CN107573318A - A kind of new gossypol Schiff bases derivative and its synthetic method for having antitumor activity - Google Patents
A kind of new gossypol Schiff bases derivative and its synthetic method for having antitumor activity Download PDFInfo
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- CN107573318A CN107573318A CN201710815412.4A CN201710815412A CN107573318A CN 107573318 A CN107573318 A CN 107573318A CN 201710815412 A CN201710815412 A CN 201710815412A CN 107573318 A CN107573318 A CN 107573318A
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- PNFPHMKKFFIXGO-UHFFFAOYSA-N CC(C)c(c(C=C(C)CC1)c1c(C=C)c1C2C=C2)c1O Chemical compound CC(C)c(c(C=C(C)CC1)c1c(C=C)c1C2C=C2)c1O PNFPHMKKFFIXGO-UHFFFAOYSA-N 0.000 description 1
Abstract
The invention discloses a kind of new gossypol Schiff bases derivative with anticancer activity and its synthetic method.Such compound is reacted in non-polar organic solvent using Rhodamine 123 and gossypol acetate as initiation material, reaction terminate after crude product separates by recrystallization, silica gel column chromatography and produces the Schiff bases compound A and compound B.This method reactions steps are few, and reaction condition is gentle, and raw material availability is high, suitable for industrialized production.
Description
Technical field
The present invention relates to medicinal chemistry arts, and in particular to a kind of new gossypol Schiff bases for having antitumor activity derives
The structure and its synthetic method of thing.
Background technology
Rhodamine 123 (Rh 123) is a kind of conventional Cationic green fluorescent dye, can pass through cell membrane so as to
Assemble in living cells mitochondria, and send yellow-green fluorescence, the fluorescence probe as detection mitochondrial membrane potential, and to cell
There is no any toxicity.As a kind of conventional biological stain material, there is research to confirm that Rhodamine 123 also has necessarily thin in itself
Cellular toxicity, it is widely used in cancer research such as：Liver cancer, carcinoma of urinary bladder, cancer of pancreas etc., researcher pass through its fluorescence in cancer cell
It is distributed so as to analyze the cancer cell situation of change under medicine effect, the research for cancer has great importance.
Gossypol is widely present in the color of the epidermal tissues such as the root of cotton, seed as a kind of sesquiterpene plant antibiotic
In plain body of gland, its pharmacological action is extensive, in addition to antifertility action also there is antitumor, anti parasitic and the biology such as antiviral to live
Property, it is particularly its significant anti-tumor capacity so that Research Prospects of the gossypol in therapeutic field of tumor are very wide.Grind at present
Study carefully and find that gossypol shows significant Inhibit proliferaton in the oncotherapies such as prostate cancer, lymthoma, head and neck neoplasm, colon cancer
With apoptosis-induced ability, further research confirms that gossypol is a kind of anti-apoptotic proteins Bcl-2/Bcl-XL little molecules in inhibiting
It agent, can specifically bind in Bcl-2/Bcl-XL BH3 sites, prevent it from forming heterodimer with pro apoptotic protein Bax etc.,
Suppress Bcl-2/Bcl-XL anti-apoptotic function, play the effect of inducing apoptosis of tumour cell.It is clinically used for malignant tumour at present
Toxic and side it is stronger, it is obvious to bone marrow inhibition, and can gradually produce drug resistance, cotton after long-term use
Phenol has significant Synergistic action as natural drug, and side effect is smaller, and its metabolite oxidation gossypol equally has in addition
Significant antitumor action.Therefore, the antitumor activity for gossypol and its derivative has become the heat of current research
Point.
Schiff base compounds are because its unique architectural feature, i.e. core group contain the N atoms with lone pair electrons, so as to have
There is good pairing ability so that such compound great characteristic in practical application, therefore, by using Luo Dan in the present invention
The aldehyde radical of exposed amino and gossypol combines to form active imine structure on bright 123, so as to obtain a kind of new gossypol schiff bases
Class compound, by illustrating that the synthetic method of the compound verifies such gossypol Schiff bases with reference to preliminary pharmacological experiment
The antitumor action of compound, it was confirmed that target compound A and B has higher medical research and application in antitumor treatment
Value.
The content of the invention
It is an object of the invention to provide a kind of new gossypol Schiff bases derivative for having antitumor activity and its preparation side
Method.
