CN102134188A - Tetrahydroanthraquinone compound Prisconnatacin and preparation method and application thereof in preparation of anti-tumor medicaments - Google Patents

Tetrahydroanthraquinone compound Prisconnatacin and preparation method and application thereof in preparation of anti-tumor medicaments Download PDF

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CN102134188A
CN102134188A CN2011100696781A CN201110069678A CN102134188A CN 102134188 A CN102134188 A CN 102134188A CN 2011100696781 A CN2011100696781 A CN 2011100696781A CN 201110069678 A CN201110069678 A CN 201110069678A CN 102134188 A CN102134188 A CN 102134188A
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prisconnatacin
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tetrahydro
anthraquinone compounds
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CN102134188B (en
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陈涛
冯世秀
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Shenzhen Xianhu Botanical Garden Shenzhen Garden Research Center
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XIANHU BOTONICAL GARDEN ADMINISTRATIVE DIVISION SHENZHEN CITY
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Abstract

The invention discloses a tetrahydroanthraquinone compound Prisconnatacin and a preparation method and application thereof in preparation of anti-tumor medicaments. The Prisconnatacin is separated from prismatomeris connata root serving as a Chinese medicinal material, and the structure of the Prisconnatacin is shown as a formula (I). The tetrahydroanthraquinone compound Prisconnatacin has high anti-tumor activity, and can be used for preparing the anti-tumor medicaments; and because the Prisconnatacin is from the prismatomeris connata root serving as the Chinese medicinal material, the source is sufficient, the separation method is simple, the toxicity is low and the use is safe. The natural active tetrahydroanthraquinone compound is few, the compound Prisconnatacin has simple structure and can be used as a precursor compound for the anti-tumor medicaments, and the structure of the compound Prisconnatacin is further modified and reformed on the basis of the conventional activity so that anti-tumor target and efficiency of the compound Prisconnatacin are improved; and the compound Prisconnatacin is used for developing the medicaments for treating liver cancer, lung cancer, breast cancer and leukemia, and has very broad development and application prospect. R1, R2 and R3 are all H, and R4 and R5 are OCH3.

