CN-122011074-A - Ganoderma lucidum triterpenoid acid compound, preparation method thereof and application thereof in preventing and treating influenza

Abstract

The invention belongs to the field of medicines, and discloses a ganoderma lucidum triterpenoid acid compound, a preparation method thereof and application thereof in preventing and treating influenza viruses. The ganoderma lucidum triterpenic acid compound (24E) -3 alpha-hydroxy-7-oxo-lanosta-8, 24-dien-26-oic acid is shown in formula I. Experiments prove that the compound has better influenza virus neuraminidase inhibitory activity, and the IC 50 of the compound is 18.3 mu M. Research shows that the compound has application prospect for further developing novel anti-influenza drugs.

Inventors

• KANG JIE
• LI YE
• LIU AILIN
• SHAO HONGJIE
• WANG CHAO
• Bai Daiming
• WU CHANGHUI
• CHEN RUOYUN

Assignees

• 中国医学科学院药物研究所
• 福建仙芝楼生物科技有限公司

Dates

Publication Date

20260512

Application Date

20241111

Claims (5)

1. 1. A ganoderma triterpene acid compound or pharmaceutically acceptable salt thereof is characterized in that the structural formula of the compound is
2. 2. A process for the preparation of a compound as claimed in claim 1, wherein, 1) Reflux-extracting dry fruiting body of Ganoderma lucidum with 90% ethanol-water for 3 times, mixing extractive solutions, concentrating under reduced pressure to obtain extract, and mixing with macroporous resin; 2) Subjecting to macroporous resin chromatography, gradient eluting with 30% ethanol-water, 60% ethanol-water, 80% ethanol-water and 95% ethanol-water to obtain 4 parts, namely DK-1-DK-4, wherein DK-3 is gradient eluted by silica gel column chromatography, and the eluent is mixed solvent of petroleum ether and ethyl acetate, gradient eluting sequentially according to volume ratio of 85:15, 80:20, 75:25, 70:30, 60:40, 50:50, and washing the chromatographic column sequentially with ethyl acetate and methanol to obtain 25 components, namely Fr.1-Fr.25. The Fr.17 is eluted by medium pressure silica gel column chromatography gradient, the eluent is petroleum ether and ethyl acetate (80:20-50:50, v/v), and the chromatographic column is washed by ethyl acetate to obtain 14 subfractions, namely Fr.17-1-Fr.17-14.Fr.17-7 is eluted by C 18 reverse column chromatography gradient, the eluent is methanol to water (50:50-75:25, v/v), and the chromatographic column is washed by 100% methanol to obtain 25 subfractions, namely Fr.17-7-1-Fr.17-7-25.Fr.17-7-21 is separated by semi-preparative reverse phase high performance liquid chromatography eluting isocratically with 55% acetonitrile-water as eluent to give the compound of claim 1.
3. 3. A pharmaceutical composition comprising a compound of claim 1 and pharmaceutically acceptable salts thereof, and a pharmaceutically acceptable carrier or excipient.
4. 4. The use of a compound as claimed in claim 1 and a pharmaceutically acceptable salt thereof for the manufacture of a medicament for the prophylaxis or/and treatment of influenza.
5. 5. The use according to claim 4, wherein said influenza comprises influenza a, influenza b, etc.

