CN108299257A - Ten disulfoxide of 2- -1,4-naphthoquinone compound, preparation method and using the compound as the drug of active constituent - Google Patents
Ten disulfoxide of 2- -1,4-naphthoquinone compound, preparation method and using the compound as the drug of active constituent Download PDFInfo
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- C07C315/00—Preparation of sulfones; Preparation of sulfoxides
- C07C315/02—Preparation of sulfones; Preparation of sulfoxides by formation of sulfone or sulfoxide groups by oxidation of sulfides, or by formation of sulfone groups by oxidation of sulfoxides
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- C07—ORGANIC CHEMISTRY
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Abstract
20 disulfoxide Isosorbide-5-Nitrae naphthoquinone compounds, preparation method and using the compound as the drug of active constituent belong to pharmaceutical technology field.Its structural formula is:The method of the present invention:One, it is dissolved in ethyl alcohol using Isosorbide-5-Nitrae naphthoquinones, 1 lauryl mercaptan is added and prepares 20 dimercapto Isosorbide-5-Nitrae naphthoquinones;Two, 20 dimercapto Isosorbide-5-Nitrae naphthoquinones are dissolved in chloroform, metachloroperbenzoic acid is added thereafter, react 1.2h under the conditions of 0 DEG C, NaHCO is added after the reaction was complete3It terminates and reacts after superfluous metachloroperbenzoic acid in solution neutralization reaction, reaction product is extracted through chloroform and saturated sodium-chloride, and anhydrous sodium sulfate drying is filtered, is concentrated and dried, 20 disulfoxide Isosorbide-5-Nitrae naphthoquinones are obtained after ethyl alcohol recrystallization.The application of the compound of the present invention and pharmaceutical composition in the drug for preparing treatment gastric cancer.
Description
Technical field
The invention belongs to pharmaceutical technology fields;More particularly to a kind of ten disulfoxide of 2- -1,4-naphthoquinone compound, preparation method and
Using the compound as the pharmaceutical composition of active constituent.
Background technology
Traditional new drug development approach is to be developed using effective components from natural materials as lead compound and study new drug.It is purple
Grass is that medicinal history is long, the extensive traditional Chinese medicine of pharmacological action, and main pharmacodynamics ingredient alkannin right and wrong are latent often with there is development
The lead compound of power.Alkannin, which is the naphthoquinone compound of representative, has anti-inflammatory, antibacterial, antiviral, anti-malarial, antitumor etc.
A variety of physiological activity.Especially in anticancer research, reports that it has and inhibited growth of tumour cell, inducing cell apoptosis, suppression
DNA topoisomerases processed inhibit protein tyrosine kinase, a variety of mechanism of action such as anti-angiogenesis.Therefore, naphthoquinones class is always
The interested a kind of compound of Many researchers.
The drug of clinical treatment gastric cancer is divided into fluorouracil drug (Tegafur, excellent fudding, 5- fluorine by the difference of the mechanism of action
Uracil etc.), cell cycle specific drugs (mitomycin, cis-platinum, adriamycin etc.), molecular targeted agents (Herceptin,
Avastin, Cetuximab etc.).Currently, clinical treatment cancer is for the purpose of killing cancer cell, but chemotherapy is not distinguished
Other ability kills a large amount of normal cell often while killing cancer cell, and epilation occurs in patient after multiple chemotherapy,
The symptoms such as lean body mass, functions of intestines and stomach are disorderly, nausea and vomiting, and low fever does not move back, these be clinically curing gastric cancer drug it is universal
Defect.
Invention content
The present invention provides a kind of ten disulfoxide of 2- -1,4-naphthoquinone compound, preparation method and with the compound be activity at
The pharmaceutical composition divided.The 1,4-naphthoquinone analog derivative that the Research foundation of the present invention does not contain hydroxyl mainly for 5,8 reduces
The toxic side effect of compound itself, curative effect is better than the anticancer drug 5 FU 5 fluorouracil (5-FU) clinically applied, and stimulates
Property and toxicity are low.Also there is certain targeting to cancer cell, it is relatively low to the lethal effect of normal cell.
