CN104311434A - Rheum emodin double-chain biquaternary ammonium salt with anti-cancer activity and preparation method of rheum emodin double-chain biquaternary ammonium salt - Google Patents

Rheum emodin double-chain biquaternary ammonium salt with anti-cancer activity and preparation method of rheum emodin double-chain biquaternary ammonium salt Download PDF

Info

Publication number
CN104311434A
CN104311434A CN201410620217.2A CN201410620217A CN104311434A CN 104311434 A CN104311434 A CN 104311434A CN 201410620217 A CN201410620217 A CN 201410620217A CN 104311434 A CN104311434 A CN 104311434A
Authority
CN
China
Prior art keywords
schuttgelb
ammonium salt
quaternary ammonium
double
mixture
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
Application number
CN201410620217.2A
Other languages
Chinese (zh)
Other versions
CN104311434B (en
Inventor
王文峰
祝云辉
王建龙
郝宪宵
罗舒维
邵敬伟
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Fuzhou University
Original Assignee
Fuzhou University
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Fuzhou University filed Critical Fuzhou University
Priority to CN201410620217.2A priority Critical patent/CN104311434B/en
Publication of CN104311434A publication Critical patent/CN104311434A/en
Application granted granted Critical
Publication of CN104311434B publication Critical patent/CN104311434B/en
Expired - Fee Related legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Landscapes

  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

The invention discloses a rheum emodin double-chain biquaternary ammonium salt with the anti-cancer activity and a preparation method of the rheum emodin double-chain biquaternary ammonium salt. The rheum emodin double-chain biquaternary ammonium salt is a mixture of a rheum emodin 1,3-site biquaternary ammonium salt and a rheum emodin 3,8-site biquaternary ammonium salt. The preparation method comprises the following steps: performing Williamson etherification reaction on rheum emodin and p-benzyl bromide in the presence of K2CO3 so as to generate a mixture of 1,3-site dibromomethylbenzyl rheum emodin and 3,8-site dibromomethylbenzyl rheum emodin, and further reacting the dibromomethylbenzyl rheum emodin mixture with tertiary amine so as to obtain the mixture of 1,3-site biquaternary ammonium salt and rheum emodin 3,8-site biquaternary ammonium salt, wherein the two biquaternary ammonium salts are isomerides which cannot be separated on a chromatographic column. The anti-cancer activity evaluation shows that the activity of the rheum emodin double-chain biquaternary ammonium salt disclosed by the invention is higher than that of monoquaternary ammonium salt, and the rheum emodin double-chain biquaternary ammonium salt can be used in a medicine for treating malignant tumor, is particularly applicable to treatment on liver cancer, has a relatively small inhibition effect on normal cells, and has relatively great application prospect.

