CN104262331A - Acridine acylhydrazone derivative, as well as preparation method and application thereof - Google Patents
Acridine acylhydrazone derivative, as well as preparation method and application thereof Download PDFInfo
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- CN104262331A CN104262331A CN201410520603.4A CN201410520603A CN104262331A CN 104262331 A CN104262331 A CN 104262331A CN 201410520603 A CN201410520603 A CN 201410520603A CN 104262331 A CN104262331 A CN 104262331A
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- acridine
- acylhydrazone
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- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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Abstract
The invention discloses an acridine acylhydrazone derivative, as well as a preparation method and application thereof. The structural formula of the acridine acylhydrazone derivative is as shown in the specification. The acridine acylhydrazone derivative has a chemical name of 2-furyl-9-acridine acylhydrazone, a molecular formula of Cl9H13N3O2 and a relative molecular weight of 315.33. The method for preparing the acridine acylhydrazone derivative is simple and convenient, and has high synthesis rate; the acridine acylhydrazone derivative can be applied to preparation of anti-tumor medicines, so that the prepared anti-tumor medicines have the effects of preventing and inhibiting tumor progression.
Description
Technical field
The present invention relates to technical field of medical chemistry, be specifically related to a kind of acridine acylhydrazone and preparation method thereof, and by acridine acylhydrazone for the preparation of on antitumor drug.
Background technology
Malignant tumour (cancer) is one of disease of society serious harm human health.Statistic data in recent years shows: global new cancer patient about 1,200 ten thousand, because of cancer mortality 7,600,000 people, about has every day 20,000 people to die from cancer.In addition, the sickness rate of cancer, also in lasting rising, estimates that the year two thousand twenty whole world new cancer patient will reach 1,500 ten thousand.Acridine compounds is the important organic synthesis intermediate of a class, and its derivative shows important biological activity, has good restraining effect to cancer cells, can be used as DNA intercalator and anticancer lead compound etc. and is applied in new drug research.People have extracted or have adopted the method for chemosynthesis to obtain a large amount of acridine compounds from natural product, have studied their pharmacologically active and the mechanism of action.Hydrazone compounds refers to the compounds containing hydrazone group (-CONHN=CH-) functional group in molecular structure, it is the product that hydrazides and aldehydes or ketones generation nucleophilic reaction are dewatered, because itself there is special biological activity as anticancer, sterilization etc., at the object that the fields such as medicine, agricultural chemicals are people's extensive concerns always, therefore, research and develop novel acylhydrazone, there is boundless prospect and practical significance.
Summary of the invention
An object of the present invention is to provide a kind of acridine acylhydrazone, this acridine acylhydrazone has anti-tumor activity.Another object is to provide a kind of method preparing this acridine acylhydrazone, and this acridine acylhydrazone can be applied in and prepares in antitumor drug, makes the antitumor drug be prepared into possess the effect of effective prevention and prohibition tumor progression.
In order to solve the problems of the technologies described above, the invention provides a kind of acridine acylhydrazone and its production and use.
The structural formula of acridine acylhydrazone of the present invention is:
The chemical name of this acridine acylhydrazone is: 2-furyl-9-acridine acylhydrazone;
The molecular formula of this acridine acylhydrazone is: C
19h
13n
3o
2;
The relative molecular weight of this acridine acylhydrazone is: 315.33.
Can prepare this acridine acylhydrazone by the following method, it comprises the steps: simple and feasiblely
1) add in thionyl chloride by 9-acridine phenylformic acid, reflux 5h, solvent evaporated under reduced pressure, gained thick white shape solid is without being separated and obtaining compound 9-acridine formyl chloride (1);
2) 9-acridine formyl chloride (1) is dissolved in chloroform, drips hydrazine hydrate, obtained 9-acridine formyl hydrazine (2) after back flow reaction 2-3h;
3) furtural is added after 9-acridine formyl hydrazine (2) being dissolved in dehydrated alcohol, reflux 1-2h, separate out yellow powder, after suction filtration, will namely obtain target product 2-furyl-9-acridine acylhydrazone (3) after described yellow powder and recrystallized from acetonitrile.
This acridine acylhydrazone may be used for preparing antitumor drug, such as makes one or more medicines in antineoplastic injection, tablet, pill, capsule, suspension agent or emulsion.
Beneficial effect of the present invention: acridine acylhydrazone of the present invention take acridine as parent nucleus, synthesize target product 2-furyl-9-acridine acylhydrazone, this structure had both had the precursor structure of acridine, again containing acylhydrazone base active structure, the anti-tumor activity of its parent nucleus itself can be strengthened, make the acridine acylhydrazone be prepared into have very strong anti-tumor activity.And preparation method's synthetic ratio of the present invention is high, and byproduct is few, effectively can be applied to and prepares in antitumor drug, and very high inhibition effect can be produced to gastric carcinoma cells, hepatoma cell strain, human lung carcinoma cell, human bladder cancer cell's strain etc.
Accompanying drawing explanation
Fig. 1 is the method route schematic diagram that the present invention prepares described acridine acylhydrazone;
Fig. 2 is that acridine acylhydrazone of the present invention and other antitumor drugs are to the medium effective concentration comparison diagram of tumor cell line.
Embodiment
Below in conjunction with embodiment, the present invention is described in further detail, can implement according to this with reference to specification sheets word to make those skilled in the art.
Embodiment 1
Fig. 1 is the method route schematic diagram that the present invention prepares described acridine acylhydrazone.Composition graphs 1, the preparation method of acridine acylhydrazone of the present invention comprises following concrete steps:
1) add in 30ml thionyl chloride by 2.23g or 10mmol 9-acridine phenylformic acid, reflux 5h, solvent evaporated under reduced pressure, gained thick white shape solid is without being separated and obtaining compound 9-acridine formyl chloride (1), and its gained productive rate is 100%;
2) 2.24g or 10mmol compound 9-acridine formyl chloride (1) is dissolved in the chloroform that 30ml Non-aqueous processing crosses, drip 3ml hydrazine hydrate, back flow reaction 2h, material after solvent is removed in cooling and dehydrated alcohol recrystallization obtain white solid, i.e. 9-acridine formyl hydrazine (2), its gained productive rate is 80%;
3) 0.1g or 1mmol furtural is added after 0.24g or 1mmol 9-acridine formyl hydrazine (2) being dissolved in 15ml dehydrated alcohol, reflux 1h, separate out yellow powder, to namely obtain target product 2-furyl-9-acridine acylhydrazone (3) after described yellow powder and recrystallized from acetonitrile after suction filtration, its gained productive rate is 78%.
Embodiment 2
Fig. 1 is the method route schematic diagram that the present invention prepares described acridine acylhydrazone.Composition graphs 1, the preparation method of acridine acylhydrazone of the present invention comprises following concrete steps:
1) with 22g9-acridine formic acid for raw material, 300ml SOCl
2as solvent, Hybrid Heating backflow 5h does acylation reaction, then solvent evaporated under reduced pressure, and gained thick white shape solid is without being separated and obtaining compound 9-acridine formyl chloride (1), and its gained productive rate is 98.2%;
2) be dissolved in 300ml chloroform by 22g9-acridine formyl chloride (1), drip 30ml hydrazine hydrate, obtained 9-acridine formyl hydrazine (2) after back flow reaction 3h, its gained productive rate is 85%;
3) 1g furtural is added after 2.9g9-acridine formyl hydrazine (2) being dissolved in 150ml dehydrated alcohol, reflux 2h, separate out yellow powder, to namely obtain target product 2-furyl-9-acridine acylhydrazone (3) after described yellow powder and recrystallized from acetonitrile after suction filtration, its gained productive rate is 82%.
The structural formula of the acridine acylhydrazone that above-described embodiment 1 and 2 is prepared into is:
The chemical name of this acridine acylhydrazone is 2-furyl-9-acridine acylhydrazone, and molecular formula is C
19h
13n
3o
2, relative molecular weight is 315.33.Obtaining its physico-chemical property through physico-chemical analysis instrument is: yellow crystals, FAB-MSm/z:316 ([M+H]
+),
1hNMR (DMSO-d
6, 400MHz), δ: 9.26 (s, 1H ,=CH), 8.41 (br, s, 1H ,-NH), 8.15 ~ 8.20 (m, 3H, ArH), 7.63 (s, 2H, ArH), 7.57 (s, 1H, ArH), 7.33 (s, 1H, ArH), 7.40 (d, 2H, J=8.40Hz, furan nucleus), 6.30 (m, 1H, furan nucleus), 6.26 (d, 1H, J=8.40Hz, furan nucleuss).
