CN114907346B - Alkaloid compound, extract and application thereof in preparation of products with respiratory syncytial virus resisting effect - Google Patents
Alkaloid compound, extract and application thereof in preparation of products with respiratory syncytial virus resisting effect Download PDFInfo
- Publication number
- CN114907346B CN114907346B CN202210545561.4A CN202210545561A CN114907346B CN 114907346 B CN114907346 B CN 114907346B CN 202210545561 A CN202210545561 A CN 202210545561A CN 114907346 B CN114907346 B CN 114907346B
- Authority
- CN
- China
- Prior art keywords
- compound
- respiratory syncytial
- syncytial virus
- extract
- formula
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 229930013930 alkaloid Natural products 0.000 title claims abstract description 42
- 230000000694 effects Effects 0.000 title claims abstract description 37
- -1 Alkaloid compound Chemical class 0.000 title claims abstract description 29
- 238000002360 preparation method Methods 0.000 title claims abstract description 6
- 241000725643 Respiratory syncytial virus Species 0.000 title abstract description 50
- 150000001875 compounds Chemical class 0.000 claims abstract description 47
- 239000003814 drug Substances 0.000 claims abstract description 21
- 241000700605 Viruses Species 0.000 claims description 14
- 230000003097 anti-respiratory effect Effects 0.000 claims description 8
- 240000005523 Peganum harmala Species 0.000 claims description 6
- 239000000443 aerosol Substances 0.000 claims description 2
- 239000002775 capsule Substances 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 238000002347 injection Methods 0.000 claims description 2
- 239000007924 injection Substances 0.000 claims description 2
- 239000007788 liquid Substances 0.000 claims description 2
- 239000006187 pill Substances 0.000 claims description 2
- 239000000843 powder Substances 0.000 claims description 2
- 239000003826 tablet Substances 0.000 claims description 2
- 239000002417 nutraceutical Substances 0.000 claims 3
- 235000021436 nutraceutical agent Nutrition 0.000 claims 3
- IWUCXVSUMQZMFG-AFCXAGJDSA-N Ribavirin Chemical compound N1=C(C(=O)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 IWUCXVSUMQZMFG-AFCXAGJDSA-N 0.000 abstract description 12
- 229960000329 ribavirin Drugs 0.000 abstract description 12
- HZCAHMRRMINHDJ-DBRKOABJSA-N ribavirin Natural products O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1N=CN=C1 HZCAHMRRMINHDJ-DBRKOABJSA-N 0.000 abstract description 12
- 230000036541 health Effects 0.000 abstract description 5
- 238000011160 research Methods 0.000 abstract description 4
- 239000004480 active ingredient Substances 0.000 abstract description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 20
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- 238000005481 NMR spectroscopy Methods 0.000 description 10
- 239000000047 product Substances 0.000 description 10
- 150000003797 alkaloid derivatives Chemical class 0.000 description 9
- 229940079593 drug Drugs 0.000 description 7
- 238000001228 spectrum Methods 0.000 description 7
- 235000005126 Peganum harmala Nutrition 0.000 description 6
- 206010061603 Respiratory syncytial virus infection Diseases 0.000 description 5
- 230000000840 anti-viral effect Effects 0.000 description 5
- 230000005764 inhibitory process Effects 0.000 description 4
- 208000030925 respiratory syncytial virus infectious disease Diseases 0.000 description 4
- 108010068327 4-hydroxyphenylpyruvate dioxygenase Proteins 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
- 238000004566 IR spectroscopy Methods 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- 238000004896 high resolution mass spectrometry Methods 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 210000000582 semen Anatomy 0.000 description 3
- 238000005084 2D-nuclear magnetic resonance Methods 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 231100000433 cytotoxic Toxicity 0.000 description 2
- 230000001472 cytotoxic effect Effects 0.000 description 2
- 230000003013 cytotoxicity Effects 0.000 description 2
- 231100000135 cytotoxicity Toxicity 0.000 description 2
- 238000010828 elution Methods 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 238000007689 inspection Methods 0.000 description 2
- 238000001819 mass spectrum Methods 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 239000013641 positive control Substances 0.000 description 2
- 208000023504 respiratory system disease Diseases 0.000 description 2
