Search

CN-121991091-A - Isodhilarane type hetero-terpene compound, and preparation method and application thereof

CN121991091ACN 121991091 ACN121991091 ACN 121991091ACN-121991091-A

Abstract

The invention discloses Isodhilarane type hetero-terpene compounds, a preparation method and application thereof, wherein the general formula of Isodhilarane type hetero-terpene compounds is shown in the formula I-III: In the formula (I) and the formula (II), the ring system framework is 6/7/6/5/6/5, in the formula (III), the ring system framework is 6/7/6/5/6;R 1 , and R 2 is selected from hydrogen or hydroxyl, and the ring system framework is methyl or hydroxymethyl. The inventor applies Isodhilarane type hetero terpene compound to the anti-hepatic fibrosis treatment for the first time, and the anti-hepatic fibrosis experiment shows that Isodhilarane type hetero terpene compound has lower cytotoxicity and better anti-hepatic fibrosis activity, and is hopeful to be developed into a novel anti-hepatic fibrosis drug.

Inventors

  • HUANG LING
  • JIANG ZHONGPING
  • RAO YONG
  • CHEN YUE

Assignees

  • 海南大学

Dates

Publication Date
20260508
Application Date
20260122

Claims (10)

  1. 1. Isodhilarane type diterpene compounds have a general formula shown in formula I-formula III: ; In the formula (I) and the formula (II), the ring system framework is 6/7/6/5/6/5, and in the formula (III), the ring system framework is 6/7/6/5/6; r 1 is selected from hydrogen or hydroxy, and R 2 is selected from methyl or hydroxymethyl.
  2. 2. The Isodhilarane-type diterpenoid compound according to claim 1, characterized in that the Isodhilarane-type diterpenoid compound is specifically: 。
  3. 3. Use of a Isodhilarane-type diterpenoid compound or a pharmaceutically acceptable derivative thereof according to claim 1 or 2 in the manufacture of an anti-liver fibrosis medicament.
  4. 4. The use according to claim 3, wherein the Isodhilarane-type diterpene compound is selected from at least one of compounds 2,3, 11, 12, 13.
  5. 5. The use according to claim 4, wherein compound 11 is capable of down-regulating the expression of fibrotic markers, including fibronectin, collagen I, and α -smooth muscle actin.
  6. 6. The use according to claim 4, wherein compound 11 is capable of reducing plasma alanine aminotransferase, aspartate aminotransferase levels, ameliorating liver damage.
  7. 7. A preparation method of Isodhilarane type hetero terpene compounds comprises the following steps: 1) Activating and culturing fungi in an enlarged manner to obtain a fermentation product; 2) Soaking the fungus ferment in ethyl acetate, filtering, concentrating under reduced pressure, and recovering solvent to obtain ethyl acetate extract of fungus; 3) Extracting the extract with ethyl acetate, subjecting the ethyl acetate extract to normal phase silica gel column chromatography, gradient eluting, and collecting eluent; 4) Concentrating the eluent, and separating by reverse phase silica gel column chromatography and high performance liquid chromatography to obtain Isodhilarane-type hetero terpene compounds.
  8. 8. The process according to claim 7, wherein in step 1) the fungus is selected from the group consisting of Penicillium species Sp.) or cyanobacteria sp.)。
  9. 9. The method according to claim 7, wherein in step 3), the eluent of the normal phase silica gel column chromatography is chloroform-methanol or dichloromethane-methanol.
  10. 10. The method according to claim 7, wherein in step 4), the eluent of the reverse phase silica gel column chromatography is methanol-water or acetone-water.

