CN105777839B - A kind of antitumoral compounds, its extracting method and its application - Google Patents
A kind of antitumoral compounds, its extracting method and its application Download PDFInfo
- Publication number
- CN105777839B CN105777839B CN201510991855.XA CN201510991855A CN105777839B CN 105777839 B CN105777839 B CN 105777839B CN 201510991855 A CN201510991855 A CN 201510991855A CN 105777839 B CN105777839 B CN 105777839B
- Authority
- CN
- China
- Prior art keywords
- cancer
- compound
- methanol
- carcinoma
- sub
- 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
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J17/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, having an oxygen-containing hetero ring not condensed with the cyclopenta(a)hydrophenanthrene skeleton
- C07J17/005—Glycosides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J21/00—Normal steroids containing carbon, hydrogen, halogen or oxygen having an oxygen-containing hetero ring spiro-condensed with the cyclopenta(a)hydrophenanthrene skeleton
Abstract
The embodiment of the invention discloses a kind of antitumoral compounds, its extracting method and its application, which has the structure of general formula (I) or general formula (II) and its optical isomer；The compounds of this invention and combinations thereof can effectively inhibit the growth of independent prostate cancer cells, variety classes kidney cancer cell and people's malignant melanoma cell, prompt the compounds of this invention and combinations thereof can be used as the drug for the treatment of tumour, have good research and development prospect.
Description
Technical field
The present invention relates to a kind of compound, the native compound that is particularly extracted from straw berry tomato, the compound
Extracting method, comprising the pharmaceutical composition of the compound and the compound and the pharmaceutical composition in the preparation of antitumor drugs
Purposes.
Background technique
Straw berry tomato Physalis pubescens L. is Solanaceae Physalis annual herb plant, Xu Guojun chief editor's
《Chinese pharmacognosy》In describe straw berry tomato band place calyx fruit it is medicinal as Chinese lantern.Straw berry tomato nature and flavor acid is flat, enters lung channel, has
There is the effect of clearing heat and detoxicating, pharynx-clearing throat-benefiting, diuresis hemostasis.It is civil to be used to treat acpuei pharyngitis significant effect.(equal China of Xu state
The Beijing pharmacognosy volume two [M]:China Medical Science Press.1996：1161-1162.) before its traditional effect and Chinese traditional treatment
The method of " row stasis and resolving masses, tonneau water channel " used by column gland cancer is just consistent.
Chemical research to monkey flower the result shows that, wherein mainly contain steroidal, alkaloid, flavones, terpene etc. at
Divide (Qiu Li chemical Constituents from Physalis alkekengi and its bioactivity research Shenyang Pharmaceutical University Ph.D. Dissertation .2007 tutor：Qiu
Peak).The Analysis of Steroids contained in monkey flower is a kind of containing 28 carbon atoms based on withanolide type
Ergot steroid-lactone compound has various pharmacological activity such as antitumor, antiparasitic, antibacterial, anti-inflammatory, immunological regulation.
Studies have reported that withanolide class compound has the function of anti-kinds of tumor cells：Physalins A and Physalins
B can be by lowering expression and the active cell apoptosis of androgen receptor to effectively inhibit Androgen Independent Prostate Cancer thin
Growth (the Han H.Y. of born of the same parents；Qiu L.；Wang X.H.；et al.Biol.Pharm.Bull.2011,34(10)1584—
1588)；Growth (Subramanian, the C. of the withanolide class compound property of can choose inhibition adrenocortical carcinoma cells；
Zhang,H.P.；Gallagher,R.；et al.World J.Surg.2014,38,1343–1352.)；Physalin A can be with
Apoptosis and autophagy (the He H. of fibrin sarcoma cell and people's malignant melanoma cell；Zang L.H.；Feng
Y.S.；et al.Physalin A Induces Apoptotic Cell Death and Protective Autophagyin
HT1080Human Fibrosarcoma Cells.Journal of Natural Products,2013,76,880–888；He
H.；Feng Y.S.；Zang L.H.；et al.Nitric oxide induces apoptosis and autophagy；
autophagy down-regulates NO synthesis in physalin A-treated A375-S2human
Melanoma cells.Food and Chemical Toxicology, 2014,71,128-135) etc..
