CN108821959A - A kind of tetrahydro anthracene compound and its preparation method and application - Google Patents
A kind of tetrahydro anthracene compound and its preparation method and application Download PDFInfo
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Abstract
The invention discloses a kind of tetrahydro anthracene compounds, shown in structural formula such as following formula (I) or following formula (II), the tetrahydro anthracene compound of this kind of structure novels has good inhibiting effect to protein kinase, with apparent anti-tumor activity, it can be used for developing the drug and antitumor, antibacterial and antiviral drugs of the complication for the treatment of albumen kinases induction.In formula (I)：R1=H, R2=H, R3=CH3, R4=H；Or：R1=H, R2=OCH3, R3=CH3, R4=H；Or：R1=H, R2=OCH3, R3=CH2OH, R4=H；Or：R1=H, R2=OH, R3=CH3, R4=Cl；Or：R1=OH, R2=OH, R3=CH3, R4=H；Or：R1=OH, R2=OCH3, R3=CH3, R4=H.
Description
Technical field
The present invention relates to actinomyces secondary metabolites to prepare reactive compound field, and in particular to a kind of tetrahydro anthracene class
Close object and preparation method thereof and in the drug for preparing the complication of kinases inhibitor, preparation treatment albumen kinases induction and
Application in antitumor, antibacterial, antiviral drugs.
Background technique
It is the important next of acquisition bioactive natural product from the novel actinomyces of extreme environment, such as desert, ocean
Source；Mangrove is one of them, and mangrove is located at the intersection of ocean and land, has contained microorganism abundant in mangrove
Resource, and because of the particularity of its local environment, so that microorganism here has adapted to the environmental characteristic that salinity is high, fluctuation is big；
Therefore, mangrove is also at the valuable source for obtaining novel sea actinomyces.According to the literature, it is many have antibacterial, it is anti-inflammatory,
The natural products of anti-tumor activity is obtained from the secondary metabolite of the marine actinomycete in mangrove source.
The tetrahydro anthracene compound being currently known is no more than 20, and this kind of compound obtains in the plant of Aloe at first
?；It is also once found in Eremurringing；In the hot fields of microbe research, Japanese scholars are for the first time in unwrapping wire thallus generation
It thanks and finds such compound in product.Such compound mainly includes okicenone (following formula (III)), gasteriacenone
(following formula (IV)), R-ASME (following formula (V)) etc., but it is previous research shows that these compounds only show weak disease-resistant original
Worm activity and weak anti-tumor activity (J.Antibiotics.1991,44,814；Molecules.2017,22,519)；Hereafter
About the bioactivity research of this kind of compound and few.In 2007, it has been found that okicenone, which has, combines human antigen
(HuR is a kind of rna binding protein to R, its overexpression in human cancer and invasion, the disease of drug resistance and prognosis mala
Disease is related.The inhibition of HuR is of great significance to anticancer) ability, and due to its special fluorescent absorption, such compound can
With the combination of tracer HuR and RNA, the transport of HuR, the physiological functions such as cytokine-expressing and T cell activation
(Nat.Chem.Biol.2007,3,508).But compared with other class compounds, activity is general.
Rho kinases (Rho associated kinase, ROCK) is to participate in cell mitogen adherency, cytoskeleton tune
A series of important enzyme of cell life phenomenons such as whole, muscle cell contraction, tumor cell invasion, ROCK2 are main hypotypes, main
It to be expressed in blood vessel and neuron.Due to ROCK it is movable to cytoskeleton adjust so it is important, the overexpression of ROCK and
The excessive activation of ROCK has both participated in the cardiovascular diseases such as the pathologic process of a variety of diseases, including myocardial ischemia, hypertension, spinal cord
Damage, spinal cord take off the central nervous diseases such as sheath, Alzheimer disease, neuroinflamation, liver, lung, renal fibrosis disease and
Various tumor diseases (Acta Pharmaceutica Sinica.2007,42,1013).
BRD albumen is the highly conserved bromoprotein matter functional domain containing about 110 amino acid in a kind of evolution, is passed through
Chromatinic assembling and acetylation and participate in signal dependence, the gene transcription regulation of non-basic.BRD albumen also can by pair
The nonhistones acetylation modification such as transcription factor and the processes such as wide participation cell cycle regulating, cell differentiation, signal transduction
(Medicinal Chemistry Letters.2012,3,691).BRD4 albumen is a part of BRD protein family, studies table
Bright, BRD4 albumen is hide with tumour and HIV closely related target spot (Journal of Virology.2009,83,1036).
Hematopoietic system cancer include AML, Burkitt lymthoma, Huppert's disease, B cell acute lymphatic leukemia model
In, by interference Brd4 more than oncogene MYC combination, the expression etc. of oncogene MYC can be inhibited.
Currently, not having been reported that display tetrahydro anthracene compound is inhibited to Rho kinases, BRD albumen.
Summary of the invention
The present invention provides a series of tetrahydro anthracene compounds of structure novels, for from the marine streptomyces of mangrove
Natural products, to protein kinase have good inhibiting effect, have apparent anti-tumor activity, can be used for developing treatment egg
The drug of the complication of white kinases induction and antitumor, antibacterial and antiviral drugs.
Specific technical solution is as follows：
Shown in a kind of tetrahydro anthracene compound, structural formula such as following formula (I) or following formula (II)：
In formula (I)：
R1=H, R2=H, R3=CH3, R4=H；
Or：R1=H, R2=OCH3, R3=CH3, R4=H；
Or：R1=H, R2=OCH3, R3=CH2OH, R4=H；
Or：R1=H, R2=OH, R3=CH3, R4=Cl；
Or：R1=OH, R2=OH, R3=CH3, R4=H；Or：R1=OH, R2=OCH3, R3=CH3, R4=H.Respectively
It is denoted as：
In the structural formula of compound 7, connection 2 ' represents the chiral carbon at 2 ' with 3 ' wave and has two kinds of structures of R/S
Type.Pass through the nuclear magnetic resonance data also provable conclusion.
Further to excavate bioactive natural product, its bioavilability is improved, the present invention is deriving from mangrove to one plant
During marine actinomycete in soil carries out system research, a series of tetrahydro anthracene compounds are obtained, by infrared, purple
Outside, mass spectrum and NMR spectrum etc. have determined the structure of this kind of compound, and further activity research shows this kind of chemical combination
Object shows good antitumor and protease and inhibits isoreactivity.
The preparation method of the tetrahydro anthracene compound, includes the following steps：
1) marine actinomycete is inoculated in Gause I fluid nutrient medium, shaking table culture, obtains seed liquor；
The marine actinomycete is the marine streptomyces Streptomyces sp.HN-A101 from mangrove, number
BNCC 212908；
2) seed liquor is inoculated in rice medium, stationary culture obtains solid fermentation product, through organic solvent
Extraction obtains crude extract afterwards several times；
3) crude extract is isolated and purified, obtains the tetrahydro anthracene class chemical combination such as formula (I) or formula (II) structure respectively
Object.
This preparation process is generated by marine actinomycete through solid-substrate fermentation, then by isolating and purifying to obtain, is easy to grasp
Make and implements.
Preferably, in step 1)：
The condition of the shaking table culture is：At 25~30 DEG C, cultivated 3~4 days in 150~200rpm shaking table；
PH=7~8 of the Gause I fluid nutrient medium are made in terms of 1L of following components by weight percent：
Preferably, in step 2)：
The rice medium is made of the following components in terms of 1L：
400~600g of rice；
Seawater surplus；
The condition of the stationary culture is：25~30 DEG C, stationary culture 50~60 days；
The organic solvent is selected from ethyl acetate, dehydrated alcohol, methanol or chloroform.
Preferably, described to isolate and purify in step 3), including：
Crude extract first uses silica gel column chromatography to carry out rough segmentation, and thin layer inspection is known, fraction required for merging；Pass through gel column again
Chromatography is finely divided, and thin layer inspection is known, and merges the component containing noval chemical compound；It is purified finally by reversed-phase preparative chromatography, respectively
To seven kinds of tetrahydro anthracene compounds of the structure as shown in above formula (I) or above formula (II).
Further preferably：
The silica gel column chromatography, the mobile phase used are 10~2 for volume ratio:1 petroleum ether-ethyl acetate solution or body
Product is than being 80~5:1 dichloro methane-methanol；Further preferably, use the column chromatography silica gel of 200~300 mesh for filler, according to
Medicinal extract and packing quality ratio are 1 after extraction concentration:10 carry out dress column, are 80 with volume ratio:1/40:1/20:1/10:1/5:1
Methylene chloride/methanol system carries out gradient elution.
