CN-122011073-A - Three-carbon-reducing ganoderma lucidum triterpenic 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 three-carbon-reducing ganoderma lucidum triterpenoid acid compound, a preparation method thereof and an application thereof in preventing and treating influenza. The three-carbon ganoderma lucidum triterpenic acid 3,7,11-Trioxo-25,26,27-trinorlanosta-8-en-24-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 5.17 mu M. Research shows that the compound has application prospect for further developing novel anti-influenza drugs.

Inventors

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

Assignees

• 福建仙芝楼生物科技有限公司
• 中国医学科学院药物研究所

Dates

Publication Date

20260512

Application Date

20241111

Claims (5)

1. 1. A three-carbon-reducing ganoderma lucidum triterpenic 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.17-7-10 is separated by semi-preparative reverse phase high performance liquid chromatography eluting isocratically with 40% 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

Three-carbon-reducing ganoderma lucidum triterpenic 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 three-carbon-reduced ganoderma lucidum triterpenic acid compound 3,7,11-trioxo-25,26,27-trinorlanosta-8-en-24-oic acid separated from ganoderma lucidum, a preparation method thereof and application thereof in resisting influenza viruses. Background 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. From 2000, ganoderma lucidum was taken as a traditional Chinese medicine and loaded in the pharmacopoeia of the people's republic of China (part one), and is a dried fruiting body of Polyporaceae (Polyporaceae) fungus ganoderma lucidum Ganoderma lucidum (Leyss. ExFr.) Karst. Or ganoderma sinensis Ganoderma sinense Zhao, xu et Zhang. In 2023, ganoderma lucidum (fruiting body of Ganoderma lucidum and Ganoderma sinense) was also included in the material category of food and Chinese medicinal materials according to the tradition. The main chemical components in Ganoderma comprise triterpene, hetero-terpene, polysaccharide, steroid, alkaloid, sesquiterpene, etc. Modern clinical and pharmacological researches have proved that ganoderma lucidum has the functions of regulating immunity, tranquilizing, allaying excitement, resisting tumor and virus, resisting inflammation, reducing blood pressure, protecting liver and the like. The ganoderma lucidum cultivated artificially at present is mainly Karst. Influenza viruses belong to the orthomyxoviridae family, being enveloped negative-strand RNA viruses, and can be classified according to antigenic characteristics into influenza a, b, c and d, with influenza a being the most threatening health to humans. Two glycoproteins exist on the surface of influenza virus, hemagglutinin (hemagglutinin, HA) and Neuraminidase (NA), respectively. Wherein NA aids in the release of progeny virus from the host cell by cleaving sialic acid on the cell surface. Neuraminidase inhibitors act against influenza virus by inhibiting the NA activity of influenza virus. Neuraminidase inhibitors currently approved by the FDA for influenza treatment include oseltamivir (oseltamivir), zanamivir (zanamivir), and peramivir (peramivir). 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. At present, no control test is performed on pregnant women, so that the NA inhibitor is all of class C according to FDA classification. 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 three-carbon-reduced ganoderma lucidum triterpenic acid 3,7,11-trioxo-25,26,27-trinorlanosta-8-en-24-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 search influenza virus neuraminidase inhibitory active 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 invention solves the technical problem of providing three-carbon-reduced ganoderma lucidum triterpenic acid 3,7,11-trioxo-25,26,27-trinorlanosta-8-en-24-oic acid, a preparation method thereof and application thereof in resisting influenza viruses. 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 the three-carbon-reduced ganoderma lucidum triterpenic acid 3,7,11-trioxo-25,26,27-trinorlanosta-8-en-24-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 three-carbon-reduced ganoderma lucidum triterpene acid 3,7,11-trioxo-25,26,27-trinorlanosta-8-en-24-oic acid, which is characterized in that: 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 extrac