CN113730392B - Application of myrtle ketone compound in preparation of antiviral veterinary drug - Google Patents
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Abstract
The invention discloses application of myrtle ketone compounds in preparation of antiviral veterinary drugs. The invention provides myrtle, extracts and fractions thereof, and myrtle ketone compounds which have obvious inhibitory action on animal viruses and small cytotoxicity, and the action mechanism of the myrtle, the extracts and the fractions thereof comprises (but is not limited to) inhibiting the animal viruses from entering cells, preventing the animal viruses from replicating in host cells and timely regulating and controlling the apoptosis program of infected cells. The myrtle ketone compound, the myrtle family plant containing the myrtle ketone compound, the extract and the fraction thereof have an inhibition effect on animal viruses, and are expected to be developed into novel antiviral veterinary drugs.
Description
Technical Field
The invention belongs to the technical field of veterinary science, and particularly relates to an application of myrtle ketone compounds in preparation of antiviral veterinary drugs.
Background art:
animal breeding is one of the important pillars of national economy, diseases occurring in animal breeding at present mainly represent multiple infections of pathogens, and 80% of pathogens of the infections are virus infections except bacteria or parasites. For example, African Swine Fever Virus (ASFV), Porcine Reproductive and Respiratory Syndrome Virus (PRRSV), Porcine Epidemic Diarrhea Virus (PEDV), and Avian Influenza Virus (AIV) which have been outbreaks in recent years have devastating effects on animal breeding industry. The virus diseases have the characteristics of high propagation speed, high mortality rate and easy drug resistance generation in veterinary clinical practice, the veterinarians clinically prohibit the use of antiviral chemical drugs (such as amantadine, rimantadine, acyclovir, ribavirin, viroline and the like) by the ministry of agriculture, the traditional Chinese medicine is an ideal choice for developing antiviral veterinary drugs due to complex active ingredients and difficult drug resistance generation, and the common antiviral traditional Chinese medicines such as isatis root, honeysuckle, fructus forsythiae and the like have no remarkable effect and have the defects of high price, drug competition with people and the like, so the development of the traditional Chinese veterinary drugs for preventing or treating the virus infectious diseases is urgently needed.
The myrtle is a Rhodomyrtus tomentosa (Ait.) Hass myrtle belonging to Rhodomyrtus (DC.) Reich of Myrtaceae (Mytaceae) Rhodomyrtus, namely Duoney, Gongma melastoma, Melastoma dodecandrum, dolichos scandens, Danlian, pyrus communis root, Reyno, Dodonald Douglas, Duchen, Zhongni, Wudu Zi, Taojiu and Danggu, mainly distributed in southern China and southeast China, especially in southern Yan, and is a commonly-used real estate drug in Guangdong. The myrtle is sweet and astringent in nature and taste, is taken as a medicine or a food by using roots, leaves, flowers and fruits, and has the effects of clearing heat, detoxifying, nourishing blood, stopping bleeding, astringing intestines, securing essence, warming the abdominal organs and benefiting muscles, so that the myrtle is an economic plant with potential development and utilization values. In addition, it has a long history of use, Tang Liu 24642from Ling exterior recorded the history: "Backwan-zi … … is sweet and soft, warms abdomen and benefits muscles. "
At present, documents and patents report that a myrtle ketone compound and a derivative thereof in myrtle have an antibacterial effect (patent application number: CN 104761565A myrtle ketone compound and application thereof in preparing antibacterial drugs; CN 108752305A closed-loop myrtle ketone analogue and application thereof in antibacterial drugs; CN 105859537A open-loop myrtle ketone analogue and preparation method thereof and application thereof in antibacterial drugs), but no research report related to the antivirus of myrtle and active ingredients thereof is found before the patent.
The invention content is as follows:
the first purpose of the invention is to provide application of myrtle ketone compounds, or stereoisomers, epimers, configurational isomers or pharmaceutically acceptable salts thereof, or hydrates of the myrtle ketone compounds, or ethanol extracts, n-hexane extracts and ethyl acetate extracts of myrtle in preparation of antiviral veterinary drugs.