The gel column chromatography is Sephadex LH-20 type, with volume ratio for 1~0:1 methylene chloride-methanol system
For mobile phase；Further preferably, in the methylene chloride-methanol system, the volume ratio of methylene chloride and methanol is 1:1 or 0:1.
The reversed-phase preparative chromatography is Sepax Amethyst C-18 type, and filler is octadecyl silane, is used
Volume ratio is 20~100：80~0 methanol-water solutions or volume ratio are 10~100:90~0 acetonitrile-water systems be mobile phase into
Row elution, collects the chromatographic peak of different retention times, recycling design respectively obtains the structure as shown in above formula (I) or above formula (II)
Seven kinds of tetrahydro anthracene compounds；Further preferably, the mobile phase used is 20~100 for volume ratio：80~0 methanol-water solution
Or acetonitrile-water system, it is eluted with 10mL/min.
Relative to existing known tetrahydro anthracene compound, seven kinds of tetrahydros anthracene compound structure prepared by the present invention is new
Grain husk is found through active testing：
Seven kinds of tetrahydro anthracene compounds prepared by the present invention make protein kinase ROCK2 and BRD4 with good inhibition
With, while having and playing antitumor latent effect as HuR protein binding molecule.Test result shows, compound 1,2,3,7
With apparent ROCK2 kinase inhibiting activity, compound 1 and 7 has good BRD4 inhibitory activity.This also illustrates system of the present invention
The structure-activity relationship of standby this kind of tetrahydro anthracene compounds is close, and the slight change of substituent group type and position can lead to work
The large change of property data.
Based on this, seven kinds of tetrahydro anthracene compounds prepared by the present invention can be used for preparing the concurrent for the treatment of albumen kinases induction
The drug of disease and antitumor, antibacterial, antiviral drugs.
The complication of the induction of protein kinase includes cardiovascular and cerebrovascular disease, type II diabetes, HIV and various tumour diseases
Disease.
The tumour include the relevant colorectal cancer of undesired cell proliferation, non-small cell lung cancer, leukaemia, liver cancer, kidney,
Prostate cancer, thyroid cancer, cutaneum carcinoma, cancer of pancreas, oophoroma, breast cancer, celiothelioma or Peripheral Nerve Sheath Tumours.
Wherein, by taking colorectal cancer as an example, the present invention determines seven kinds of compounds to two plants of colon cancer cells with srb assay
The cytotoxic activity of HCT116 and SW620, it is found that compound 1 and compound 2 have significant antitumor work to above-mentioned cell
Property.
Compared with prior art, the invention has the advantages that：
A kind of totally seven kinds of tetrahydro anthracene compounds disclosed by the invention, are sent out by marine actinomycete through natural solid culture medium
Ferment generates, such compound structure is novel, wherein compound 1~3 is including the substituent group in known compound structure basis
The adjustment of type and position, but their anti-tumor activity significantly increases compared with known compound, and this also illustrates this
The structure-activity relationship of a kind of tetrahydro anthracene compound is close；Compound 4 introduces-Cl at 10, this be find for the first time it is halogen-containing
Such compound；In compound 5 and 6, the hydroxyl direction in two chiral carbons is consistent and is reported for the first time；Compound 7 is at 5
It has been grafted a complicated macoradical, has produced biggish variation in structure.
The present invention also has found that this kind of compound for protein kinases ROCK2 and BRD4 have good inhibiting effect for the first time,
And due to its special UV absorption, the binding molecule that also can be used as HuR albumen plays antineoplastic action, can inhibit tumour
The growth of cell；Anticancer, antibacterial, it is antiviral and in terms of have potential application.
Specific embodiment
Strain source
Marine actinomycete Streptomyces chartreusis BNCC 212908 of the present invention is received using Beijing North and creates connection
The product of Bioteknologisk Institut.
Embodiment 1
One, the fermentation of microorganism and the extraction of secondary metabolite
1) marine actinomycete Streptomyces sp.HN-A101 is inoculated in 500mL conical flask, every bottle contains 250ml
Gause I fluid nutrient medium (in terms of culture medium 1L, soluble starch 20g, KNO31g；K2HPO40.5g, MgSO4·7H2O
0.5g, NaCl 0.5g, FeSO47H2O 0.01g, surplus is seawater), 180 revs/min shaking table culture 3 days, obtain at 28 DEG C
To the fermentation medium for being inoculated with marine actinomycete；
2) the fermentation medium 13.5ml for being inoculated with marine actinomycete in step 1) is taken, is inoculated in solid medium, altogether
300 bottles (40g/ bottles of rice, 60mL/ bottles of seawater), stationary culture 60 days at 28 DEG C obtain the solid hair containing such compound
Ferment product.
