Emodin and fluorouracil combined compound having antitumor activity and preparation method thereof

A technology with anti-tumor activity and fluorouracil, which is applied in the field of emodin and 5-fluorouracil compound and its preparation, can solve the problems of lack of selectivity between tumor cells and normal cells, high cytotoxicity, and large toxic and side effects, so as to improve the therapeutic dose Close to the toxic dose, enrich the structure-activity relationship, and reduce toxicity

Inactive Publication Date: 2013-06-05
XUZHOU NORMAL UNIVERSITY
View PDF7 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] The purpose of the present invention is to provide an anti-tumor active emodin and 5-fluorouracil compound and its preparation method, to solve the problem of the small selectivity of 5-fluorouracil to tumor cells, the large toxic and side effects, and the existence of hydroxyl groups in the emodin structure. Its cytotoxicity is relatively high, and it lacks selectivity for tumor cells and normal cells

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Emodin and fluorouracil combined compound having antitumor activity and preparation method thereof
  • Emodin and fluorouracil combined compound having antitumor activity and preparation method thereof
  • Emodin and fluorouracil combined compound having antitumor activity and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0034] Example 1: 1-hydroxy-6,8-dimethoxy-3-methyl-9,10-anthraquinone 2

[0035] Emodin (4.05 g, 0.015 mol) was dissolved in acetone (150 ml), potassium carbonate (8.28 g, 0.06 mol) was added, dimethyl sulfate (4.0 ml) was added under stirring, and refluxed for 5 h. Acetone was distilled off, water was added, extracted with dichloromethane, dried over anhydrous sodium sulfate, and separated by column chromatography (dichloromethane) to obtain 3.17 g of a yellow solid with a yield of 71%. 1 H NMR (400 MHz, CDCl 3 ) δ7.58 (s, 1H), 7.47 (d, J = 2.4 Hz, 1H), 7.08 (s, 1H), 6.79 (d, J = 2.4 Hz, 1H), 4.03 (s, 3H), 3.99 (s, 3H), 2.43 (s, 3H).

Embodiment 2

[0036] Example 2: 1-hydroxy-6,8-dimethoxy-2-hydroxymethyl-3-methyl-9,10-anthraquinone 3

[0037] 1-Hydroxy-6,8-dimethoxy-3-methyl-9,10-anthraquinone 2 (149 mg, 0.5 mmol) was dissolved in methanol (75 ml), and sodium hydroxide (1 M, 0.5 ml). Then, the reaction flask was cooled in an ice-water bath, protected by nitrogen, and an aqueous solution of sodium dithionite (131 mg, 0.75 mmol) was added via a syringe, and 37% aqueous formaldehyde (1 mL) was added after 5 minutes. After 30 minutes, the reaction solution was poured into ice water containing 3% hydrogen peroxide. After oxidizing for 30 minutes, acidify to weak acidity with hydrochloric acid. Extracted with dichloromethane, dried over anhydrous sodium sulfate, and separated by column chromatography (dichloromethane: methanol = 100: 1) to obtain 135 mg of a yellow solid with a yield of 82%. 1 H NMR (400 MHz, DMSO- d 6 ) δ13.66 (s, 1H), 7.38 (s, 1H), 7.18 (s, 1H), 6.93 (s, 1H), 4.94 (t, J = 5.2 Hz, 1H), 4.55 (d, J = ...

Embodiment 3

[0038] Example 3: 1,6,8-trimethoxy-2-hydroxymethyl-3-methyl-9,10-anthraquinone 4

[0039] 1-Hydroxy-6,8-dimethoxy-2-hydroxymethyl-3-methyl-9,10-anthraquinone 3 (656 mg, 2.0 mmol) was dissolved in acetone (50 ml) and potassium carbonate was added (1.38 g, 10 mmol), and dimethyl sulfate (0.38 mL, 4.0 mmol) was added dropwise with stirring. After refluxing for 16 hours, the acetone was distilled off under reduced pressure. Add water, extract with dichloromethane, dry over anhydrous sodium sulfate, and separate by column chromatography (dichloromethane: methanol = 100: 1) to obtain 554 mg of a yellow solid with a yield of 81%. 1 H NMR (400 MHz, CDCl 3 ) δ7.84 (s, 1H), 7.34 (d, J = 2.0 Hz, 1H), 6.78 (d, J = 2.0 Hz, 1H), 4.82 (s, 2H), 4.02 (s, 3H), 3.99 (s, 3H), 3.97 (s, 3H), 2.53 (s, 3H).

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

No PUM Login to view more

Abstract

The invention discloses an emodin and fluorouracil combined compound having antitumor activity and a preparation method thereof. The combined compound belongs to a derivative of an antitumor medicine. The emodin and 5-FU combined derivative is 3-substituted 1-(1,6,8-trimethoxy-3-methyl-9,10-anthraquinone-2-methyl)-5-fluorouracil derivative, and includes: using emodin as a raw material and performing 6,8-dimethylation, 2-hydroxymethylation, 1-methylation and 2-hydroxymethyl chloro substitution, connecting the product of the 2-hydroxymethyl chloro substitution to the N1-position of 5-FU, and subjecting the obtained combined compound to N3-alkylation with different alkyl halides or substituted benzyl chlorides. The emodin and fluorouracil combined compound having antitumor activity disclosedby the invention has high selectivity for tumor cells and normal cells and can be used for preparing medicines for treating cancers. In-vitro antitumor experiments indicate the combined compound provided by the invention has much lower toxicity to normal cells than 5-FU and emodin.

Description

technical field [0001] The invention relates to a derivative used for antitumor drugs, in particular to a compound of emodin and 5-fluorouracil with antitumor activity and a preparation method thereof. Background technique [0002] At present, it is very common to use two or more antitumor drugs simultaneously in the treatment of tumors. If the combination can play a synergistic effect, a low-dose drug can be used to achieve the same or better therapeutic effect as a single drug, reducing the occurrence of adverse reactions. Many combinations are the combination of antineoplastic drugs with different mechanisms, such as cyclophosphamide, an alkylating agent that damages DNA structure and function, and methotrexate, an antimetabolite drug that prevents DNA repair, which can often produce synergistic effects and improve the therapeutic index . The way of this combined administration can be to apply the two medicines directly or connect them through a link. [0003] 5-Fluoro...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
Patent Type & Authority Patents(China)
IPC IPC(8): C07D239/553C07D405/06A61K31/513A61P35/00
Inventor 赵立明蒋继宏金海善刘金娟张黎明
Owner XUZHOU NORMAL UNIVERSITY
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap