Synthesis of Echinocystic Acid Derivatives and Inhibitory Effect on Lipase

Xue WANG; Min-lun NAN; Xue BAI; Yu-fang HE; Yu-wei ZHAO; Chuan-jing LI; Zhong-mei HE

doi:10.13422/j.cnki.syfjx.20191416

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Synthesis of Echinocystic Acid Derivatives and Inhibitory Effect on Lipase

Resource and Quality Evaluation | 更新时间：2021-02-09

- Synthesis of Echinocystic Acid Derivatives and Inhibitory Effect on Lipase
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 25, Issue 20, Pages: 125-130(2019)
- 作者机构：
  
  1.吉林农业大学，长春　 130118；
  2.吉林省中医药科学院，长春　 130012；
  3.长春中医药大学，长春　 130118；
  4.吉林省吉测检测技术有限公司，长春　 130118
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20191416
  CLC： R284.2; R289; R22; R2-031
- Received：25 March 2019，
  
  Published Online：04 April 2019，
  
  Published：20 October 2019
- 稿件说明：
移动端阅览
Xue WANG, Min-lun NAN, Xue BAI, et al. Synthesis of Echinocystic Acid Derivatives and Inhibitory Effect on Lipase[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(20): 125-130.
DOI：

Xue WANG, Min-lun NAN, Xue BAI, et al. Synthesis of Echinocystic Acid Derivatives and Inhibitory Effect on Lipase[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(20): 125-130. DOI： 10.13422/j.cnki.syfjx.20191416.

摘要

目的：

刺囊酸属于齐墩果烷型五环三萜类化合物，由于刺囊酸的首要结构特点为环系稳定，活性位点较少，因此该文主要对刺囊酸的结构进行修饰，合成一系列刺囊酸衍生物，以此来提高其生物利用度，并研究其抑制脂肪酶活性。

方法：

以天然脂肪酶抑制剂刺囊酸为原料，设计、合成新型刺囊酸衍生物，然后采用2，4-二硝基苯酚丁酸酯(2，4-dinitrophenyl butanoate，PNPB)法对其抑制脂肪酶作用进行研究。

结果：

合成了9个化合物，利用红外光谱，紫外，质谱，核磁共振谱等技术来表征其结构，经鉴定均为新化合物。进一步进行抑制脂肪酶活性实验，结果表明，所合成化合物

1～9

均对脂肪酶具有抑制作用，半抑制浓度(IC

)分别为7.03，2.05，2.14，3.65，3.24，0.28，0.34，0.46，0.39 g·L

－1

，其对脂肪酶的抑制率均明显高于先导化合物刺囊酸(IC

＝7.17 g·L

－1

)，且化合物

6～9

的抑制活性较强于阳性药奥利司他(Orlistat)(IC

＝0.53 g·L

－1

)，各化合物对脂肪酶抑制活性依次为化合物

奥利司他

刺囊酸。

结论：

以刺囊酸为先导化合物进行设计、合成衍生物，从而提高抑制脂肪酶活性的研究思路是可行的。

Abstract

Objective:

Echinocystic acid(EA)is a kind of oleanolic pentacyclic triterpenoid compound

due to its main structural features of stability and less active sites

the structures of EA were modified in this paper to synthesize a series of EA derivatives

improve their bioavailability

and investigate their inhibitory effect on lipase.

Method:

In this study

EA derivatives were designed and synthesized from EA

which is a natural lipase inhibitor. Their inhibitory effects on lipase were tested by using 2

4-dinitrophenyl butanoate(PNPB) method.

Result:

Nine compounds were synthesized

and their structures were characterized by infrared spectrum (IR)

ultraviolet spectrum (UV)

mass spectrum (MS)

nuclear magnetic resonance spectrum (

H-NMR and

C-NMR)

all of which were identified as new compounds. Further experiments on the inhibitory effect on lipase showed that compounds

1-9

had higher inhibitory effects than EA

=7.03

2.05

2.14

3.65

3.24

0.28

0.34

0.46

and 0.39 g·L

-1

. Compounds

6-9

had higher inhibitory effect than Orlistat(IC

=0.53 g·L

-1

). Inhibition rates were as follows:

Orlistat

EA.

Conclusion:

It is feasible to design and synthesize derivatives with EA as the lead compound to improve the inhibitory effect on lipase.

关键词

Keywords

references

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