- 239000002356 single layer Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 229920001817 Agar Polymers 0.000 description 1
- 208000006820 Arthralgia Diseases 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 241000711920 Human orthopneumovirus Species 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 241000711504 Paramyxoviridae Species 0.000 description 1
- 241000159204 Peganum Species 0.000 description 1
- 208000008765 Sciatica Diseases 0.000 description 1
- 235000005811 Viola adunca Nutrition 0.000 description 1
- 240000009038 Viola odorata Species 0.000 description 1
- 235000013487 Viola odorata Nutrition 0.000 description 1
- 235000002254 Viola papilionacea Nutrition 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 150000001336 alkenes Chemical group 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 239000003443 antiviral agent Substances 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- GHQPBDDZGPAVJP-UHFFFAOYSA-N azanium;methanol;hydroxide Chemical compound N.O.OC GHQPBDDZGPAVJP-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 230000003833 cell viability Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000005100 correlation spectroscopy Methods 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 231100000517 death Toxicity 0.000 description 1
- 241001493065 dsRNA viruses Species 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000001052 heteronuclear multiple bond coherence spectrum Methods 0.000 description 1
- 238000000990 heteronuclear single quantum coherence spectrum Methods 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 238000010166 immunofluorescence Methods 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 238000010829 isocratic elution Methods 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- VMGAPWLDMVPYIA-HIDZBRGKSA-N n'-amino-n-iminomethanimidamide Chemical compound N\N=C\N=N VMGAPWLDMVPYIA-HIDZBRGKSA-N 0.000 description 1
- 231100000065 noncytotoxic Toxicity 0.000 description 1
- 230000002020 noncytotoxic effect Effects 0.000 description 1
- 231100000028 nontoxic concentration Toxicity 0.000 description 1
- 239000002777 nucleoside Substances 0.000 description 1
- 150000003833 nucleoside derivatives Chemical class 0.000 description 1
- 238000000238 one-dimensional nuclear magnetic resonance spectroscopy Methods 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 230000036285 pathological change Effects 0.000 description 1
- 231100000915 pathological change Toxicity 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 238000002953 preparative HPLC Methods 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 238000010298 pulverizing process Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000008707 rearrangement Effects 0.000 description 1
- 238000000611 regression analysis Methods 0.000 description 1
- BOLDJAUMGUJJKM-LSDHHAIUSA-N renifolin D Natural products CC(=C)[C@@H]1Cc2c(O)c(O)ccc2[C@H]1CC(=O)c3ccc(O)cc3O BOLDJAUMGUJJKM-LSDHHAIUSA-N 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 238000002495 two-dimensional nuclear magnetic resonance spectrum Methods 0.000 description 1
- 238000002211 ultraviolet spectrum Methods 0.000 description 1
- 241000712461 unidentified influenza virus Species 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/105—Plant extracts, their artificial duplicates or their derivatives
-
- 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
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
-
- 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
Abstract
The invention relates to the technical field of pharmaceutical chemistry, and particularly discloses an alkaloid compound, an extract and application thereof in preparation of a product with an effect of resisting respiratory syncytial virus. The alkaloid compound has a structure shown in a formula I. The research shows that: the alkaloid compound with the structure shown in the formula I has very obvious activity of resisting respiratory syncytial virus, and the activity of resisting the respiratory syncytial virus is superior to that of a positive medicament ribavirin; therefore, the compound has important application value when being used as an active ingredient for preparing the medicine or the health care product with the effect of resisting the respiratory syncytial virus.
Description
Technical Field
The invention relates to the technical field of pharmaceutical chemistry, in particular to an alkaloid compound, an extract and application thereof in preparing a product with an effect of resisting respiratory syncytial virus.
