CN103896932A - Isoxazolyl aryl chalcone derivative as well as preparation method and application thereof - Google Patents
Isoxazolyl aryl chalcone derivative as well as preparation method and application thereof Download PDFInfo
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- CN103896932A CN103896932A CN201410155774.1A CN201410155774A CN103896932A CN 103896932 A CN103896932 A CN 103896932A CN 201410155774 A CN201410155774 A CN 201410155774A CN 103896932 A CN103896932 A CN 103896932A
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- isoxazolyl
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- chalcone derivative
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- GEPPOERBQSRWAT-KPKJPENVSA-N Cc1c(C(/C=C/c2ccccc2)=O)c(-c(cc2)ccc2[N+]([O-])=O)n[o]1 Chemical compound Cc1c(C(/C=C/c2ccccc2)=O)c(-c(cc2)ccc2[N+]([O-])=O)n[o]1 GEPPOERBQSRWAT-KPKJPENVSA-N 0.000 description 2
- KNYOFFSYJFXTRD-KPKJPENVSA-N Cc1c(C(/C=C/c2ccc(C)cc2)=O)c(-c(cc2)ccc2[N+]([O-])=O)n[o]1 Chemical compound Cc1c(C(/C=C/c2ccc(C)cc2)=O)c(-c(cc2)ccc2[N+]([O-])=O)n[o]1 KNYOFFSYJFXTRD-KPKJPENVSA-N 0.000 description 1
- NZZWMGBSHBTCAV-CMDGGOBGSA-N Cc1c(C(/C=C/c2ccc[s]2)=O)c(-c(cc2)ccc2[N+]([O-])=O)n[o]1 Chemical compound Cc1c(C(/C=C/c2ccc[s]2)=O)c(-c(cc2)ccc2[N+]([O-])=O)n[o]1 NZZWMGBSHBTCAV-CMDGGOBGSA-N 0.000 description 1
- GIAKWNVHHDZPMX-UHFFFAOYSA-N Cc1c(C(CCc2ccc(C)cc2)=O)c(-c(cc2)ccc2[N+]([O-])=O)n[o]1 Chemical compound Cc1c(C(CCc2ccc(C)cc2)=O)c(-c(cc2)ccc2[N+]([O-])=O)n[o]1 GIAKWNVHHDZPMX-UHFFFAOYSA-N 0.000 description 1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
- C07D261/02—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings
- C07D261/06—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members
- C07D261/08—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
Abstract
The invention relates to an isoxazolyl aryl chalcone derivative as well as a preparation method and application thereof. The structural formula of the isoxazolyl aryl chalcone derivative is shown in (I), (II) or (III) in the specification. The preparation method is characterized by using ethanol as a solvent and sodium hydroxide as a catalyst to react 5-methyl-3-(4-nitrophenyl)isoxazole-4-aceton with aromatic aldehyde with equal molar weight at room temperature for 5-6 hours; re-crystallizing a crude product with ethanol. The product can obviously inhibit proliferation of four human lung cancer cells and has better application values.
Description
Technical field
The present invention designs a kind of chalcone derivative, relates in particular to a kind of isoxazolyl aryl chalcone derivative and its preparation method and application.
Background technology
Lung cancer is as a kind of serious disease, and the number more lethal than the cancer of any other type is all many.In youngster in the past 10 years, although the mankind are obtaining huge progress aspect cancer therapy drug research.But exploitation has simple structure, more effective cancer therapy drug remains the severe challenge that chemist faces.
Cinnamophenone compound is also the very important organic compound of a class, and natural cinnamophenone compound is present in the root, leaf, stem of plant widely, shows many interesting pharmacologically actives.Cinnamophenone and derivative thereof are the products of aromatic aldehyde ketone generation cross aldol condensation; in its molecular structure, there are two α that aromatic ring is connected; the system of beta-unsaturated carbonyl; there is larger flexibility; can from different receptors bind; therefore there is biological activity widely, as biological activitys such as anticancer, anti-inflammatory, antibacterial, parasiticide, antiviral, treatment diabetes, neuroprotective, antianaphylaxis, anti-gastric-ulcer and spasmolysis.Cinnamophenone compound can cell death inducing, is regarded as most promising cancer therapy drug.
Some cancer therapy drugs clinically due to nucleic acid in amino interact, thereby there is genotoxicity.Comparatively speaking, researcher does not find that cinnamophenone has this important toxic side effect.In recent years, the structural modification of cinnamophenone and bioactivity research thereof become hot research both domestic and external field.In the design of novel drugs, the combination of different pharmacology monomers can cause interesting bioactive compounds to produce.Therefore the molecule that, contains different pharmaceutical monomer may be right the treatment of cancer favourable.Our design, composite structure novelty in a molecule, there is the compound of isoxzzole and cinnamophenone monomer simultaneously, and inquire into its impact of cell toxicant on human lung carcinoma cell line.
