CN104288133B - 3,5-diisoamyl thiazolinyl, 2,4, the purposes of 4 '-trihydroxy chalcone and derivant thereof and preparation - Google Patents

3,5-diisoamyl thiazolinyl, 2,4, the purposes of 4 '-trihydroxy chalcone and derivant thereof and preparation Download PDF

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CN104288133B
CN104288133B CN201410483832.3A CN201410483832A CN104288133B CN 104288133 B CN104288133 B CN 104288133B CN 201410483832 A CN201410483832 A CN 201410483832A CN 104288133 B CN104288133 B CN 104288133B
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chalcone
hydrogen
solution
geranyl
derivant
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王浩猛
刘江
严志红
雷亚楠
郁彭
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Hefei Longzhiyun Pharmaceutical Technology Co ltd
Shanghai Weishi Health Management Co ltd
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Abstract

The invention belongs to noval chemical compound preparation method and antitumor cytolytic activity field thereof, especially a kind of 3,5-diisoamyl thiazolinyl, 2,4, the purposes of 4 '-trihydroxy chalcone and derivant thereof and preparation, R in structural formula 1for hydrogen or isopentene group, R 2for hydrogen or isopentene group, R 3for hydrogen or methyl, R 4for hydrogen or methyl, R 5for hydrogen or methyl, wherein R 1-r 5be asynchronously hydrogen.Its antitumor cytolytic activity three kinds of tumor cells used are respectively human leukemia cell (K562), human colon cancer cell (HT-29), human liver cancer cell (HepG2).The application synthesizes this type of pair and replaces chalcones derivant, and part for synthesize first, and has carried out the mensuration of cell in vitro anti-tumor activity, and result shows this type of partial derivatives has certain inhibit activities (IC to three kinds of tumor cells 50aMP.AMp.Amp lt; 10 μMs), have potential anti-tumor biological, this analog derivative synthetic route is short, and simply, yield is higher for synthesis technique and purification process.

Description

3,5-diisoamyl thiazolinyl, 2,4, the purposes of 4 '-trihydroxy chalcone and derivant thereof and preparation
Technical field
The invention belongs to compounds process for production thereof and antitumor cytolytic activity field, especially 3,5-diisoamyl thiazolinyls, the purposes of 2,4,4'-trihydroxy chalcone and derivant thereof and preparation.
Technical background
Chalcone compounds is extensively present in occurring in nature, is the natural organic-compound that a class is present in the multiple medicinal plants such as Radix Glycyrrhizae, Flos Carthami, and its basic skeleton structure is 1,3-diphenylprop ketenes.Because chalcone compounds molecule has larger flexibility, from different receptors bind, many-sided biologic activity can be shown.Scientist has carried out extensive and deep research to it in recent years, particularly on the various biological activity researchs such as antitumor, parasiticide, AntiHIV1 RT activity, antiinflammatory and exploitation, achieves progress faster.
In a large amount of chalcone derivatives of bibliographical information, majority is on A phenyl ring, carry out a monosubstituted base derivative synthesis, other on B ring, carry out reacting derivative replace, on A phenyl ring two replace chalcone synthesis and the research report of bioactive mensuration and structure activity relationship thereof less, therefore this type of chalcone derivative of the present invention and antitumor cytolytic activity result can to chalcone antitumor mechanism and the research of structure activity relationship certain help is provided.
3,5-diisoamyl thiazolinyl, the existing effect of 2,4,4 ' trihydroxy chalcone is malaria, and applicant, by confirming, finds its New function.
Summary of the invention
The object of the present invention is to provide a kind of 3,5-diisoamyl thiazolinyl, 2,4, the purposes of 4'-trihydroxy chalcone and derivant thereof and preparation, and carried out 3,5-diisoamyl thiazolinyl, 2,4, the mensuration of 4'-trihydroxy chalcone cell in vitro anti-tumor activity, the 3 kinds of tumor cells measured are respectively human leukemia cell (K562), human colon cancer cell (HT-29) and human liver cancer cell (HepG2), and result shows this analog derivative part and has good anti-tumor biological (IC 50<10).