Background
Human Respiratory Syncytial Virus (RSV) is an enveloped negative strand RNA virus of the paramyxoviridae family. Respiratory syncytial virus infection is the leading cause of respiratory disease, resulting in over 300 million respiratory syncytial virus-associated respiratory disease cases and 20 million respiratory syncytial virus-associated deaths worldwide each year. Currently, antiviral therapy is an important option for the treatment of respiratory syncytial virus infection. Ribavirin is an FDA approved antiviral drug for treatment of RSV infection and is a nucleoside analog directed to RNA transcription and replication. However, excessive use of such drugs has led to the emergence of drug-resistant strains. Therefore, there is a need to develop new alternative antiviral molecules against respiratory syncytial virus.
The semen Pegani Harmalae is dried mature seed of semen Pegani Harmalae (L.) of Peganum of Zygophyloaceae. The peganum harmala is mainly distributed in arid grassland and desert areas such as Xinjiang, inner Mongolia, ningxia, qinghai and Gansu. Peganum harmala seed is a famous drug with a long history of use and is listed in the drug Standard of Ministry of health of the people's republic of China. It is widely used as traditional Chinese medicine, uighur medicine and Mongolian medicine for treating arthralgia, rheumatoid arthritis, sciatica, etc. Previous chemical component researches on peganum harmala seeds show that the plant contains a large amount of alkaloid components and has wide biological activities including antiviral activity, antitumor activity, antioxidant activity, antibacterial activity and the like. However, no alkaloid fraction isolated from Peganum harmala has been reported to have activity against Respiratory Syncytial Virus (RSV).
In addition, the structure and the variety of the alkaloid are various, and the antiviral effects of the alkaloids with different structures are completely different; for example, an alkaloid can act against influenza virus, but it does not necessarily have an anti-respiratory syncytial virus effect; even though it has the effect of resisting the respiratory syncytial virus, the effect of the alkaloids with different structures on resisting the respiratory syncytial virus is different; especially, alkaloids with stronger respiratory syncytial virus resistance than ribavirin are rarely reported. Therefore, the alkaloid with the effect of resisting the respiratory syncytial virus, particularly the alkaloid with the effect of resisting the respiratory syncytial virus stronger than that of ribavirin, has important application value.
Disclosure of Invention
In order to overcome at least one technical problem in the prior art, the invention provides a brand new alkaloid compound; the alkaloid compound has excellent effect of resisting respiratory syncytial virus, and the effect of resisting the respiratory syncytial virus is stronger than that of ribavirin.
The technical scheme of the invention is as follows:
an alkaloid compound having the structure shown in formula I:
the alkaloid compound (abbreviated as PG) with the structure shown in the formula I is a brand new compound; the research shows that: IC of alkaloid compound with structure shown as formula I on respiratory syncytial virus 50 5.01 +/-0.14 mu M; significantly less than the IC of the positive drug ribavirin for respiratory syncytial virus 50 (8.71 +/-0.95 mu M); the alkaloid compound with the structure shown in the formula I has very obvious activity of resisting respiratory syncytial virus, and the activity of resisting the respiratory syncytial virus is obviously superior to that of a positive medicament ribavirin; this technical effect is unexpected by the person skilled in the art.
The invention also provides application of the alkaloid compound in preparation of a product with an effect of resisting respiratory syncytial virus.
The alkaloid compound with the structure shown in the formula I has excellent anti-respiratory syncytial virus activity; therefore, the compound has important application value when being used as an active ingredient for preparing products with the effect of resisting the respiratory syncytial virus.
Preferably, the product is a medicament or health product.
Preferably, the medicine or health care product contains a therapeutically effective amount of the compound with the structure shown in the formula I and a pharmaceutically acceptable carrier.
Preferably, the medicament or the health-care product is in the form of powder, pills, tablets, capsules, oral liquid, aerosol or injection.
The invention also provides an extract which contains the alkaloid compound with the structure shown in the formula I.
Preferably, the mass fraction of the alkaloid compound with the structure shown in the formula I in the extract is 1-80%.