But it is so far, very few to the active constituent report of straw berry tomato both at home and abroad, to explore this with medical value
Whether plant (i.e. straw berry tomato) has anti-tumor active ingredient, and inventor carries out in straw berry tomato with antitumor active constituent
Research.
Summary of the invention
Primary and foremost purpose of the present invention be to provide in straw berry tomato plant have antitumor compound, extracting method and its
Prepare the application in anti-tumor drug.
Another object of the present invention is to provide composition including above compound and its in the preparation of antitumor drugs
Application.
The purpose of the invention is achieved by the following technical solution：
First aspect present invention provides a kind of antitumoral compounds, has general formula (I), general formula (II) or both optics different
The structure of structure body：
Wherein, in general formula (I), 2-3,5-6 are singly-bound or double bond；R1For OH or carbonyl；R2For H, OH or group D,
E；R3For H or OH；R4For OH or R4With R5It is combined into group B；R5For H, Cl or R5With R4It is combined into group B；R6For H or group C；
R7For H or group C；R8For OH, group A or R8With R9It is combined into group B；R9For OH or R9With R8It is combined into group B；R10For OH,
Carbonyl or group A；
The group A, group B, group C, group D and group E are respectively：
In some preferred embodiments of first aspect present invention, the compound includes：
Physapubside A(1)、Physapubside B(2)、Physapubside C(3)、Physapubside D
(4)、Physapubescin E(5)、Physapubescin F(6)、Physapubescin G(7)、Physapubescin H
(8)、Physapubescin I(9)、Physapubescin J(10)、Physapubescin K(11)、Physapubescin
L(12)、Physapubescin M(13)、Physapubescin N(14)、Physapubescin O(15)、
Any one of Physapubescin P (16), Physapubescin Q (17), Physapubescin R (18), from chemical combination
The structural formula of object 1-18 is respectively：
The preparation method of above compound includes following operating procedure：Using Physalis annual herb plant straw berry tomato
The drying cauline leaf and/or fruit of Physalis pubescens L. is raw material, the ethyl alcohol or methanol for being 1-99% with volume fraction
Aqueous solution refluxing extraction 1-3 times, every time extract 1-48 hour, merging obtain extracting solution, by extracting solution remove solvent obtain always
Medicinal extract；
Total medicinal extract is extracted with organic solvent, organic extract liquid is obtained, is obtained after organic extract liquid is concentrated organic
Solvent layer medicinal extract；The organic solvent is one of methanol, ethyl alcohol, acetone, ethyl acetate, chloroform, petroleum ether and n-butanol
Or it is several；
Organic solvent layer medicinal extract is separated by chromatography, obtains above-mentioned compound；The Extracting temperature
It is 20-100 DEG C, preferably 40-90 DEG C.
Second aspect of the present invention provides a kind of vegetable hair Calyx seu fructus physalis extract including above compound.
Third aspect present invention provides one or more of a kind of pharmaceutical composition, including above compound.
Fourth aspect present invention provides a kind of pharmaceutical composition comprising the above compound containing therapeutically effective amount or
Its pharmaceutically acceptable salt and pharmaceutically acceptable carrier and/or excipient.
It is anti-in preparation that fifth aspect present invention provides above-mentioned compound, vegetable hair Calyx seu fructus physalis extract and pharmaceutical composition
Application in tumour medicine.
Described tumour includes but is not limited to：Various entity tumors and leukaemia, such as lung cancer, bronchiolar carcinoma, liver cancer, ovary
Cancer, cervix cancer, bladder cancer, carcinoma of testis, clear-cell carcinoma, cancer of pancreas, gastric cancer, osteocarcinoma, cancer of the esophagus, colon cancer, cholangiocarcinoma, forefront
Gland cancer, choriocarcinoma, melanoma, spongiocytoma, neurofibroma, fibrosarcoma, lymphangioma etc..
Containing compound or composition of the present invention treatment genitourinary cancers drug can for suitable for
The application forms such as oral or injection, for example, can be tablet, capsule, pulvis, syrup, injection etc..