3) fermentation liquid isometric ethyl acetate normal pressure extraction 3 times containing tetrahydro anthracene compound in step 2) is taken, often
Secondary 24 hours, gained leaching liquor was concentrated under reduced pressure, and obtained the crude extract containing tetrahydro anthracene compound.
Two, the separating-purifying of compound
Gained crude extract is separated with silica gel column chromatography, the filler used is the column chromatography silica gel of 200~300 mesh.
It is 1 according to medicinal extract after extraction concentration and packing quality ratio:10 carry out dress column.It is 80 with volume ratio:1/40:1/20:1/10:1/5:
1 methylene chloride/methanol system gradient elution, thin layer inspection are known the fraction containing noval chemical compound, are merged.The handy Sephadex of institute
LH-20 type gel column chromatography is finely divided, and the mobile phase used is 1 for volume ratio:1 or 0:1 methylene chloride/methanol system,
Knowledge method is equally examined using thin layer, the component containing noval chemical compound is merged, last obtained component reversed-phase high performance liquid chromatography point
From (Sepax Amethyst C-18 (5 μm, 21.2 × 250mm) chromatographic column, Detection wavelength 272nm), the mobile phase used is body
Product is than being 20~100：80~0 methanol/acetonitrile-water system collects the chromatography of different retention times with 10mL/min gradient elution
Peak, recycling design are respectively obtained containing the tetrahydro anthracene compound 1-7 in the present invention.
Compound 1,40：60 acetonitrile-water system isocratic elutions, 10mL/min, retention time 62min；
Compound 2,55：45 methanol-water solution isocratic elutions, 10mL/min, retention time 65min；
Compound 3,22：78 acetonitrile-water system isocratic elutions, 10mL/min, retention time 15min；
Compound 4,50~80：50~20 methanol-water solution gradient elution 80min, 10mL/min, retention time 39min；
Compound 5,25~40：75~60 acetonitrile-water system gradient elution 60min, 10mL/min, retention time 23min；
Compound 6,50~80：50~20 methanol-water solution gradient elution 80min, 10mL/min, retention time
48.5min；
Compound 7,40~100：60~0 acetonitrile-water system gradient elution 60min, 10mL/min, retention time 20min.
Three, the identification of compound
Compound 1：Molecular formula is speculated as C according to high resolution mass spectrum HR-ESI-MS15H14O3([M+H]+243.1021,
calculated 243.1016).Infrared spectra adsorption is：3396cm-1(phenolic hydroxyl group), 1617cm-1(unsaturated double-bond, carbonyl
Base), 1047cm-1(fragrant hydrogen).Ultra-violet absorption spectrum：225nm,272nm,376nm.
Nuclear magnetic resonance data (1H NMR 600MHz,13C NMR 150MHz, solvent C D3) and signals assignment such as 1 institute of table OD
Show：
Table 1
Compound 2：Molecular formula is speculated as C according to high resolution mass spectrum HR-ESI-MS16H16O4([M+Na]+295.0798,
calculated 295.0941).Infrared spectra adsorption is：3369cm-1(phenolic hydroxyl group), 1606cm-1(unsaturated double-bond, carbonyl
Base), 1044cm-1(fragrant hydrogen).Ultra-violet absorption spectrum：222nm,260nm,385nm.
Nuclear magnetic resonance data (1H NMR 600MHz,13C NMR 150MHz, solvent C D3) and signals assignment such as 2 institute of table OD
Show：
Table 2
Compound 3：Molecular formula is speculated as C according to high resolution mass spectrum HR-ESI-MS16H16O5([M+Na]+311.0891,
calculated 311.0890).Infrared spectra adsorption is：3291cm-1(phenolic hydroxyl group), 1621cm-1(unsaturated double-bond, carbonyl
Base), 1044cm-1(fragrant hydrogen).Ultra-violet absorption spectrum：224nm,271nm,374nm.