Further preferably, the mass fraction of the alkaloid compounds with the structure shown in the formula I in the extract is 5-50%.
More preferably, the mass fraction of the alkaloid compounds with the structure shown in the formula I in the extract is 10-30%.
Preferably, the extract is prepared from peganum harmala serving as a raw material.
Because the alkaloid compound with the structure shown in the formula I has excellent effect of resisting respiratory syncytial virus; therefore, one skilled in the art would expect that the alkaloid compounds having the structure shown in formula I would also have an anti-respiratory syncytial virus effect.
The invention also provides application of the extract in preparing a product with the effect of resisting the respiratory syncytial virus.
Has the beneficial effects that: the invention provides an alkaloid compound with a brand-new structure; the research shows that: the alkaloid compound with the structure shown in the formula I has very obvious activity of resisting respiratory syncytial virus, and the activity of resisting the respiratory syncytial virus is obviously superior to that of a positive medicament ribavirin; in addition, the SI value of the alkaloid compound with the structure shown in the formula I reaches 15.1, and the safety range is wider. Therefore, the compound has important application value when being used as an active ingredient for preparing the medicine or the health care product with the effect of resisting the respiratory syncytial virus.
Drawings
FIG. 1 shows the chemical structure of compound PG.
FIG. 2 is the molecular number of Compound PG.
FIG. 3 is a graph showing the experimental results of the inhibition of Respiratory Syncytial Virus (RSV) by Compound PG; wherein, FIG. 3A shows the cytotoxic effect of compound PG on HEp-2; FIGS. 3B and 3C are graphs showing the inhibitory effect of compound PG and the positive control drug ribavirin on Respiratory Syncytial Virus (RSV) at various concentrations; figure 3D is the effect of compound PG on Respiratory Syncytial Virus (RSV) proliferation at different times; FIG. 3E shows the effect of immunofluorescence on the expression of F protein representative of viruses at various concentrations of compound PG.
Fig. 4 is a high resolution mass spectrum of compound PG.
FIG. 5 shows the UV spectrum (in methanol) of compound PG.
FIG. 6 shows an infrared spectrum (KBr pellet) of Compound PG.
FIG. 7 shows NMR of Compound PG 1 H spectrum (600 MHz in DMSO).
FIG. 8 is a compoundNuclear magnetic resonance of PG 13 C spectrum (150 MHz in DMSO).
FIG. 9 shows the nuclear magnetic resonance DEPT-135 spectrum (150 MHz in DMSO) of compound PG.
FIG. 10 shows NMR of Compound PG 1 H- 1 H COSY spectra (150 MHz in DMSO).
FIG. 11 shows the NMR HSQC spectra (150 MHz in DMSO) of compound PG.
FIG. 12 shows the NMR HMBC spectra (150 MHz in DMSO) of compound PG.
FIG. 13 shows the NOESY spectrum (150 MHz in DMSO) of compound PG.
Detailed Description
In order that the invention may be more clearly understood, it will now be further described with reference to the following examples and the accompanying drawings. The examples are for illustration only and do not limit the invention in any way. In the examples, each raw reagent material is commercially available, and the experimental method not specifying the specific conditions is a conventional method and a conventional condition well known in the art, or a condition recommended by an instrument manufacturer.
Example 1
Pulverizing dried 15.0kg semen Pegani Harmalae, and cold extracting with 95% ethanol at room temperature to obtain total extract 1.6kg. In order to enrich the alkaloid components in the extract, the total extract is processed by an acid-extraction-alkali-precipitation method to obtain 378.0g of total alkaloid components. Subjecting the total alkaloid components to 200-300 mesh silica gel column chromatography, and purifying with CH 2 Cl 2 MeOH system gradient elution (1000 → 0 → 1), combined according to TLC inspection, yielded 7 fractions (fr.a-G). The fr.d (27.5 g) fractions were subjected to gradient elution by ODS column chromatography using methanol/water (0 → 100 → 0) as the mobile phase, and combined according to TLC inspection to give 5 sub-fractions (fr.d 1-5), and fr.d3 (5.1 g) was further subjected to preparative HPLC (methanol-water-ammonia as the mobile phase, isocratic elution with a volume ratio of methanol: water: ammonia =60 R Fraction corresponding to chromatographic peak of =16.2 min) to obtain compound PG, namely the alkaloid compound with the structure shown in formula I.