The structure of the myrtle ketone compound is shown as a formula I:
wherein R is 1 Is hydrogen, or C1-C15 straight chain, branched chain naphthenic base or aromatic group containing benzene ring;
R 2 and R 3 、R 4 Each is independently selected from hydrogen, or a substituent group selected from the following;
wherein n is any number from 0 to 15, R 8 And R 9 Each independently selected from hydrogen, or C1-C15 straight chain, branched chain cycloalkyl or aromatic group containing benzene ring, or R 8 And R 9 Form a cycloalkyl, heterocycle.
Preferably, n is 1 to 8.
Preferably, R is 1 Is a straight chain, branched chain or cyclic alkyl of C3-C10.
More preferably, the myrtle ketone compound is as follows:
the veterinary drug is a drug for preventing or treating porcine reproductive and respiratory syndrome, porcine epidemic diarrhea and avian influenza.
The myrtle extract, fraction and myrtle ketone compound provided by the invention can be extracted from any part of the whole plant of myrtle, which is a myrtaceae plant, by a physical and/or chemical method, and can also be extracted from other myrtaceae plants to obtain the application of veterinary drugs for preventing or treating virus infectious diseases.
The invention provides myrtle, extracts and fractions thereof, and myrtle ketone compounds which have obvious inhibitory action on animal viruses and small cytotoxicity, and the action mechanism of the myrtle, the extracts and the fractions thereof comprises (but is not limited to) inhibiting the animal viruses from entering cells, preventing the animal viruses from replicating in host cells and timely regulating and controlling the apoptosis program of infected cells. The myrtle ketone compound, the myrtle family plant containing the myrtle ketone compound, the extract and the fraction thereof have an inhibition effect on animal viruses, and are expected to be developed into novel antiviral veterinary drugs.
The specific implementation mode is as follows:
the following examples are further illustrative of the present invention and are not intended to be limiting thereof.
Example 1:
the invention is illustrated below with reference to specific examples. It will be understood by those skilled in the art that these examples are for illustrative purposes only and are not intended to limit the scope of the present invention in any way.
The experimental procedures in the following examples are all conventional ones unless otherwise specified. The raw materials and reagents used in the following examples are all commercially available products unless otherwise specified.
Example 1 isolation of Myrtaceae plants from Myrtaceae
1.1 plant Material
The plant Myrtus communis of Myrtaceae Myrtus is used as an experimental raw material, and the plant is widely distributed in the south of China, especially in the south of Lingnan. The plant material of the experiment is collected from Nankang county (region) of Ganzhou city in Jiangxi province, 20kg after being dried, and is identified as the myrtle (R.tominosa) of myrtle in Myrtaceae by the researchers of the Wangfang country in south China, academy of China. Plant specimens are currently available in the laboratories for natural products and chemical and biological research in the plantations of south China, academy of sciences.
1.2 laboratory instruments and reagents
The optical rotation data was measured using a Perkin-Elmer 341polar imeter (Perkin-Elmer Co., U.S.A.). The UV spectrum was measured by a Perkin-Elmer Lambda 35UV-vis spectrophotometer (Perkin-Elmer Co., U.S.A.) using methanol or chloroform as a solvent. The IR spectrum was measured by a Bruker Vertex 33infrared spectrophotometer (Bruker, Germany) which required sheeting prior to measurement. The NMR hydrogen, carbon, DEPT-135 and two-dimensional spectra were determined by Bruker AVIII500 superconducting NMR from Bruker, TMS being an internal standard, delta being ppm and J being Hz. The preparative HPLC is L3000 type HPLC (Beijing Innovation technology Co., Ltd.), and the chromatographic column is C18 column (ALLTIMAC1810U, 250nm × 10nm, 3mL/min), and is equipped with single wavelength ultraviolet detector. High resolution mass spectra were determined by a Bruker Bio TOF IIIQ mass spectrometer from Bruker. 100-200, 200-300 and 300-400 mesh silica gel and thin-layer chromatography plates are produced by Qingdao spectral separation materials, Inc. MCI gel (CHP20P,75-150mm) was manufactured by Mitsubishi chemical corporation of Japan. Sephadex LH-20 gel was produced by Amersham biosciences, Sweden. The organic solvent is from Shanghai chemical materials, Inc. The thin-layer chromatography developer is 5% concentrated sulfuric acid-ethanol solution, and compounds with ultraviolet absorption need to be observed under an ultraviolet lamp. The proportion of the mixed solvent used in the experimental process is volume ratio.
1.3 obtaining the extract
Sufficiently crushing (20KG) the dried myrtle leaves, extracting 3 times (30L multiplied by 3) with a 95% ethanol aqueous solution with volume fraction, carrying out rotary evaporation on the combined solvents under reduced pressure to obtain a brown syrupy residue which is an ethanol part (2.5KG), suspending the brown syrupy residue in water (1:1, weight ratio), extracting (3L multiplied by 3) with n-hexane, and carrying out rotary drying on the extracted part by using the solvent to obtain the n-hexane part; extracting with ethyl acetate (3L × 3), and spin-drying the extracted part with solvent to obtain ethyl acetate part and the residual water part to obtain water part.
1.4 isolation to obtain monomeric Compounds
In the experiment, the n-hexane part and/or the ethyl acetate part of myrtle leaves are/is completely dissolved in a sample mixing pot by using chloroform as little as possible, then 500g of silica gel (80-100 meshes) is used for mixing the samples, the mixture is uniformly stirred, after the solvent is completely volatilized, the samples are loaded by a dry method, gradient elution is carried out by using an n-hexane-ethyl acetate system 10:1, 5:1, 2:1, 1:1 and 0:1v/v, finally, a column is flushed by using methanol, fractions with the same main point are combined after TLC thin-layer chromatography detection, and TLC detection (a developing solvent n-hexane: ethyl acetate is 5:1v/v) is collected to show blue fluorescence under an ultraviolet lamp; performing MCI column chromatography to remove pigment, performing Sephadex LH-20 gel column chromatography, performing gradient elution with n-hexane-ethyl acetate system (8:1 → 1:1v/v), and collecting blue fluorescence under ultraviolet lamp by TLC detection (developing solvent n-hexane: ethyl acetate 5:1 v/v); c2, orange part under the action of sulfuric acid-ethanol color developing agent. And Fr, carrying out Sephadex LH-20 gel column chromatography on the C2, and eluting with chloroform-methanol (1:1v/v) to obtain compounds 2-h, 3 and 4. Rf for compounds 2-h, 3 and 4 were 0.4, 0.35, 0.42, respectively, as determined by TLC (developing solvent n-hexane: ethyl acetate: -4: 1 v/v).
The compound 2-h is a compound myrtle ketone, is a light yellow needle crystal and is easily dissolved in chloroform; nuclear magnetic data: 1 HNMR(CDCl 3 ,500MHz):δ H 6.12(1H,s,H-5),4.27(1H,t,J＝5.6Hz,H-9),2.99(3H,m,H-1”,H-2”),2.28(1H,dp,J＝13.3,6.6Hz,H-3'),1.55,1.43,1.41,1.37(each 3H,s,H-11,H-12,H-13,H-14),0.98(6H,d,J＝6.7,Hz,H-4',H-5'),0.87,0.83(each 3H,d,J＝6.0Hz,H-3”,H-4”)； 13 C NMR(CDCl 3 125 MHz. delta.C 212.2(C-3),206.7(C-1'),198.3(C-1),167.5(C-4a),162.8(C-8),158.7(C-6),155.7(C-10a),114.3(C-9a),107.7(C-7),106.4(C-8a),94.7(C-5),56.1(C-2),53.2(C-2'),46.4(C-4),45.8(C-1 "), 25.5(C-9),25.5 (C-2"), 25.2,25.1(C-13, C-14),24.7,24.6(C-11, C-12),24.2(C-3'),23.5,23.2(C-3 ', C-4', 22.8, 22.8(C-4', C-5 '). The structural formula of compounds 2-h is shown below:
the compound 3 is myrtle isopropyl ketone, yellow jelly and is easily dissolved in chloroform; nuclear magnetic data: 1 HNMR(CDCl 3 ,500MHz):δ H 0.85(d,J＝6.3Hz,3H,4”-CH 3 ),0.86(d,J＝6.3Hz,3H,3”-CH 3 ),0.99(d,J＝6.6Hz,3H,5'-CH 3 ),1.01(d,J＝6.6Hz,3H,4'-CH 3 ),1.38(s,10-CH 3 ),1.41(s,11-CH3),1.46(s,13-CH 3 ),1.62(s,12-CH3),1.35(obscured,1H,2”-H),1.35(obscured,2H,1”-H),2.35(qqdd,J＝6.8,6.8,6.6,6.6Hz,1H,3'-H),2.93(dd,J＝17.2,6.1Hz,1H,2'-Ha),3.17(dd,J＝17.2,7.3Hz,1H,2'-Hb),4.29(t,J＝6.1Hz,1H,9-H),6.25(s,1H,7-H),8.08(s,1H,OH),13.49(s,1H,OH)； 13 C NMR(CDCl 3 ,126MHz):δC 211.8(C-3),203.9(C-1'),198.5(C-1),167.4(C-4a),159.8(C-6),159.7(C-8),153.1(C-4b),114.6(C-9a),106.0(C-5),105.5(c-8a),100.2(C-7),56.1(C-2),53.4(C-2'),47.3(C-4),46.9(C-1 "), 25.4(C-13),25.0(C-9),24.8 (C-2"), 24.7(C-12),24.5(C-3'),24.5(C-11),24.2(C-10),23.4(C-3 "), 23.1 (C-4"), 22.9(C-4'),22.6 (C-5'). The structural formula of compound 3 is shown below:
compound 4 is myrciaroneA, a yellow amorphous powder, readily soluble in chloroform; spectral data: UV λ max 299nm, "a" D +7.5 ° (c ═ 0.24, CHCl3), HR-MS; m/z 429.2282[ M + H ]] + (calcd.for C 2 5H 33 O 6 429.2268) nuclear magnetic data: 1 HNMR(CDCl 3 ,500MHz):6.07(1H,s,H-5),4.24(1H,t,J＝5.9Hz,H-9),3.88(1H,m,J＝6.6,H-2’),1.41-1.44(2H,obscure,H-1”),1.36-1.46(2H,obscure,H-2”),1.36(3H,s,2-Me),1.39(3H,s,2-Me),1.42(3H,s,4-Me),1.54(3H,s,4-Me),1,20(3H,d,J＝5.5Hz,2’-Me),1.19(3H,d,J＝6,6Hz,2’-Me),0.83(3H,d,J＝6.0Hz,2”-Me),0.87(3H,d,J＝6.0Hz,2”-Me). 13 C NMR(CDCl 3 197.5(C-1),56.1(C-2),212.1(C-3),47.1(C-4),166.8(C-4a),94.5(C-5),158.0(C-6),106.7(C-7),158.0(C-8),106.7(C-8a),25.2(C-9),114.2(C-9a),155.6(C-10a),210.9(C-1 '), 39.8 (C-2'), 45.9(C-1 "), 25.1 (C-2"), 24.2(2-Me),24.5(2-Me),24.6(4-Me),24.7(4-Me),19.1(2 '-Me), 19.2 (2' -Me),23.1(2 '-Me), 23.5 (2' -Me), compound 4, the formula is shown below:
example 2 analysis of antiviral Activity of Myrtus communis extract, fraction, Myrtle ketone Compounds
2.1 preparation of cells and viruses
The African green monkey kidney cells Marc145 and Vero-E6 and the dog kidney cell MDCK are subcultured according to the conventional method, and the cell density is adjusted to 2 multiplied by 10 4 -1×10 5 one/mL was seeded into 96-well plates and the cells in the wells were grown to a complete monolayer ready for use.
