Phenylbutyryl curcumin derivate and application thereof in anti-tumor drug preparation

A technology of phenylbutyryl curcumin and anti-tumor drugs, which is applied in the application field of phenylbutyryl curcumin derivatives and their preparation, and preparation of anti-tumor drugs, which can solve the problem of low bioavailability, restriction of curcumin, and difficulty in achieving effective Concentration and other issues, to achieve the effect of increased life extension rate and strong anti-tumor effect

Inactive Publication Date: 2010-09-15
FUJIAN MEDICAL UNIV
View PDF5 Cites 6 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, Cur is unstable, metabolizes rapidly in the body, has low bioavailability, and is difficult to reach an effective concentration in the body, which seriously restricts the development of curcumin into an effective anticancer drug.

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
  • Phenylbutyryl curcumin derivate and application thereof in anti-tumor drug preparation
  • Phenylbutyryl curcumin derivate and application thereof in anti-tumor drug preparation
  • Phenylbutyryl curcumin derivate and application thereof in anti-tumor drug preparation

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 14

[0032] The synthesis of embodiment 14-[two (2-chloroethyl) amino] phenylbutyryl curcumin (compound 1)

[0033] EDCI 1.92g (10mmol) was dissolved in anhydrous dichloromethane 200ml, stirred under ice bath and added curcumin 7.36g (20mmol), DMAP 0.244g (2mmol), then slowly added dropwise dissolved 4-[bis(2 -Chloroethyl)amino]benzenebutyric acid 3.04g (10mmol) in dichloromethane 200ml, continued stirring reaction at room temperature for 6 hours. Wash with distilled water, dry the organic phase with anhydrous magnesium sulfate, filter and concentrate to obtain the crude product, the crude product is separated by medium pressure preparative chromatography, reverse C18 column, mobile phase methanol: water 50% → 100% (volume percentage) gradient elution, Obtain 4-[two (2-chloroethyl) amino] phenylbutyryl curcumin pure product 1.30g, productive rate 20%, chemical structural formula is as follows:

[0034]

[0035] Molecular formula C 35 h 37 Cl 2 NO 7 , mp100-102℃

[0036] 1...

Embodiment 24

[0037] Embodiment 24, the synthesis of 4'-[bis(2-chloroethyl)amino]bisphenylbutyryl curcumin (compound 2)

[0038] EDCI 1.92g (10mmol) was dissolved in anhydrous dichloromethane 100ml, stirred under ice bath and added curcumin 1.84g (5mmol), DMAP 0.122g (1mmol), then slowly added dropwise dissolved 4-[bis(2 -Chloroethyl)amino]benzenebutyric acid 3.04g (10mmol) in dichloromethane 200ml, continue stirring reaction at room temperature for 6 hours. Wash with distilled water, dry the organic phase with anhydrous magnesium sulfate, filter and concentrate to obtain the crude product, the crude product is separated by medium pressure preparative chromatography, reverse C18 column, mobile phase methanol: water 50% → 100% (volume percentage) gradient elution, Obtain 4,4'-[bis(2-chloroethyl) amino] bisphenylbutyryl curcumin pure product (compound 2) 1.88g, productive rate 40%, chemical structural formula is as follows:

[0039]

[0040] C 49 h 54 C 14 N 2 o 8 , mp58-60℃, 1 H NM...

Embodiment 3

[0041] Example 3 Effect of compound 1 on mouse liver cancer H22 xenograft model

[0042] 3.1 Materials

[0043] 8-12 weeks old Kunming healthy mice, female, weighing (20±2) g; the mice were provided by the Experimental Animal Center of Fujian Medical University (Certificate No. SCXK (Fujian) 200420002). Mouse hepatoma cell line H22. Compound 1 was formulated to the required concentration before use.

[0044] 3.2 Method

[0045] 3.2.1 Establishment of tumor-bearing mouse model

[0046] H22 tumor cells were passed on for more than two generations, and the number of cells was adjusted to 10 7 / ml, 0.2mL / mouse was inoculated subcutaneously in the right forelimb of mice, inoculated 2 mice, waited for about two weeks, stripped the tumor, homogenized, and inoculated 80 mice.

[0047] 3.2.2 Grouping

[0048] A: Divided into 3 groups: the mice 24 hours after the inoculation of tumor strains were randomly divided into 3 groups: Group I was the normal saline control group, compound...

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 relates to phenylbutyryl curcumin derivate and application thereof in anti-tumor drug preparation, in particular to 4-(di(2-chloroethyl) amino) phenylbutyryl curcumin, 4,4'-(di(2-chloroethyl)amino) diphenylbutyryl curcumin, pharmaceutically acceptable salts and a preparation method thereof, and applications of 4-(di(2-chloroethyl) amino) phenylbutyryl curcumin, and 4,4'-(di(2-chloroethyl)amino) di phenylbutyryl curcumin in anti-tumor drug preparation. The phenylbutyryl curcumin derivate can be used for (but not limited to) preparing drugs for treating leukemia, skin cancer, gastric cancer, colon cancer, liver cancer, breast cancer or prostatic cancer. The derivate has obvious inhibition on a plurality of animal tumor cell transplanting modules, especially for the human chronic granulocytic leukemia model constructed by NOD-SCID mice inoculated with the human chronic granulocytic leukemia K562 cell stain, the life prolonging rate is obviously enhanced, and the serious toxicity to mice does not exist.

Description

technical field [0001] The invention belongs to the field of pharmacy, and in particular relates to a phenylbutyryl curcumin derivative, a preparation method thereof, and an application thereof in the preparation of antitumor drugs. Background technique [0002] Curcumin (Cur for short) is an active ingredient extracted from the rhizomes of turmeric, curcuma, turmeric, etc. It has a good potential for clinical application. However, Cur is unstable, metabolizes rapidly in the body, has low bioavailability, and it is difficult to reach an effective concentration in the body, which seriously restricts the development of curcumin into an effective anticancer drug. Synthesis of curcumin derivatives through structural modification to improve bioavailability and prolong bioelimination half-life t 1 / 2 There's important meaning. Contents of the invention [0003] One of the objects of the present invention is to provide 4-[bis(2-chloroethyl) amino] phenylbutyryl curcumin and 4,4...

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 Applications(China)
IPC IPC(8): C07C229/42C07C227/18A61K31/216A61P35/00A61P35/02
CPCC07C227/18A61K31/216C07C229/42A61P35/00A61P35/02
Inventor 许建华刘洋林燕芳吴枝娟黄秀旺吴丽贤郭晓丹吴敏
Owner FUJIAN MEDICAL UNIV
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