The basis of structure identification:
the structure of compound PG was obtained by analysis of high resolution mass spectrometry (HRESIMS), infrared spectroscopy (IR), one-dimensional and two-dimensional nuclear magnetic resonance spectroscopy (NMR).
Determination of molecular weight 255.1126 2M + H by high resolution mass spectrum HRESIMS: m/z] + (theoretical value: 255.1128) and shows a molecular formula of C 15 H 14 N 2 O 2 。
The data obtained by infrared spectroscopy showed the presence of an amino group (3441 cm) -1 ) And a benzene ring (1625, 1453cm -1 )。
TABLE 1 one-and two-dimensional NMR spectroscopic data (DMSO, delta in ppm, J in Hz) for Compound PG
Nuclear magnetic resonance hydrogen spectrum ( 1 H NMR) and assignments, see table 1. Data show that Compound PG has an AMX spin system [ delta ] H 8.15(1H,d,J＝8.7Hz),7.30(1H,d,J＝2.2Hz),6.91(1H,dd,J＝8.7,2.2Hz)]Two olefin proton signals [ delta ] H 8.44(1H,d,J＝4.9Hz),8.29(1H,d,J＝4.9Hz)]Hydrogen proton signal of one methoxy group [ delta ] H 3.86(3H,s)]And an ethyl proton signal [ delta ] H 3.33(2H,q,J＝7.3Hz),1.19(3H,t,J＝7.3Hz)]。
According to nuclear magnetic resonance carbon spectrum ( 13 C NMR) and assignments, see table 1. The data show that compound PG has 7 quaternary carbons (containing two vicinal oxygens), 5 tertiary carbons, 1 secondary carbon, and 2 primary carbons (containing one vicinal oxygen), for a total of 15 carbon signals.
The data and the binding relationship of the two-dimensional nuclear magnetic resonance spectrum are shown in table 1.
The molecular number of compound PG is shown in FIG. 2.
EXAMPLE 2 test of PG Activity against respiratory syncytial Virus for Compound
1. Cell for determination of compound by MTT methodToxicity, 1.5X 10 4 The individual cells were plated in 96-well plates and were 5% CO at 37 deg.C 2 Culturing for 18h in an incubator;
2. agar overlay cultures containing different concentrations of compound (100. Mu.M, 50. Mu.M, 25. Mu.M, 12.5. Mu.M, 6.25. Mu.M, 3.125. Mu.M) were added;
3. after 48h of cell culture, treating for 4h by using an MTT method;
4. subsequently, the supernatant was removed, and then dimethyl sulfoxide (DMSO) was added to dissolve blue-violet crystalline formazan;
5. absorbance was measured at 570nm and Cytotoxic Concentration (CC) of 50% was obtained by nonlinear regression analysis of cell viability 50 )；
6. Testing the antiviral activity of the compound at a first concentration of maximal non-cytotoxic concentration (MNCC);
7. cell suspension (1.5X 10 per well) 4 Individual cells) were seeded in each well of a 96-well plate;
after 8.18h, monolayer HEp-2 cells were treated with RSV virus and varying concentrations of compound PG and cultured for 72h;
9. observing the pathological change degree of syncytium of each hole by a microscope, and observing and evaluating the concentration of inhibiting half of CPE, namely the half maximum Inhibitory Concentration (IC) 50 )。
10. Monolayer HEp-2 cells were treated with a mixture of equal volumes of RSV virus (MOI = 0.1) and 40 μ M compound PG. Ribavirin (40 μm) was used as a positive control. After 24h of culture, HEp-2 cells were stained with an anti-RSV F antibody and the fluorescence intensity of the cells was observed by a fluorescence microscope.
