromine by Isosorbide-5-Nitrae-dihydroxyanthraquinone with to dibenzyl bromine reaction;
2) synthesis of anthraquinone benzyl bromine quaternary ammonium salt: anthraquinone dibenzyl bromine and methyl di-n-octyl reactive tertiary amine are obtained anthraquinone benzyl bromine quaternary ammonium salt;
3) synthesis of hydroxyanthraquinone bi-quaternary ammonium salt: anthraquinone benzyl bromine quaternary ammonium salt and trolamine are reacted obtained Isosorbide-5-Nitrae-dihydroxyanthraquinone bi-quaternary ammonium salt.
More specifically, the concrete steps of this preparation method are:
1) there-necked flask will be placed in dibenzyl bromine, add acetone, and make it dissolve; By Isosorbide-5-Nitrae-dihydroxyanthraquinone and K
2cO
3jolting in Erlenmeyer flask heating in water bath dissolve, and proceed to constant pressure funnel, liquid in constant pressure funnel is slowly instilled there-necked flask after dissolving, after back flow reaction 24h yellow clarified liq, be poured into water stirring at room temperature 1h, suction filtration obtains Orange red solid; Solid CH
2cl
2carry out purification by silica gel column chromatography after dissolving, obtain anthraquinone dibenzyl bromine;
2) by anthraquinone dibenzyl bromine CHCl
3dissolve, control temperature of reaction 40 DEG C, add the methyl di-n-octyl tertiary amine with anthraquinone dibenzyl bromine equimolar amount, after reaction 2h, obtain yellow liquid; Liquid is spin-dried for rear silica gel column chromatography and carries out gradient elution, obtained anthraquinone benzyl bromine quaternary ammonium salt; The eluent CH of gradient elution
2cl
2: CH
3cH
2oH is from 40:1 → 25:1 (v/v) graded;
3) in there-necked flask, anthraquinone benzyl bromine quaternary ammonium salt is dissolved in chloroform, loads constant pressure funnel after trolamine being dissolved in chloroform, slowly triethanolamine solution is instilled in there-necked flask, stirred at reflux reaction 6h; Revolve after reaction terminates and steam except desolventizing, solid silicagel column carries out gradient elution, obtained hydroxyanthraquinone bi-quaternary ammonium salt; Elution order is CH
2cl
2→ CH
2cl
2/ EtOH:40:1 (v/v) → 25:1 → 20:1 → 15:1.
The application in anticancer medicine prepared by the two benzyl quaternary ammonium salt of Isosorbide-5-Nitrae-dihydroxyanthraquinone as mentioned above with water-soluble and antitumour activity, and described cancer cells comprises HL-60 cells and K562 and gastric carcinoma cell line SGC-7901.
Remarkable advantage of the present invention is:
The two benzyl quaternary ammonium salt synthesis step of Isosorbide-5-Nitrae-dihydroxyanthraquinone obtained by the present invention is relatively simple, has good restraining effect to multiple cancer cells.And this compound has water-soluble, easily transports in vivo, injection injection can be made and use.And lipophilic cation drug toxicity is less, be developed as having a bright future of cancer therapy drug, there is very high using value.
Accompanying drawing explanation
Fig. 1 is the synthetic route chart of the two benzyl quaternary ammonium salt of Isosorbide-5-Nitrae-dihydroxyanthraquinone;
Fig. 2 is the water-soluble result of spectrophotometry test Isosorbide-5-Nitrae-dihydroxyanthraquinone bi-quaternary ammonium salt.
Embodiment
More being convenient to make content of the present invention understand, below in conjunction with embodiment, technical solutions according to the invention are described further, but the present invention being not limited only to this.
Embodiment 1
1) synthesis of anthraquinone dibenzyl bromine
1.5034g(5.70mmol is added successively in the there-necked flask of 250mL) to dibenzyl bromine (trade(brand)name α, α '-dibromo p-Xylol), 200mg(1.45mmol) K
2cO
3with 70mL acetone, stirring heating backflow under nitrogen protection; In 150mL Erlenmeyer flask, add 0.2003g(0.83mmol successively simultaneously) Isosorbide-5-Nitrae-dihydroxyanthraquinone, 300mg(2.17mmol) K
2cO
3with 70mL acetone, with hollow plug jam-pack bottleneck (anti-oxidation), put and heat in a water bath, limit heating edge jolting, can observe a lot of bubbles and emerge, will constantly exit in centre.When not having bubble to overflow, liquid portion wherein being proceeded in constant pressure funnel, is slowly added drop-wise to there-necked flask.Obtain yellow clarified liq after reaction 24h, pour in 500mL water, stirring at room temperature 1h, with cloth funnel suction filtration, after drying, obtain orange-red solid; By solid CH
2cl
2dissolve, add silica gel, rotate evaporate to dryness (dry method loading), then use silicagel column to purify to product, use CH
2cl
2as eluent, obtain orange/yellow solid 205mg (i.e. compound 1), characterization data is as follows: productive rate is 40.8%;
1hNMR (400MHz, CDCl
3) δ: 8.24 (d, J=6.0Hz, 1H, Ar-H), 8.23 (d, J=6.0Hz, 1H, Ar-H), 7.77 (d, J=5.6Hz, 1H, Ar-H), 7.76 (d, J=5.6Hz, 1H, Ar-H), 7.61 (d, J=8.0Hz, 4H, Ar-H), 7.48 (d, J=8.0Hz, 4H, Ar-H), 7.31 (s, 2H, Ar-H), 5.27 (s, 4H, OCH
2ar), 4.54 (s, 4H, ArCH
2br); ESI-MSm/z605.3 (M+H)
+.
2) synthesis of anthraquinone benzyl bromine quaternary ammonium salt
Add anthraquinone dibenzyl bromine (0.1000g, 0.17mmol) and 30mL chloroform in the there-necked flask of 50mL successively, reflux also stirs; Then add 30 μ L (0.09mmol) methyl dioctyl tertiary amines, reaction 2h, obtains yellow liquid, revolves to steam to obtain orange/yellow solid except after desolventizing; Then silicagel column is used to carry out gradient elution to gained solid, elution order is methylene dichloride/ethanol=50:1 → methylene dichloride/ethanol=40:1 → methylene dichloride/ethanol=35:1 → methylene dichloride/ethanol=30:1 → methylene dichloride/ethanol=25:1 → methylene dichloride/ethanol=20:1, obtains orange/yellow solid anthraquinone benzyl bromine quaternary ammonium salt 39.6mg; Characterization of The Products data are as follows: productive rate is 51.2%;
1hNMR (400MHz, CDCl3) δ: 8.19 (m, 2H, Ar-H), 7.73 (m, 6H, Ar-H), 7.61 (d, J=7.6Hz, 2H, Ar-H), 7.46 (d, J=8.0Hz, 2H, Ar-H), 7.30 (d, J=6.8Hz, 2H, Ar-H), 5.23 (s, 2H, OCH
2ar), 5.22 (s, 2H, OCH
2ar), 5.07 (s, 2H, ArCH
2n), 4.53 (s, 2H, ArCH
2br), 3.41 (t, J=6.0Hz, 4H, 2 × NCH
2), 3.23 (s, 6H, 2 × NCH
3), 1.80 (m, 4H, 2 × NCH
2c
h 2), 1.28 (m, 20H, 2 × (CH
2)
5), 0.89 (t, J=6.8Hz, 6H, 2 × CH
3); ESI-MSm/z780.44 (M-Br
-)
+; HRMS (ESI
+): calcdforC
46h
68n
2o
7[M-2Br]
2+/ 2=380.2514; Found, 380.2517.