Advantage and effect of the present invention：(1) a series of compound and combinations thereof of structure novels is provided；(2) body is used
Outer screening active ingredients system carries out activity rating, and discovery the compounds of this invention and combinations thereof can effectively inhibit hormonal independent
The growth of prostate gland cancer cell, variety classes kidney cancer cell and people's malignant melanoma cell, prompt the compounds of this invention and
Its composition can be used as the drug for the treatment of tumour, have good research and development prospect.
Specific embodiment
Technical solution of the present invention is described below in conjunction with specific embodiment, described embodiment is only this
Invention a part of the embodiment, instead of all the embodiments.Based on the embodiments of the present invention, those of ordinary skill in the art exist
Every other embodiment obtained under the premise of creative work is not made, shall fall within the protection scope of the present invention.
Embodiment 1：Isolating active compound is extracted from straw berry tomato cauline leaf
Solanaceae Physalis annual herb plant straw berry tomato Physalis pubescens L. is dry cauline leaf (9.3kg), uses
75% ethanol water refluxing extraction 2 times, 2 hours every time, combined extract was recovered under reduced pressure solvent, total medicinal extract is obtained after concentration
(1170.0g).Total medicinal extract is distributed in the water of 4 times of amounts, respectively with isometric petroleum ether, ethyl acetate, extracting n-butyl alcohol three
It is secondary, solvent is recovered under reduced pressure and obtains petroleum ether layer medicinal extract 15.0g, ethyl acetate layer medicinal extract 99.0g and n-butanol layer medicinal extract 200.0g,
Remaining water layer 850.0g.
Ethyl acetate layer medicinal extract passes through silica gel column chromatography, methylene chloride-methanol (100：1~0：100) gradient elution obtains
9 sub- fractions (Fr.1~Fr.9).Sub- fraction Fr.3 passes through silica gel column chromatography, dichloromethane-acetone (100：1~0：100) terraced
Degree elution, obtains 8 sub- fractions (Fr.31~Fr.38), Fr.35 is through Sephadex LH-20 column chromatography, methylene chloride-methanol
(1：1) it elutes, using preparative high-performance liquid chromatographic, methanol-water (70：30) compound 9 (8.9mg), is obtained；Fr.36 warp
Sephadex LH-20 column chromatography, methylene chloride-methanol (1：1) it elutes, Fr.361 is obtained, using silica gel column chromatography (hexamethylene-
Ethyl acetate) gradient elution, 2 sub- fractions (Fr.3611~Fr.3612) are obtained, Fr.3611 is by preparing high-efficient liquid phase color
Spectrum, methanol-water (60：40) compound 16 (17.9mg), is obtained；Fr.3612 passes through preparative high-performance liquid chromatographic, methanol-water
(60：40) compound 15 (85.0mg) and compound 8 (19.6mg), are obtained；Sub- fraction Fr.4 passes through silica gel column chromatography, hexamethylene
Alkane-ethyl acetate (100：1~0：100) gradient elution obtains 8 sub- fractions (Fr.41~Fr.48), and Fr.44 is through Sephadex
LH-20 column chromatography, methylene chloride-methanol (1：1) sub- fraction Fr.441 is eluted to obtain, using ODS column chromatography, methanol-water (10：
90~100：0) gradient elution obtains sub- fraction Fr.4413, and Fr.4413 passes through preparative high-performance liquid chromatographic, methanol-water (70：30),
Obtain compound 10 (75.2mg)；Fr.46 is through Sephadex LH-20 column chromatography, methylene chloride-methanol (1：1) it elutes sub to evaporate
Fr.463, Fr.463 is divided to cross preparative high-performance liquid chromatographic, methanol-water (60：40) compound 11 (76.5mg) and compound, are obtained
17(252.0mg)；Fr.47 is through Sephadex LH-20 column chromatography, methylene chloride-methanol (1：1) sub- fraction Fr.471 is eluted to obtain,
Fr.471 crosses preparative high-performance liquid chromatographic, methanol-water (50：50) compound 12 (1600.0mg), is obtained；Fr.48 warp
Sephadex LH-20 column chromatography, methylene chloride-methanol (1：1) sub- fraction Fr.481 is eluted to obtain, Fr.481, which is crossed, prepares efficient liquid
Phase chromatography, methanol-water (50：50) compound 13 (132.0mg), is obtained.