Summary of the invention
The object of this invention is to provide isoxazolyl aryl chalcone derivative and its preparation method and application.The present invention has done the research of a series of antitumour activitys to synthetic isoxazolyl aryl chalcone derivative, experimental result shows that synthetic isoxazolyl aryl chalcone compounds can effectively suppress the propagation of multiple mankind's lung carcinoma cell.This type of isoxazolyl aryl chalcone derivative novel structure, antitumour activity is higher, therefore has very large promotion and application space.
The technical scheme that the present invention takes:
Isoxazolyl aryl chalcone derivative, structural formula is as (I), (II) or (III):
The preparation method of isoxazolyl aryl chalcone derivative:
(1) make solvent with ethanol and be placed in reactor, add aromatic aldehyde; (2) add and 5-methyl-3-(4-nitrophenyl) isoxzzole-4-ethyl ketone of aromatic aldehyde equimolar amount, stir, molten clear; (3) add 10% sodium hydroxide solution, stirring at room temperature reaction 5-6h; (4) filter to obtain thick product, crude product ethyl alcohol recrystallization.
Aromatic aldehyde described in above-mentioned steps (1) is 2 thiophene carboxaldehyde, phenyl aldehyde or 4-tolyl aldehyde.
Described alcohol solvent consumption is every gram of 5-methyl-3-(4-nitrophenyl) isoxzzole-4-ethyl ketone 60-80ml.
The application of described isoxazolyl aryl chalcone derivative in cancer therapy drug.
A kind of anticancer pharmaceutical composition, the above-mentioned isoxazolyl aryl chalcone derivative that contains survival dose, or formed by above-mentioned isoxazolyl aryl chalcone derivative and the acceptable auxiliary material of survival dose.
Beneficial effect of the present invention:
(1) reaction is carried out at normal temperatures and pressures, simple to operate, safety; (2) last handling process is easy, and yield is high, and cost is low; (3) technological process is environmentally friendly, meets the requirement of Green Chemistry; (4) gained isoxazolyl aryl chalcone derivative can significantly suppress the propagation of multiple lung cancer cell line.
Accompanying drawing explanation
Fig. 1 is the hydrogen nuclear magnetic resonance spectrogram of embodiment 1 product.
Embodiment
Below the specific embodiment of the present invention is elaborated.But, the invention is not restricted to following embodiment, can in the scope of main points, carry out various distortion and implement.
Embodiment 1 the present embodiment provides the preparation of isoxazolyl thienyl chalcone derivative:
Measure 60mL ethanol and be placed in reactor as solvent, 2 thiophene carboxaldehyde (4mmol) and 5-methyl-3-(4-nitrophenyl)-4-ethyl ketone (4mmol, 1g) are added in reactor, stirring, molten clear; Add again the NaOH aqueous solution (10%, 1.5mL), stir, room temperature reaction 5h, reaction finishes (TLC detection).Suction filtration, resistates washes with water three times, is dried to obtain light yellow isoxazolyl thienyl chalcone derivative.Crude product ethyl alcohol recrystallization, yield 65%.
Isoxazolyl thienyl chalcone derivative hydrogen spectrum data:
1H?NMR(400MHz，DMSO-d
6，δ)：2.69(s，3H，CH
3)，6.58(d，1H，COCH＝，J＝15.60Hz)，7.14-7.81(m，3H，Thiophene?ring)，7.74(d，1H，＝CH，J＝15.60Hz)，7.86(d，2H，PhH，J＝8.40Hz)，8.34(d，2H，PhH，J＝8.40Hz).
Embodiment 2 the present embodiment provide the preparation of isoxazolyl phenyl chalcone derivative:
Measure 150mL ethanol and be placed in reactor as solvent, phenyl aldehyde (8mmol) and 5-methyl-3-(4-nitrophenyl)-4-ethyl ketone (8mmol, 2g) are added in reactor, stirring, molten clear; Add again the NaOH aqueous solution (10%, 3mL), stir, room temperature reaction 5h, reaction finishes (TLC detection).Suction filtration, resistates washes with water three times, is dried to obtain white isoxazolyl phenyl chalcone derivative.Crude product ethyl alcohol recrystallization, yield 81%.
Embodiment 3 the present embodiment provide the preparation of isoxazolyl p-methylphenyl chalcone derivative:
Measure 240mL ethanol and be placed in reactor as solvent, 4-tolyl aldehyde (12mmol) and 5-methyl-3-(4-nitrophenyl)-4-ethyl ketone (12mmol, 3g) are added in reactor, stirring, molten clear; Add again the NaOH aqueous solution (10%, 4.5mL), stir, room temperature reaction 6h, reaction finishes (TLC detection).Suction filtration, resistates washes with water three times, is dried to obtain white isoxazolyl p-methylphenyl chalcone derivative.Crude product ethyl alcohol recrystallization, yield 49%.