Nuclear magnetic resonance data (1H NMR 600MHz,13C NMR 150MHz, solvent DMSO-d6) and signals assignment such as table 3
It is shown：
Table 3
Compound 4：Molecular formula is speculated as C according to high resolution mass spectrum HR-ESI-MS15H13ClO4([M+Na]+315.0392,
317.0368calculated 315.0395,317.0365).Infrared spectra adsorption is：3299cm-1(phenolic hydroxyl group), 1605cm-1
(unsaturated double-bond, carbonyl), 1176cm-1(fragrant hydrogen).Ultra-violet absorption spectrum：229nm,275nm,379nm.
Nuclear magnetic resonance data (1H NMR 600MHz,13C NMR 150MHz, solvent C DCl3) and signals assignment such as 4 institute of table
Show：
Table 4
Compound 5：Molecular formula is speculated as C according to high resolution mass spectrum HR-ESI-MS15H14O5([M+Na]+
297.0735calculated 297.0733).Infrared spectra adsorption is：3234cm-1(phenolic hydroxyl group), 1602cm-1It is (unsaturated double
Key, carbonyl), 1015cm-1(fragrant hydrogen).Ultra-violet absorption spectrum：226nm,272nm,379nm.According to the coupling constant leg of 1H NMR
Hydroxyl in short two chiral carbons is towards unanimously.
Nuclear magnetic resonance data (1H NMR 600MHz,13C NMR 150MHz, solvent C D3) and signals assignment such as 5 institute of table OD
Show：
Table 5
Compound 6：Molecular formula is speculated as C according to high resolution mass spectrum HR-ESI-MS15H14O5([M+Na]+
311.0892calculated 311.0890).Infrared spectra adsorption is：3392cm-1(phenolic hydroxyl group), 1608cm-1It is (unsaturated double
Key, carbonyl), 1139cm-1(fragrant hydrogen).Ultra-violet absorption spectrum：224nm,273nm,378nm.According to the coupling constant leg of 1H NMR
Hydroxyl in short two chiral carbons is towards unanimously.
Nuclear magnetic resonance data (1H NMR 600MHz,13C NMR 150MHz, solvent C DCl3) and signals assignment such as 6 institute of table
Show：
Table 6
Compound 7：Molecular formula is speculated as C according to high resolution mass spectrum HR-ESI-MS22H24O8([M+H]+
417.1542calculated 417.1544).Infrared spectra adsorption is：3340cm-1(phenolic hydroxyl group), 1604cm-1It is (unsaturated double
Key, carbonyl), 1097cm-1(fragrant hydrogen).Ultra-violet absorption spectrum：227nm,275nm,384nm.
Nuclear magnetic resonance data (1H NMR 600MHz,13C NMR 150MHz, solvent C D3OD) and signals assignment such as table 7 and
Shown in continued 7：
Table 7
Continued 7
In compound 7, the chiral carbon at the place C-2 ' is isomerization, and compound 7 is a diastereoisomer, parent nucleus
Chemical shift is consistent, but the chemical shift at substituent group slightly has difference (continued 7)
Four, the anti-tumor activity of compound
Compound 1-7 is determined to the cytotoxic activity of two plants of colon cancer cells HCT116 and SW620 with srb assay, is changed
Closing object 1 and 2 has significant anti-tumor activity；In addition, compound 1,2,3,7 has apparent ROCK2 kinase inhibiting activity, change
Closing object 1 and 7 has good BRD4 inhibitory activity.Compound 1-7 anti-tumor activity and kinase inhibiting activity (aPositive control)
As a result such as the following table 8, in table,aRepresent positive control.
Table 8
Claims (10)
1. a kind of tetrahydro anthracene compound, which is characterized in that shown in structural formula such as following formula (I) or following formula (II)：
In formula (I)：
R1=H, R2=H, R3=CH3, R4=H；
Or：R1=H, R2=OCH3, R3=CH3, R4=H；
Or：R1=H, R2=OCH3, R3=CH2OH, R4=H；
Or：R1=H, R2=OH, R3=CH3, R4=Cl；
Or：R1=OH, R2=OH, R3=CH3, R4=H；
Or：R1=OH, R2=OCH3, R3=CH3, R4=H.
2. a kind of preparation method of tetrahydro anthracene compound according to claim 1, which is characterized in that including following step
Suddenly：
1) marine actinomycete is inoculated in Gause I fluid nutrient medium, shaking table culture, obtains seed liquor；
The marine actinomycete is marine streptomyces the Streptomyces sp.HN-A101, number BNCC from mangrove
212908；
2) seed liquor is inoculated in rice medium, stationary culture obtains solid fermentation product, extracts through organic solvent
Obtain crude extract afterwards several times；
3) crude extract is isolated and purified, obtains the tetrahydro anthracene compound such as formula (I) or formula (II) structure respectively.