In order to solve the above technical problems, the structural formula of ten disulfoxide of 2- -1,4-naphthoquinone compound of the present invention is:
Preparation method carries out in the steps below:
One, 1,4-naphthoquinone is dissolved in ethyl alcohol (amount of ethyl alcohol meets fully dissolving 1,4-naphthoquinone), 12 sulphur of 1- is added
Alcohol reacts 2h~4h at room temperature, and sodium dichromate and the concentrated sulfuric acid is then added, the reaction was continued 5min-10min, with chloroform and saturation
Sodium chloride extracts, and anhydrous sodium sulfate drying, filtering is concentrated under reduced pressure drying, obtains ten dimercaptos of 2- -1,4-naphthoquinone;
Two, the ten dimercapto -1,4- naphthoquinones of 2- that step 1 obtains is dissolved in chloroform (the amount satisfaction of chloroform fully dissolving 2-
Ten dimercaptos -1,4-naphthoquinone), metachloroperbenzoic acid is then added, 1.2h is reacted under the conditions of 0 DEG C, after the reaction was complete
10% (quality) NaHCO is added3Reaction is terminated in solution neutralization reaction after superfluous metachloroperbenzoic acid, reaction product is through chlorine
Imitative to be extracted with saturated nacl aqueous solution, anhydrous sodium sulfate drying is filtered, is concentrated and dried, and 12 Asias 2- are obtained after ethyl alcohol recrystallization
Sulfone -1,4- naphthoquinones.
It further limits, the molar ratio of 1- lauryl mercaptans and 1,4-naphthoquinone is 1.2 in step 1:1.
It further limits, the molar ratio of sodium dichromate and 1,4-naphthoquinone is 1 in step 1:2, the concentrated sulfuric acid and 1,4-naphthoquinone rub
You are than being 1:5.
The molar ratio of metachloroperbenzoic acid and ten dimercapto -1,4- naphthoquinones of 2- is 1.2 in step 2:1.
The pharmaceutical composition of the present invention contains claim 1 compound and pharmaceutically acceptable carrier of therapeutically effective amount.
The application of the compound of the present invention and pharmaceutical composition in the drug for preparing treatment gastric cancer.
Pharmaceutically acceptable carrier described above refers to the pharmaceutical carrier of pharmaceutical field routine, such as:Diluent, excipient are such as
Water etc., filler such as starch slurry, hydroxypropyl methylcellulose, povidone, syrup etc., wetting agent such as ethyl alcohol, water etc., disintegrant is such as dry to form sediment
Powder, Sodium Hydroxymethyl Stalcs, low-substituted hydroxypropyl cellulose, gas-producing disintegrant, crospovidone etc., sorbefacient such as sulfuric acid
Calcium, calcium monohydrogen phosphate, light magnesium oxide, calcium carbonate etc., absorption carrier such as chitosan etc., lubricant for example magnesium stearate, poly- diethanol,
Talcum powder, hydrogenated vegetable oil, superfine silica gel powder etc., colorant such as titanium dioxide, sunset yellow, methylenum careuleum, medicinal iron oxide red etc., packet
Clothing material such as acrylic resin, hydroxyl methylcellulose, povidone, cellacefate etc..In addition it can which it is added in the composition
Its auxiliary material such as flavouring agent and sweetener etc..
The Pharmaceutical composition of the present invention can be applied to the trouble for needing this treatment by way of oral, rectum or parenteral administration
Person.When for taking orally, it can be made into conventional solid pharmaceutical preparation such as tablet, capsule, pulvis, granule etc., liquid preparation is made
Such as water or oil-suspending agent or other liquid preparations such as syrup, oral solution, elixir;When for parenteral administration, it can be made into
Solution, powder needle, water or oleaginous suspension of injection etc..Preferred form is tablet, coated tablet, capsule, granule, takes orally
Liquid and injection.
The various dosage forms of the Pharmaceutical composition of the present invention can be prepared according to the conventional production process of pharmaceutical field.Such as make this change
It closes object active constituent to mix with one or more carriers, is then made into required dosage form.