The object of the invention is to be achieved through the following technical solutions:
Advantage of the present invention and good effect:
1, the present invention have that synthetic route is short, simple to operate, reaction condition is gentle, synthesis technique and purification process is simple, yield advantages of higher.
2, the present invention synthesizes a large amount of diverse location, the two of different substituents replace chalcones derivant, and has carried out the mensuration of cell in vitro anti-tumor activity, and result shows this analog derivative part and has good anti-tumor biological (IC 50<10).
3, antitumor cytolytic activity result can be offered help to chalcone derivative structure activity relationship and antitumor mechanism research.
4, the present invention have simple to operate, reaction condition is gentle, synthesis technique and purification process simple, yield advantages of higher, and antitumor cytolytic activity result can be offered help to structure activity relationship and antitumor mechanism research.
Accompanying drawing explanation
Fig. 1 is the proton nmr spectra of 3,5-diisoamyl thiazolinyl, 2,4,4'-trihydroxy chalcone.
Fig. 2 is the proton nmr spectra of 3,5-diisoamyl thiazolinyl, 2,4,4'-trimethoxy chalcone.
Fig. 3 is 3-geranyl, 5 iso-amylene, the proton nmr spectra of 2,4,4'-trihydroxy chalcone.
Fig. 4 is 3-geranyl, 5 iso-amylene, the proton nmr spectra of 2,4,4'-trimethoxy chalcone.
Fig. 5 is 3-iso-amylene, 5-geranyl, the proton nmr spectra of 2,4,4'-trihydroxy chalcone.
Fig. 6 is 3-iso-amylene, 5-geranyl, the magnetic resonance hydrogen spectrum of 2,4,4'-trimethoxy chalcone.
Fig. 7 is the proton nmr spectra of 3,5-bis-geranyl, 2,4,4'-trihydroxy chalcone.
Fig. 8 is the proton nmr spectra of 3,5-bis-geranyl, 2,4,4'-trimethoxy chalcone.
Concrete embodiment
In order to understand the present invention, below in conjunction with embodiment, the invention will be further described: following embodiment is illustrative, is not determinate, can not limit protection scope of the present invention with following embodiment.
3,5-diisoamyl thiazolinyls of the present invention, the application of 2,4,4'-trihydroxy chalcone in the medicine of preparation quality tumor, described 3,5-diisoamyl thiazolinyls, the structural formula of 2,4,4'-trihydroxy chalcone is as follows:
A kind of 3,5-diisoamyl thiazolinyl, the derivant of 2,4,4'-trihydroxy chalcone, and the application of this derivant in the medicine of preparation quality tumor, structure is as follows:
Wherein R 1for hydrogen or isopentene group, R 2for hydrogen or isopentene group, R 3for hydrogen or methyl, R 4for hydrogen or methyl, R 5for hydrogen or methyl, and be hydrogen when R1-R5 is different.
3,5-diisoamyl thiazolinyl, the method for the derivant of 2,4,4'-trihydroxy chalcone, synthetic route is as follows:
Preparation method is illustrated below by embodiment.
Embodiment 1
Concrete steps are as follows:
(1) synthesis of synthetic intermediate 2,4-dimethoxy methyl ether 1-Phenylethanone.
Get 2, 4-resacetophenone 1.0g (6.57mmol) puts into 100mL round-bottomed flask, add the anhydrous DCM of 10ml, chloromethyl methyl ether 1.16g (14.5mmol) is added after adding NaH630mg (15.78mmol) under 0 DEG C of stirring state, stirred at ambient temperature 2h, TLC detection reaction is complete, rear reaction is poured in frozen water, stir 15min, then three times are extracted with ethyl acetate, merge organic facies, anhydrous sodium sulfate drying, desolventizing is revolved in decompression, petroleum ether: ethyl acetate=10:1, 200 order purification by silica gel column chromatography, give light yellow oil 1.45g, productive rate is 90%.
(2) synthetic intermediate 2,4-dimethyl methyl ether, the synthesis of 5-Iodoacetophenone
10ml dry DMF dissolves 2,4-dimethoxy methyl ether 1-Phenylethanone. 1g (4.16mmol), NIS1.03g (4.58mmol), after be warming up to 50 DEG C, reaction 2h after, TLC detection reaction is complete, rear reaction is poured in frozen water, stirs 15min, is then extracted with ethyl acetate three times, merge organic facies, anhydrous sodium sulfate drying, desolventizing is revolved in decompression, petroleum ether: ethyl acetate=10:1,200 order purification by silica gel column chromatography, give light yellow oil 1.1g, productive rate is 70%.
(3) synthetic intermediate 2,4,4'-trimethoxy methyl ether, the synthesis of 5-iodine chalcone
To 2 in ethanol, 4-dimethyl methyl ether, 5-Iodoacetophenone (366mg, 1mmol) with 4-methoxymethoxy benzaldehyde (174.41mg, slowly add 60%KOH (2ml) in solution (5mL) solution of stirring 1.05mmol) at 0 DEG C, then reactant mixture be warmed to room temperature and stir 12 hours.After having reacted, reactant mixture ethyl acetate (3 × 20mL) is extracted.Organic layer is merged, with saturated nacl aqueous solution washing, by dried over sodium sulfate, filters, and concentrate under vacuo, petroleum ether: ethyl acetate=10:1,200 order purification by silica gel column chromatography, obtain yellow oil 2,4,4'-trimethoxy methyl ether, 5-iodine Cha Er 475mg, productive rate is 92%.
(4) synthetic intermediate 2,4,4'-trimethoxy methyl ether, the synthesis of 5-isopentene group chalcone
PdCl is added in the solution in dry DMF (3mL) 2(dppf) (36.6mg, 0.05mmol), 2,4,4'-trimethoxy methyl ether, 5-iodine chalcone (514mg, 1.0mmol) with isopentene group borate (235mg, in agitating solution 1.2mmol), add cesium carbonate (456mg, 1.4mmol).Mixture is heated by 70 DEG C microwave and carries out 2 hours.Reactant mixture is cooled, and is monitored by TLC.After having reacted, reactant mixture is filtered and vaporising under vacuum.Petroleum ether: ethyl acetate=10:1,200 order purification by silica gel column chromatography, obtain yellow oil 2,4,4'-trimethoxy methyl ether, and 5-isopentene group chalcone 384mg, productive rate is 84%.
(5) synthetic intermediate 2-hydroxyl, 4,4'-dimethoxy methyl ether, the synthesis of 5-isopentene group chalcone
2,4,4'-trimethoxy methyl ether, in the solution of 5-isopentene group chalcone (100mg, 0.22mmol) in MeOH (2mL), add after stirring 15min in 1N aqueous hydrochloric acid solution (1ml) at 0 DEG C, monitored by TLC, MeOH is removed under vacuo.In ethyl acetate (10mL), then add and be separated each layer.Aqueous layer with ethyl acetate (2 × 10ml) extracts, and merges organic layer, uses MgSO 4drying, vacuum concentration, petroleum ether: ethyl acetate=10:1,200 order purification by silica gel column chromatography, obtain yellow solid 53mg, and productive rate is 75%.
