Unlock instant, AI-driven research and patent intelligence for your innovation.

Natural triterpene-iridoid glycoside dimer hybrid and its preparation and use in the preparation of acl inhibitors

A technology of iridoid glycoside dimer and hybrid, which can be applied in the field of medicine and can solve the problems of low affinity, limited development, weak specificity and the like

Active Publication Date: 2022-07-26
TAIZHOU UNIV
View PDF0 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Except for Bempedoic acid, the development of other ACL inhibitors is limited due to their low cell penetration, low affinity with ACL, and poor specificity.

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
  • Natural triterpene-iridoid glycoside dimer hybrid and its preparation and use in the preparation of acl inhibitors
  • Natural triterpene-iridoid glycoside dimer hybrid and its preparation and use in the preparation of acl inhibitors
  • Natural triterpene-iridoid glycoside dimer hybrid and its preparation and use in the preparation of acl inhibitors

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0040] Example 1: Preparation of Compounds abelifloroside A and abelifloroside B

[0041] 0.4 kg of A. x grandiflora flowers were dried, pulverized, and extracted with 75% ethanol solution at room temperature for 5 times, each 2L for 24 hours. The combined extracts were filtered and concentrated under reduced pressure to obtain 67 g of total extract (semi-dry). After the total extract was dispersed with 1 L of water, it was successively extracted three times with equal volumes of petroleum ether, ethyl acetate and n-butanol. The extract was concentrated under reduced pressure to obtain petroleum ether fraction (17.2 g), ethyl acetate fraction (16.3 g) and n-butanol fraction (20.6 g).

[0042] The ethyl acetate fraction (16.3 g) was eluted with a gradient of ethanol-water (30:70→50:50→70:30→85:15→100:0; v / v) through macroporous resin column chromatography, and collected The obtained lower column liquid was identified by TLC thin layer chromatography, and the lower column liqu...

Embodiment 2

[0055] Example 2: ACL Inhibitory Activity Test

[0056] Experimental method: In this experiment, the ATP-dependent citrate lyase ACL can catalyze the conversion of citrate into acetyl-CoA, and then produce the precursor molecule of fatty acid synthesis - malonyl-CoA. This reaction is accompanied by the consumption of ATP, so the ADP-Glo ​​Kinase Assay Kit can be used to detect the change of ATP to indirectly reflect the inhibitory effect of the compound on ACL enzyme activity.

[0057]Specifically, the percent inhibition rate of ACL enzyme activity was investigated when the concentration of the compound isolated and purified in Example 1 was 20 μg / mL, and the test results showed that the inhibition rates of abelifloroside A and abelifloroside B were 96.4% and 84.1%, respectively. %.

[0058] Further determination of IC 50 Value: The sample was dissolved in DMSO to make a suitable concentration before use, 3 times of dilution, 7 dilutions, three duplicate wells, and 2 μL of t...

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 present application discloses a natural triterpene- iridoid glycoside dimer hybrid compound and its preparation and use in the preparation of ACL inhibitors. The structural formula of the triterpene- iridoid glycoside dimer hybrid compound is as follows: Such as formula (1) or formula (2): the present application carried out ATP-citrate lyase (ATP-citrate lyase, ACL on the obtained triterpene-iridoid glycoside dimer hybrid abelifloroside A and abelifloroside B) ) inhibitory activity experiment, showing that the compound has obvious ACL inhibitory activity, can be used for the preparation of drugs for diseases mediated by ACL or as a leading compound of such drugs, and has anti-hyperlipidemia, atherosclerosis, fatty liver, type II Diabetes, cancer, and other ACL-mediated diseases have therapeutic effects and thus have enormous potential use in the pharmaceutical field.

Description

technical field [0001] The application relates to the technical field of medicine, in particular to a natural triterpene-iridoid glycoside dimer hybrid and its preparation and preparation of an ATP-citrate lyase (ATP-citrate lyase, ACL) inhibitor. use. Background technique [0002] ATP-citrate lyase (ACL) is a key enzyme in glucose metabolism and fatty acid and cholesterol biosynthesis. Its substrates and products are key intermediates in glucose metabolism and can be used as substrates for fatty acid synthesis. . Human ACL enzyme protein is a homotetramer composed of 4 identical 120KDa subunits, each polypeptide chain contains 1101 amino residues (Singh et al, J. Biol. Chem. 1976, 251, 5254-5250) . ACL is a cytoplasmic enzyme that catalyzes the conversion of citrate and coenzyme A to acetyl-CoA and oxaloacetate with concomitant hydrolysis of ATP. ACL is highly expressed in adipogenic cells such as liver, kidney, pancreas, and cholinergic neurons (Beigneux et al., J. Bio...

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): C07J71/00A61P3/06A61P9/10A61P3/10A61P3/04A61P1/16A61P35/00
CPCC07J71/0005A61P3/06A61P9/10A61P3/10A61P3/04A61P1/16A61P35/00
Inventor 胡金锋万江金则新姜春筱
Owner TAIZHOU UNIV