Ursolic acid derivative with anti-cancer activity and preparation method thereof

A technology of ursolic acid and its derivatives, which is applied in the field of ursolic acid derivatives with anti-tumor activity and its preparation, and can solve problems such as synthesis and targeting studies that have not been reported.

Inactive Publication Date: 2012-06-27
FUZHOU UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, ursolic acid is used as the lead compound to connect folic acid, and the synthesis and targeting research of this kind of compound have not been reported at home and abroad.

Method used

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  • Ursolic acid derivative with anti-cancer activity and preparation method thereof
  • Ursolic acid derivative with anti-cancer activity and preparation method thereof
  • Ursolic acid derivative with anti-cancer activity and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0043] Preparation of 3-O acetyl ursolic acid (compound II):

[0044] Weigh 0.7062 g ursolic acid, add 30 mL pyridine, stir to dissolve, add 1.8 mL acetic anhydride dropwise, add a small amount of DMAP, and stir at room temperature for 16 h. After the reaction is over, adjust the pH to 3-4 with 2 N HCl and evaporate. Solvent, filter with suction, wash the filter cake with water to neutral, dry at normal pressure at 100°C, load the dried product dry, and purify by column chromatography (petroleum ether (60-90°C): ethyl acetate=3:1), Anhydrous ethanol is hot melted, cooled and recrystallized to obtain 3-O acetyl ursolic acid.

[0045] Properties: white powder; yield: 86.17%.

[0046] IR Data (KBr, cm -1 ) And its attribution: υ: 3293 (OH stretching vibration), 2927 (CH stretching vibration), 1736 (s, C=O stretching vibration), 1370 (UA A zone characteristic absorption), 1245 (s, COC asymmetric stretching vibration) ) cm -1 .

[0047] ESI-MS : M / z 497.5 [M-H] + , 521.5[M+Na] + .

[00...

Embodiment 2

[0050] Preparation of N-[3β-acetoxy-arbutane-12-ene-28-acyl]-aminoethylenediamine (compound Ⅲ):

[0051] Weigh 0.1954 g 3-O acetyl ursolic acid and dissolve it in 20 mL CH 2 Cl 2 In, 0.19 mL of oxalyl chloride was added dropwise in batches, and the reaction was stirred at room temperature for 24 h. The solvent and gas generated by the reaction were evaporated to obtain the crude product of 3-O-acetyl UA acid chloride intermediate, which was directly entered into the next reaction. Add 20 mL CH to the above intermediate 2 Cl 2 , Triethylamine adjust the pH of the solution to 8-9, add 0.19 mL of ethylenediamine, stir for 3 h at room temperature, after the reaction, add 10 mL of distilled water to the reaction solution, adjust the pH to 3-4 with 2N HCl, filter, and wash the filter cake with water To the filtrate pH is neutral, dry. Purification by column chromatography (chloroform: acetone (v: v)=1:5), hot dissolving in absolute ethanol, cooling and recrystallization to obtain N-[3β...

Embodiment 3

[0057] Preparation of N-[3β-hydroxy-arbutane-12-ene-28-acyl]-aminoethylenediamine (Compound IV):

[0058] Weigh 0.5859g of N-[3β-acetoxy-arbutane-12-ene-28-acyl]-aminoethylenediamine and dissolve it in 20 ml CH 3 Add 2.0ml 4N NaOH to OH-THF (1:1.5 v:v), stir at room temperature and react for 3.5 hours. The reaction is complete. Add appropriate amount of water to the mixture, adjust pH to 3-4 with 2 N HCl, and evaporate under reduced pressure. Solvent, wash with water and precipitate to neutral, purify by column chromatography (chloroform: acetone=1:5), dissolve in anhydrous ethanol, cool and recrystallize to obtain N-[3β-hydroxy-arbutane-12-ene-28- Acyl]-aminoethylenediamine.

[0059] Properties: white powder; yield: 85.7%.

[0060] IR Data (KBr, cm-1) and its attribution: υ: 3384 (OH stretching vibration), 2926 (CH stretching vibration), 1636 (s, C=O stretching vibration, amide I peak), 1528 (NH bending vibration, amide Peak Ⅱ), 1378 (characteristic absorption in UA A zone).

[006...

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Abstract

The invention provides an ursolic acid derivative, which is N-[3beta-acetoxy-ursa-12- alkene-28-acyl]-aminoethylenediamine-folic acid. A natural product ursolic acid is structurally transformed to obtain N-[3beta-acetoxy-ursa-12- alkene-28-acyl]-aminoethylenediamine-folic acid (I), N-[3beta-acetoxy-ursa-12-alkene-28-acyl]-aminoethylenediamine (III) and N-[3beta-acetoxy-ursa-12- alkene-28-acyl]-aminoethylenediamine (IV). The in vitro cell proliferation inhibition test shows that the proliferation inhibition effect of the compounds I, III and IV on tested tumor cell lines HepG2, of BGC823, A-375, Hela and the like is superior to that of the ursolic acid, and the toxic effect of the compounds I, III and IV on human embryonic lung fibroblasts (HELF) is lower than that of the ursolic acid. The in vitro anti-tumor effect of the compound III is the best, and the compound I has certain targeting.

Description

technical field [0001] The invention relates to an ursolic acid derivative and a preparation method thereof, in particular to an ursolic acid derivative with antitumor activity and a preparation method thereof. Background technique [0002] Ursolic acid (Ursolic acid, UA), also known as ursolic acid, ursolic acid, belongs to pentacyclic triterpenoids, chemical name (3β)-3-Hydroxyurs-12-en-28-oic acid, its relative molecular weight is 456.68, and the molecular formula is C 30 h 48 o 3 , which is widely distributed in nature in the form of free or glycosides. Pharmacological studies have found that ursolic acid has a wide range of biological effects, and ursolic acid has a variety of biological activities, such as anti-cancer, anti-HIV, anti-liver damage, anti-malarial, anti-inflammatory and antibacterial, etc., especially anti-cancer The activity is the most significant, and its anti-cancer spectrum is broad. It not only has resistance to various carcinogens and carcinoge...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07J63/00A61P35/00
Inventor 邵敬伟王继闯
Owner FUZHOU UNIV
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