(6) synthetic intermediate 2-O-isopentene group, 4,4'-dimethoxy methyl ether, the synthesis of 5-isopentene group chalcone
2-hydroxyl, 4,4'-dimethoxy methyl ether, 5-isopentene group chalcone (480mg, 1mmol) with NaH (52mg, slowly add isoprenyl bromide (282mg, 1.3mmol) in solution (5mL) solution of stirring 1.3mmol) in dry DMF to stir 2 hours at 0 DEG C.Reactant mixture is monitored by TLC.After having reacted, by reactant mixture dilute with water, use CH 2cl 2(20ml) in.By organic layer H 2o (3 × 10ml) washs, through Mg 2sO 4and concentrating under reduced pressure.Petroleum ether: ethyl acetate=10:1,200 order purification by silica gel column chromatography, obtain colorless oil 550mg, and productive rate is: 89%.
(7) synthetic intermediate 2-hydroxyl-3,5-diisoamyl thiazolinyl, the synthesis of 4,4'-dimethoxy methyl ether chalcone
Add 2-isopentene group at dry toluene 15mL, 4,4'-dimethoxy methyl ether, slowly adds 100-200 order in the solution in the agitating solution of 5-isopentene group chalcone (617mg, 1mmol) room temperature, then carries out 4 hours by reactant mixture at 140 DEG C, has reacted rear, has been concentrated under vacuo by reactant mixture, petroleum ether: ethyl acetate=10:1, and 200 order purification by silica gel column chromatography, obtain yellow oil 60mg, and productive rate is 9%.
(8) synthesis of 2,4,4'-trihydroxy-3,5-diisoamyl thiazolinyl chalcone is synthesized
Add 2-hydroxyl-3-isopentene group at 0 DEG C, 4,4'-dimethoxy methyl ether, in the solution of 5-isopentene group chalcone (60mg, 0.1mmol) in THF (6mL), add 98%H 2sO 4(0.5ml), in isopropyl alcohol (1ml), monitored by TLC after 2 hours in stirred at ambient temperature, after having reacted, reactant mixture is concentrated under vacuo, petroleum ether: ethyl acetate=10:1,200 order purification by silica gel column chromatography, obtain yellow solid 45mg, and productive rate is 79%.
1HNMR(DMSO400MHz):δ/ppm1.33(t,3H,J＝7.2,CH 3),4.39(m,2H,J＝7.2),7.92(s,1H,ArH),8.08(s,1H,ArH),10.95(s,1H,NH).
(9) synthesis of 2,4,4'-trimethoxy-3,5-diisoamyl thiazolinyl chalcone is synthesized
2,4,4'-trihydroxy-3,5-diisoamyl thiazolinyl chalcone (480mg, 1mmol) with NaH (52mg, slowly add iodomethane (282mg, 1.3mmol) in solution (5mL) solution of stirring 1.3mmol) in dry DMF to stir 2 hours at 0 DEG C.Reactant mixture is monitored by TLC.After having reacted, by reactant mixture dilute with water, use CH 2cl 2(20ml) in.By organic layer H 2o (3 × 10ml) washs, through Mg 2sO 4and concentrating under reduced pressure.Petroleum ether: ethyl acetate=10:1,200 order purification by silica gel column chromatography, obtain yellow oil 550mg, and productive rate is: 89%.
(10) synthetic intermediate 2,4,4'-trimethoxy methyl ether, the synthesis of 5-geranyl chalcone
PdCl is added in the solution in dry DMF (3mL) 2(dppf) (36.6mg, 0.05mmol), 2,4,4'-trimethoxy methyl ether, 5-iodine chalcone (514mg, 1.0mmol) with geranyl borate (335mg, in agitating solution 1.2mmol), add cesium carbonate (456mg, 1.4mmol).Mixture is heated by 70 DEG C microwave and carries out 2 hours.Reactant mixture is cooled, and is monitored by TLC.After having reacted, reactant mixture is filtered and vaporising under vacuum.Petroleum ether: ethyl acetate=10:1,200 order purification by silica gel column chromatography, obtain yellow oil 2,4,4'-trimethoxy methyl ether, and 5-geranyl chalcone 384mg, productive rate is 84%.
(11) synthetic intermediate 2-hydroxyl, 4,4'-dimethoxy methyl ether, the synthesis of 5-geranyl chalcone
2,4,4'-trimethoxy methyl ether, in the solution of 5-geranyl chalcone (100mg, 0.22mmol) in MeOH (2mL), add after stirring 15min in 1N aqueous hydrochloric acid solution (1ml) at 0 DEG C, monitored by TLC, MeOH is removed under vacuo.In ethyl acetate (10mL), then add and be separated each layer.Aqueous layer with ethyl acetate (2 × 10ml) extracts, and merges organic layer, uses MgSO 4drying, vacuum concentration, petroleum ether: ethyl acetate=10:1,200 order purification by silica gel column chromatography, obtain yellow solid 53mg, and productive rate is 75%.
(12) synthetic intermediate 2-O-isopentene group, 4,4'-dimethoxy methyl ether, the synthesis of 5-geranyl chalcone
2-hydroxyl, 4,4'-dimethoxy methyl ether, 5-geranyl chalcone (480mg, 1mmol) with NaH (52mg, slowly add isoprenyl bromide (282mg, 1.3mmol) in solution (5mL) solution of stirring 1.3mmol) in dry DMF to stir 2 hours at 0 DEG C.Reactant mixture is monitored by TLC.After having reacted, by reactant mixture dilute with water, use CH 2cl 2(20ml) in.By organic layer H 2o (3 × 10ml) washs, through Mg 2sO 4and concentrating under reduced pressure.Petroleum ether: ethyl acetate=10:1,200 order purification by silica gel column chromatography, obtain colorless oil 550mg, and productive rate is: 89%.
(13) synthetic intermediate 2-hydroxyl-3-isopentene group, 4,4'-dimethoxy methyl ether, the synthesis of 5-geranyl chalcone
Add 2-O-isopentene group at dry toluene 15mL, 4,4'-dimethoxy methyl ether, slowly adds 100-200 order in the solution in the agitating solution of 5-geranyl chalcone (617mg, 1mmol) room temperature, then carries out 4 hours by reactant mixture at 140 DEG C, has reacted rear, has been concentrated under vacuo by reactant mixture, petroleum ether: ethyl acetate=10:1, and 200 order purification by silica gel column chromatography, obtain yellow oil 60mg, and productive rate is 9%.
(14) 2,4,4'-trihydroxy-3-isopentene group is synthesized, the synthesis of 5-geranyl chalcone
Add 2-hydroxyl-3-isopentene group at 0 DEG C, 4,4'-dimethoxy methyl ether, in the solution of 5-geranyl chalcone (60mg, 0.1mmol) in THF (6mL), add 98%H 2sO 4(0.5ml), in isopropyl alcohol (1ml), monitored by TLC after 2 hours in stirred at ambient temperature, after having reacted, reactant mixture is concentrated under vacuo, petroleum ether: ethyl acetate=10:1,200 order purification by silica gel column chromatography, obtain yellow solid 45mg, and productive rate is 79%.
(15) synthesis of 2,4,4'-trimethoxy-3-isopentene group 5-geranyl chalcone is synthesized
2,4,4'-trihydroxy-3-isopentene group 5-geranyl chalcone (480mg, 1mmol) with NaH (52mg, slowly add iodomethane (282mg, 1.3mmol) in solution (5mL) solution of stirring 1.3mmol) in dry DMF to stir 2 hours at 0 DEG C.Reactant mixture is monitored by TLC.After having reacted, by reactant mixture dilute with water, use CH 2cl 2(20ml) in.By organic layer H 2o (3 × 10ml) washs, through Mg 2sO 4and concentrating under reduced pressure.Petroleum ether: ethyl acetate=10:1,200 order purification by silica gel column chromatography, obtain yellow oil 550mg, and productive rate is: 89%.