The Pharmaceutical composition of the present invention preferably comprises the active constituent that molar ratio is 0.1%-99.5%, most preferably molar ratio
For the active constituent of 0.5%-95%.
The amount of application of the Pharmaceutical composition of the present invention can according to route of administration, patient age, weight, body surface area, treated
The variations such as the type and severity of disease, daily dose can be 0.01-100mg/m2Body surface area, preferably 10-100 mg/
m2Body surface area.It one or many can apply.
The present invention provides a kind of new ten disulfoxide of compound 2- -1,4-naphthoquinone, and the 5 of the compound, 8 do not contain any substitution
Base, and 2 are replaced by sulfydryl, and 2 sulphur are oxidized to sulfoxide so that naphthoquinone compound has more superior active anticancer.
The present invention lowers the phosphorylation level of Akt, makes pro apoptotic protein Bad, cleaved- by the phosphorylation level of up-regulation JNK
Caspase-3 and cleaved-PARP expression quantity gradually rises, and pro-caspase-3 and pro-PARP are continuously decreased, anti-apoptotic
Protein Bcl-2 expression quantity continuously decreases, and then induces stomach cancer cell that apoptosis occurs.
Present invention uses ethyl alcohol recrystallization method, the purity and final product that improve compound prepare yield
The compound of the present invention activity is high, using low concentration compound when can kill cancer cell well.
The compound of the present invention has certain targeting to cancer cell, and relatively low to normal cell toxicity.
The synthetic method craft of the compound of the present invention is simple, easy to operate.
The compound of the present invention is almost without by-product, product purity 98%.
The compound of the present invention yield is higher, yield general 48%.
The compound of the present invention cost is relatively low.
Description of the drawings
Fig. 1 is lethal effects of the DSNQ to human gastric cancer ags cell;
Fig. 2 is lethal effects of the DSNQ to human gastric cancer MKN-28 cells;
Fig. 3 is lethal effects of the DSNQ to human gastric cancer MKN-45 cells;
Fig. 4 is lethal effects of the DSNQ to human gastric cancer SNU-5 cells;
Fig. 5 is lethal effects of the DSNQ to human gastric cancer SNU-216 cells;
Fig. 6 is lethal effects of the DSNQ to human gastric cancer SNU-484 cells;
Fig. 7 is lethal effects of the DSNQ to human gastric cancer NCI-N87 cells;
Fig. 8 is lethal effects of the DSNQ to human gastric cancer YCC-1 cells;
Fig. 9 is lethal effects of the DSNQ to human gastric cancer YCC-6 cells;
Figure 10 is lethal effects of the DSNQ to human gastric cancer YCC-16 cells;
Figure 11 is lethal effects of the DSNQ to human gastric cancer KATO-3 cells;
Figure 12 A are after DSNQ handles ags cell, to utilize fluorescence microscope Apoptosis situation map;
Figure 12 B are the quantitative analysis figure of Figure 12 A;
Figure 13 A are after DSNQ handles ags cell, to utilize Apoptosis by Flow Cytometry situation map;
Figure 13 B are the quantitative analysis figure of Figure 13 A;
Figure 14 A are after DSNQ handles ags cell, and Western blotting methods detect the expression feelings of downstream apoptotic GAP-associated protein GAP
Condition;
Figure 14 B are the quantitative analysis figure of Figure 14 A;
Figure 15 A are after DSNQ handles ags cell, and Western blotting methods detect the expression feelings of upstream apoptosis-related protein
Condition;
Figure 15 B are the quantitative analysis figure of Figure 15 A.
Specific implementation mode
Below in conjunction with the accompanying drawings and specific embodiment the present invention is described further:
Embodiment:The preparation of ten disulfoxide -1,4- naphthoquinones of 2- in the present embodiment:
(1) synthesis of ten dimercapto -1,4- naphthoquinones of 2-
In 100ml reaction bulbs, 1,4-naphthoquinone 158.15mg (1mmol) and ethyl alcohol 30ml is added, 1- ten is added after mixing
After reacting 3h at room temperature, 59.6 mg of sodium dichromate (0.2mmol) is added into mixture by two mercaptan, 266.6 μ 1 (1.5mmol)
With 40.8 μ 1 (0.75mmol) of the concentrated sulfuric acid, terminate after reacting 10min.It is extracted through chloroform and saturated nacl aqueous solution, it is appropriate anhydrous
Sodium sulphate is dried, and filtering is concentrated under reduced pressure into drying, obtains crude product, prepared through TLC, obtains ten dimercaptos of 2- -1,4-naphthoquinone.
(2) synthesis (DSNQ) of ten disulfoxide -1,4- naphthoquinones of 2-
In 50ml reaction bulbs, ten dimercaptos of above-mentioned product 2- -1,4-naphthoquinone 302.43mg (1mmol) and chloroform 20ml is added,
It is slowly added into metachloroperbenzoic acid (MCPBA) 207.08mg (1.2mmol), 0 DEG C of reaction 1.2h is added 10% after the reaction was complete
NaHCO3Solution terminates reaction.It is extracted through chloroform and saturated sodium-chloride, anhydrous sodium sulfate drying, filtering is concentrated to dryness, obtains
Crude product is prepared through TLC, and ten disulfoxide of 2- -1,4-naphthoquinone is obtained after ethyl alcohol recrystallization, (the character of product:Blackish green crystal).Production
The structural formula of product:
Product purity 98%.
Using following verification experimental verification invention effects:
One, lethal effects of the DSNQ to cancer cell
Experimental method:(MTT experiment)
1. inoculating cell:9 kinds of stomach cancer cells are made into list respectively with DMEM the or RPMI1640 culture mediums containing 10% fetal calf serum
A cell suspension is 199 μ l per pore volume with 10000, every hole cell inoculation to 96 orifice plates;
2. cultivating cell:5%CO2, 37 DEG C are incubated for 24 hours, until adherent cell monolayers are paved with bottom hole;
3. serum starvation:The culture medium containing 1% fetal calf serum is replaced before dosing 2h;
4. drug-treated:The DSNQ prepared is handled into 11 kinds of gastric carcinoma cells (AGS, MKN-28, MKN-45, SNU- for 24 hours respectively
5, SNU-216, SNU-484, NCI-N87, YCC-1, YCC-6, YCC-16 and KATO-3) 0.1,0.3,1,3,10,30 and 100 μ
M;
5. color reaction:MTT solution (5mg/ml, DMSO dissolve, pH 7.4) 20 μ l are added to continue after being incubated 2-4 h per hole, carefully
Supernatant culture medium in hole is sucked, is washed 2 times using PBS, adds 100 μ l dimethyl sulfoxide (DMSO)s (DMSO) per hole, is shaken on horizontal shaker
10min makes crystallization fully dissolve;
6. colorimetric:490nm wavelength is selected, each hole absorbance value is measured on enzyme-linked immunosorbent assay instrument, is recorded as a result, with a concentration of
Abscissa, cell survival rate are that ordinate draws cell growth block diagram, the result is shown in Figure 1-Figure 11 and table 1.
Interpretation of result:
In Fig. 1-Figure 11 it can be seen that DSNQ to human gastric cancer AGS, MKN-28, MKN-45, SNU-5, SNU-216, SNU-484,
NCI-N87, YCC-1, YCC-6, YCC-16 and KATO-3 cell all have good lethal effect, and killing intensity is dense with drug
The increase of degree and gradually rise.
By the following table 1 it can also be seen that DSNQ pairs of 11 kinds of gastric carcinoma cells all have good lethal effect, especially gastric cancer AGS,
Sensitivity highest of the MKN-28 and MKN-45 cells to DSNQ.