Its structural formula of compound of the present invention is as shown in formula A and formula B：
The technical scheme is that it is initiation material in non-polar organic solvent to use Rhodamine 123 and gossypol acetate
Reaction, silica gel column chromatography is carried out after being recrystallized by polar solvent and obtains two kinds of new gossypol Schiff bases derivatives.
The synthetic route of the compound provided by the invention is as follows：
In order to realize said synthesis route, synthesis step of the invention is as follows：
(1) Rhodamine 123 and gossypol are dissolved in non-polar organic solvent respectively, heating reflux reaction 10~14 hours；
(2) thin-layer chromatography method tracking reaction stops heating to complete, and mixture A and B are filtered to obtain after cooling down reaction solution；
(3) mixture A and B crude product are added in reactor, add polar organic solvent and recrystallized, decompression is dense
Contract to obtain solid-liquid mixed concentrated liquid；
(4) column chromatography for separation is carried out to solid-liquid mixed concentrated liquid obtained by above-mentioned (3), TCL tracks to target product A and product
B is enriched with fully respectively；Fractional Collections eluent concentrates respectively, stand crystallization after filter, be drying to obtain target product A and product B.
The preferred toluene of non-polar organic solvent, chloroform, more preferably ethyl acetate, chloroform in above-mentioned steps (1).
The mol ratio of gossypol acetate and Rhodamine 123 in above-mentioned steps (1) is 1:2~1:2.5, more preferably 1:
2.2。
Reaction time in above-mentioned steps (1) is preferably 10~12 hours, more preferably 12 hours.
Recrystallization polar solvent in above-mentioned steps (3) is preferably acetone or methanol, more preferably acetone.
Column chromatography eluent in above-mentioned steps (4) is preferably chloroform：Methanol=10：1.
The advantage of the invention is that：Reaction raw materials are cheap and easy to get, and reactions steps are few, and processing safety is high, reaction raw materials profit
High with rate, suitable for industrialized production, compound structure is novel and has higher researching value.
Specific embodiment
With reference to specific embodiment, the present invention is further elaborated.These embodiments are only in order at the mesh of explanation
, and do not limit the scope of the invention and essence.
Embodiment 1
Compound A dimethyl2,2'- (6,6'- ((1Z, 1'E)-((1,1', 6,6', 7,7'-hexahydroxy-5,
5'-diisopropyl-3,3'-dimet hyl-[2,2'-binaphthalene]-8,8'-diyl)bis
(methanylylidene))bis(azanylylidene))bis(3-imino-3H-xanthe ne-9,6-diyl))
Dibenzoate and compound B (Z)-methyl2- (6- (((8'-formyl-1,1', 6,6', 7,7'-hexahydroxy-5,
5'-diisopropyl-3,3'-dimethyl-[2,2'-binaphthalen]-8-yl)methylene)amino)-3-
Imino-3H-xanthen-9-yl) be nzoate preparation.
Accurately weigh gossypol acetate 103.71mg (0.2mmol) and Rhodamine 123 131.7mg (0.4mmol) is used respectively
It is placed in after the dissolving of 20mL chloroforms and then mixing in round-bottomed flask, 40 DEG C is warming up under magnetic agitation, is reacted 12 hours.Thin-layer chromatography
Method tracking reaction removes condensing unit, mixture A, B crude product is filtered to obtain after reaction solution cooling, by institute to complete, stopping heating
The crude product obtained adds after 25ml acetone is recrystallized and concentrates reaction solution, and concentrate is through 100ml eluents chloroform-methanol (10:
1) elute, compound A and B are enriched with according to TCL tracking result Fractional Collections eluents, pregnant solution stands analysis respectively repeatedly
Crystalline substance, suction filtration are drying to obtain compound A-40 .52g, compound B0.15g, and total moles yield is 67%.
Compound A:
1H-NMR(300MHz,DMSO-d6)δ(ppm):11.04 (2H, s), 9.74 (2H, s), 8.12 (2H, d, J=
7.5Hz), 8.01 (2H, d, J=10.9Hz), 7.82 (2H, s), 7.50-7.68 (6H, m, J=7.5Hz, J=1.5Hz), 7.14
(2H, d, J=7.5Hz), 6.93 (2H, s), 6.81-6.83 (4H, m, J=1.5Hz), 6.01 (2H, d), 5.54 (6H, s),
3.78 (6H, s), 2.71 (2H, m, J=6.8Hz), 2.63 (6H, s), 1.25 (12H, d, J=6.8Hz)；13C-NMR(75MHz,
DMSO-d6)δ(ppm):167.2,165.3,154.2,153.7,152.8,151.8,149.2,147.1,143.1,141.4,
138.4,133.3,132.4,131.5,130.2,130.8,130.2,129.7,127.7,126.5,126.0,125.2,
118.8,117.0,116.4,115.4,113.3,111.2,110.1,103.9,100.4,52.5,28.4,27.1,22.8；MS
(ESI)for(M+H)+:1171.4.
Compound B:
1H-NMR(300MHz,DMSO-d6)δ(ppm):10.84(1H,s),10.11(1H,s),9.53(1H,s),8.21
(2H, d, J=10.9Hz), 8.04 (2H, s), 7.44-7.79 (3H, m, J=7.5Hz), 7.32 (1H, s), 7.01 (1H, s),
6.91-6.94 (2H, m, J=1.5Hz), 6.42 (1H, d), 5.62 (6H, s), 3.82 (3H, s), 2.74 (2H, m, J=
6.8Hz), 2.66 (6H, s), 1.22 (12H, d, J=6.8Hz)；13C-NMR(75MHz,DMSO-d6)δ(ppm):194.1,
167.0,163.3,153.0,152.8,152.1,148.9,145.1,143.1,141.6,138.4,134.1,132.4,
132.1,131.9,130.8,127.7,126.6,126.0,124.8,117.8,116.6,116.0,115.4,114.4,
113.9,112.3,111.2,110.1,105.9,102.4,54.5,29.4,26.1,21.5；MS(ESI)for(M+H)+:
845.3.
Embodiment 2
Compound A dimethyl2,2'- (6,6'- ((1Z, 1'E)-((1,1', 6,6', 7,7'-hexahydroxy-5,
5'-diisopropyl-3,3'-dimet hyl-[2,2'-binaphthalene]-8,8'-diyl)bis
(methanylylidene))bis(azanylylidene))bis(3-imino-3H-xanthe ne-9,6-diyl))
Dibenzoate and compound B (Z)-methyl2- (6- (((8'-formyl-1,1', 6,6', 7,7'-hexahydroxy-5,
5'-diisopropyl-3,3'-dimethyl-[2,2'-binaphthalen]-8-yl)methylene)amino)-3-
Imino-3H-xanthen-9-yl) be nzoate preparation.
Accurately weigh gossypol acetate 103.71mg (0.2mmol) and Rhodamine 123 158.1mg (0.48mmol) is used respectively
It is placed in after the dissolving of 25mL toluene and then mixing in round-bottomed flask, 60 DEG C is warming up under magnetic agitation, is reacted 12 hours.Thin-layer chromatography
Method tracking reaction removes condensing unit, mixture A, B crude product is filtered to obtain after reaction solution cooling, by institute to complete, stopping heating
The crude product obtained adds after 25ml ethanol is recrystallized and concentrates reaction solution, and concentrate is through 200ml eluents chloroform-methanol (10:
1) elute, compound A and B are enriched with according to TCL tracking result Fractional Collections eluents, pregnant solution stands analysis respectively repeatedly
Crystalline substance, suction filtration are drying to obtain compound A-40 .42g, compound B0.17g, and total moles yield is 53%.
Embodiment 3
Compound A dimethyl2,2'- (6,6'- ((1Z, 1'E)-((1,1', 6,6', 7,7'-hexahydroxy-5,
5'-diisopropyl-3,3'-dimet hyl-[2,2'-binaphthalene]-8,8'-diyl)bis
(methanylylidene))bis(azanylylidene))bis(3-imino-3H-xanthe ne-9,6-diyl))
Dibenzoate and compound B (Z)-methyl2- (6- (((8'-formyl-1,1', 6,6', 7,7'-hexahydroxy-5,
5'-diisopropyl-3,3'-dimethyl-[2,2'-binaphthalen]-8-yl)methylene)amino)-3-
Imino-3H-xanthen-9-yl) be nzoate preparation.
Accurately weigh gossypol acetate 103.71mg (0.2mmol) and Rhodamine 123 168.1mg (0.5mmol) is used respectively
It is placed in after the dissolving of 25mL ethyl acetate and then mixing in round-bottomed flask, 60 DEG C is warming up under magnetic agitation, is reacted 12 hours.Thin layer
Chromatography method tracking is reacted to complete, stopping heating, removes condensing unit, mixture A, B crude product is filtered to obtain after reaction solution cooling,
The crude product of gained is added after 25ml acetone is recrystallized and concentrates reaction solution, concentrate is through 200ml eluent chloroform-methanols
(5:1) elute, compound A and B are enriched with repeatedly according to TCL tracking result Fractional Collections eluents, pregnant solution difference is quiet
Crystallization is put, suction filtration is drying to obtain compound A-40 .37g, compound B0.15g, and total moles yield is 47%.
Embodiment 4
The antitumor activity test of the compounds of this invention
Cytostatic to tumor cell experiment is carried out to the compound of the present invention, test method is using conventional mtt assay.
Cell line is selected：Human Prostate Cancer Cells (DU145), human lung carcinoma cell (A-549), gastric carcinoma cells (SGC-
7901).Nutrient solution is that DMEM+15%NBS+ is dual anti-.
The preparation of sample liquid：After being dissolved with DMSO (Merck), add 100 μm of ol/L solution that PBS (-) is made into or
Uniform suspension, then with DMSO PBS (-) dilution, ultimate density is respectively 0.1,1,10,20,40,60,80,100 μ
mol/L。
It is molten that the antineoplastic gossypol acetate (Acetate gossypol) of listing with same condition is made into reference substance
Liquid.
Cell culture：Adherent growth tumor cell is incubated at containing 10% inactivation NBCS and penicillin, strepto-
In the 1640 culture medium of plain (each 1,000,000 U/L), 37 DEG C are placed in, 5%CO2, cultivate in the CO2gas incubator of saturated humidity.
Cell attachment is grown, and passes on 1 time within every 2~3 days, pours out nutrient solution first during passage, and PBS is washed 2 times, after pancreatin digestion, is added new
Fresh nutrient solution piping and druming is uniform, and adjustment cell to debita spissitudo is moved into new blake bottle, and addition nutrient solution is to appropriate.Take the logarithm
Growth period cell is used to test.
Mtt assay detects cytoactive and IC50Measure：
Experimental principle：The MTT of yellow can be reduced into bluish violet product not soluble in water by dehydrogenase in living cells mitochondria
Formazan (MTT formazan), and be deposited in cell, the amount of generation is directly proportional to number of viable cells, and dead cell is not this
Function.DMSO can dissolve bluish violet crystal, and shade is directly proportional to contained amount, therefore the light absorbs determined with ELIASA
Value can reflect cell survival rate.
Experimental method：Take the logarithm growth period cell, digestion, count, 96 well culture plates are inoculated in 2 × 104/mL density
In, per the μ l of hole 100.Culture 24 hours after, by testing compound with 0.1,1,10,20,40,60,80,100 μm of ol/L concentration at
Manage cell.The each concentration of experimental group sets 5 multiple holes, is compared with the nutrient solution containing 0.4%DMSO.After medicine acts on 48 hours,
Supernatant is removed, 100 μ l MTT (2- (4,5- dimethyl -2- thiazolyls) -3,5- diphenyl -2H- tetrazoliums hydrobromate) are added per hole
(1mg/mL), continue culture 4 hours, abandon supernatant, 100 μ l DMSO are added per hole, vibration is mixed, surveyed with ELIASA at 570nm
Absorbance is determined, using IC50Software for calculation obtains half-inhibition concentration (IC50)。
Result of the test refers to table 1, wherein, sample refers to the gossypol Schiff bases derivative prepared in corresponding embodiment, sample
The corresponding specific numbering for preparing compound resulting in embodiment of product numbering.
Half-inhibition concentration IC of the compound of table 1 to different tumour cells50(unit：μmol/L)
Detection data show that compound A and B shows good antitumor work in the 3 kinds of cell lines tested
Property, good antitumor activity is also shown in different cell lines.Above test result indicates that, compound of the invention
With good antitumor activity, the research available for antineoplastic.
Claims (9)
1. structural formula (A) and the compound shown in (B),
2. compound according to claim 1, it is characterised in that：Using Rhodamine 123 and gossypol acetate as initiation material in
Synthesized in non-polar organic solvent.