(16) synthetic intermediate 2-O-geranyl, 4,4'-dimethoxy methyl ether, the synthesis of 5-isopentene group chalcone
2-hydroxyl, 4,4'-dimethoxy methyl ether, 5-isopentene group chalcone (480mg, 1mmol) with NaH (52mg, slowly add geranyl bromide (282mg, 1.3mmol) in solution (5mL) solution of stirring 1.3mmol) in dry DMF to stir 2 hours at 0 DEG C.Reactant mixture is monitored by TLC.After having reacted, by reactant mixture dilute with water, use CH 2cl 2(20ml) in.By organic layer H 2o (3 × 10ml) washs, through Mg 2sO 4and concentrating under reduced pressure.Petroleum ether: ethyl acetate=10:1,200 order purification by silica gel column chromatography, obtain colorless oil 550mg, and productive rate is: 89%.
(17) synthetic intermediate 2-hydroxyl, 3-geranyl, 4,4'-dimethoxy methyl ether, the synthesis of 5-isopentene group chalcone
Add 2-O-geranyl at dry toluene 15mL, 4,4'-dimethoxy methyl ether, slowly adds 100-200 order in the solution in the agitating solution of 5-isopentene group chalcone (617mg, 1mmol) room temperature, then carries out 4 hours by reactant mixture at 140 DEG C, has reacted rear, has been concentrated under vacuo by reactant mixture, petroleum ether: ethyl acetate=10:1, and 200 order purification by silica gel column chromatography, obtain yellow oil 60mg, and productive rate is 9%.
(18) 2,4,4'-trihydroxy-3-geranyl is synthesized, the synthesis of 5-isopentene group chalcone
Add 2-hydroxyl at 0 DEG C, 3-geranyl, 4,4'-dimethoxy methyl ether, in the solution of 5-isopentene group chalcone (60mg, 0.1mmol) in THF (6mL), add 98%H 2sO 4(0.5ml), in isopropyl alcohol (1ml), monitored by TLC after 2 hours in stirred at ambient temperature, after having reacted, reactant mixture is concentrated under vacuo, petroleum ether: ethyl acetate=10:1,200 order purification by silica gel column chromatography, obtain yellow solid 45mg, and productive rate is 79%.
(19) 2,4,4'-methoxyl group-3-geranyl is synthesized, the synthesis of 5-isopentene group chalcone
2,4,4'-trihydroxy-3,5-diisoamyl thiazolinyl chalcone (480mg, 1mmol) with NaH (52mg, slowly add iodomethane (282mg, 1.3mmol) in solution (5mL) solution of stirring 1.3mmol) in dry DMF to stir 2 hours at 0 DEG C.Reactant mixture is monitored by TLC.After having reacted, by reactant mixture dilute with water, use CH 2cl 2(20ml) in.By organic layer H 2o (3 × 10ml) washs, through Mg 2sO 4and concentrating under reduced pressure.Petroleum ether: ethyl acetate=10:1,200 order purification by silica gel column chromatography, obtain yellow oil 550mg, and productive rate is: 89%.
(20) synthetic intermediate 2-O-geranyl, 4,4'-dimethoxy methyl ether, the synthesis of 5-geranyl chalcone
2-hydroxyl, 4,4'-dimethoxy methyl ether, 5-geranyl chalcone (480mg, 1mmol) with NaH (52mg, slowly add geranyl (282mg, 1.3mmol) in solution (5mL) solution of stirring 1.3mmol) in dry DMF to stir 2 hours at 0 DEG C.Reactant mixture is monitored by TLC.After having reacted, by reactant mixture dilute with water, use CH 2cl 2(20ml) in.By organic layer H 2o (3 × 10ml) washs, through Mg 2sO 4and concentrating under reduced pressure.Petroleum ether: ethyl acetate=10:1,200 order purification by silica gel column chromatography, obtain colorless oil 550mg, and productive rate is: 89%.