N-butanol fraction (100g) passes through silica gel column chromatography, methylene chloride-methanol (100:1~0:100) gradient elution,
9 sub- fractions (B1~B9) are obtained.B2 (7.5g) fraction passes through silica gel column chromatography, methylene chloride-methanol (30:1~0:1) terraced
Degree elution obtains 3 sub- fractions (B21~B23), and B22 passes through Sephadex LH-20 column chromatography, and methanol elutes to obtain B222,
B222 is by preparing thin layer (methanol is solvent), open ODS column chromatography, methanol-water (10:90,30:70,40:60,80:20)
Gradient elution and preparative high-performance liquid chromatographic (methanol：Water=50:50) compound 14 (23.0mg) is purified to obtain；B3 (15.2g) evaporates
Divide through silica gel column chromatography, methylene chloride-methanol (50:1~10:1) gradient elution obtains 6 sub- fractions (B31~B36).Son
Fraction B 35 is through open ODS column chromatography, methanol-water (10:90,30:70,50:50,80:20,100:0) gradient elution obtains 8 sons
Fraction (B351~B358) has crystal precipitation in B356, after recrystallizing methanol compound 2 (101.0mg)；B6 (12g) fraction
Pass through silica gel column chromatography, methylene chloride-methanol (6:1) isocratic elution obtains 3 sub- fractions (B61~B63).B63 is through mesolow
ODS column chromatography, methanol-water (10:90~80:20) gradient elution obtains 14 sub- fractions (B63-1~B63-14), B63-13 warp
Silica gel column chromatography, methylene chloride-methanol (5:1) isocratic elution and through Sephadex LH-20 column chromatography, methanol elutes to obtain B63-
13-1, B63-13-1 are through preparative high-performance liquid chromatographic, methanol-water (72：28) isolated compound 4 (75.0mg)；B7(30g)
Fraction passes through silica gel column chromatography, methylene chloride-methanol (8:1~3:1) gradient elution obtains 4 sub- fractions (B71~B74),
B74 fraction obtains 2 fractions (B741~B742) using water and ethyl alcohol as eluant, eluent respectively, B742 is anti-through polyamide column chromatography
Again through Sephadex LH-20 column chromatography, methanol is eluted, then through preparative high-performance liquid chromatographic, methanol/water (60：40) it, separates
To compound 1 (43.0mg).B8 (19g) uses repeatedly silica gel column chromatography with methylene chloride-methanol system ladder, removes most of color
It after element, is purified by flash through Sephadex LH-20 column chromatography, methanol repeatedly, then passes through preparative high-performance liquid chromatographic, methanol-water
(55：45), isolated compound 3 (110.0mg).
Embodiment 2：Isolating active compound is extracted from physalis pubescens fruit
The fruit (17.5kg) of Solanaceae Physalis annual herb plant straw berry tomato Physalis pubescens L. is used
75% ethanol water refluxing extraction 2 times, 2 hours every time, combined extract was recovered under reduced pressure solvent, total medicinal extract is obtained after concentration
(1420.0g).Total medicinal extract is distributed in the water of 4 times of amounts, respectively with isometric petroleum ether, ethyl acetate, extracting n-butyl alcohol three
It is secondary, solvent is recovered under reduced pressure and obtains petroleum ether layer medicinal extract 49.0g, ethyl acetate layer medicinal extract 46.0g and n-butanol layer medicinal extract 70.0g,
Remaining water layer 1246.0g.
