AU2020102164A4 - Compound with antiviral effect and use thereof - Google Patents
Compound with antiviral effect and use thereof Download PDFInfo
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- AU2020102164A4 AU2020102164A4 AU2020102164A AU2020102164A AU2020102164A4 AU 2020102164 A4 AU2020102164 A4 AU 2020102164A4 AU 2020102164 A AU2020102164 A AU 2020102164A AU 2020102164 A AU2020102164 A AU 2020102164A AU 2020102164 A4 AU2020102164 A4 AU 2020102164A4
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- stellera chamaejasme
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
- A61K31/05—Phenols
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
- A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/16—Antivirals for RNA viruses for influenza or rhinoviruses
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
- A61K2236/333—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using mixed solvents, e.g. 70% EtOH
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/39—Complex extraction schemes, e.g. fractionation or repeated extraction steps
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/50—Methods involving additional extraction steps
- A61K2236/51—Concentration or drying of the extract, e.g. Lyophilisation, freeze-drying or spray-drying
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/50—Methods involving additional extraction steps
- A61K2236/53—Liquid-solid separation, e.g. centrifugation, sedimentation or crystallization
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/50—Methods involving additional extraction steps
- A61K2236/55—Liquid-liquid separation; Phase separation
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/47—Euphorbiaceae (Spurge family), e.g. Ricinus (castorbean)
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/83—Thymelaeaceae (Mezereum family), e.g. leatherwood or false ohelo
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
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- Saccharide Compounds (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
Disclosed in the present invention are a compound with antiviral effect and use
thereof. Through extensive experimental screening, the present invention has found
that stellera chamaejasme aglycone and stellera chamaejasme glucoside have a
significant antiviral effect, particularly a significant inhibitory effect on enteroviruses
and influenza viruses, and can be used to prepare antiviral drugs. In particular, they
have a good prevention and treatment effect on hand-foot-mouth disease and
influenza. The subject matter of the present invention can be prepared into drugs
convenient for administration with a convenient and pharmaceutically acceptable
carrier.
Description
The present invention relates to the field of biomedicine, and specifically, the present invention relates to a compound with antiviral effect and use thereof.
Enteroviruses include 71 serotypes of poliovirus, Coxsackievirus, enterocytopathic human orphan virus, and new enterovirus. For infectious diseases caused by enterovirus, mild clinical manifestations are merely lassitude, fatigue, low fever, etc., and in severe cases, they may induce systemic infection, so that important organs such as brain, spinal cord, heart, and liver are damaged and the prognosis is poor, leaving sequelae or causing death.
Enterovirus 71 (EV71), Coxsackievirus A16 (CA16), Coxsackievirus A6 (CA6), and Coxsackievirus A10 (CA10) are the main pathogens that cause hand-foot-mouth disease in infants and young children in the Asia-Pacific region. Among several pathogens that cause hand-foot-mouth disease, EV71 is the main pathogen that causes severe hand-foot-mouth disease. The prevention and treatment of hand-foot-mouth disease is still an urgent public health issue to be solved.
Influenza (also referred to as flu for short) is an acute respiratory infection caused by influenza viruses, and it is also a highly contagious and fast-spreading disease. The onset symptoms thereof are acute high fever, general pain, significant fatigue, and mild respiratory symptoms. Due to its high mutation rate, people populations are generally susceptible, and the incidence is relatively high. It has caused multiple outbreaks all over the world, including China, which seriously endangers human life and health.
Object of the invention: the object of the present invention is to provide a compound with antiviral effect and use thereof in the prevention and treatment of viral diseases.
Technical solution: to achieve the above object, the present invention adopts the following technical solution:
A compound with antiviral effect, which is stellera chamaejasme aglycone and stellera chamaejasme glucoside, respectively.
The two compounds has the structure as shown below: CHe
SH 0 0
OH CO 800
stellera chamaejasme aglycone and stellera chamaejasme glucoside
Use of the compound with antiviral effect of the present invention in preparing antiviral drugs.
The use of the present invention, wherein the virus is human enterovirus A, human enterovirus B, human enterovirus C, or human enterovirus D.
Use of the compound with antiviral effect of the present invention in preparing drugs for prevention and treatment of hand-foot-mouth disease, aseptic meningitis, meningitis, poliomyelitis, or acute respiratory diseases caused by viruses.
The use of the present invention, wherein the virus is influenza virus, coronavirus or SARS virus.
The use of the present invention, wherein the compound is prepared into tablets, capsules, granules, injections, pills, or suppositories with a pharmaceutically acceptable carrier.
Advantageous effect: through extensive experimental screening, the present invention has found that the above two compounds have a significant antiviral effect, particularly a significant inhibitory effect on enteroviruses and influenza viruses, and can be used to prepare antiviral drugs. In particular, they have a good prevention and treatment effect on hand-foot-mouth disease and influenza. The subject matter of the present invention can be prepared into drugs convenient for administration with a convenient and pharmaceutically acceptable carrier.
The two compounds of the present invention are prepared by the following method:
The root of stellera chamaejasme was extracted twice with 95% ethanol under reflux for 2 hours each time. Extracts were combined and concentrated. The concentrated extract was suspended in water and extracted with petroleum ether, chloroform and ethyl acetate, respectively. The petroleum ether part was subjected to silica gel column chromatography (eluted with petroleum ether and ethyl acetate) to obtain 10 components (Al-A10). Component A7 was further resolved on a silica gel column using gradient elution with petroleum ether and ethyl acetate (100:0, 100:1, :1, 20:1, 10:1, 5: 1, and 1:1) to obtain 15 fractions (A11-A25). Fraction A18 was further subjected to silica gel column chromatography, eluted with petroleum ether and ethyl acetate (50:1, 20:1, 10:1, 5:1, 3:1, 1:1, 1:2, and 1:5) to give compound 1: stellera chamaejasme aglycone.
The ethyl acetate part was subjected to silica gel column chromatography (eluted with petroleum ether and ethyl acetate), to obtain 8 eluted components by TLC tracking. Component B3 was further eluted on a silica gel column with petroleum ether and ethyl acetate (100:1, 50:1, 20:1, 10:1, 5:1, 2:1, and 1:1), to obtain 10 eluted fractions (B9-B18) by TLC tracking. Eluted fraction B15 was again subjected to silica gel column chromatography using gradient elution with petroleum ether and ethyl acetate (40:1, 20:1, 10:1, 5:1, 2:1, 1:1, and 1:2) to give compound 2: stellera chamaejasme glucoside.
Through extensive experimental screening, the present invention has found that the compound NZY602 can inhibit the replication of enteroviruses in vitro. The present invention will be further described below in connection with specific examples, but these examples should not be construed as limiting the present invention.
Example 1: Detection of anti-enteroviral activity of a compound
1. Experimental materials
Viruses: EV71 virus strain, Coxsackievirus A2 (CV-A2), Coxsackievirus BI
(CV-B1), human Poliovirus 1 (PV-1), and EV-D68, donated by Nanjing University of Traditional Chinese Medicine.
Compounds to be tested: stellera chamaejasme aglycone and stellera chamaejasme glucoside described above, self-made in the laboratory, with a purity of above 98%.
2. Experimental method
Monolayer cells in a 96-well plate were washed twice with PBS, and dilutions containing about 100TCID 50 of EV71 virus, Coxsackievirus A2 (CV-A2), Coxsackievirus BI (CV-BI), human Poliovirus 1 (PV-1), and EV-D68 virus were added, each in 100 [L/well. The cells were incubated in a 37°C, 5% CO2 incubator for 2 hours, and the virus solution was discarded. The process above was made in duplicate. Then, two-fold serial dilutions of stellera chamaejasme aglycone and stellera chamaejasme glucoside were added separately, with 4 replicate wells for each concentration. With the maximum non-toxic concentration as the initial drug concentration, the cells were incubated in a 37°C, 5% CO 2 incubator for 2 days. The cells was observed for lesions, and stained with MTT to determine OD values. Half effective concentration (IC50) was calculated with Reed-Muench method, and selective index (SelectiveIndex, SI) was calculated: SI= TC50/IC50).
3. Experimental Results
The present invention evaluates the anti-enteroviral efficacy of stellera chamaejasme aglycone and stellera chamaejasme glucoside by MDCK cell lesion inhibition method and MTT method, specifically shown in Table 1:
Table 1 Evaluation on the inhibitory efficacy of stellera chamaejasme aglycone and stellera chamaejasme glucoside against enteroviruses
stellera chamaejasme aglycone stellera chamaejasme glucoside enterovirus TC50 IC 50 selective TC50 IC 50 selective index index ( g/mL) ( g/mL) SI ( g/mL) ( g/mL) SI
EV71 virus 32.27 6.67 4.90 32.27 4.87 6.63 CV-A2 32.27 6.98 4.62 32.27 5.02 6.43 CV-B1 32.27 10.54 3.06 32.27 6.52 4.95
PV-1 32.27 15.08 2.14 32.27 8.15 3.95 EV-D68 32.27 4.75 6.79 32.27 2.03 15.90 virus
The experimental results in Table 1 above show that the chamaejasme aglycone and chamaejasme glucoside provided by the present invention have a good inhibitory effect on enteroviruses of various subtypes, and the activity of chamaejasme glucoside is stronger than that of aglycone.