(21) synthetic intermediate 2-hydroxyl-3,5-bis-geranyl, the synthesis of 4,4'-dimethoxy methyl ether chalcone
Add 2-O-geranyl at dry toluene 15mL, 4,4'-dimethoxy methyl ether, slowly adds 100-200 order in the solution in the agitating solution of 5-geranyl chalcone (617mg, 1mmol) room temperature, then carries out 4 hours by reactant mixture at 140 DEG C, has reacted rear, has been concentrated under vacuo by reactant mixture, petroleum ether: ethyl acetate=10:1, and 200 order purification by silica gel column chromatography, obtain yellow oil 60mg, and productive rate is 9%.
(22) synthesis of 2,4,4'-trihydroxy-3,5-bis-geranyl chalcone is synthesized
Add 2-hydroxyl-3-geranyl at 0 DEG C, 4,4'-dimethoxy methyl ether, in the solution of 5-geranyl chalcone (60mg, 0.1mmol) in THF (6mL), add 98%H 2sO 4(0.5ml), in isopropyl alcohol (1ml), monitored by TLC after 2 hours in stirred at ambient temperature, after having reacted, reactant mixture is concentrated under vacuo, petroleum ether: ethyl acetate=10:1,200 order purification by silica gel column chromatography, obtain yellow solid 45mg, and productive rate is 79%.
(23) synthesis of 2,4,4'-trimethoxy-3,5-bis-geranyl chalcone is synthesized
2,4,4'-trihydroxy-3-isopentene group 5-geranyl chalcone (480mg, 1mmol) with NaH (52mg, slowly add iodomethane (282mg, 1.3mmol) in solution (5mL) solution of stirring 1.3mmol) in dry DMF to stir 2 hours at 0 DEG C.Reactant mixture is monitored by TLC.After having reacted, by reactant mixture dilute with water, use CH 2cl 2(20ml) in.By organic layer H 2o (3 × 10ml) washs, through Mg 2sO 4and concentrating under reduced pressure.Petroleum ether: ethyl acetate=10:1,200 order purification by silica gel column chromatography, obtain yellow oil 550mg, and productive rate is: 89%.
Embodiment 7
The preparation of solution:
The preparation of DMEMlowglucose culture fluid: buy HyCloneMEMlowglucose culture medium, every bottle of 500mL, add the hyclone of 10% and the mycillin solution of 1%, namely every bottle of culture medium adds the hyclone of 50mL and the mycillin of 5mL, being configured in superclean bench of culture medium is carried out, the preservation of 4 DEG C, rear placement refrigerator.
The preparation of DMEM/F-12 culture fluid: buy HyCloneMEM/F-12 culture medium, every bottle of 500mL, add the hyclone of 10% and the mycillin solution of 1%, namely every bottle of culture medium adds the hyclone of 50mL and the mycillin of 5mL, being configured in superclean bench of culture medium is carried out, the preservation of 4 DEG C, rear placement refrigerator.
The preparation of PBS buffer: in 1000mL conical flask, takes sodium chloride 8g, potassium chloride 0.2g, disodium hydrogen phosphate dodecahydrate 2.9g, potassium dihydrogen phosphate 0.2g, is settled to 1000mL after adding the abundant stirring and dissolving of 800mL pure water, places the preservation of 4 DEG C, refrigerator after autoclaving.
The preparation of MTT solution: take MTT dry powder 0.5g, is dissolved in 100mLPBS buffer, after degerming with 0.22 μM of membrane filtration, places the preservation of-12 DEG C, refrigerator.
The concrete steps of antitumor cytolytic activity:
Antitumor cytolytic activity of the present invention 3 tumor cells used: human liver cancer cell (HepG2), leukaemia (K562) and human colon cancer cell (HT-29).