Ethyl acetate layer medicinal extract passes through silica gel column chromatography, methylene chloride-methanol (100：1~0：100) gradient elution obtains
10 sub- fractions (E1~E10).Sub- fraction E3 passes through silica gel column chromatography, methylene chloride-methanol (100：0~0：100) gradient is washed
It is de-, 6 sub- fractions (E31~E36) are obtained, E32 is through Sephadex LH-20 column chromatography, methylene chloride-methanol (1：1) it elutes,
It obtains E322 and obtains 8 sub- fractions (E3221~E3228) using silica gel column chromatography (cyclohexane-ethyl acetate) gradient elution,
E3227 passes through preparative high-performance liquid chromatographic, methanol-water (67：33) compound 11 (92.0mg), is obtained；Sub- fraction E5 passes through poly-
Amide column chromatography, methanol-water (10：90~100：0) gradient elution obtains 3 sub- fractions (E51~E53), and E51 passes through silica gel
Column chromatography, (cyclohexane-acetone) gradient elution obtain 12 sub- fractions (E51-1~E51-12), and E51-8 passes through ODS column color
Spectrum, methanol-water gradient elution obtain 6 sub- fractions (E51-8-1~E51-8-6), and E51-8-4 is by preparing high-efficient liquid phase color
Spectrum, methanol-water (52：48) compound 12 (19.0mg), is obtained；E51-10 is obtained by ODS column chromatography, methanol-water gradient elution
To 4 sub- fractions (E51-10-1~E51-10-4), E51-10-3 by silica gel preparative thin layer chromatography (methylene chloride-methanol=
10：1) E51-10-3-3 is obtained, using preparative high-performance liquid chromatographic, methanol-water (48：52) compound 18 (34.0mg), is obtained；
E52 obtains 5 sub- fractions (E521~E525) through Sephadex LH-20 column chromatography, methanol elution, and E523 prepares thin by silica gel
Layer chromatography (hexamethylene：Acetone=1：1) E5232 is obtained, (methanol-water) is recrystallized and obtains compound 5 (20.0mg).Sub- fraction E6 is logical
Cross polyamide column chromatography, methanol-water (10：90~100：0) gradient elution obtains 6 sub- fractions (E61~E66), E61 warp
Sephadex LH-20 column chromatography, methanol elution, obtains 3 sub- fractions (E611~E613), and E612 is by silica gel column chromatography, and (two
Chloromethanes-acetone) gradient elution, 5 sub- fractions (E6121~E6125) are obtained, E6123 passes through preparative high-performance liquid chromatographic, first
Alcohol-water (67：33) compound 13 (64.0mg), is obtained.Sub- fraction E7 passes through silica gel preparative thin layer chromatography, dichloromethane-acetone
(15：1~1：1) gradient elution, obtains 8 sub- fractions (E71~E78), and E74 is by ODS column chromatography, methanol-water gradient elution,
6 sub- fractions (E741~E746) are obtained, E746 passes through preparative high-performance liquid chromatographic, methanol-water (67：33) compound 6, is obtained
(77.0mg).Sub- fraction E8 obtains 6 sub- fractions (E81~E86) through Sephadex LH-20 column chromatography, methanol elution, and E83 is logical
ODS column chromatography is crossed, methanol-water gradient elution obtains 9 sub- fractions (E831~E839), and E839 is by preparing high-efficient liquid phase color
Spectrum, methanol-water (55：45) compound 2 (35.0mg), is obtained.
N-butanol layer medicinal extract passes through silica gel column chromatography, methylene chloride-methanol (100：1~0：100) gradient elution obtains 12
A sub- fraction (B1~B12).B2 obtains 8 sub- fractions (B21~B28), B26 by ODS column chromatography, methanol-water gradient elution
Pass through silica gel column chromatography, methylene chloride-methanol (20：1) isocratic elution obtains sub- fraction B 261, and B261 is by preparation efficient liquid phase
Chromatography, methanol-water (65：35) compound 12 (12.2mg), 13 (44.2mg), are obtained.B11 passes through silica gel column chromatography, dichloromethane
Alkane-methanol (100：1~0：100) gradient degree elutes, and obtains 6 sub- fractions (B11-1~B11-6), and B11-5 passes through ODS column color
Spectrum, methanol-water gradient elution obtain 14 sub- fractions (B11-5-1~B11-5-14), and B11-5-14 is through Sephadex LH-20
Column chromatography, methanol elution obtain sub- fraction B 11-5-14-2, and B11-5-14-2 passes through preparative high-performance liquid chromatographic, methanol-water (70：
30) it, obtains compound 4 (19.0mg), compound 4 obtains its aglycon, compound 7 through cellulose hydrolyzation.B12 passes through silicagel column
Chromatography, methylene chloride-methanol (100：1~0：100) gradient degree elutes, and obtains 5 sub- fractions (B12-1~B12-5), B12-5
By ODS column chromatography, methanol-water gradient elution obtains 7 sub- fractions (B12-5-1~B12-5-7), and B12-5-4 is by preparation
High performance liquid chromatography, methanol-water (50：50) compound 3 (509.0mg), is obtained；B12-5-5 is through Sephadex LH-20 column color
Spectrum, methanol elution obtain sub- fraction B 12-5-5-4, and B12-5-5-4 passes through preparative high-performance liquid chromatographic, methanol-water (50：50) it, obtains
To compound 1 (24.0mg).
