Preparation method and application of alkannin analogue based on anthraquinone structure

A technology for shikonin and analogs, which is applied in the field of preparation of shikonin analogs, can solve problems such as failure to provide naphthenic ring modification, and achieve the effects of simple preparation method, reduced toxicity, and rich structure-activity relationship

Inactive Publication Date: 2016-05-25
XUZHOU NORMAL UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

At the same time, most of the shikonin derivatives reported in the current literature are structurally modified on the basis of retaining their naphthalene nucleus structure (Journal of Medicinal Chemistry, 38, 1044-1047, 1995.) (European Journal of Medicinal Chemistry, 45, 2713- 2718, 2010.) (European Journal of Medicinal Chemistry, 46, 3934-3941, 2011.) (Bioorganic Medicinal Chemistry Letters, 22, 1582-1586, 2012.), failed to provide the content of modifying naphthalene ring to quinzarine ring

Method used

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  • Preparation method and application of alkannin analogue based on anthraquinone structure
  • Preparation method and application of alkannin analogue based on anthraquinone structure
  • Preparation method and application of alkannin analogue based on anthraquinone structure

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Experimental program
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Embodiment 1

[0023] General synthesis of 2-(4-substituted phenyl-1-hydroxy-3-butene)-1,4-dihydroxy-9,10-anthraquinone derivatives 3a-p:

[0024] 1,4-Dihydroxyanthraquinone 1 (0.5mmol) was dissolved in methanol (10ml), and sodium hydroxide solution (1N, 2.5ml) was added. Under nitrogen protection, sodium dithionite (1.0 mmol) dissolved in water (2 mL) was added. After stirring for 10 minutes, β,γ-unsaturated aldehyde 2 (1.0 mmol) was added and reacted at 0°C for 3 hours. The reaction solution was poured into 10 mL of ice water added with 30% hydrogen peroxide (2 mL), and stirred for 10 minutes. Add hydrochloric acid solution (3N, 1mL) to acidify, extract with dichloromethane, wash with saturated sodium bicarbonate solution, wash with water, wash with saturated brine, and dry over anhydrous magnesium sulfate. Separation by column chromatography gave orange-red solid 3.

[0025] 2-(4-Phenyl-1-hydroxy-3-butene)-1,4-dihydroxy-9,10-anthraquinone 3a

[0026] Yield 80%; mp130-132oC; 1 HNMR (4...

Embodiment 2

[0057] Example 2: In vitro cell activity test of compounds 3a-p.

[0058] The growth inhibitory effect of the compound of the present invention on human cervical cancer cell HeLa, human breast cancer cell MDA-MB-231, human pancreatic cancer cell MiaPaca-2, human breast cancer cell MCF-7 and human normal breast epithelial cell MCF10 was determined. According to the inhibition rate of the target compound on cell growth at different concentrations, the concentration of the compound that inhibits cell growth to 50% was calculated, and shikonin was used as a positive control. The results are listed in Table 2, with IC 50 Value representation.

[0059] Table 2 Toxicity IC of target compounds to different tumor cells and normal cells 50 (μM)

[0060]

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Abstract

The invention discloses a preparation method and application of alkannin analogue based on an anthraquinone structure. The alkannin analogue based on the anthraquinone structure is a 2-(4-substituted phenyl-1-hydroxy-3-butene)-1, 4-dyhydroxy-9, 10-anthraquinone derivative. The preparation method of the alkannin analogue comprises the following steps: 1, 4-dihydroxy anthraquinone is adopted as a raw material, hydroxyalkyl is introduced into the 2-position of 1, 4-dihydroxy anthraquinone by hydroxyalkylation, and the alkannin analogue is obtained. Compared with alkannin, the alkannin analogue has the advantages that toxicity to normal cells is outstandingly reduced, and a good foundation is laid for developing clinically available efficient and low-toxicity antitumor drugs by means of further research and development of the compounds.

Description

technical field [0001] The invention relates to a shikonin analog used for antitumor, in particular to a preparation method and application of the shikonin analog based on an anthraquinone structure. Background technique [0002] Malignant tumors are diseases that seriously threaten human health. Although there are many kinds of anti-tumor drugs in clinical practice, these drugs also have a large toxic effect on normal cells while exerting therapeutic effects. These side effects reduce the clinical efficacy of chemotherapy drugs. Therefore, it is of great clinical significance to develop anti-tumor drugs that selectively act on tumor cells with little or no damage to normal cells. [0003] Natural products are an important source of drug lead structures. Many commonly used clinical drugs, especially anticancer drugs, are derived from natural products. Shikonin is an active ingredient in the plant Comfrey, which has significant antitumor activity. Researchers used shikon...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C50/34C07C46/00A61P35/00
CPCC07C50/34C07C46/00
Inventor 赵立明曹风霞金海善
Owner XUZHOU NORMAL UNIVERSITY
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