Description

Schuttgelb double-strand bi-quaternary ammonium salt with antitumour activity and preparation method thereof
Technical field
The present invention is specifically related to a kind of Schuttgelb double-strand bi-quaternary ammonium salt with antitumour activity and preparation method thereof and application.
Background technology
Schuttgelb (1,3,8-trihydroxy-6-methylanthraquinone, emodin) is the natural anthraquinone derivative separated from polygonaceae plant, and its structural formula is: .Modern medicine confirms, and Schuttgelb has spectrum antitumour activity, all has restraining effect to tens kinds of cancer cells such as liver cancer, cancer of the stomach.But itself still exists some shortcomings, as not high enough in poorly water-soluble, antitumour activity, do not reach the requirement of direct patent medicine.Therefore, carrying out chemically modified to Schuttgelb, improve its water-soluble and antitumour activity, is the main direction of studying being developed into PTS.(Wang Conghui, Zhang Fengsen, the Du Huadong etc. such as Wang Conghui, " synthesis of two long-chain Schuttgelb quaternary ammonium salt derivative and Anticancer Activities ", University of Fuzhou's journal (natural science edition), 2011,39(3)) find on Schuttgelb, introduce the antitumour activity that long carbon chain quaternary ammonium salt can significantly improve Schuttgelb, shown that long carbon chain quaternary ammonium salt is the good pharmacophore of Schuttgelb.
Summary of the invention
The object of the present invention is to provide a kind of Schuttgelb double-strand bi-quaternary ammonium salt with antitumour activity and preparation method thereof, by introducing two quaternary ammonium salt long-chains on Schuttgelb, to improve Schuttgelb antitumour activity further.
For achieving the above object, the present invention adopts following technical scheme:
Have a Schuttgelb double-strand bi-quaternary ammonium salt for antitumour activity, it is Schuttgelb 1, the mixture of 3 bi-quaternary ammonium salts and Schuttgelb 3,8 bi-quaternary ammonium salts;
The structural formula of described Schuttgelb 1,3 bi-quaternary ammonium salts is:
；
The structural formula of described Schuttgelb 3,8 bi-quaternary ammonium salts is:
；
Wherein, R 1for C 9h 19or C 10h 21, R 2for C 10h 21.
The described preparation method with the Schuttgelb double-strand bi-quaternary ammonium salt of antitumour activity, be by Schuttgelb with to dibenzyl bromine at K 2cO 3there is lower generation Williamson etherification reaction, generate dibromo xylyl Schuttgelb mixture, then by dibromo xylyl Schuttgelb mixture and reactive tertiary amine, obtain Schuttgelb 1, the mixture of 3 bi-quaternary ammonium salts and Schuttgelb 3,8 bi-quaternary ammonium salts;
Its synthetic route is shown below:
。
Its preparation method specifically comprises the following steps:
1) synthesis of dibromo xylyl Schuttgelb mixture: Schuttgelb is dissolved in acetone, adds the K of two equivalents 2cO 3, add again after 65 DEG C of reflux 20 min two equivalents to dibenzyl bromine, reaction 2h after be cooled to room temperature; In solution, add rare HCl adjust pH=6, the more a large amount of precipitation of the precipitation that adds water; After suction filtration, gained precipitation is separated through silica gel column chromatography wash-out, obtains 1,3 dibromo xylyl Schuttgelbs ( 1) and 3,8 dibromo xylyl Schuttgelbs ( 2) mixture;
2) synthesis of Schuttgelb double-strand bi-quaternary ammonium salt mixture: by obtained for step 1) 1,3 dibromo xylyl Schuttgelbs ( 1) and 3,8 dibromo xylyl Schuttgelbs ( 2) mixture add CHCl 3in, add the tertiary amine of mixture two equivalent after heating for dissolving, stir lower back flow reaction 12h, be cooled to room temperature; Revolve to steam and obtain orange solids except gained solid after desolventizing is separated through silica gel column chromatography wash-out, be Schuttgelb 1,3 bi-quaternary ammonium salts ( 3a-3b) and Schuttgelb 3,8 bi-quaternary ammonium salts mixture ( 4a-4b).
Step 1) eluent used is methylene dichloride; Step 2) eluent used is that 20:1 is formulated by volume for methylene dichloride and ethanol.
Gained Schuttgelb double-strand bi-quaternary ammonium salt can be used for preparing cancer treatment drugs; Described cancer comprises liver cancer HepG2.
remarkable advantage of the present invention is:the antitumour activity of the Schuttgelb double-strand bi-quaternary ammonium salt obtained by the present invention is better than Schuttgelb mono-quaternaries.Cancer cell in vitro Inhibition test shows that gained Schuttgelb double-strand bi-quaternary ammonium salt can effective killing hepatoma HepG2 cell, simultaneously to normal cell (HELF, lung fibroblast) toxicity less, there is good antitumour activity, use it for oncotherapy and have a good application prospect.
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: dibromo xylyl Schuttgelb 1with 2synthesis
By 100mg(0.37mmol) Schuttgelb, 100mg(0.74mmol) K 2cO 3put into 250ml there-necked flask with the acetone of 100ml, controlling oil bath temperature is 65 DEG C, after reflux 20 min, add dibenzyl bromine 195mg(0.74mmol), be cooled to room temperature after reaction 2h, in solution, add dilute hydrochloric acid solution regulate pH=6, add 200mL elutriation and go out a large amount of yellow solid, suction filtration, gained solid is dried, dissolving, uses a dry method on a sample, through silica gel column chromatography, take methylene dichloride as eluent, be separated and obtain orange solids.After measured, its be compound 6-methyl-8-hydroxyl-1,3-bis-(to brooethyl benzyloxy)-9,10-anthraquinones ( 1) and 6-methyl isophthalic acid-hydroxyl-3,8-bis-(to brooethyl benzyloxy)-9,10-anthraquinones ( 2) mixture, be abbreviated as 1+ 2, both mol ratios are about 2:1, R f=0.87.Characterization of The Products data are as follows:
Compound 1+ 2, productive rate 45%; M. p:218-221 DEG C. 1HNMR(500MHz，CDCl 3)?δ：13.24?(s，0.5H，OH)，13.21?(s，1.0H，OH)，7.81?(d， J=1.0Hz，0.5H，Ar-H)，7.61?(m，4.0H，ArO C 6 H 4 Br)，7.58?(d， J=2.5Hz，1.0H，Ar-H)，7.50?(t， J=2.5Hz，2.0H，ArO C 6 H 4 Br)，7.48?(d， J=2.5Hz，2.0H，ArO C 6 H 4 Br)，7.47?(m，4.0H，ArO C 6 H 4 Br)，7.44?(s，1.0H，Ar-H)，7.41?(d， J=2.5Hz，0.5H，Ar-H)，7.19?(s，0.5H，Ar-H)，7.13?(d， J=0.5Hz，1.0H，Ar-H)，6.90?(d， J=2.5Hz，1.0H，Ar-H)，6.80?(d， J=2.5Hz，0.5H，Ar-H)，5.30?(s，2.0H，ArO CH 2 C 6H 4CH 2Br)，5.23?(s，2.0H，ArO CH 2 C 6H 4CH 2Br)，5.21?(s，1.0H，ArO CH 2 C 6H 4CH 2Br)，5.15?(s，1.0H，ArO CH 2 C 6H 4CH 2Br)，4.55?(s，2.0H，ArOCH 2C 6H 4 CH 2 Br)，4.54?(ArOCH 2C 6H 4 CH 2 Br)，2.50?(s,?1.5H,?Ar CH 3 )，2.46?(s，3.OH，Ar CH 3 )。
Embodiment 2:1, the synthesis of 3 bi-quaternary ammonium salts and 3,8 bi-quaternary ammonium salts
Dibromo xylyl Schuttgelb that Example 1 obtains ( 1+ 2)100mg(0.16mmol) add together with 20ml chloroform in 100ml there-necked flask, reflux adds 0.32mmol tertiary amine after dissolving, stir lower back flow reaction 12h, be cooled to room temperature, revolve and steam except gained solid after desolventizing is through silica gel column chromatography, with methylene dichloride: ethanol=20:1 (v/v) is eluent, be separated and obtain orange solids.After measured, it is Schuttgelb 1,3 bi-quaternary ammonium salts ( 3a-3b) and Schuttgelb 3,8 bi-quaternary ammonium salts ( 4a-4b) miscellany, be abbreviated as 3a-3b+ 4a-4b.With the difference of tertiary amine, compound 3with 4mol ratio different, Characterization of The Products data are as follows:
Compound 3a+ 4a(mol ratio is about 5:1), productive rate 41%; M. p. 128-130 DEG C. 1H?NMR(400Hz，CDCl 3)?δ：13.21?(s，1.0H，OH)，13.13?(s，0.2H，OH)，7.74?(s，1.0H，ArOCH 2C 6 H 4-)，7.72?(s，1.0H，ArOCH 2C 6 H 4-)，7.67-7.65?(m，2.0H，ArOCH 2C 6 H 4-)，7.64?(s，0.4H，ArOCH 2C 6 H 4)，7.61-7.59(m，2.0H，ArOCH 2C 6 H 4)，7.58?(s，0.4H，ArOCH 2C 6 H 4)，7.52(s，1.2H，Ar-H)，7.36(s，0.2H，Ar-H?)，7.35?(m，0.4H，ArOCH 2C 6 H 4)，7.33(s，1.0H，ArOCH 2C 6 H 4)，7.31(s，1.0H，ArOCH 2C 6 H 4)，7.19(s，0.2H，ArOCH 2C 6 H 4)，7.17(s，0.2H，ArOCH 2C 6 H 4)，7.11(s，0.2H，Ar-H)，7.09?(d， J=2.4Hz，1.0H，Ar-H)，7.02?(s，1.0H，Ar-H)，6.61?(d， J=2.4Hz，1.0H，Ar-H)，6.44(d， J=2.0Hz，0.2H，Ar-H)，5.37?(s，0.4H，ArOC H 2C 6H 4)，5.29-5.26?(m，4.4H，ArOC H 2C 6H 4)，5.21?(s，0.4H，-C 6H 4C H 2N +)，5.11?(s，0.4H，-C 6H 4C H 2N +)，5.08?(s，2.0H，-C 6H 4C H 2N +)，4.94?(s，2.0H，-C 6H 4C H 2N +)，3.40?(m，9.6H，2×C H 2N +C H 2)，3.18?(s，6.0H，2×N +CH 3)，3.14(s，1.2H，2×N +CH 3)，2.45?(s，0.6H，ArCH 3)，2.39?(s，3.0H，ArCH 3)，1.92-1.82[m，9.6H，2×N +(CH 2C H 2-) 2]，1.39-1.28?(m，62.4H，2×N +C 2H 4(C H 2) 6CH 3+2×N +C 2H 4(C H 2) 7CH 3)，0.89?(m，14.4H，4×R-C H 3)。ESI-MS， m/z：535.75[M-2Br -] 2+。Anal.?Calcd?for?C 71H 110Br 2N 2O 5·0.5H 2O：C?68.75，H?9.02，N?2.26，Found：C?68.83，H?9.31，N?2.35。
Compound 3b+ 4b(mol ratio is greater than 20:1), productive rate 43%; M. p. 217-221 DEG C. 1H?NMR(400Hz,CDCl 3)?δ：13.17?(s，1H，OH)，7.79-7.77?(m，2H，ArOCH 2C 6 H 4)，7.72-7.70?(m，2H，ArOCH 2C 6 H 4)，7.64-7.62?(m，2H，ArOCH 2C 6 H 4)，7.51?(s，1H，Ar-H)，7.40-7.38?(m，2H，ArOCH 2C 6 H 4)，7.06?(d， J=2.0Hz，1H，Ar-H)，7.01?(s，1H，Ar-H)，6.56?(d， J=2.0Hz，1H，Ar-H)，5.26?(s，2H，ArOC H 2C 6H 4)，5.24?(s，2H，ArOC H 2C 6H 4)，5.08?(s，2H，C 6H 4C H 2N +)，4.98?(s，2H，C 6H 4C H 2N +)，3.69-3.54?(m，8H，2×C H 2N +C H 2)，3.28?(s，6H，2×N +CH 3)，2.39?(s，3H，ArCH 3)，1.85-1.78[m，8H，2×N +(CH 2C H 2-) 2]，1.26?(m，56H，4×N +C 2H 4(C H 2) 7CH 3)，0.89?(m，12H，4×N +C 9H 18C H 3)。ESI-MS，? m/z：549.67[M-2Br -] 2+。Anal.?Calcd?for?C 73H 118Br 2N 2O 5·2H 2O：C?67.68，H?9.18，N?2.16，Found：C?67.55，H?9.49，N?2.21。
Embodiment 3: cancer cell multiplication Inhibition test
By Schuttgelb 1,3 and 3,8 bi-quaternary ammonium salts ( 3a+4a) and ( 3b+4b) as test medicine, with substratum by drug dilution; Get liver cancer cell Hep2 and normal cell HELF, its density 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 224 h are cultivated in incubator; Remove old substratum, add test medicine, every hole 100 μ l, separately establishes blank group and Schuttgelb group, and often group establishes 3 multiple holes.After drug effect 24h, 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 l DSMO, and vibration 10min, microplate reader measures each hole absorbance value (OD value) in 570 nm wavelength places, calculation of half inhibitory concentration IC 50.Result is as shown in table 1.
Table 2 processes rear cancer cells and Normocellular activity (IC 50, μm ol/L)
Experimental result shows, Schuttgelb 1,3 and 3,8 bi-quaternary ammonium salts ( 3a+4awith 3b+4b) all good antitumour activity is shown to liver cancer cell, although to normal cells show larger toxicity, drug combination often can reduce the toxic side effect of medicine, therefore have good application prospect when drug combination Therapeutic cancer.
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 (5)

1. there is a Schuttgelb double-strand bi-quaternary ammonium salt for antitumour activity, it is characterized in that: described Schuttgelb double-strand bi-quaternary ammonium salt is Schuttgelb 1, the mixture of 3 bi-quaternary ammonium salts and Schuttgelb 3,8 bi-quaternary ammonium salts;
The structural formula of described Schuttgelb 1,3 bi-quaternary ammonium salts is:
；
The structural formula of described Schuttgelb 3,8 bi-quaternary ammonium salts is:
；
Wherein, R 1for C 9h 19or C 10h 21, R 2for C 10h 21.
2. there is a preparation method for the Schuttgelb double-strand bi-quaternary ammonium salt of antitumour activity as claimed in claim 1, it is characterized in that: by Schuttgelb with to dibenzyl bromine at K 2cO 3there is lower generation Williamson etherification reaction, generate dibromo xylyl Schuttgelb mixture, then by dibromo xylyl Schuttgelb mixture and reactive tertiary amine, obtain Schuttgelb 1, the mixture of 3 bi-quaternary ammonium salts and Schuttgelb 3,8 bi-quaternary ammonium salts.
3. there is the preparation method of the Schuttgelb double-strand bi-quaternary ammonium salt of antitumour activity according to claim 2, it is characterized in that: specifically comprise the following steps:
1) synthesis of dibromo xylyl Schuttgelb mixture: Schuttgelb is dissolved in acetone, adds the K of two equivalents 2cO 3, add again after 65 DEG C of reflux 20 min two equivalents to dibenzyl bromine, reaction 2h after be cooled to room temperature; In solution, add rare HCl adjust pH=6, the more a large amount of precipitation of the precipitation that adds water; After suction filtration, gained precipitation is separated through silica gel column chromatography wash-out, obtains 1, the mixture of 3 dibromo xylyl Schuttgelbs and 3,8 dibromo xylyl Schuttgelbs;
2) synthesis of Schuttgelb double-strand bi-quaternary ammonium salt mixture: 1,3 the dibromo xylyl Schuttgelbs and 3 obtained by step 1), the mixture of 8 dibromo xylyl Schuttgelbs adds CHCl 3in, add the tertiary amine of mixture two equivalent after heating for dissolving, stir lower back flow reaction 12h, be cooled to room temperature; Revolve and steam except gained solid after desolventizing obtains orange solids through the separation of silica gel column chromatography wash-out, be Schuttgelb 1, the mixture of 3 bi-quaternary ammonium salts and Schuttgelb 3,8 bi-quaternary ammonium salts.
4. there is the preparation method of the Schuttgelb double-strand bi-quaternary ammonium salt of antitumour activity according to claim 3, it is characterized in that: step 1) eluent used is methylene dichloride; Step 2) eluent used is that 20:1 is formulated by volume for methylene dichloride and ethanol.
5. an application for Schuttgelb double-strand bi-quaternary ammonium salt as claimed in claim 1, is characterized in that: for the preparation of cancer treatment drugs;
Described cancer comprises liver cancer HepG2.
CN201410620217.2A 2014-11-07 2014-11-07 Schuttgelb double-strand bi-quaternary ammonium salt with antitumour activity and preparation method thereof Expired - Fee Related CN104311434B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201410620217.2A CN104311434B (en) 2014-11-07 2014-11-07 Schuttgelb double-strand bi-quaternary ammonium salt with antitumour activity and preparation method thereof