Porcine Reproductive and Respiratory Syndrome Virus (PRRSV), Porcine Epidemic Diarrhea Virus (PEDV) and Avian Influenza Virus (AIV) are respectively and correspondingly inoculated on Marc145, Vero-E6 and MDCK monolayer cells, incubated for 1h at 37 ℃, supernatant is removed, 3 percent FBS DMEM maintenance solution containing pancreatin is replaced, when the cells are subjected to 100 percent of pathological changes, freeze thawing is carried out for three times, the supernatant is collected as prepared seed virus, and TCID is used as prepared seed virus 50 The titer of the virus was determined.
TCID 50 The determination of (1): monolayer cells cultured in 96-well plates, supernatant was removed and washed twice with PBS, and 100. mu.L of diluted virus was added in duplicate, each dilution set at 8 replicates, incubated at 37 ℃ for 2h, supernatant was removed and washed twice with PBS, and 150. mu.L of virus-maintenance solution containing pancreatin (DEME medium containing 3% FBS, 1% penicillin mixed solution) was added. After three days, the lesion count lesion wells were observed under a microscope, and the virus titer TCID was calculated by the Reed-Muench method 50 。
2.2 determination of cytotoxicity
After diluting the sample by using a cell maintenance solution (DEME culture solution containing 3% FBS and 1% streptomycin mixed solution) continuously by 2 times, adding the diluted sample to a 96-well culture plate with cells growing into a monolayer, adding 100 mu L of the diluted sample to each well, repeating 3 wells for each dilution, additionally arranging a cell control group without the added sample, culturing the cell control group in a 5% CO2 incubator at 37 ℃ for 72 hours, and observing and recording the condition of cytopathic effect (CPE) every day. And after the culture is carried out for 72 hours, abandoning the supernatant, washing the supernatant for 2 times by using PBS buffer solution, adding 20 mu L of MTT into each hole, continuing to culture the supernatant for 4 hours, abandoning the MTT supernatant, adding 150 mu L of LDMSO into each hole, shaking the mixture for 5 to 10min, and measuring OD570 by using an enzyme labeling instrument after the crystals are completely dissolved. Calculating the pathogenic rate of drug induced cells, CC, based on the degree of CPE and the measured OD 50 Is the drug concentration that causes 50% of the cells to develop lesions.
2.3 inhibition of viral replication by samples
After the cells in the 96-well plate had grown into a monolayer, the culture was aspirated and 100 × TCID was used 50 Adsorbing 100 μ L of virus, incubating at 37 deg.C for 1h, washing off free virus, adding compound diluted by maintenance solution (DEME culture solution containing 3% FBS and 1% streptomycin mixture) at multiple ratio of 100 μ L, repeating for 3 wells at each dilution, and setting cell control group without sample and virus, virus control group without sample and virus, and 5% CO at 37 deg.C 2 And (4) continuously culturing, observing cytopathic effect, determining whether the cytopathic effect is a specific pathology caused by the virus, ending the test when the CPE of the virus control group reaches 80% -90%, and recording the CPE of each hole. Discarding the supernatant, washing with PBS buffer solution for 2 times, adding 20 μ LMTT into each well, culturing for 4h, discarding the MTT supernatant, adding 150 μ LDMSO into each well, shaking for 5-10min, and measuring OD570 with enzyme labeling instrument after the crystal is completely dissolved. The rate of inhibition of the virus by the sample was calculated by the following formula. The concentration of the sample that inhibits half of the cells from infecting the virus (IC) was determined as a result of CPE and inhibition rate 50 ). Finally, the selection index SI ═ CC is calculated 50 /IC 50
TABLE 1 Myrtle extract fraction, fraction antiviral activity and cytotoxicity
Screening anti-PRRSV, PEDV and IAV activities of the ethanol extract, the n-hexane part, the ethyl acetate part and the water part of the myrtle respectively, and finding that the ethanol extract, the n-hexane part and the ethyl acetate part have good antiviral activities, particularly the n-hexane part has stronger antiviral activity and relatively better selectivity (larger SI value), so that main antiviral active ingredients in the myrtle are considered to be easier to enrich in the n-hexane part. And (3) further performing silica gel column chromatography, MCI column chromatography and Sephadex LH-20 gel column chromatography on the n-hexane part, gradually separating to obtain a Fr.C fraction and a Fr.C2 fraction, and enhancing the antiviral activity, which indicates that the antiviral active ingredients are further enriched.
TABLE 2 anti-viral activity and cytotoxicity of myrtle ketone monomeric compounds
The separated myrtle ketone compounds 2-h, 3 and 4 are respectively subjected to anti-PRRSV, PEDV and IAV activity screening, and the results in table 2 show that the myrtle ketone compounds 2-h, 3 and 4 have antiviral activities of different degrees, particularly the compounds 2-h and 4, the selectivity coefficient SI is more than 10, and the antiviral effect is remarkable and the cytotoxicity is relatively low.
In conclusion, the invention provides application of myrtaceae plants and extracts, fractions and monomeric compounds contained in the myrtaceae plants and having a structural formula I in antiviral veterinary drugs.
The above description of the specific embodiments of the present invention is not intended to limit the present invention, and those skilled in the art may make various changes and modifications according to the present invention without departing from the spirit of the present invention, which is defined by the scope of the appended claims.
Claims (4)
1. The application of the myrtle ketone compound, or a stereoisomer, an epimer, a configurational isomer or a pharmaceutically acceptable salt thereof, or a hydrate of the myrtle ketone compound and the stereoisomer, the epimer, the configurational isomer or the pharmaceutically acceptable salt thereof in preparing medicaments for resisting porcine reproductive and respiratory syndrome virus, porcine epidemic diarrhea virus and avian influenza virus;
the structure of the myrtle ketone compound is shown as a formula I:
formula I
Wherein the content of the first and second substances,R 1 is hydrogen, C1-C15 straight chain or branched chain;
R 2 and R 3 、R 4 Each independently selects hydrogen;
or the myrtle ketone compound is shown as follows:
2. the use of claim 1, wherein R is 1 Is a straight chain or branched chain of C3-C10.
3. The use according to claim 1, wherein the myrtle ketone compound is a compound represented by any one of the following structural formulae:
。
4. the extract of the myrtle leaves is extracted by an organic solvent, the organic solvent comprises one or a mixture of more of ethanol, acetone, methanol, ethyl acetate and n-hexane, or fractions or parts of the extract which is concentrated, distributed, enriched and purified by a physical and chemical method, and the application of the extract in the preparation of the drugs for resisting porcine reproductive and respiratory syndrome virus, porcine epidemic diarrhea virus and avian influenza virus.
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| CN114948936B (en) * | 2022-05-05 | 2023-03-21 | 中国科学院华南植物园 | Natural antiviral atomized liquid and preparation method and application thereof |
| CN115626906B (en) * | 2022-10-25 | 2023-08-22 | 中国科学院华南植物园 | Industrial extraction method of high-purity myrtle ketone |
| CN116491586B (en) * | 2022-10-25 | 2023-09-29 | 中国科学院华南植物园 | Myrtle ketone microcapsule for promoting growth of animal and application thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104761565A (en) * | 2015-04-16 | 2015-07-08 | 中国科学院华南植物园 | Myrtle ketone compound and application thereof in preparation of antibacterial medicines |
| CN110279688A (en) * | 2019-06-26 | 2019-09-27 | 暨南大学 | A kind of multi-ring polyketide is preparing the application in anti-herpesvirus medicament |
-
2020
- 2020-05-29 CN CN202010478809.0A patent/CN113730392B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104761565A (en) * | 2015-04-16 | 2015-07-08 | 中国科学院华南植物园 | Myrtle ketone compound and application thereof in preparation of antibacterial medicines |
| CN110279688A (en) * | 2019-06-26 | 2019-09-27 | 暨南大学 | A kind of multi-ring polyketide is preparing the application in anti-herpesvirus medicament |
Non-Patent Citations (1)
| Title |
|---|
| 药用植物桃金娘开发研究;高桂花等;《辽宁中医药大学学报》;20150131;第17卷(第01期);134-137 * |
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