TABLE 2 anti-RSV activity of compound PG
As can be seen from the experimental data in Table 2, the IC of the compound PG with the structure shown in the formula I on the respiratory syncytial virus 50 5.01 +/-0.14 mu M; far less than the IC of positive drug ribavirin for respiratory syncytial virus 50 (8.71. + -. 0.95. Mu.M); this indicates that compound PG of formula I has the structureThe anti-respiratory syncytial virus activity is very obvious and is obviously superior to that of a positive medicine ribavirin; this technical effect is unexpected by the person skilled in the art.
In addition, as can be seen from the experimental data in table 2, the SI value of the compound PG against the respiratory syncytial virus reaches 15.1, which is far greater than the minimum standard 1.00, which indicates that the compound PG has a greater safety range when being used for preparing the anti-respiratory syncytial virus medicament.
Further, FIG. 3A shows cytotoxicity (CC) of Compound PG against Hep-2 cells 50 ) 75.81. + -. 1.75 μm. Infection of Hep-2 cells with different titers of RSV virus (MOI =0.1,1 or 5) assessed compound PG tolerance to high titer virus infection (fig. 3B). Plaque inhibition assay then tested compound PG for inhibition of respiratory syncytial virus at non-toxic concentrations (fig. 3C). The results show that the compound PG and RSV viruses act on Hep-2 cells simultaneously, can obviously reduce the virus yield and have concentration dependence. Virus production assays (fig. 3D) showed that progeny virus numbers reached a plateau at day 3 post Respiratory Syncytial Virus (RSV) infection. The compound PG (40 μm) has obvious inhibition effect on Respiratory Syncytial Virus (RSV) within 1d-4 d. These data indicate that the anti-respiratory syncytial virus effect of compound PG is not due to cytotoxicity. Green fluorescence represents the F protein of the virus, with high levels of F protein observed in the virus group. The green fluorescence associated with respiratory syncytial virus infection was significantly reduced upon addition of compound PG (fig. 3E). According to the data, different titers of compound PG can be shown to remarkably inhibit respiratory syncytial virus infection.
It will be appreciated by those skilled in the art that the use of the present invention is not limited to the specific applications described above. The invention is also not limited to the preferred embodiments thereof with respect to the specific elements and/or features described or depicted herein. It should be understood that the invention is not limited to the disclosed embodiment or embodiments, but is capable of numerous rearrangements, modifications and substitutions without departing from the scope of the invention as set forth and defined by the following claims.
Claims (11)
1. An alkaloid compound having a structure according to formula I:
2. the use of alkaloids according to claim 1 for the preparation of a product having an anti-respiratory syncytial virus effect.
3. The use according to claim 2, wherein the product is a pharmaceutical or nutraceutical product.
4. The use of claim 3, wherein the medicament or nutraceutical comprises a therapeutically effective amount of a compound having the structure of formula I and a pharmaceutically acceptable carrier.
5. The use of claim 3, wherein the pharmaceutical or nutraceutical is in the form of powder, pill, tablet, capsule, oral liquid, aerosol, or injection.
6. An extract characterized by containing an alkaloid compound having a structure represented by formula I;
7. the extract as claimed in claim 6, wherein the mass fraction of the alkaloid compounds with the structure shown in formula I in the extract is 1-80%.
8. The extract as claimed in claim 7, wherein the mass fraction of the alkaloid compounds with the structure shown in formula I in the extract is 5-50%.
9. The extract as claimed in claim 8, wherein the mass fraction of the alkaloid compounds with the structure shown in formula I in the extract is 10-30%.