3. synthetic method according to claim 2, it is characterised in that synthetic route is as follows：
Specific preparation process is as follows：
(1) Rhodamine 123 and gossypol are dissolved in non-polar organic solvent respectively, heating reflux reaction 10~14 hours；
(2) thin-layer chromatography method tracking reaction stops heating to complete, and mixture A and B are filtered to obtain after cooling down reaction solution；
(3) mixture A and B crude product are added in reactor, add polar organic solvent and recrystallized, is concentrated under reduced pressure
Solid-liquid mixed concentrated liquid；
(4) column chromatography for separation is carried out to solid-liquid mixed concentrated liquid obtained by above-mentioned (3), TCL tracks to target product A and product B and divided
Fu Ji not be fully；Fractional Collections eluent concentrates respectively, stand crystallization after filter, be drying to obtain target product A and product B.
4. target product A according to claim 3 synthetic method, it is characterised in that：It is nonpolar in above-mentioned steps (1)
The preferred toluene of organic solvent, chloroform, more preferably ethyl acetate, chloroform.
5. target product A according to claim 3 synthetic method, it is characterised in that：Acetic acid cotton in above-mentioned steps (1)
The mol ratio of phenol and Rhodamine 123 is 1:2~1:2.5, more preferably 1:2.2.
6. target product A according to claim 3 synthetic method, it is characterised in that：During reaction in above-mentioned steps (1)
Between be preferably 10~12 hours, more preferably 12 hours.
7. target product A according to claim 3 synthetic method, it is characterised in that：Recrystallization in above-mentioned steps (3)
Polar solvent is preferably acetone or methanol, more preferably acetone.
8. target product A according to claim 3 synthetic method, it is characterised in that：Column chromatography in above-mentioned steps (4)
Eluent is preferably chloroform：Methanol=10：1.
9. application of the compound shown in claim 1 in treatment prostate cancer, lung cancer or gastric cancer medicament is prepared.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109942455A (en) * | 2019-03-10 | 2019-06-28 | 陕西科技大学 | Gossypol with anti-tumor activity-Eflornithine schiff base compounds and its synthetic method |
| CN112624942A (en) * | 2020-07-08 | 2021-04-09 | 陕西盘龙医药股份有限公司 | Gossypol isocyanate derivative with anti-leukemia activity and synthesis method thereof |
| CN114315673A (en) * | 2022-01-12 | 2022-04-12 | 陕西科技大学 | Gossypol-selenocysteine Schiff base compound and synthetic method and application thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102311449A (en) * | 2010-07-02 | 2012-01-11 | 中国科学院上海生命科学研究院 | Application of gossypol derivative to preparing anti-tumor medicament |
| CN105503627A (en) * | 2015-12-10 | 2016-04-20 | 武汉大学 | Novel gossypol Schiff-base derivative and preparation and application thereof |
| CN106232109A (en) * | 2014-02-27 | 2016-12-14 | 国立癌中心 | Comprise gossypol and the phenformin pharmaceutical composition for treatment of cancer as active component |
-
2017
- 2017-09-12 CN CN201710815412.4A patent/CN107573318A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102311449A (en) * | 2010-07-02 | 2012-01-11 | 中国科学院上海生命科学研究院 | Application of gossypol derivative to preparing anti-tumor medicament |
| CN106232109A (en) * | 2014-02-27 | 2016-12-14 | 国立癌中心 | Comprise gossypol and the phenformin pharmaceutical composition for treatment of cancer as active component |
| CN105503627A (en) * | 2015-12-10 | 2016-04-20 | 武汉大学 | Novel gossypol Schiff-base derivative and preparation and application thereof |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109942455A (en) * | 2019-03-10 | 2019-06-28 | 陕西科技大学 | Gossypol with anti-tumor activity-Eflornithine schiff base compounds and its synthetic method |
| CN112624942A (en) * | 2020-07-08 | 2021-04-09 | 陕西盘龙医药股份有限公司 | Gossypol isocyanate derivative with anti-leukemia activity and synthesis method thereof |
| CN112624942B (en) * | 2020-07-08 | 2024-04-02 | 陕西盘龙医药股份有限公司 | Gossypol isocyanate derivative with anti-leukemia activity and synthesis method thereof |
| CN114315673A (en) * | 2022-01-12 | 2022-04-12 | 陕西科技大学 | Gossypol-selenocysteine Schiff base compound and synthetic method and application thereof |
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