Section (MS, NMR) is learned to do by physicochemical constant and Modern spectroscopy, in conjunction with document related data, identifies their knot
Structure, compound 1-18 are to have no noval chemical compound reported in the literature, as follows：
The physical chemistry and constant of each noval chemical compound of gained are as follows：
1 colourless platelet (methanol) of compound；Fusing point：241℃；(c 0.06, methanol)；IR(KBr)νmax
cm-1：3458,2939,2898,1640,1459,1385,1062,1048；ESI-TOF-MS(Positive)m/z：818.4527
(calcd.for C40H64O16NH4, 818.4538), molecular formula C40H64O16；1H-NMR(600MHz,Pyridine-d5) and13C-NMR(150MHz,Pyridine-d5) data are shown in Table 1.
2 white powder of compound；(c=0.07, methanol)；IR(KBr)νmax cm-1：3448,2938,
2858,1728,1630,1463,1385,1169,1103,1067,1021；ESI-TOF-MS(Positive)m/z：661.3560
(calcd.for C34H54NaO11：661.3558), molecular formula C34H54O11；1H-NMR(600MHz,Pyridine-d5) and13C-NMR(150MHz,Pyridine-d5) data are shown in Table 1.
3 white powder of compound；(c 0.07, methanol)；IR(KBr)νmax cm-1：3396,2940,
2897,1658,1435,1076,1044,894；ESI-TOF-MS(Positive)m/z：825.4243(calcd for
C40H66O16Na, 825.4249), molecular formula C40H66O16；1H-NMR(600MHz,Pyridine-d5) and13C-NMR
(150MHz,Pyridine-d5) data are shown in Table 1.
4 white powder of compound；(c 0.06, methanol)；IR(KBr)νmax cm-1：3406,2941,
2842,1658,1436,1051,1046,899；ESI-TOF-MS(Positive)m/z：853.4538(calcd.for
C42H70O16Na, 853.4562), molecular formula C42H70O16；1H-NMR(600MHz,Pyridine-d5) and13C-NMR
(150MHz,Pyridine-d5) data are shown in Table 1.
5 white powder of compound；(c=0.07, methanol)；IR(KBr)νmax cm-1：3458,2942,
2904,1721,1641,1462,1384,1262,1143,1054,1025；ESI-TOF-MS(Positive)m/z：499.3035
(calcd.for C28H44NaO6：499.3036), molecular formula C28H44O6；1H-NMR(600MHz,CDCl3) and13C-NMR
(150MHz,CDCl3) data are shown in Table 2.
6 white powder of compound (methanol)；(c=0.10, methanol)；IR(KBr)νmax cm-1：3422,
2972,2937,2856,2825,1641,1463,1384,1109,1078,1050,1029；ESI-TOF-MS(Positive)m/
z：501.3184(calcd.for C28H46NaO6, 501.3192), molecular formula C28H46O6；1H-NMR(600MHz,
Pyridine-d5) and13C-NMR(150MHz,Pyridine-d5) data are shown in Table 2.
7 white powder of compound (methanol)；(c=0.15, methanol)；IR(KBr)νmax cm-1：3422,
2918,2847,1598,1384,1055,1032；ESI-TOF-MS(Positive)m/z：529.3501(calcd.for
C30H50NaO6, 529.3505), molecular formula C30H50O6；1H-NMR(400MHz,Pyridine-d5) and13C-NMR(150MHz,
Pyridine-d5) data are shown in Table 2.