10. The extract according to claim 6, wherein the extract is prepared from harmel seeds.
11. Use of an extract according to any one of claims 6 to 10 for the preparation of a product having an anti-respiratory syncytial virus effect.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210545561.4A CN114907346B (en) | 2022-05-19 | 2022-05-19 | Alkaloid compound, extract and application thereof in preparation of products with respiratory syncytial virus resisting effect |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210545561.4A CN114907346B (en) | 2022-05-19 | 2022-05-19 | Alkaloid compound, extract and application thereof in preparation of products with respiratory syncytial virus resisting effect |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN114907346A CN114907346A (en) | 2022-08-16 |
| CN114907346B true CN114907346B (en) | 2023-03-31 |
Family
ID=82767723
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202210545561.4A Active CN114907346B (en) | 2022-05-19 | 2022-05-19 | Alkaloid compound, extract and application thereof in preparation of products with respiratory syncytial virus resisting effect |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN114907346B (en) |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20140154813A1 (en) * | 2012-11-30 | 2014-06-05 | Sicpa Holding Sa | Marking of material, marked material and process of authentication or dilution determination |
| JP2021518413A (en) * | 2018-03-20 | 2021-08-02 | アイカーン スクール オブ メディシン アット マウント サイナイ | Kinase inhibitor compounds and compositions and usage |
-
2022
- 2022-05-19 CN CN202210545561.4A patent/CN114907346B/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| CN114907346A (en) | 2022-08-16 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US7732458B2 (en) | Methods for preparing dehydrocavidine, dehydroapocavidine or their composition, their use and medicinal composition containing them | |
| KR100896700B1 (en) | A.tuberosum Rottl. extract having an activity of activating choline acetyltransferase in brain nerve cells | |
| CN110511255B (en) | Novel iridoid glycoside compound and preparation method and application thereof | |
| Ogbeide et al. | Antiplasmodial and acute toxicity studies of fractions and cassane-type diterpenoids from the stem bark of Caesalpinia pulcherrima (L.) Sw | |
| Nguyen et al. | Phenolic compounds from Caesalpinia sappan | |
| CN112159376A (en) | Sesterterpene compound and application thereof in preparing anti-inflammatory drugs | |
| CN108640968A (en) | A kind of meroterpenoids compound and its purposes in preparing anti-inflammatory drug | |
| CN104382968B (en) | Extraction method of andrographolide, andrographolide pharmaceutical composition and application | |
| CN105131008B (en) | Preparation method and application of prenylated flavonoid compound with anti-hepatoma activity | |
| CN114907346B (en) | Alkaloid compound, extract and application thereof in preparation of products with respiratory syncytial virus resisting effect | |
| EP3281945A1 (en) | Phillygenin glucuronic acid derivative, preparation method and application thereof | |
| KR101131224B1 (en) | Coumarin compounds from Corydalis heterocarpa and Anticancer composition containing the same | |
| CN107708717B (en) | Application of rhinacanthin quinone C as nerve cell apoptosis inhibitor | |
| CN101555206B (en) | Angustifolia lignans, preparing method and application thereof | |
| JP5462996B2 (en) | A hepatoprotective agent obtained from the bonsai, a pharmaceutical or food containing the hepatoprotectant, and a novel Megastigman compound obtained from the bonsai. | |
| CN115894414A (en) | Amide lignanoid compound prepared from white English, and preparation method and application thereof | |
| CN113754620B (en) | Lignan amide compound in fructus cannabis, and preparation method and application thereof | |
| CN109705183B (en) | Clerodendrum cyrtonema metabolite, pharmaceutical composition thereof, preparation method and application thereof | |
| CN110452278A (en) | Smelly seven secondary metabolites and preparation method thereof and its application in pharmacy | |
| CN115433152B (en) | Compound separated from golden silk plum fruit, preparation method and application | |
| CN112047887B (en) | Tinospora sinensis amide and preparation method and application thereof | |
| CN114601821A (en) | Application of compound in preparation of product with antiviral effect | |
| CN109575089B (en) | Acylated glucose compounds, pharmaceutical composition, preparation method and application thereof | |
| KR101457520B1 (en) | Composition containing neorhodomela extracts or polybromocatechol from neorhodomela extracts having antiviral activity | |
| CN116969927B (en) | Compound extracted and separated from long pepper and application of compound in preparation of anti-inflammatory drugs |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |