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CN-122005566-A - Phenanthroindolizidine application of alkaloid

CN122005566ACN 122005566 ACN122005566 ACN 122005566ACN-122005566-A

Abstract

The invention provides application of phenanthroindolizidine alkaloids, which relates to the technical field of phenanthroindolizidine alkaloids biological medicines, wherein the phenanthroindolizidine alkaloids are 13a alpha-6-O-desmethyl antofine, the compound has dual pharmacological activities of nanomolar anti-inflammatory activity and remarkable antiviral activity, in-vitro pharmacological experiments prove that the 13a alpha-6-O-desmethyl antofine can obviously inhibit release of Nitric Oxide (NO), IC 50 is as low as 0.55+/-0.006 nM, and the compound has almost NO influence on cell viability and extremely low cytotoxicity in the concentration range. In addition, the compound also shows excellent antiviral activity in the anti-influenza virus and coronavirus OC43 activities, so that 13a alpha-6-O-desmethyl antofine can be used as a candidate lead compound for developing high-efficiency and low-toxicity anti-inflammatory and antiviral drugs.

Inventors

  • BAI CHANGCAI
  • MA BIAO
  • HAN LU
  • YANG WENLI
  • ZHU CAIXIA
  • WEN FEI
  • WANG XUEMEI

Assignees

  • 宁夏医科大学

Dates

Publication Date
20260512
Application Date
20260129

Claims (10)

  1. 1. The application of the phenanthroindolizidine alkaloid is characterized in that the phenanthroindolizidine alkaloid is 13a alpha-6-O-desmethyl antofine, and the structural formula is shown as follows: ; the application of the 13a alpha-6-O-desmethyl antofine in preparing anti-inflammatory or antiviral drugs.
  2. 2. The use of the phenanthroindolizidine alkaloids according to claim 1, wherein in the use of 13 a-6-O-desmethylantofine for preparing anti-inflammatory drugs, the half inhibition concentration IC 50 =0.55±0.006 nM of 13 a-6-O-desmethylantofine on LPS-induced RAW 264.7 cells NO is 0.006 nM to 0.4 nM.
  3. 3. The use of the phenanthroindolizidine alkaloids according to claim 1, wherein the 13a alpha-6-O-desmethyl antofine is used for preparing antiviral drugs, the antiviral drugs are anti-influenza virus or anti-coronavirus OC43.
  4. 4. The use of the phenanthroindolizidine alkaloids according to claim 3, wherein the concentration of 13a α -6-O-desmethyl antofine is 10 μmol.
  5. 5. The use of the phenanthroindolizidine alkaloids according to claim 4, wherein the antiviral agent is an anti-influenza virus.
  6. 6. The use of the phenanthroindolizidine alkaloids according to any one of claims 1-5, wherein the medicament is in the form of a tablet, capsule, granule, spray, nano-preparation, controlled release preparation, sustained release preparation, oral liquid, powder, granule or injection.
  7. 7. The use of the phenanthroindolizidine alkaloids according to claim 6, wherein the medicament further comprises pharmaceutically acceptable carriers and excipients.
  8. 8. The use of the phenanthroindolizidine alkaloids according to claim 6, wherein the 13a alpha-6-O-desmethyl antofine is extracted from the head of a melon, the extraction steps being as follows: S1, airing whole herb of the Laoguo head, cutting off roots, crushing to obtain coarse powder of overground parts of the Laoguo head, extracting the coarse powder of the Laoguo head with ethanol for a plurality of times by adopting an ultrasonic auxiliary soaking method, combining extracting solutions, concentrating under reduced pressure, and drying in vacuum to obtain an ethanol extract of the Laoguo head; S2, dissolving the ethanol extract of the Laoguo head, degreasing with petroleum ether in advance, extracting for a plurality of times with an ethyl acetate solvent, merging organic layers, concentrating under reduced pressure, and drying to obtain an ethyl acetate extraction part of the ethanol extract of the Laoguo head; S3, adopting macroporous adsorption resin, carrying out gradient elution on an ethyl acetate extraction part of the ethanol extract of the Laotou cucurbitae by sequentially passing 20-35% ethanol aqueous solution, 40-60% ethanol aqueous solution and 70-85% ethanol aqueous solution, and collecting fractions eluted by CKE 3; S4, separating CKE3-C fraction by normal phase silica gel column chromatography, collecting CKE3-CB as second fraction, further separating CKE3-CB by C18 reverse phase column chromatography, silica gel column chromatography, gel column chromatography and semi-preparative liquid chromatography, and repeatedly purifying to obtain 13a alpha-6-O-desmethyl antofine.
  9. 9. The use of the phenanthroindolizidine alkaloids according to claim 8, wherein in the step S1, the purity of ethanol is 70% -90%, and the condition of ultrasonic extraction is that the feed-liquid ratio is 1:10-20, the extraction temperature is 50-60 ℃ and the extraction time is 2-4 h.
  10. 10. Use of a Laoguan head for the preparation of an anti-inflammatory or antiviral medicament, characterized in that it comprises 13a alpha-6-O-desmethyl antofine according to any one of claims 1 to 9.