Embodiment 3
The acridine acylhydrazone that above-described embodiment 1 and 2 prepares is carried out anti tumor activity in vitro experiment:
Adopt MTT method, carry out vitro cytotoxicity mensuration.Target product 2-furyl-9-acridine acylhydrazone embodiment 1 and 2 obtained and urinary bladder carcinoma T24 cell line strain, people's gastric cancer cell line MGC-803, liver cancer BEL-7404 cell strain, lung cancer NCI-H460 cell distinguish 24 hours action time, acridine acylhydrazone of the present invention carries out contrast experiment with when identical action time to the medium effective concentration of tumor cell line at identical tumor cell line with other antitumor drug, and result as shown in Figure 2.
As can be seen from the result of embodiment 3, acridine acylhydrazone of the present invention shows through anticancer experiment in vitro, and this compound has strong anti-tumor activity.2-furyl-9-acridine acylhydrazone of the present invention can make one or more medicines in antineoplastic injection, tablet, pill, capsule, suspension agent or emulsion.Acridine acylhydrazone of the present invention and the medicine be prepared into thereof can produce very high inhibition effect to gastric carcinoma cells, hepatoma cell strain, human lung carcinoma cell, human bladder cancer cell's strain etc.Can obtain from the correlation data of Fig. 2, it is the most obvious to the restraining effect of urinary bladder carcinoma T24 cell line strain, treatment bladder cancer better effects if, and the present invention is that the new antitumor drug of research and development provides new thinking.
Although embodiment of the present invention are open as above, but it is not restricted to listed in specification sheets and embodiment utilization, it can be applied to various applicable the field of the invention completely, for those skilled in the art, can easily realize other amendment, therefore do not deviating under the universal that claim and equivalency range limit, the present invention is not limited to specific details.
Claims (3)
1. an acridine acylhydrazone, is characterized in that, the structural formula of described acridine acylhydrazone is:
The chemical name of described acridine acylhydrazone is: 2-furyl-9-acridine acylhydrazone;
The molecular formula of described acridine acylhydrazone is: C
19h
13n
3o
2;
The relative molecular weight of described acridine acylhydrazone is: 315.33.
2. a preparation method for acridine acylhydrazone as claimed in claim 1, is characterized in that, comprise the steps:
1) add in thionyl chloride by 9-acridine phenylformic acid, reflux 5h, solvent evaporated under reduced pressure, gained thick white shape solid is without being separated and obtaining compound 9-acridine formyl chloride (1);
2) 9-acridine formyl chloride (1) is dissolved in chloroform, drips hydrazine hydrate, obtained 9-acridine formyl hydrazine (2) after back flow reaction 2-3h;
3) furtural is added after 9-acridine formyl hydrazine (2) being dissolved in dehydrated alcohol, reflux 1-2h, separate out yellow powder, after suction filtration, will namely obtain target product 2-furyl-9-acridine acylhydrazone (3) after described yellow powder and recrystallized from acetonitrile.
3. a purposes for acridine acylhydrazone as claimed in claim 1, is characterized in that, described acridine acylhydrazone is as the purposes preparing antitumor drug.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105503824A (en) * | 2015-12-02 | 2016-04-20 | 广西中医药大学 | Acridine derivative, preparation method thereof and application of acridine derivative as anti-angiogenesis drug |
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2014
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| JPS6281371A (en) * | 1985-10-03 | 1987-04-14 | Wako Pure Chem Ind Ltd | Novel acridine derivative |
| CN101121711A (en) * | 2007-09-19 | 2008-02-13 | 山东大学 | Pyrazolcarbazone derivatives and application thereof |
| CN101402620A (en) * | 2008-11-25 | 2009-04-08 | 中国农业大学 | Benzoyl hydrazone compounds with antineoplastic activity |
| US20130150254A1 (en) * | 2010-12-09 | 2013-06-13 | John J. Naleway | Reagents and methods for direct labeling of nucleotides |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105503824A (en) * | 2015-12-02 | 2016-04-20 | 广西中医药大学 | Acridine derivative, preparation method thereof and application of acridine derivative as anti-angiogenesis drug |
| CN105503824B (en) * | 2015-12-02 | 2018-04-17 | 广西中医药大学 | Acridine derivatives and preparation method thereof and as the purposes in anti-angiogenic medicaments |
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| CN104262331B (en) | 2016-07-06 |
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