Description

Ganoderma lucidum triterpenoid acid compound, preparation method thereof and application thereof in preventing and treating influenza Technical Field The invention relates to the field of medicines, in particular to a novel ganoderma lucidum triterpenic acid compound (24E) -3 alpha-hydroxy-7-oxo-lanosta-8, 24-dien-26-oic acid separated from ganoderma lucidum, a preparation method thereof and application thereof in resisting influenza viruses. Background Ganoderma lucidum is a generic term for fungi of the genus Ganoderma (Ganoderma) of the family Polyporaceae (Polyporaceae). 120 species are available worldwide, 106 species are available in China, and the fungus is used as both medicine and food. Lucid ganoderma is originally carried in Shen nong Ben Cao Jing (Shen nong's herbal), and is characterized by superior quality, sweet, flat, nontoxic, easy to extract qi, good in color and tendons and bones. The Chinese pharmacopoeia prescribes that the dried fruiting bodies of Ganoderma lucidum Ganoderma lucidum (Leyss. ExFr.) Karst or Ganoderma sinense Ganoderma sinense Zhao, xuet Zhang are legal medicinal materials. The main chemical components in Ganoderma comprise triterpene, hetero-terpene, polysaccharide, steroid, alkaloid, sesquiterpene, etc. The ganoderma lucidum has the effects of tonifying qi and soothing nerves, and relieving cough and asthma, and is mainly used for treating restlessness of heart spirit, insomnia and palpitation, cough and asthma due to lung deficiency, consumptive disease and shortness of breath, anorexia and the like. The ganoderma lucidum cultivated artificially at present is mainly Karst. Influenza is an acute respiratory infection caused by influenza virus. Seasonal influenza is common throughout the world. Symptoms of influenza include acute fever, cough, sore throat, body pain, and weakness. There are 4 types of influenza viruses, type a, type b, type c and type d, where transmission of influenza a and type b causes seasonal disease epidemics and only influenza a causes pandemics. Currently prevalent in humans are influenza a subtype H1N1 and H3N2 viruses. Neuraminidase (NA) is one of the important targets for the action of anti-influenza drugs. When NA of influenza virus is inhibited, newly synthesized progeny virus will accumulate on the surface of host cells and cannot be released, thus blocking the next step of spreading and infecting new cells. NA inhibitors currently in clinical use are designed based on the sialic acid isomer 2, 3-didehydro-2-deoxy-N-acetylneuraminic acid (DANA). The U.S. Food and Drug Administration (FDA) classifies drugs into A, B, C, D, X classes based on their effects on fetal teratogenicity, both in animal experiments and clinical experience. Wherein, the C-type medicine is animal research, which proves that the medicine is harmful to fetus (teratogenesis or embryonic death, etc.), or pregnant women without control are not researched, or pregnant women and animals are not researched. The medicament can be used only after weighing benefit to pregnant women more than harm to fetuses. Since no control was performed on pregnant women, NA inhibitors were all class C according to FDA grading. Ganoderma lucidum is classified as the upper grade product, has no toxicity, can be taken for a long time, and has almost no toxic or side effect. The new ganoderma lucidum triterpenic acid (24E) -3 alpha-hydroxy-7-oxo-lanosta-8, 24-dien-26-oic acid related to the research is a new compound, and has the neuraminidase inhibitory activity of influenza virus for the first time. So far, the above research results have not been reported in patents or documents. The invention aims to fully develop traditional Chinese medicine resources in China, and find anti-influenza virus compounds with unique chemical structures, strong activity and small toxic and side effects, so as to provide novel anti-influenza virus medicines for clinical research. Disclosure of Invention The technical problem solved by the invention is to provide ganoderma lucidum triterpenic acid (24E) -3 alpha-hydroxy-7-oxo-lanosta-8, 24-dien-26-oic acid, a preparation method thereof and application thereof in preventing and treating influenza virus. In order to solve the technical problems of the invention, the invention provides the following technical scheme: according to the technical scheme, the first aspect of the invention provides ganoderma lucidum triterpenic acid (24E) -3 alpha-hydroxy-7-oxo-lanosta-8, 24-dien-26-oic acid. Is characterized in that the structural formula of the compound is The second aspect of the technical scheme of the invention provides a preparation method of the ganoderma lucidum triterpenic acid (24E) -3 alpha-hydroxy-7-oxo-lanosta-8, 24-dien-26-oic acid in the first aspect: 1) Reflux-extracting dry fruiting body of Ganoderma lucidum with 90% ethanol-water for 3 times, mixing extractive solutions, concentrating under reduced pressure to obtain extract, and mixing with macroporous r