Description

Phenanthroindolizidine application of alkaloid Technical Field The invention belongs to the technical field of phenanthroindolizidine alkaloid biological medicines, and particularly relates to application of phenanthroindolizidine alkaloids. Background The Laoguan head (Cynanch mu m komarovii Al. Iljinski., abbreviated CK) belongs to the genus Cynanchum (Cynanch mu Linn.) of the family Asclepiadaceae, and is additionally provided with aliases such as Cynanchum otophyllum, etc. The Chinese medicinal composition is mainly distributed in northwest regions of China, like Ningxia, gansu, and North highland area of inner Mongolia, and is a traditional folk medicinal material. From the aspect of medicinal properties, the Lao Gua is bitter in taste and warm in nature, and has the effects of activating blood, relieving pain and diminishing inflammation. In recent years, with the continuous and deep research on the phytochemical components of the Laoguan, the main active components of the Laoguan are gradually clear, and the Laoguan is mainly composed of phenanthroindolizidine alkaloid, C21 steroid and glycoside compounds thereof. The alkaloid contained in the Laoguan head takes the phenanthroindolizidine alkaloid as a core, and the alkaloid not only has obvious anticancer activity, but also plays an important role in immunoregulation, so that the structural modification and total synthesis research of the phenanthroindolizidine alkaloid are also widely focused. In view of the above, the invention provides a new application of the phenanthroindolizidine alkaloid compound, adds a new drug selection in the field of biomedical treatment, and lays a foundation for subsequent drug research and development and clinical application. Disclosure of Invention The application of the phenanthroindolizidine alkaloid is characterized in that the phenanthroindolizidine alkaloid is 13a alpha-6-O-desmethyl antofine, and the structural formula is shown as follows: ; The application of 13a alpha-6-O-desmethyl antofine (13 a alpha-6-O-desmethylantofine) in preparing anti-inflammatory or antiviral drugs. Preferably, in the application of 13a alpha-6-O-desmethylanthracene in preparing anti-inflammatory drugs, the half inhibition concentration IC 50 =0.55+/-0.006 nM of 13a alpha-6-O-desmethylanthracene on NO of RAW 264.7 cells induced by LPS at the concentration of 0.006 nM-0.4 nM. Preferably, the application of the 13a alpha-6-O-desmethyl antofine in preparing antiviral drugs is anti-influenza virus or anti-coronavirus OC43. Preferably, the concentration of 13a alpha-6-O-desmethylantofine is 10 micromolar. Preferably, the antiviral is anti-influenza virus. Preferably, the medicament is a tablet, a capsule preparation, a granule, a spray, a nano preparation, a controlled release preparation, a sustained release preparation, an oral liquid, powder, medicinal granules or an injection preparation. Preferably, the medicament further comprises a pharmaceutically acceptable carrier and an auxiliary material. Preferably, the 13a alpha-6-O-desmethyl antofine is extracted from the head of a melon, and the extraction steps are as follows: S1, airing whole herb of the Laoguo head, cutting off roots, crushing to obtain coarse powder of overground parts of the Laoguo head, extracting the coarse powder of the Laoguo head with ethanol for a plurality of times by adopting an ultrasonic auxiliary soaking method, combining extracting solutions, concentrating under reduced pressure, and drying in vacuum to obtain an ethanol extract of the Laoguo head; S2, dissolving the ethanol extract of the Laoguo head, degreasing with petroleum ether in advance, extracting for a plurality of times with an ethyl acetate solvent, merging organic layers, concentrating under reduced pressure, and drying to obtain an ethyl acetate extraction part of the ethanol extract of the Laoguo head; S3, adopting macroporous adsorption resin, carrying out gradient elution on an ethyl acetate extraction part of the ethanol extract of the Laotou cucurbitae by sequentially passing 20-35% ethanol aqueous solution, 40-60% ethanol aqueous solution and 70-85% ethanol aqueous solution, collecting fractions eluted by CKE3, carrying out gradient elution on the fractions eluted by CKE3 by adopting a silica gel column chromatography, and collecting eluted third fractions CKE3-C by using dichloromethane/methanol again. S4, separating CKE3-C fraction by normal phase silica gel column chromatography, collecting CKE3-CB as second fraction, further separating CKE3-CB by C18 reverse phase column chromatography, silica gel column chromatography, gel column chromatography and semi-preparative liquid chromatography, and repeatedly purifying to obtain 13a alpha-6-O-desmethyl antofine. Preferably, in the step S1, the purity of the ethanol is 70-90%, and the ultrasonic extraction conditions are that the feed-liquid ratio is 1:10-20, the extraction temperature is 50-60 ℃ and the extraction time is 2-4 h. Use of a