ICs of 1 DSNQ of table to gastric carcinoma cells lethal effect50Value
Two, apoptosis-induced effects of the DSNQ to cancer cell
Experimental method:(experiment in vitro-Annexin V-FITC decoration methods)
1. inoculating cell:It is made into individual cells suspension with the culture medium containing 10% fetal calf serum, is connect with 10,000, every hole cell
Kind is 1ml to 12 orifice plates, per pore volume;
2. cultivating cell:5%CO2, 37 DEG C are incubated for 24 hours, until adherent cell monolayers are paved with bottom hole;
3. drug-treated:It is added the DSNQ for preparing, processing different time (3,6,12 and for 24 hours);
4. being washed 2 times with PBS, 195 μ lAnnexin V-FITC combination liquid are added, add 5 μ lAnnexin V-FITC gently
Mixing;
5. 10 μ, 1 propidium iodides (Propidium Iodide, PI) dyeing liquor is added, gently mixing;
6. room temperature (20-25 DEG C) is protected from light incubation 15 minutes;
7. (A) is contaminated in the change of the form and color of fluorescence microscopy microscopic observation cell, green fluorescence for AnnexinV-FITC
Color positive cell, red fluorescence are propidium iodide positive cells.It is only dyed by green fluorescence, and the cell of small volume is apoptosis
Cell;By red or green and red double dyes, and the larger cell of volume is non-viable non-apoptotic cell;The cell not being colored is normal thin
Born of the same parents.200 cells of random observation, acquire the percentage shared by various cells, and each sample counting is averaged for 3 times;
(B) simultaneously, apoptosis of the Flow Cytometry methods detection DSNQ to gastric carcinoma cells is also utilized.
Interpretation of result
After with (final concentration of 1.47 μM) of DSNQ processing human gastric cancer ags cells 3,6,12 and for 24 hours, Annexin V-FITC/ are carried out
The bis- dye experiments of PI, and in fluorescence microscopy microscopic observation.It can be seen that the increasing with compound processing time from Figure 12 A and 12B
Add, Annexin V-FITC fluorescence intensities also gradually increase, and Apoptosis degree also dramatically increases.Especially work as time-triggered protocol
When for 24 hours, the fluorescence intensity highest of cell.Flow cytometry results also indicate that apoptosis rate prolongs with DSNQ processing times
Length dramatically increases (Figure 13 A and 13B).As a result illustrate, DSNQ can effectively induce the apoptosis of ags cell, and present the time according to
Lai Xing.
Three, the molecular mechanism of DSNQ cancer cell specific induction of apoptosis
Experimental method:(experiment in vitro-Western blotting methods)
1. cracking:Cell is collected, 100 μ l cell pyrolysis liquids are added, crack 30min on ice;
2. centrifuging:4 DEG C, 12000r centrifuges 30min, takes supernatant, and measuring the protein at 595nm by ultraviolet specrophotometer inhales
Light value;
3. electrophoresis:Take 30 μ g, 5 × buffer loadings of total protein, 12%SDS-PAGE electrophoretic separation;
4. transferring film:Protein is gone on NC films, skimmed milk closes 1h;
5. the NC films after closing with an anti-binding, are being incubated overnight on 4 DEG C of shaking tables respectively;
6. being washed 5 times with TBST, each 5min.The secondary antibody of HRP labels is added in incubation at room temperature 1h, film is washed with TBST.
7. developing the color:ECL chemical illuminating reagents develop the color, and internal reference uses β-actin.It is taken a picture, is divided by MicroChemi 4.0
Analysis.
Interpretation of result:After with (final concentration of 1.47 μM) of DSNQ processing human gastric cancer ags cells 3,6,12 and for 24 hours, carry out
Western blotting experiments.It can be seen that the display of western blot results promotees apoptosis from Figure 15 A-15B and 14A-14B
Albumen p-JNK, Bad, cleaved-caspase-3 and cleaved-PARP expression quantity gradually increases, Pro-caspase-3 and
Pro-PARP expression quantity gradually decreases;Suppression apoptotic proteins p-STAT3 and Bcl-2 expression quantity gradually decreases.
In conclusion DSNQ can promote JNK signal paths, to induce gastric cancer AGS thin by inhibiting STAT3 signal paths
Apoptosis occurs for born of the same parents.