3) synthesis of Isosorbide-5-Nitrae-dihydroxyanthraquinone bi-quaternary ammonium salt
55.4mg(0.064mmol is added successively in the there-necked flask of 100mL) anthraquinone benzyl bromine quaternary ammonium salt and 50mL chloroform (dewatering), reflux, temperature controls at 40 DEG C, and stirs; Get 0.0213g(0.142mmol) trolamine and 10mL chloroform (dewatering) in constant pressure funnel, be slowly dropped in there-necked flask, reaction 6h, carry out degree with thin-layer chromatography monitoring reaction; After reaction terminates yellow liquid, question response liquid cooling but, to transfer them in round-bottomed flask and to rotate evaporate to dryness, obtaining yellow solid; Then use silicagel column (post height about 10cm) to carry out gradient elution purification, adopt wet method loading, elution order is CH
2cl
2→ CH
2cl
2: EtOH=40:1 (v/v) → 25:1 → 20:1 → 15:1, obtains yellow solid 37.2mg, i.e. Isosorbide-5-Nitrae-dihydroxyanthraquinone bi-quaternary ammonium salt (9).Characterization of The Products data are as follows: productive rate 57.6%;
1hNMR (400MHz, CDCl
3) δ: 7.77 (m, 2H, Ar-H), 7.66 (m, 8H, Ar-H), 7.42 (m, 2H, Ar-H), 6.96 (s, 2H, Ar-H), 5.05 (s, 4H, OCH
2ar), 4.81 (s, 4H, ArCH
2n), 4.28 (m, 6H, C
h 2oH), 3.68 (m, 6H, NC
h 2cH
2oH), 3.13 (s, 3H, NCH
3), 2.66 (s, 3H, CH
2o
h), 1.89 (m, 4H, NCH
2c
h 2), 1.25 (m, 20H, 10 × CH
2), 0.85 (t, J=6.0Hz, 6H, 2 × CH
3); ESI-MSm/z425.6 (M-2Br)
2+; HRMS (ESI
+): calcdforC
53h
74n
2o
7[M-2Br]
2+/ 2=425.2743; Found, 425.2730.
Application Example 1
Isosorbide-5-Nitrae-dihydroxyanthraquinone bi-quaternary ammonium salt is to leukemia cell and proliferation of human gastric cancer cell Inhibition test:
Using Isosorbide-5-Nitrae-dihydroxyanthraquinone bi-quaternary ammonium salt as test medicine, with substratum by drug dilution; The density of leukemia (HL60 and K562) cell and cancer of the stomach (SGC7901) cell is adjusted to 1 × 10
5individual/mL, is inoculated in 96 orifice plates, and every hole 100 μ L, puts 37 DEG C, 5%CO
224h is cultivated in incubator; Remove old substratum, add test medicine, every hole 100 μ L, separately establishes blank group, and often group establishes 3 multiple holes.After drug effect 48h, inhale and abandon pastille substratum, in every hole, add serum-free, without phenol red 1640 substratum 100 μ L, then add MTT solution 10 μ L, continue to hatch 4h, stop cultivating; Supernatant liquor in 96 orifice bores is abandoned in careful suction, and every hole adds 100 μ LDSMO, and vibration 10min, microplate reader measures each hole absorbance value (OD value) in 570nm wavelength place, calculation of half inhibitory concentration IC
50value.Result is as shown in table 1.
Table 11,4-dihydroxyanthraquinone bi-quaternary ammonium salt is to the inhibit activities (IC of leukemia cell and stomach cancer cell
50, μm ol/L)
Experimental result shows, Isosorbide-5-Nitrae-dihydroxyanthraquinone bi-quaternary ammonium salt shows good inhibit activities to two kinds of hemopathy cell HL60 and K562 and gastric carcinoma cell line SGC-7901, and its antitumour activity about improves 4-5 doubly compared with water-fast primer Isosorbide-5-Nitrae-dihydroxyanthraquinone.
2) the water-soluble test of Isosorbide-5-Nitrae-dihydroxyanthraquinone bi-quaternary ammonium salt and Isosorbide-5-Nitrae-dihydroxyanthraquinone mono-quaternaries:
Isosorbide-5-Nitrae-dihydroxyanthraquinone the bi-quaternary ammonium salt taking 10.7mg is made into the aqueous solution of 5mL, and concentration is 2.122 × 10
-3m; Measure respectively 10 μ L, 20 μ L, 30 μ L, 40 μ L, 50 μ L above-mentioned solution dilution become the aqueous solution of 3mL, the concentration of solution is respectively 7.073 × 10
-6m, 1.415 × 10
-5m, 2.122 × 10
-5m, 2.829 × 10
-5m, 3.537 × 10
-5m; Test them and be respectively 0.3085,0.4434,0.5684,0.6994,0.8383 at the ultraviolet absorptivity at 260nm place.Absorbancy according to the known solution of langbobier law is directly proportional to concentration, therefore obtains straight-line equation y=0.17838+18420.61617x according to above data fitting, R
2=0.99825.
The preparation of saturated solution, gets Isosorbide-5-Nitrae-a small amount of water dissolution of dihydroxyanthraquinone bi-quaternary ammonium salt, by ultrasonic make its as far as possible many dissolving after ensure to also have solid in solution; After leaving standstill an evening, solid does not disappear, then supernatant liquor is saturated solution; Recording its uv-absorbing at 260nm place after the saturated solution getting 5 μ L is diluted to 4mL is 0.8224, and bringing the saturated aqueous solution concentration that above-mentioned gained equation can obtain Isosorbide-5-Nitrae-dihydroxyanthraquinone bi-quaternary ammonium salt into is 0.0280M (28.2mg/mL).