Description

Isodhilarane type hetero-terpene compound, and preparation method and application thereof Technical Field The invention relates to the technical field of hetero-terpene compounds, in particular to Isodhilarane-type hetero-terpene compounds, a preparation method and application thereof. Background Liver fibrosis is a dynamic, reversible pathological process characterized by damage to and repair of abnormal liver tissue, activation or transformation of Hepatic Stellate Cells (HSCs) and hepatocytes leading to excessive extracellular matrix (ECM) deposition. Gradual accumulation of fibrotic tissue accelerates loss of liver function, and eventually may progress to cirrhosis or liver cancer, severely threatening the physical health of humans. Continuous liver injury in various chronic liver diseases (such as viral hepatitis, alcoholic and non-alcoholic fatty liver, bile stasis, autoimmune hepatitis and the like) can lead to liver fibrosis, and 75-80% of patients can develop cirrhosis or liver cancer if not intervened in time. And with a continuously high incidence of obesity and metabolic dysfunction related diseases, patients with liver fibrosis will continue to increase. Because of the multiple causative factors and complex pathological mechanisms of liver fibrosis, the development of anti-liver fibrosis drugs is extremely challenging, and although significant progress has been made in causal treatment (e.g., antiviral drugs against chronic hepatitis b and c, immunosuppressants against autoimmune hepatitis can effectively delay the progression of fibrosis for a particular liver disease), no targeted anti-liver fibrosis therapeutic drugs have been approved at present. Therefore, the research and development of the anti-hepatic fibrosis medicine with a new structure and a new mechanism is significant. Disclosure of Invention The invention aims to provide Isodhilarane-type hetero-terpene compounds, a preparation method and application thereof, which can be used for developing anti-hepatic fibrosis drugs. The technical scheme adopted by the invention for realizing the technical purpose is as follows: The invention provides Isodhilarane-type hetero terpene compounds, the general formula of which is shown in the formulas I-III: In the formula (I) and the formula (II), the ring system framework is 6/7/6/5/6/5, and in the formula (III), the ring system framework is 6/7/6/5/6; r 1 is selected from hydrogen or hydroxy, and R 2 is selected from methyl or hydroxymethyl. Preferably, the Isodhilarane-type hetero terpene compound is specifically:。 the invention also provides application of the Isodhilarane type hetero terpene compound or the pharmaceutically acceptable derivative thereof in preparing anti-hepatic fibrosis drugs. Preferably, the Isodhilarane-type diterpene compound is selected from at least one of compounds 2,3, 11, 12, 13. More preferably, compound 11 is capable of down-regulating the expression of fibrotic markers, including fibronectin, collagen I, and alpha-smooth muscle actin. More preferably, compound 11 is capable of reducing plasma alanine aminotransferase, aspartate aminotransferase levels, ameliorating liver damage. The invention also provides a preparation method of Isodhilarane-type hetero-terpene compounds, which comprises the following steps: 1) Activating and culturing fungi in an enlarged manner to obtain a fermentation product; 2) Soaking the fungus ferment in ethyl acetate, filtering, concentrating under reduced pressure, and recovering solvent to obtain ethyl acetate extract of fungus; 3) Extracting the extract with ethyl acetate, subjecting the ethyl acetate extract to normal phase silica gel column chromatography, gradient eluting, and collecting eluent; 4) Concentrating the eluent, and separating by reverse phase silica gel column chromatography and high performance liquid chromatography to obtain Isodhilarane-type hetero terpene compounds. Preferably, in step 1), the fungus is selected from the group consisting of Penicillium species @Sp.) or cyanobacteriasp.)。 Preferably, in step 3), the eluent of the normal phase silica gel column chromatography is chloroform-methanol or dichloromethane-methanol. Preferably, in step 4), the eluent of the reverse phase silica gel column chromatography is methanol-water or acetone-water. The beneficial effects of the invention are as follows: The inventor prepares a new Isodhilarane type hetero terpene compound, applies the Isodhilarane type hetero terpene compound to the aspect of liver fibrosis treatment for the first time, and shows that the Isodhilarane type hetero terpene compound has lower cytotoxicity and better liver fibrosis resistance activity through the liver fibrosis resistance experimental result, and is hopeful to be developed into a novel liver fibrosis resistance drug or health care product, and especially the compound 11 has larger development potential. Drawings FIG. 1-FIG. 2 are nuclear magnetic resonance hydrogen spectra and carbon s