Anticancer Activities
Lung carcinoma cell H1792, A549, H157 and Calu-1 are inoculated in 96 porocyte culture plates, the RPMI-1640 culture medium culturing that contains 5% foetal calf serum with 100 μ L, second day dosing drug treating.After processing finishes, measure cell survival rate by sulphonyl rhodamine B (SRB) method, concrete operation step is as follows: add the TCA of 100 cold μ L10% to each hole, cultivate 1 hour at 4 ℃, remove medium; With distilled water wash plate 5 times, and at air drying, remove TCA; Add 50 μ L SRB solution to dry orifice plate, shake 5 minutes, the acetic acid washing lotion washing with 1% 5 times, removes unconjugated dyestuff, at the washed orifice plate of air drying; The highly basic (pH=10.5) that adds the buffering of 100 μ L10mM, dissolves the SRB of combination in every hole, and jolting 5 minutes; Be that 540nm microplate reader is surveyed a hole absorbancy by operation wavelength.SRB is directly proportional to viable count in the absorbancy (OD) in each hole.The impact of halogenophenyl chalcone derivative on lung carcinoma cell surviving rate, in table 1,2 and 3.
The impact of table 1 isoxazolyl thienyl chalcone derivative on four kinds of lung carcinoma cell surviving rates
The impact of table 2 isoxazolyl phenyl chalcone derivative on four kinds of lung carcinoma cell surviving rates
The impact of table 3 isoxazolyl p-methylphenyl chalcone derivative on four kinds of lung carcinoma cell surviving rates
Can be seen by data in table, three kinds of isoxazolyl aryl chalcone derivatives have and suppress active four kinds of Human Lung Cancer cells, have good application space.
Claims (6)
1. isoxazolyl aryl chalcone derivative, structural formula is as (I), (II) or (III):
2. a preparation method for isoxazolyl aryl chalcone derivative, is characterized in that, step is as follows:
(1) make solvent with ethanol and be placed in reactor, add aromatic aldehyde;
(2) add and 5-methyl-3-(4-nitrophenyl) isoxzzole-4-ethyl ketone of aromatic aldehyde equimolar amount, stir, molten clear;
(3) add 10% sodium hydroxide solution, stirring at room temperature reaction 5-6h;
(4) filter to obtain thick product, crude product ethyl alcohol recrystallization.
3. the preparation method of isoxazolyl aryl chalcone derivative according to claim 2, is characterized in that, the aromatic aldehyde described in step (1) is 2 thiophene carboxaldehyde, phenyl aldehyde or 4-tolyl aldehyde.
4. isoxazolyl aryl chalcone derivative according to claim 2, is characterized in that, described alcohol solvent consumption is every gram of 5-methyl-3-(4-nitrophenyl) isoxzzole-4-ethyl ketone 60-80ml.
5. the application of isoxazolyl aryl chalcone derivative claimed in claim 1 in anticancer about thing.
6. a cancer therapy drug, is characterized in that, the isoxazolyl aryl chalcone derivative claimed in claim 1 that contains survival dose, or formed by isoxazolyl aryl chalcone derivative claimed in claim 1 and the acceptable auxiliary material of survival dose.
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| CN201410155774.1A CN103896932A (en) | 2014-04-18 | 2014-04-18 | Isoxazolyl aryl chalcone derivative as well as preparation method and application thereof |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105330610A (en) * | 2015-11-16 | 2016-02-17 | 马海峰 | Medicine composition for treating gingivitis |
| CN114751870A (en) * | 2022-02-28 | 2022-07-15 | 贵州医科大学 | 2- (isoxazole-5-yl) phenyl-3, 4-dihydroxy benzoate and derivative thereof, and synthesis method and application thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1998058913A1 (en) * | 1997-06-19 | 1998-12-30 | Indena S.P.A. | Chalcones having antiproliferative activity |
| CN102344351A (en) * | 2011-07-29 | 2012-02-08 | 中山大学 | Aryl-substituted chalcones compound, its preparation method and its application |
-
2014
- 2014-04-18 CN CN201410155774.1A patent/CN103896932A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1998058913A1 (en) * | 1997-06-19 | 1998-12-30 | Indena S.P.A. | Chalcones having antiproliferative activity |
| CN102344351A (en) * | 2011-07-29 | 2012-02-08 | 中山大学 | Aryl-substituted chalcones compound, its preparation method and its application |
Non-Patent Citations (1)
| Title |
|---|
| MAOSHENG WAN，等: "Synthesis and evaluation of novel isoxazolyl chalcones as potential anticancer agents", 《BIOORGANIC CHEMISTRY》, vol. 54, 15 March 2014 (2014-03-15), pages 38 - 43 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105330610A (en) * | 2015-11-16 | 2016-02-17 | 马海峰 | Medicine composition for treating gingivitis |
| CN114751870A (en) * | 2022-02-28 | 2022-07-15 | 贵州医科大学 | 2- (isoxazole-5-yl) phenyl-3, 4-dihydroxy benzoate and derivative thereof, and synthesis method and application thereof |
| CN114751870B (en) * | 2022-02-28 | 2023-10-20 | 贵州医科大学 | 2- (isoxazole-5-yl) phenyl-3, 4-dihydroxybenzoate and derivative thereof, and synthetic method and application thereof |
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Application publication date: 20140702 |