3. the preparation method of tetrahydro anthracene compound according to claim 2, which is characterized in that in step 1)：
The condition of the shaking table culture is：At 25~30 DEG C, cultivated 3~4 days in 150~200rpm shaking table；
PH=7~8 of the Gause I fluid nutrient medium are made in terms of 1L of following components by weight percent：
4. the preparation method of tetrahydro anthracene compound according to claim 2, which is characterized in that in step 2)：
The rice medium is made of the following components in terms of 1L：
400~600g of rice；
Seawater surplus；
The condition of the stationary culture is：25~30 DEG C, stationary culture 50~60 days；
The organic solvent is selected from ethyl acetate, dehydrated alcohol, methanol or chloroform.
5. the preparation method of tetrahydro anthracene compound according to claim 2, which is characterized in that in step 3), described point
From purifying, including：
Crude extract first uses silica gel column chromatography to carry out rough segmentation, and thin layer inspection is known, fraction required for merging；Pass through gel column chromatography again
It is finely divided, thin layer inspection is known, and the component containing noval chemical compound is merged；Purified finally by reversed-phase preparative chromatography, respectively obtain as
Seven kinds of tetrahydro anthracene compounds of structure shown in upper formula (I) or above formula (II).
6. the preparation method of tetrahydro anthracene compound according to claim 5, it is characterised in that：
The silica gel column chromatography, the mobile phase used are 10~2 for volume ratio:1 petroleum ether-ethyl acetate solution or volume ratio
It is 80~5:1 dichloro methane-methanol；
The gel column chromatography is Sephadex LH-20 type, with volume ratio for 1~0:1 methylene chloride-methanol system is stream
Dynamic phase；
The reversed-phase preparative chromatography is Sepax Amethyst C-18 type, uses volume ratio for 20~100：80~0 methanol-waters
System or volume ratio are 10~100:90~0 acetonitrile-water systems are that mobile phase is eluted, and collect the chromatography of different retention times
Peak, recycling design respectively obtain seven kinds of tetrahydro anthracene compounds of the structure as shown in above formula (I) or above formula (II).
7. a kind of tetrahydro anthracene compound according to claim 1 is preparing the application in kinases inhibitor.
8. tetrahydro anthracene compound according to claim 7 exists preparing the application in kinases inhibitor, feature
In the protein kinase includes ROCK2, BRD4 or HuR.
9. a kind of tetrahydro anthracene compound according to claim 1 is in the medicine of the complication of preparation treatment albumen kinases induction
Application in object.
10. a kind of tetrahydro anthracene compound according to claim 1 is preparing anti-tumor drug, antibacterials and disease-resistant
Application in cytotoxic drug.
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| CN113801006A (en) * | 2021-09-28 | 2021-12-17 | 烟台水禾土生物科技有限公司 | Actetrophenone A compound and preparation and application thereof |
| CN114276227A (en) * | 2021-12-31 | 2022-04-05 | 山东省千佛山医院 | Aurora kinase inhibitor and application thereof in preparation of antitumor drugs |
| WO2023067617A1 (en) * | 2021-10-20 | 2023-04-27 | Council Of Scientific & Industrial Research | A process for the preparation of tetrahydroanthracenes from streptomyces spp. and anticancer activity thereof |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN113801006A (en) * | 2021-09-28 | 2021-12-17 | 烟台水禾土生物科技有限公司 | Actetrophenone A compound and preparation and application thereof |
| CN113801006B (en) * | 2021-09-28 | 2022-07-12 | 烟台水禾土生物科技有限公司 | Actetrophenone A compound and preparation and application thereof |
| WO2023067617A1 (en) * | 2021-10-20 | 2023-04-27 | Council Of Scientific & Industrial Research | A process for the preparation of tetrahydroanthracenes from streptomyces spp. and anticancer activity thereof |
| CN114276227A (en) * | 2021-12-31 | 2022-04-05 | 山东省千佛山医院 | Aurora kinase inhibitor and application thereof in preparation of antitumor drugs |
| CN114276227B (en) * | 2021-12-31 | 2023-10-13 | 山东省千佛山医院 | Aurora kinase inhibitor and application thereof in preparation of antitumor drugs |
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