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

Drug design method based on natural product, pentacyclic triterpenoid compound, preparation method and application of pentacyclic triterpenoid compound

A technology for pentacyclic triterpenes and natural products, applied in the field of biomedicine, can solve problems such as unfavorable efficacy or toxicity, low abundance of natural products, unfriendly environment, etc. active effect

Pending Publication Date: 2020-09-04
HUAZHONG AGRI UNIV
View PDF5 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] In view of the above defects or improvement needs of the prior art, the present invention provides a drug design method based on natural products, the purpose of which is to transform the drug to be improved by screening natural product reference molecules with the same similar activity and higher abundance. Natural products, and according to this method, a pentacyclic triterpenoid compound, its preparation method and application are provided, thus solving the problems of environmental unfriendliness or high cost caused by the low abundance of many effective natural products, as well as drug efficacy or Toxicity is not conducive to the technical problems of finished medicine

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
  • Drug design method based on natural product, pentacyclic triterpenoid compound, preparation method and application of pentacyclic triterpenoid compound
  • Drug design method based on natural product, pentacyclic triterpenoid compound, preparation method and application of pentacyclic triterpenoid compound
  • Drug design method based on natural product, pentacyclic triterpenoid compound, preparation method and application of pentacyclic triterpenoid compound

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0084] Example 1 Application of the natural product-based design method provided by the present invention, such as figure 1 The shown design of anti-inflammatory active molecules includes the following steps:

[0085] (1) Choosing Tripterygium Wilfordii as the natural product molecule to be improved, namely the template molecule;

[0086] Tripterygium wilfordii is an active pentacyclic triterpene natural product isolated from the rhizome of the Euonymus family plant Tripterygium wilfordii. Its structure is as follows figure 2 Shown. Although Tripterygium wilfordii has potent anti-inflammatory, anti-tumor activity and obesity treatment effects, some poor pharmacological properties and low abundance will seriously hinder its preparation. Tripterygium wilfordii is not a drug molecule with excellent drug properties, but it is a good drug research leader.

[0087] (2) Using the molecular structure of Tripterygium wilfordii as a template molecule, natural triterpene molecules with simila...

Embodiment 2

[0097] The steps are the same as in Example 1, the template molecule is corosolic acid, the reference molecule is 18-β glycyrrhetinic acid, the biological content is higher than 1%, and the similarity score between the two is 0.4.

[0098] Corosolic acid is a triterpene compound naturally present in Lagerstroemia grandiflora in the Rosaceae plant (Figure-4). It can exist freely in plants or in the form of saponin. In plants, it often coexists with its isomer maslinic acid (2α-hydroxyoleanolic acid), similar in structure and chemical properties, and it is difficult to separate. The results of in vivo and in vitro experiments show that corosolic acid can promote the absorption and utilization of glucose by cells by promoting the transport of glucose, thereby achieving its blood sugar lowering effect. Its excitatory effect on glucose transport is similar to insulin, therefore, corosolic acid is also called plant insulin. The results of animal experiments show that corosolic acid ha...

Embodiment 3

[0101] Example 3 Synthesis and identification of 3,11-dicarbonyl-1,12-diene-2-hydroxy-oleanane-30 carboxylic acid (GA-02)

[0102] The structural modification scheme and synthetic route using 18-β glycyrrhetinic acid as template molecule are as Figure 5 Shown. Transfer the 3-en-3-hydroxy-2-one structural module of Tripterygium wilfordii to the A ring of glycyrrhetinic acid, keeping the other structures of 18-β-glycyrrhetinic acid unchanged; the preparation method of the designed compound is as follows: 18 -β-Glycyrrhetinic acid was prepared by oxidation of John's reagent to obtain 3,11-dicarbonyl-12-ene-oleanorane-30 carboxylic acid (2); compound (2) was subjected to potassium tert-butoxide in tert-butanol solvent Prepared by oxygen oxidation to obtain 3,11-dicarbonyl-1,12-diene-2-hydroxy-oleanolane-30 carboxylic acid (3); compound (3) is recrystallized from methanol / dichloromethane mixed solvent to obtain crystals Like pure products. The specific implementation plan is as fol...

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 a drug design method based on a natural product, a pentacyclic triterpenoid compound, and a preparation method and application of the pentacyclic triterpenoid compound. The design method comprises the following steps: (1) acquiring template molecules; (2) selecting a natural product which is similar to the template structure in a threshold range and has the specific biological activity as an alternative reference molecule set; (3) selecting one or more reference molecules from the reference molecule set, and comparing with the template molecule to obtain different active functional groups; and constructing the active functional groups with difference on a molecular skeleton which is commonly possessed by the template molecule and the reference molecule. According tothe invention, a cheap lead compound which is easy to obtain in quantity is successfully designed to replace triterpene molecules by taking the biological content of a plant triterpene natural product in a host plant and a numerical value similar to the structures of tripterine and a crosolic acid compound as screening conditions; experiments prove that the traditional Chinese medicine composition has obvious physiological activity of resisting inflammation and metabolic syndrome caused by chronic inflammation.

Description

Technical field [0001] The invention belongs to the field of biomedicine, and more specifically, relates to a drug design method based on natural products, a pentacyclic triterpenoid compound, a preparation method and application thereof. Background technique [0002] Although drug developers in various countries have invested considerable manpower and material resources in combinatorial chemistry, the only new chemical entity drug discovered through this route so far is sorafenib, which was approved by the FDA in 2005 for the treatment of renal cell carcinoma. Natural products play an important role and irreplaceable status in the research and development of new drugs. Compared with synthetic compounds, natural products have more stereogenic centers, more fused, bridged or spiro ring structures, diverse molecular structures and the characteristics of easy combination with biological macromolecules, novel structures and important biological The activity determines its unparallel...

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
IPC IPC(8): C07J63/00A61K31/56A61P29/00A61P3/00A61P3/04A61P3/10
CPCC07J63/008A61K31/56A61P29/00A61P3/00A61P3/04A61P3/10G16C20/50
Inventor 胡学博周波石乐
Owner HUAZHONG AGRI UNIV