In contrast, also test anthraquinone benzyl bromine mono-quaternaries 8(structural formula simultaneously and see Fig. 2) water-soluble.Anthraquinone benzyl bromine mono-quaternaries 8 does not have water-soluble, is difficult to prepare the corresponding aqueous solution.Get 100mL redistilled water, add 1mg anthraquinone benzyl bromine mono-quaternaries 8, sonic oscillation is placed after 30 minutes and is spent the night.After second day, orange solids anthraquinone benzyl bromine mono-quaternaries 8 is still high-visible, show that the water-soluble of anthraquinone benzyl bromine mono-quaternaries 8 is less than 1mg/100mL, show that the introducing of second short carbon chain quaternary ammonium salt can make the water-soluble raising more than 2800 times of rhabarberone quaternary ammonium salt.
Above-described embodiment shows that Isosorbide-5-Nitrae-dihydroxyanthraquinone bi-quaternary ammonium salt that this patent synthesizes has water-soluble and antitumour activity concurrently, therefore has the higher market potential being developed as cancer therapy drug.
The foregoing is only preferred embodiment of the present invention, all equalizations done according to the present patent application the scope of the claims change and modify, and all should belong to covering scope of the present invention.
Claims (9)
1. there is the two benzyl quaternary ammonium salt of Isosorbide-5-Nitrae-dihydroxyanthraquinone that is water-soluble and antitumour activity, it is characterized in that: its molecular structural formula is:
。
2. prepare a method for the two benzyl quaternary ammonium salt of the Isosorbide-5-Nitrae-dihydroxyanthraquinone as claimed in claim 1 with water-soluble and antitumour activity, it is characterized in that: first obtained anthraquinone dibenzyl bromine:
, more obtained anthraquinone benzyl bromine quaternary ammonium salt:
, the finally two benzyl quaternary ammonium salt of obtained Isosorbide-5-Nitrae-dihydroxyanthraquinone:
.
3. there is the preparation method of the two benzyl quaternary ammonium salt of Isosorbide-5-Nitrae-dihydroxyanthraquinone that is water-soluble and antitumour activity according to claim 2, it is characterized in that: concrete steps are:
1) synthesis of anthraquinone dibenzyl bromine: first obtain anthraquinone dibenzyl bromine by Isosorbide-5-Nitrae-dihydroxyanthraquinone with to dibenzyl bromine reaction;
2) synthesis of anthraquinone benzyl bromine quaternary ammonium salt: anthraquinone dibenzyl bromine and methyl di-n-octyl reactive tertiary amine are obtained anthraquinone benzyl bromine quaternary ammonium salt;
3) synthesis of hydroxyanthraquinone bi-quaternary ammonium salt: anthraquinone benzyl bromine quaternary ammonium salt and trolamine are reacted obtained Isosorbide-5-Nitrae-dihydroxyanthraquinone bi-quaternary ammonium salt.
4. there is the preparation method of the two benzyl quaternary ammonium salt of Isosorbide-5-Nitrae-dihydroxyanthraquinone that is water-soluble and antitumour activity according to claim 3, it is characterized in that: step 1) is specially: there-necked flask will be placed in dibenzyl bromine, and add acetone, and make it dissolve; By Isosorbide-5-Nitrae-dihydroxyanthraquinone and K
2cO
3jolting in Erlenmeyer flask heating in water bath dissolve, and proceed to constant pressure funnel, liquid in constant pressure funnel is slowly instilled there-necked flask after dissolving, after back flow reaction 24h yellow clarified liq, be poured into water stirring at room temperature 1h, suction filtration obtains Orange red solid; Solid CH
2cl
2carry out purification by silica gel column chromatography after dissolving, obtain anthraquinone dibenzyl bromine.
5. there is the preparation method of the two benzyl quaternary ammonium salt of Isosorbide-5-Nitrae-dihydroxyanthraquinone that is water-soluble and antitumour activity according to claim 3, it is characterized in that: step 2) be specially: by anthraquinone dibenzyl bromine CHCl
3dissolve, control temperature of reaction 40 DEG C, add the methyl di-n-octyl tertiary amine with anthraquinone dibenzyl bromine equimolar amount, after reaction 2h, obtain yellow liquid; Liquid is spin-dried for rear silica gel column chromatography and carries out gradient elution, obtained anthraquinone benzyl bromine quaternary ammonium salt.
