Andrographolide decahydronaphthalene structurally modified derivative series II and its preparation method and use

A technology of andrographolide and decalin, applied in the field of medicine, can solve problems such as lack of effective prevention and treatment methods, and achieve the effects of expanding the range of options, good application and development prospects, and improving myocardial fibrosis.

Active Publication Date: 2021-12-24
ZHENGZHOU UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Statistics show that the 5-year survival rate is less than 50%, and the 10-year survival rate is about 30%. At present, there is still a lack of effective prevention and treatment methods

Method used

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  • Andrographolide decahydronaphthalene structurally modified derivative series II and its preparation method and use
  • Andrographolide decahydronaphthalene structurally modified derivative series II and its preparation method and use
  • Andrographolide decahydronaphthalene structurally modified derivative series II and its preparation method and use

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0033] Example 1 Compounds of the present invention inhibit the migration of human hepatic stellate cells LX-2

[0034] Under the stimulation of various inflammatory mediators, growth factors and other cytokines, hepatic stellate cells migrate to the inflammatory site of the damaged liver tissue, and then proliferate, activate, and synthesize ECM components such as collagen, which is the key to the development of liver fibrosis. Therefore, the scratch injury method was used to evaluate the anti-hepatic fibrosis effect of the compound of the present invention.

[0035] 1) Cell culture and drug treatment

[0036] Using human hepatic stellate cells LX-2 (provided by Beijing Beina Chuanglian Institute of Biotechnology), compared with andrographolide, the in vitro anti-hepatic fibrosis effect of the compound of the present invention was studied. LX-2 cells were cultured in RPMI1640 medium containing 10% (V / V) fetal bovine serum, 100 μg / mL streptomycin, and 100 IU / mL penicillin in ...

Embodiment 2

[0044] Example 2 Compounds of the present invention inhibit TGF-β1-induced transformation of human type II alveolar epithelial cells A549 to mesenchymal cells

[0045] The type II alveolar epithelial cells in the alveoli are stimulated by cytokines such as inflammatory mediators and growth factors, and the cell shape changes from pebble-like to spindle-like, completing the epithelial-mesenchymal transition (EMT) and possessing the function of mesenchymal cells , and then synthesize collagen fibers, a large amount of collagen fiber deposition can aggravate the course of interstitial pulmonary fibrosis. Therefore, the morphological observation method was used to evaluate the anti-pulmonary fibrosis effect of the compounds of the present invention.

[0046] 1) Cell culture and drug treatment

[0047] Using human type II alveolar epithelial cells A549, compared with andrographolide, the in vitro anti-pulmonary fibrosis effect of the compound of the present invention was studied. ...

Embodiment 3

[0055] Example 3 Compounds of the present invention inhibit TGF-β1-induced transformation of human proximal renal tubular epithelial cells HK-2 to mesenchymal cells

[0056] Early studies have found that renal tubular epithelial cells can transdifferentiate into fibroblasts and express their marker protein fibroblast-specific protein 1 (FSP1, fibroblast-specific protein 1), renal tubular epithelial cells-mesenchymal cell transdifferentiation is the key factor for renal interstitial fibers One of the important pathogenesis of cancer. Therefore, the anti-renal fibrosis effect of the compound of the present invention was evaluated by the morphological observation method after TGF-β1 stimulation.

[0057] 1) Cell culture and drug treatment

[0058] Using human proximal renal tubular epithelial cells HK-2 (provided by China Center for Type Culture Collection), compared with andrographolide AD, the in vitro anti-renal fibrosis effect of the compound of the present invention was stu...

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Abstract

The invention belongs to the technical field of medicine, discloses the application of andrographolide derivatives in the preparation of medicines for preventing and treating fibrosis of various tissues and organs of human body, and relates to the structure-modified derivatives of andrographolide decahydronaphthalene. It has the structure of general formula II. Experiments have proved that this type of compound significantly inhibits the migration and activation of hepatic stellate cells LX‑2; significantly inhibits TGF‑β1-induced mesenchymal transition (EMT) of human alveolar type II-like cells A549 and kidney epithelial cells HK‑2. Significantly inhibited the migration of primary human cardiac fibroblasts HCFB induced by angiotensin Ⅱ (Ang Ⅱ). Using this type of compound as an active ingredient to prepare anti-fibrosis drugs of human tissues and organs has high efficiency and low toxicity, and provides a new drug approach for the treatment and prevention of diseases related to fibrosis, thereby expanding the optional range of clinical medication, and has the advantages of Good prospects for application development.

Description

technical field [0001] The invention relates to an andrographolide derivative, a synthesis method and its application as an anti-hepatic fibrosis drug, in particular to a decahydronaphthalene structure-modified derivative of andrographolide, which belongs to the technical field of medicine. Background technique [0002] Human tissue and organ fibrosis is a chronic disease that occurs mostly in the liver, lungs, heart, kidneys and other parts. 1 / 3 of the world's people die from tissue fibrosis and the resulting organ failure fibrosis. The reason is that after the human epithelial tissue is continuously damaged, the stimulation-related effector cells proliferate excessively, making the extracellular matrix (ECM) ) is deposited in large quantities, and tissue fibrosis occurs, which eventually leads to the gradual loss of biological functions of the tissue. Organs with more epithelial tissue are more likely to be affected. Therefore, fibrosis occurs more frequently in organs su...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D407/06C07D307/58A61P1/16A61P11/00A61P13/12A61P9/00
Inventor 徐海伟戴桂馥黄俊刘宏民黄瑞彬闫光明杨卫张颜
Owner ZHENGZHOU UNIV
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