Claims (8)
- The structural formula of ten disulfoxide -1,4- naphthoquinone compounds of 1.2- is:
- 2. the preparation method of claim 1 compound, this method carry out in the steps below:One, 1,4-naphthoquinone is dissolved in ethyl alcohol, 1- lauryl mercaptans is added, reacted 2h~4h at room temperature, dichromic acid is then added Sodium and the concentrated sulfuric acid, the reaction was continued 5min-10min are extracted with chloroform and saturated sodium-chloride, and anhydrous sodium sulfate drying is filtered, decompression It is concentrated and dried, obtains ten dimercaptos of 2- -1,4-naphthoquinone;Two, ten dimercaptos of 2- -1,4-naphthoquinone that step 1 obtains is dissolved in chloroform, metachloroperbenzoic acid is added thereafter, 1.2h is reacted under the conditions of 0 DEG C, 10% (quality) NaHCO is added after the reaction was complete3Superfluous m-chloro mistake in solution neutralization reaction Reaction is terminated after oxybenzoic acid, reaction product is extracted through chloroform and saturated sodium-chloride, anhydrous sodium sulfate drying, filtering, and concentration is dry It is dry, ten disulfoxide of 2- -1,4-naphthoquinone is obtained after ethyl alcohol recrystallization.
- 3. preparation method according to claim 2, it is characterised in that 1- lauryl mercaptans and 1,4-naphthoquinone described in step 1 Molar ratio is 1.2:1.
- 4. preparation method according to claim 2, it is characterised in that sodium dichromate and 1,4-naphthoquinone rubs described in step 1 You are than being 1:2.
- 5. preparation method according to claim 2, it is characterised in that mole of the concentrated sulfuric acid and 1,4-naphthoquinone described in step 1 Than being 1:5.
- 6. preparation method according to claim 2, it is characterised in that metachloroperbenzoic acid described in step 2 and 2- 12 The molar ratio of sulfydryl -1,4- naphthoquinones is 1.2:1.
- 7. for treating the pharmaceutical composition of gastric cancer, wherein the compound of the claim 1 containing therapeutically effective amount and pharmaceutically may be used The carrier of receiving.
- 8. application of the compound of claim 1 in the drug for preparing treatment gastric cancer.
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Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN105541679A (en) * | 2016-01-25 | 2016-05-04 | 黑龙江八一农垦大学 | 2-octyl sulfoxide-1,4-naphthoquinone compound |
CN105541678A (en) * | 2016-01-25 | 2016-05-04 | 黑龙江八一农垦大学 | Preparation method of 2-butyl sulfoxide-1,4-naphthoquinone |
CN105541676A (en) * | 2016-01-25 | 2016-05-04 | 黑龙江八一农垦大学 | 2-butyl sulfoxide-1,4-naphthoquinone compound |
CN105646300A (en) * | 2016-01-25 | 2016-06-08 | 黑龙江八农垦大学 | Method for preparing 2-octyl sulfoxide-1,4-naphthoquinone |
-
2017
- 2017-10-30 CN CN201711038922.1A patent/CN108299257A/en active Pending
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN105541679A (en) * | 2016-01-25 | 2016-05-04 | 黑龙江八一农垦大学 | 2-octyl sulfoxide-1,4-naphthoquinone compound |
CN105541678A (en) * | 2016-01-25 | 2016-05-04 | 黑龙江八一农垦大学 | Preparation method of 2-butyl sulfoxide-1,4-naphthoquinone |
CN105541676A (en) * | 2016-01-25 | 2016-05-04 | 黑龙江八一农垦大学 | 2-butyl sulfoxide-1,4-naphthoquinone compound |
CN105646300A (en) * | 2016-01-25 | 2016-06-08 | 黑龙江八农垦大学 | Method for preparing 2-octyl sulfoxide-1,4-naphthoquinone |
Non-Patent Citations (1)
Title |
---|
KYEONG LEE等: "Synthesis of a novel series of 2-alkylthio substituted naphthoquinones as potent acyl-CoA: Cholesterol acyltransferase (ACAT) inhibitors", 《EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY》 * |
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