Example 2: Detection of anti-influenza activity of a compound
1. Experimental materials
Viruses: H1N, H3N2 and H9N2 virus strains, donated by Nanjing University of Traditional Chinese Medicine.
Compounds to be tested: stellera chamaejasme aglycone and stellera chamaejasme glucoside described above, self-made in the laboratory, with a purity of above 98%.
2. Experimental method.
Monolayer cells in a 96-well plate were washed once with PBS, and dilutions containing about 100TCID 50 of influenza virus were added in 100 pL/well. The cells were incubated in a 37°C, 5% CO 2 incubator for 2 hours. The virus solution was discarded. The process above was made in duplicate. Two-fold serial dilutions of stellera chamaejasme aglycone and stellera chamaejasme glucoside were added separately, with 4 replicate wells for each concentration. With the maximum non-toxic concentration as the initial drug concentration, the cells were incubated in a 37°C, 5% CO2 incubator for 2 days. The cells was observed for lesions, and stained with MTT to determine OD values. Half effective concentration (IC50) calculated with Reed-Muench method, and selective index (SelectiveIndex, SI) was calculated: SI= TC50/IC50).
3. Experimental Results.
The efficacy of stellera chamaejasme aglycone and stellera chamaejasme glucoside are evaluated by MDCK cell lesion inhibition method and MTT method. The results are shown in Table 2 below. The results show that the stellera chamaejasme aglycone and stellera chamaejasme glucoside provided by the present invention have a good inhibitory effect on influenza viruses of various subtypes. The activity of stellera chamaejasme glucoside is stronger than that of stellera chamaejasme aglycone. They are particularly sensitive to influenza subtype HINI.
Table 2 Evaluation on the inhibitory efficacy of stellera chamaejasme aglycone and stellera chamaejasme glucoside against different influenza viruses
stellera chamaejasme aglycone stellera chamaejasme glucoside Influenza TC50 IC 50 selective TC50 IC 50 selective virus index index subtype ( g/mL) ( g/mL) SI ( g/mL) ( g/mL) SI HIN 32.22 3.17 10.16 32.22 1.58 20.39 H3N2 32.22 3.79 8.50 32.22 2.75 11.72 H9N2 32.22 5.17 6.23 32.22 3.70 8.71 The examples described above, representing only several implementations of the present invention, are specifically described in detail above, but they are not to be construed as limiting the scope of the present invention. It should be noted that several variations and modifications can be made by those of ordinary skill in the art without departing from the concept of the present invention, and that these variations and modifications all fall within the scope of protection of the present invention.
Claims (6)
1. A compound with antiviral effect, wherein the compound having the structure as
shown below:
=CH
CHCO OH
H~4- tOOH 3 HO
°" and H H
2. Use of the compound with antiviral effect of claim 1 in preparing an antiviral drug.
3. The use according to claim 2, wherein the virus is human enterovirus A, human
enterovirus B, human enterovirus C, or human enterovirus D.
4. Use of the compound with antiviral effect of claim 1 in preparing drugs for
prevention and treatment of hand-foot-mouth disease, aseptic meningitis, meningitis,
poliomyelitis, or acute respiratory diseases caused by viruses.
5. The use according to claim 2, wherein the virus is influenza virus, coronavirus or
SARS virus.
6. The use according to claim 2, wherein the compound is prepared into tablets,
capsules, granules, injections, pills, or suppositories with a pharmaceutically
acceptable carrier.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010095982.2 | 2020-02-17 | ||
| CN202010095982.2A CN111202725A (en) | 2020-02-17 | 2020-02-17 | Compound with antiviral effect and application thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AU2020102164A4 true AU2020102164A4 (en) | 2020-11-05 |
Family
ID=70782617
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2020102164A Ceased AU2020102164A4 (en) | 2020-02-17 | 2020-08-10 | Compound with antiviral effect and use thereof |
Country Status (2)
| Country | Link |
|---|---|
| CN (1) | CN111202725A (en) |
| AU (1) | AU2020102164A4 (en) |
-
2020
- 2020-02-17 CN CN202010095982.2A patent/CN111202725A/en active Pending
- 2020-08-10 AU AU2020102164A patent/AU2020102164A4/en not_active Ceased
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| Publication number | Publication date |
|---|---|
| CN111202725A (en) | 2020-05-29 |
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