6. there is the preparation method of the two benzyl quaternary ammonium salt of Isosorbide-5-Nitrae-dihydroxyanthraquinone that is water-soluble and antitumour activity according to claim 5, it is characterized in that: the eluent CH of gradient elution
2cl
2: CH
3cH
2oH is from 40:1 → 25:1 (v/v) graded.
7. have 1 of water-soluble and antitumour activity according to claim 3, the preparation method of the two benzyl quaternary ammonium salt of 4-dihydroxyanthraquinone, it is characterized in that: step 3) is specially: in there-necked flask, anthraquinone benzyl bromine quaternary ammonium salt is dissolved in chloroform, constant pressure funnel is loaded after trolamine being dissolved in chloroform, slowly triethanolamine solution is instilled in there-necked flask, stirred at reflux reaction 6h; Revolve after reaction terminates and steam except desolventizing, solid silicagel column carries out gradient elution, obtained hydroxyanthraquinone bi-quaternary ammonium salt.
8. there is the preparation method of the two benzyl quaternary ammonium salt of Isosorbide-5-Nitrae-dihydroxyanthraquinone that is water-soluble and antitumour activity according to claim 7, it is characterized in that: elution order is CH
2cl
2→ CH
2cl
2/ EtOH:40:1 (v/v) → 25:1 (v/v) → 20:1 (v/v) → 15:1 (v/v).
9. the application in anticancer medicine prepared by the two benzyl quaternary ammonium salt of Isosorbide-5-Nitrae-dihydroxyanthraquinone as claimed in claim 1 with water-soluble and antitumour activity, and described cancer cells comprises HL-60 cells and K562 and gastric carcinoma cell line SGC-7901.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510966462.3A CN105523948B (en) | 2015-12-22 | 2015-12-22 | 1,4-dihydroxy anthraquinone bisbenzyl quaternary ammonium salt having water solubility and anticancer activity |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510966462.3A CN105523948B (en) | 2015-12-22 | 2015-12-22 | 1,4-dihydroxy anthraquinone bisbenzyl quaternary ammonium salt having water solubility and anticancer activity |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN105523948A true CN105523948A (en) | 2016-04-27 |
| CN105523948B CN105523948B (en) | 2017-05-10 |
Family
ID=55766520
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510966462.3A Expired - Fee Related CN105523948B (en) | 2015-12-22 | 2015-12-22 | 1,4-dihydroxy anthraquinone bisbenzyl quaternary ammonium salt having water solubility and anticancer activity |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105523948B (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109970570A (en) * | 2019-03-16 | 2019-07-05 | 福建医科大学附属协和医院 | One kind, which has, inhibits the active preparation method to dibenzyl bromine bi-quaternary ammonium salt of leukaemia cell |
| CN111039806A (en) * | 2019-12-27 | 2020-04-21 | 福州大学 | Hydroxy benzoquinone biquaternary ammonium salt and preparation and application thereof |
| CN111193055A (en) * | 2020-01-08 | 2020-05-22 | 中盐金坛盐化有限责任公司 | Application of quaternary ammonium salt type anthraquinone active substance and organic water phase salt cavity battery |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103936788A (en) * | 2014-02-22 | 2014-07-23 | 福州大学 | Emodin quaternary phosphonium salt with antitumor activity, and preparation method thereof |
| CN104311434A (en) * | 2014-11-07 | 2015-01-28 | 福州大学 | Rheum emodin double-chain biquaternary ammonium salt with anti-cancer activity and preparation method of rheum emodin double-chain biquaternary ammonium salt |
| CN105152941A (en) * | 2015-07-27 | 2015-12-16 | 福州大学 | Anthraquinone compound with both alkylation reactive group and lipophilic positive ion |
-
2015
- 2015-12-22 CN CN201510966462.3A patent/CN105523948B/en not_active Expired - Fee Related
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103936788A (en) * | 2014-02-22 | 2014-07-23 | 福州大学 | Emodin quaternary phosphonium salt with antitumor activity, and preparation method thereof |
| CN104311434A (en) * | 2014-11-07 | 2015-01-28 | 福州大学 | Rheum emodin double-chain biquaternary ammonium salt with anti-cancer activity and preparation method of rheum emodin double-chain biquaternary ammonium salt |