Description

Tetrahydro-anthraquinone compounds Prisconnatacin and preparation method thereof and the application in the preparation antitumor drug
Technical field:
The invention belongs to the medical compounds field, be specifically related to a kind of come from the Chinese medicinal materials xanthorrhiza have tetrahydro-anthraquinone compounds Prisconnatacin of anti-tumor activity and preparation method thereof, with and application in the preparation antitumor drug.
Background technology:
Medicinal plant is from the existing so far kind more than 5,000 of " Shennong Bencaojing " record, and the clinical kind more than 1,000 that also has commonly used plays an important role for human opposing various diseases from ancient times to the present always.After the seventies in 20th century, modern separation technology extensively rose, the isolating active natural product had become the human new drug of excavating as new drug or as the precursor compound of developing new drug from the plant with long medicinal history, overcomes the breach of complex disease.In recent years, international medical giant has invested Chinese abundant resources of medicinal plant to sight especially, by setting up the external of integral framework and activity in vivo screening model, traditional Chinese medicinal components and monomeric compound thereof are carried out full scan, therefrom excavate efficient, low toxicity, novel structure is easy to the bioactive natural product of structural modification and transformation, as the medicine or the lead drug of treatment cancer, HIV and sudden communicable disease.
Cancer rises to gradually to threatening No. second killer of human health, and what make that medical circle puzzles is also not have good medicine can be applied to the clinical cancer of eliminating at present.Anthracene nucleus class (anthracyclines) medicine is a medicine of using maximum treatment cancers at present clinically, it also is relatively effective medicine, this class medicine mainly contains Zorubicin (doxorubicin), daunomycin (daunomycin), mitoxantrone (mitoxantrone), epirubicin (epirubicin), idarubicin (idarubicin), be the derivative of anthraquinone analog compound, have the effect of inducing apoptosis of tumour cell.But the selectivity of but finding them in secular clinical use gradually is low, when suppressing tumor propagation, normal cell also there is very big lethality, cause very strong toxic side effect, weak show as vomiting, weak, apocleisis, dizziness, serious finds that then heart is had serious damage, even cerebral nerve also had destruction, limited their uses clinically.Therefore, it is little to seek new toxic side effect, and the medicine of the treatment cancer of wide material sources has seemed urgent day by day.
Xanthorrhiza is the root of Rubiaceae South Mountain flower (Prismatomeris connata), as a kind of Chinese medicinal materials among the people, has the history of being used as medicine of two thousand years, be mainly used in treatment hepatitis, pneumonia, leukemia, diseases such as thalassemia, especially the treatment for silicosis has unique effect.This plant is rich in a large amount of anthraquinone analog compounds, has report to show that anthraquinone analog compound is the activeconstituents of this plant.From this plant, seek the active quinones of efficient, low toxicity, develop, have far-reaching researching value and social effect as the medicine or the prodrug of treatment cancer with antitumor action.
Summary of the invention:
First purpose of the present invention provides a kind of new tetrahydro-anthraquinone compounds Prisconnatacin with antitumor action who obtains that separates from the Chinese medicinal materials xanthorrhiza, its structure is suc as formula shown in (I).
Tetrahydro-anthraquinone compounds Prisconnatacin of the present invention, concrete structure is suc as formula shown in (I).
Figure BDA0000051500920000021
R wherein 1=R 2=R 3=H, R 4=R 5=OCH 3
Second purpose of the present invention provides the preparation method suc as formula the tetrahydro-anthraquinone compounds Prisconnatacin shown in (I).This preparation method may further comprise the steps:
(a) pulverize xanthorrhiza is dried in the shade back, use the aqueous ethanolic solution lixiviate, after vat liquor concentrates crude extract;
(b) crude extract is suspended in water, use sherwood oil, ethyl acetate extraction successively, after acetic acid ethyl acetate extract concentrated, through silica gel column chromatography, with the chloroform-methanol is eluent, and from 95: 5~50: 50 gradient elutions of volume ratio, the component that gradient elution is got off can be that 3: 1 solution system unfolded components are again through silica gel column chromatography with chloroform-acetone volume ratio in thin-layer chromatography, with chloroform-acetone volume ratio is 5: 1 solution system wash-out, yellow powder shape Compound P risconnatacin.
Aqueous ethanolic solution in the described step (a) is preferably the aqueous ethanolic solution of volume fraction 95%.
The present invention proves that by experiment tetrahydro-anthraquinone compounds Prisconnatacin of the present invention can effectively suppress the propagation of kinds of tumor cells, can be used as antitumor drug and prodrug is developed, and can be receivable any one formulation on the medicine.
Therefore the 3rd purpose of the present invention provides the application of tetrahydro-anthraquinone compounds Prisconnatacin in the preparation antitumor drug.