Utilize human liver cancer cell HepG2 active testing
The culture fluid that HepG2 cell uses is the Pen .-Strep solution containing 1%, the DMEM cell culture fluid of the hyclone of 10%, and condition of culture is 37 DEG C, containing 5%CO 2constant incubator.Concrete steps:
(1), after cell being counted with blood counting chamber, 5x10 is diluted to with DMEMlowglucose culture fluid 4individual/mL;
(2) in each hole of 96 orifice plates, 100 μ L cell suspension piping and druming mixings are added, incubator 37 DEG C of incubation 24h;
(3) wanted test compounds is diluted to 5 kinds of concentration: 2mM, 0.2mM, 20 μMs, 2 μMs, 0.2 μM, according to concentration successively dosing 0.5 μ L/ hole, incubator 37 DEG C of incubation 48h;
(4) MTT that concentration is 5mg/mL is added, incubator 37 DEG C of incubation 4h;
(5) add DMSO by cytolysis, microplate reader surveys the OD value under 490nm and 630nm;
(6) process data, calculate IC according to OD value 50value.
Utilization utilizes Leukemia K562 cell active testing
The culture fluid that K562 cell uses is the Pen .-Strep solution containing 1%, the PRMI1640 cell culture fluid of the hyclone of 10%, and condition of culture is 37 DEG C, containing 5%CO 2constant incubator.Concrete steps:
(1), after cell being counted with blood counting chamber, 5x10 is diluted to RPMI culture fluid 4individual/mL;
(2) in each hole of 96 orifice plates, 100 μ L cell suspension are added, incubator 37 DEG C of incubation 2h;
(3) wanted test compounds is diluted to 5 kinds of concentration: 2mM, 0.2mM, 20 μMs, 2 μMs, 0.2 μM, according to concentration successively dosing 0.5 μ L/ hole, incubator 37 DEG C of incubation 48h;
(4) MTT that concentration is 5mg/mL is added, incubator 37 DEG C of incubations 4 hours;
(5) add isopropyl alcohol and hydrochloric acid lysate, microplate reader surveys the OD value under 570nm and 630nm;
(6) process data, calculate IC according to OD value 50value.
Utilization utilizes human leukemia cell HT-29 active testing
The culture fluid that HT-29 cell uses is the Pen .-Strep solution containing 1%, the DMEM/F-12 cell culture fluid of the hyclone of 10%, and condition of culture is 37 DEG C, containing 5%CO 2constant incubator.Concrete steps:
(1), after cell being counted with blood counting chamber, 5x10 is diluted to with DMEM/F-12 culture fluid 4individual/mL;
(2) in each hole of 96 orifice plates, 100 μ L cell suspension piping and druming mixings are added, incubator 37 DEG C of incubation 24h;
(3) wanted test compounds is diluted to 5 kinds of concentration: 2mM, 0.2mM, 20 μMs, 2 μMs, 0.2 μM, according to concentration successively dosing 0.5 μ L/ hole, incubator 37 DEG C of incubation 48h;
(4) MTT that concentration is 5mg/mL is added, incubator 37 DEG C of incubation 4h;
(5) add DMSO by cytolysis, microplate reader surveys the OD value under 490nm and 630nm;
(6) process data, calculate IC according to OD value 50value.
Table 1 is the compound carrying out antitumor cytolytic activity of synthesis
The result that table 2 measures for antitumor activity of compound

Claims (3)

1.3,5-diisoamyl thiazolinyl, the application of 2,4,4'-trihydroxy chalcone in the medicine of preparation treatment tumor, described 3,5-diisoamyl thiazolinyls, the structural formula of 2,4,4 ' trihydroxy chalcone is as follows:
2. a diisoamyl thiazolinyl, the derivant of 2,4,4'-trihydroxy chalcone, it is characterized in that, structure is as follows:
substituent kind is as follows:
3. prepare 3,5-diisoamyl thiazolinyls according to claim 2 for one kind, the method for the derivant of 2,4,4'-trihydroxy chalcone, is characterized in that: synthetic route is as follows:
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