| CN105152941A (en) * | 2015-07-27 | 2015-12-16 | 福州大学 | Anthraquinone compound with both alkylation reactive group and lipophilic positive ion |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109970570A (en) * | 2019-03-16 | 2019-07-05 | 福建医科大学附属协和医院 | One kind, which has, inhibits the active preparation method to dibenzyl bromine bi-quaternary ammonium salt of leukaemia cell |
| CN109970570B (en) * | 2019-03-16 | 2022-03-18 | 福建医科大学附属协和医院 | Preparation method of p-dibenzyl bromide biquaternary ammonium salt with leukemia cell activity inhibition function |
| CN111039806A (en) * | 2019-12-27 | 2020-04-21 | 福州大学 | Hydroxy benzoquinone biquaternary ammonium salt and preparation and application thereof |
| CN111039806B (en) * | 2019-12-27 | 2021-04-27 | 福州大学 | Hydroxy benzoquinone biquaternary ammonium salt and preparation and application thereof |
| CN111193055A (en) * | 2020-01-08 | 2020-05-22 | 中盐金坛盐化有限责任公司 | Application of quaternary ammonium salt type anthraquinone active substance and organic water phase salt cavity battery |
Also Published As
| Publication number | Publication date |
|---|---|
| CN105523948B (en) | 2017-05-10 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN105523948A (en) | 1,4-dihydroxy anthraquinone bisbenzyl quaternary ammonium salt having water solubility and anticancer activity | |
| CN105669657A (en) | Benzopyran-4-one substituted naphthalimide-polyamine conjugate and preparing method and usage thereof | |
| CN108484699A (en) | Bipyridyliums alkaloid, preparation method and use | |
| CN113150058B (en) | Tripterine derivative and preparation method and application thereof | |
| CN104086617B (en) | Close dimethylamine derivative, the preparation method and its usage of flowers and trees ketone Cleistanone | |
| CN104311434B (en) | Schuttgelb double-strand bi-quaternary ammonium salt with antitumour activity and preparation method thereof | |
| CN107417752A (en) | One kind has compound of active anticancer and its preparation method and application | |
| CN105152941B (en) | Anthraquinone compound with both alkylation reactive group and lipophilic positive ion | |
| CN105399640A (en) | Aloe-emodin biquaternary ammonium salt with water solubility and anticancer activity and preparation thereof | |
| CN110078695A (en) | A kind of quercetin derivative and preparation method thereof | |
| CN104356014B (en) | Schuttgelb strand bi-quaternary ammonium salt with antitumour activity and preparation method thereof | |
| CN104211697B (en) | Berberinc derivate and application thereof | |
| Singh et al. | Efficient synthesis of naphthodiazacrown ethers | |
| CN105367575B (en) | A kind of folacin compound, its preparation method and medical usage | |
| CN105017042A (en) | Preparation methods for anthraquinone and naphthoquinone quaternary ammonium salts with leukemia resisting function | |
| CN109675050A (en) | Using camptothecine as the conjugate and its preparation and application of the analog of parent nucleus and nonsteroidal anti-inflammatory drug | |
| CN102516219A (en) | Halogenated polyhydroxy xanthene derivatives, preparation method and use thereof | |
| CN103408597B (en) | A kind of Aromatic ruthenium complex and synthetic method thereof | |
| CN104387399A (en) | Synthetic method of oxidized nantenine and application of oxidized nantenine | |
| Mustafa et al. | Synthesis, antioxidant and antitumor activities of new coumarins grafted to 5-fluorouracil | |
| CN106543155B (en) | Chalcone and flavonoid derivative as aurora kinase inhibitor | |
| CN102924429A (en) | 1,2-naphthaquinone derivatives and preparation method thereof | |
| Raju et al. | Regioselective synthesis and antioxidant activity of a novel class of mono and C2-symmetric bis-1, 2, 3-triazole and acridinedione grafted macromolecules | |
| CN107096027B (en) | Photosensitizer for identifying tumor cells through pH control and preparation method and application thereof | |
| CN109053488A (en) | A kind of preparation method and its antitumor application of the Schiff base complex of palladium |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into 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: 20170510 Termination date: 20191222 |