Tetrahydro-anthraquinone compounds Prisconnatacin anti-tumor activity height of the present invention can be used to prepare antitumor drug, and it stems from traditional Chinese medicine material xanthorrhiza, and the source is sufficient, and separation method is simple, and toxicity is little, and is safe in utilization.The active tetrahydro-anthraquinone compounds of natural origin is less, and Compound P risconnatacin is simple in structure, can be used as the precursor compound of antitumor drug, on existing active basis, carry out further structural modification and transformation, improve its antineoplastic targeting and high efficiency, be used for exploitation treatment liver cancer, lung cancer, mammary cancer and leukemic medicine, its development and application prospect is very wide.
Embodiment:
Following examples are to further specify of the present invention, rather than limitation of the present invention.
Embodiment 1:
One, the preparation method of tetrahydro-anthraquinone compounds Prisconnatacin
Root-the xanthorrhiza (5kg) of South Mountain flower (P.connata) is pulverized after air-dry, is 95% aqueous ethanolic solution lixiviate at normal temperatures 2 times with the 20L volume fraction, each 48 hours, and the merging ethanol extract, concentrating under reduced pressure gets thick extracted extract 800g.Gained medicinal extract becomes suspension with the 1000mL water dissolution, uses isopyknic sherwood oil and ethyl acetate extraction 4 times more successively respectively, and combined ethyl acetate extraction liquid, concentrating under reduced pressure get the 420g of ethyl acetate extraction portion.Ethyl acetate extraction portion is through normal pressure silica gel column chromatography chromatography, with the chloroform-methanol is eluent, carried out gradient elution in 95: 5 to 50: 50 from volume ratio, detect the merging same composition with thin-layer chromatography, the available successively chloroform of gradient elution obtained component-acetone volume ratio is 10: 1, and chloroform-acetone volume ratio is 9: 1, and chloroform-acetone volume ratio is 3: 1, and the chloroform-methanol volume ratio is that 85: 15 and chloroform-methanol volume ratio are to launch at 8: 2, is divided into five components.In thin-layer chromatography, can be 3: 1 solution system unfolded components with chloroform-acetone volume ratio, separate through the normal pressure silica gel column chromatography, it with chloroform-acetone volume ratio 5: 1 solution system wash-out, eluate gets yellow powder shape Compound P risconnatacin 56mg behind concentrate drying, this compound identifies that through structural analysis its spectroscopy data are as follows: molecular formula C 17H 18O 6, HR-ESI-MS:341.0995 ([M+Na] +, calcd.for C 17H 18O 6Na) .ESI-MS:341 ([M+Na] +), 659 ([2M+Na] +), 317 ([M-H] -), 352.3 ([M+C1] -) .mp 265-267 ℃, (c 0.6, MeOH) .UV (MeOH): 217.5 (4.39), 265.0 (4.24), 290.9 (3.96), 413.9 (3.84) .IR (KBr): 3488,2975,1637,1610,1589,1498,1457,1421,1319,1286,1141,1062. 1H-NMR (CDCl 3, 400MHz): 2.94 (dd, J=19.0,5.6, H-1a), 2.30 (dd, J=19.0,7.9, H-1b), 1.92 (m, H-2), 3.74 (td, J=8.1,4.8, H-3), 3.03 (dd, J=19.0,4.8, H-4a), 2.53 (dd, J=19.0,8.1, H-4b), 7.25 (s, H-8), 1.12 (d, J=6.8,2-CH 3), 3.99 (s, 6-OCH 3), 4.00 (s, 7-OCH 3), 12.26 (s, 5-OH). 13C-NMR (CDCl 3, 100MHz): 24.1 (C-1), 28.9 (C-2), 65.8 (C-3), 26.2 (C-4), 150.8 (C-5), 136.5 (C-6), 152.9 (C-7), 99.0 (C-8), 178.5 (C-9), 184.1 (C-10), 106.1 (C-11), 123.0 (C-12), 138.7 (C-13), 138.5 (C-14), 12.6 (CH 3-2), 56.3 (OCH 3-6), 51.7 (OCH 3-7).
Therefore separate the yellow powder shape Compound P risconnatacin that obtains, its structure is suc as formula shown in (I):
Figure BDA0000051500920000051
R wherein 1=R 2=R 3=H, R 4=R 5=OCH 3Compound.
Two, mtt assay is measured the experiment of tetrahydro-anthraquinone compounds Prisconnatacin anti-tumor activity.
The present invention adopts the experiment of cell in vitro poison, by detecting the survival rate behind the adding Prisconnatacin in the isolated culture human cancer cell, measures the anti-tumor activity of Compound P risconnatacin.
The tumor cell line of choosing has people's nonsmall-cell lung cancer H520, A549, H549,1299, human liver cancer cell HepG2, human breast cancer cell MCF7, Human Prostate Cancer Cells PC3, LNcaP, DU145,22RV1, people's colon-cancer cell SW480, HCT116, human melanoma cell MMRu, people's chronic myelogenous leukemia cell K562.Adopt mtt assay (reference Mosmann T.Rapid colorimetric assay for cellular growth and survival-application to proliferation and cytotoxicity assays.J Immunol Methods, 1983,65 (1-2), 55-63.) survival rate (or mortality ratio) of measuring every kind of tumour cell is 50% o'clock 503nhibiting concentration IC 50
Microplate reader is measured the OD value in each hole under 562nm.
Inhibition rate of tumor cell (%)=1-(dosing group OD value/cell control group OD value) * 100%
With logarithm 1gC (X-coordinate) mapping of inhibiting rate (ordinate zou), try to achieve IC to drug level 50Value.
Tetrahydro-anthraquinone compounds Prisconnatacin is to the 503nhibiting concentration IC of above-mentioned tumor cell line 50As shown in table 1, as can be seen from Table 1, tetrahydro-anthraquinone compounds Prisconnatacin of the present invention has effectively suppressed the propagation of above-mentioned tumor cell line, it suppresses the active higher of tumor cell proliferation, can be used to prepare antitumor drug, and, therefore can on existing structure, further modify and transform because tetrahydro-anthraquinone compounds Prisconnatacin of the present invention is simple in structure, improve its antineoplastic targeting and high efficiency, the development and application prospect is very wide.
The cell in vitro poison experimental result (IC of table 1:Prisconnatacin 50μ M)
Figure BDA0000051500920000061

Claims (5)

1. tetrahydro-anthraquinone compounds Prisconnatacin, its structure is suc as formula shown in (I).
R wherein 1=R 2=R 3=H, R 4=R 5=OCH 3
2. the preparation method of the described tetrahydro-anthraquinone compounds of claim 1 Prisconnatacin is characterized in that, may further comprise the steps:
(a) pulverize xanthorrhiza is dried in the shade back, use the aqueous ethanolic solution lixiviate, after vat liquor concentrates crude extract;
(b) crude extract is suspended in water, use sherwood oil, ethyl acetate extraction successively, after acetic acid ethyl acetate extract concentrated, through silica gel column chromatography, with the chloroform-methanol is eluent, and from 95: 5~50: 50 gradient elutions of volume ratio, the component that gradient elution is got off can be that 3: 1 solution system unfolded components are again through silica gel column chromatography with chloroform-acetone volume ratio in thin-layer chromatography, with chloroform-acetone volume ratio is 5: 1 solution system wash-out, yellow powder shape Compound P risconnatacin.
3. the preparation method of tetrahydro-anthraquinone compounds Prisconnatacin according to claim 2 is characterized in that, the aqueous ethanolic solution in the described step (a) is the aqueous ethanolic solution of volume fraction 95%.
4. the application of the described tetrahydro-anthraquinone compounds of claim 1 Prisconnatacin in the preparation antitumor drug.
5. the application of tetrahydro-anthraquinone compounds Prisconnatacin according to claim 4 in the preparation antitumor drug, its spy is that described tumour is liver cancer, lung cancer, mammary cancer or leukemia.
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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110256225A (en) * 2018-07-16 2019-09-20 自然资源部第三海洋研究所 A kind of naphthoquinone compound CWL-168, preparation method and its usage
CN112694507A (en) * 2020-12-31 2021-04-23 中山大学 Tetrahydro anthraquinone glycoside compound and application thereof in preparation of antitumor drugs
CN112972459A (en) * 2021-03-04 2021-06-18 广西国际壮医医院 Application of radix astragali monomer in liver protection
CN114404487A (en) * 2022-02-15 2022-04-29 广西白云山盈康药业有限公司 Application of radix astragali or its extract in preparing medicine for treating glioma

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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101773495A (en) * 2010-02-03 2010-07-14 中国科学院昆明植物研究所 Anti-tumor medicinal composition and application and preparation method thereof
CN101851272A (en) * 2009-03-31 2010-10-06 苏州金昊药业开发有限公司 Glaucocalyxin B, derivative, preparation method and application thereof
CN101928293A (en) * 2010-01-27 2010-12-29 中国科学院昆明植物研究所 Bisindole alkaloid compound, medicine composition thereof and preparation method and application of medicine composition

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101851272A (en) * 2009-03-31 2010-10-06 苏州金昊药业开发有限公司 Glaucocalyxin B, derivative, preparation method and application thereof
CN101928293A (en) * 2010-01-27 2010-12-29 中国科学院昆明植物研究所 Bisindole alkaloid compound, medicine composition thereof and preparation method and application of medicine composition
CN101773495A (en) * 2010-02-03 2010-07-14 中国科学院昆明植物研究所 Anti-tumor medicinal composition and application and preparation method thereof

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110256225A (en) * 2018-07-16 2019-09-20 自然资源部第三海洋研究所 A kind of naphthoquinone compound CWL-168, preparation method and its usage
CN112694507A (en) * 2020-12-31 2021-04-23 中山大学 Tetrahydro anthraquinone glycoside compound and application thereof in preparation of antitumor drugs
CN112694507B (en) * 2020-12-31 2022-03-29 中山大学 Tetrahydro anthraquinone glycoside compound and application thereof in preparation of antitumor drugs
CN112972459A (en) * 2021-03-04 2021-06-18 广西国际壮医医院 Application of radix astragali monomer in liver protection
CN114404487A (en) * 2022-02-15 2022-04-29 广西白云山盈康药业有限公司 Application of radix astragali or its extract in preparing medicine for treating glioma
CN114404487B (en) * 2022-02-15 2023-11-10 广西白云山盈康药业有限公司 Application of radix astragali or its extract in preparing medicine for treating glioma

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