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201410620217.2A CN104311434B (en) 2014-11-07 2014-11-07 Schuttgelb double-strand bi-quaternary ammonium salt with antitumour activity and preparation method thereof

Publications (2)

Publication Number Publication Date
CN104311434A true CN104311434A (en) 2015-01-28
CN104311434B CN104311434B (en) 2015-10-14

Family

ID=52366783

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201410620217.2A Expired - Fee Related CN104311434B (en) 2014-11-07 2014-11-07 Schuttgelb double-strand bi-quaternary ammonium salt with antitumour activity and preparation method thereof

Country Status (1)

Country Link
CN (1) CN104311434B (en)

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105152941A (en) * 2015-07-27 2015-12-16 福州大学 Anthraquinone compound with both alkylation reactive group and lipophilic positive ion
CN105399640A (en) * 2015-12-22 2016-03-16 福州大学 Aloe-emodin biquaternary ammonium salt with water solubility and anticancer activity and preparation thereof
CN105481742A (en) * 2015-12-01 2016-04-13 福建医科大学附属协和医院 Anthraquinonyl thioureas with anti-leukemia activity and water solubility, and preparation method thereof
CN105523948A (en) * 2015-12-22 2016-04-27 福州大学 1,4-dihydroxy anthraquinone bisbenzyl quaternary ammonium salt having water solubility and anticancer activity
CN111039806A (en) * 2019-12-27 2020-04-21 福州大学 Hydroxy benzoquinone biquaternary ammonium salt and preparation and application thereof

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102249941A (en) * 2011-05-24 2011-11-23 福州大学 Monohydroxy di(n-decyl) emodin quaternary ammonium salt with anticancer activity

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102249941A (en) * 2011-05-24 2011-11-23 福州大学 Monohydroxy di(n-decyl) emodin quaternary ammonium salt with anticancer activity

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
JINGWEI SHAO ET AL: "Synthesis and antitumor activity of emodin quaternary ammonium salt derivatives", 《EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY》, vol. 56, 7 August 2012 (2012-08-07), pages 308 - 319 *
郑君婷: "大黄素衍生物的合成及其抑制白血病细胞增殖作用的研究", 《中国实验血液学杂志》, vol. 21, no. 1, 31 December 2013 (2013-12-31), pages 53 - 56 *

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105152941A (en) * 2015-07-27 2015-12-16 福州大学 Anthraquinone compound with both alkylation reactive group and lipophilic positive ion
CN105481742A (en) * 2015-12-01 2016-04-13 福建医科大学附属协和医院 Anthraquinonyl thioureas with anti-leukemia activity and water solubility, and preparation method thereof
CN105399640A (en) * 2015-12-22 2016-03-16 福州大学 Aloe-emodin biquaternary ammonium salt with water solubility and anticancer activity and preparation thereof
CN105523948A (en) * 2015-12-22 2016-04-27 福州大学 1,4-dihydroxy anthraquinone bisbenzyl quaternary ammonium salt having water solubility and anticancer activity
CN105523948B (en) * 2015-12-22 2017-05-10 福州大学 1,4-dihydroxy anthraquinone bisbenzyl quaternary ammonium salt having water solubility and anticancer activity
CN105399640B (en) * 2015-12-22 2017-06-06 福州大学 Aloe-emodin bi-quaternary ammonium salt and its preparation with water-soluble and active anticancer
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

Also Published As

Publication number Publication date
CN104311434B (en) 2015-10-14

Similar Documents

Publication Publication Date Title
CN104311434B (en) Schuttgelb double-strand bi-quaternary ammonium salt with antitumour activity and preparation method thereof
Lolak et al. Design, synthesis and biological evaluation of novel ureido benzenesulfonamides incorporating 1, 3, 5-triazine moieties as potent carbonic anhydrase IX inhibitors
Cao et al. Synthesis and structure–activity relationships of harmine derivatives as potential antitumor agents
CN101967105B (en) Beta-hydroxy protected didecyl quaternary ammonium salt with anticancer activity and preparation method thereof
WO2018149231A1 (en) 7h-pyrrolo[2,3-d]pyrimidine derivative and anti-tumour use thereof
CN107021945A (en) A kind of analog derivative of myricetin containing piperazine acidamide and preparation method thereof
EP3487859B1 (en) Antimetastatic 2h-selenopheno[3,2-h]chromenes, synthesis thereof, and methods of using same agents
CN104387389A (en) 1,2,3-Triazole-flavonoid compound-sophocarpidine ternary conjugate and use
CN106749097B (en) A kind of chloro- 2- aminobenzothiazole analog derivative of 6- and its preparation method and application
CN103819350A (en) Chemical modification method capable of improving producing ability of reactive oxygen species (ROS) of rheum emodin
CN104086617B (en) Close dimethylamine derivative, the preparation method and its usage of flowers and trees ketone Cleistanone
CN102249941A (en) Monohydroxy di(n-decyl) emodin quaternary ammonium salt with anticancer activity
CN104356014B (en) Schuttgelb strand bi-quaternary ammonium salt with antitumour activity and preparation method thereof
CN104447322B (en) Single Demethoxycurcumin soluble derivative and its production and use
CN101941914B (en) Hydroxyl whole-protection didecyl quaternary ammonium with anti-tumor activity and preparation method thereof
CN105254679B (en) Single 6- (azacyclo- substitution) anthraquinone platinous chloride complex and its preparation method and application
CN102241598A (en) Monohydroxy emodin dioctyl quaternary ammonium salt with anticancer activity
Mustafa et al. Prodrug of 5-fluorouracil and 5-ethynyluracil: Synthesis, characterization, and release study
CN102381951A (en) Cyclohexanone-contained mono-carbonyl analogues of curcumin and usage thereof
CN105523948A (en) 1,4-dihydroxy anthraquinone bisbenzyl quaternary ammonium salt having water solubility and anticancer activity
CN102173997A (en) Liver cancer, gastric cancer and cervical cancer-resistant archen derivative and preparation method thereof
CN105017042A (en) Preparation methods for anthraquinone and naphthoquinone quaternary ammonium salts with leukemia resisting function
Mustafa et al. Synthesis, antioxidant and antitumor activities of new coumarins grafted to 5-fluorouracil
JP6694894B2 (en) Glococalixin A derivative, its preparation method and application
CN101186606A (en) Ampelopsin derivative, synthesizing method thereof and application of the same in preparing antineoplastic medicine

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
C14 Grant of patent or utility model
GR01 Patent grant
CF01 Termination of patent right due to non-payment of annual fee

Granted publication date: 20151014

Termination date: 20191107

CF01 Termination of patent right due to non-payment of annual fee