8 colorless needle crystals of compound (methanol)；Fusing point：118℃；(c=0.135, methanol)；IR
(KBr)νmax cm-1：3455,2934,1716,1678cm-1；UVλmax(methanol) nm (log ε):214(3.73)；HR-ESI-MS
(positive)m/z:553.2778(calcd for C30H42O8Na, 553.2777), molecular formula C30H42O8；1H-NMR
(300MHz,CD3OD) and13C-NMR(75MHz,CD3OD) data are shown in Table 2.
9 white powder of compound；(c=0.10, methanol)；IR(KBr)νmax cm-1：3451,2925,
1733,1675cm-1；UVλmax(methanol) nm (log ε):222(3.77)；HR-ESI-MS(positive)m/z:537.2817
(calcd for C30H42O7Na,537.2828)；Molecular formula is C30H42O7；1H-NMR(600MHz,CDCl3) and13C-NMR
(75MHz,CDCl3) data are shown in Table 3.
10 white powder of compound；(c=0.215, methanol)；IR(KBr)νmax cm-1：3456,2930,
1737,1673cm-1；UVλmax(methanol) nm (log ε):213(3.72)；HR-ESI-MS(positive)m/z:567.2928
(calcd for C31H44O8Na, 567.2934), molecular formula C31H44O8；1H-NMR(600MHz,CDCl3) and13C-NMR
(150MHz,CDCl3) data are shown in Table 3.
11 white powder of compound；(c=0.33, methanol)；IR(KBr)νmax cm-1：3466,2965,
1746,1679cm-1；UVλmax(methanol) nm (log ε):216(3.71)；HR-ESI-MS(positive)m/z:611.2823
(calcd for C32H44O10Na, 611.2827), molecular formula C32H44O10；1H-NMR(600MHz,CDCl3) and13C-NMR
(150MHz,CDCl3) data are shown in Table 3.
12 white powder of compound；(c=0.545 methanol), IR (KBr) νmax cm-1：3442,2961,
1733,1676cm-1,UVλmax(methanol) nm (log ε):214(3.77)；HR-ESI-MS(negative)m/z:547.2915
(calcd for C30H43O9, 547.2907), molecular formula C30H44O9；1H-NMR(600MHz,Pyridine-d5) and13C-NMR
(150MHz,Pyridine-d5) data are shown in Table 3.
13 white powder of compound；(c=0.135 methanol)；IR(KBr)νmax cm-1：3446,2978,
1743,1676cm-1,UVλmax(methanol) nm (log ε):213(3.74)；HR-ESI-MS(positive)m/z:629.2936
(calcd.for C32H46O11Na, 629.2938), molecular formula C32H46O11；1H-NMR(600MHz,Pyridine-d5) and13C-NMR(150MHz,Pyridine-d5) data are shown in Table 4.
14 white powder of compound,(c=0.045 methanol)；IR(KBr)νmax cm-1：3464,2972,
2906,1734,1681,1453,1376,1257,1077,1040；HR-TOF-MS provides m/z:607.2636(calcd.for
C30H45ClO9Na, 607.2650), molecular formula C30H42O8；1H-NMR(600MHz,Pyridine-d5) and13C-NMR
(100MHz,Pyridine-d5) data are shown in Table 4.
15 white, needle-shaped crystals of compound (methanol)；Fusing point：195℃；(c=0.145 methanol)；IR
(KBr)νmax cm-1：3397,2942,1734,1663,1459,1372,1249,1107,1054cm-1,UVλmax(methanol) nm
(logε):213(3.60)；HR-ESI-MS(positive)m/z:567.2925(calcd for C31H44O8Na,
567.2934), molecular formula C31H44O8；1H-NMR(300MHz,CDCl3) and13C-NMR(75MHz,CDCl3) data are shown in Table 4.
16 white powder of compound,(c=0.25, methanol), IR (KBr) νmax cm-1：3461,2934,
1735,1683,1462,1382,1260,1089,1044cm-1,UVλmax(methanol) nm (log ε):216(3.92),HR-ESI-MS
(positive)m/z:589.2532(calcd for C30H43O8ClNa, 589.2544), molecular formula C30H43O8Cl；1H-NMR
(600MHz,CDCl3) and13C-NMR(150MHz,CDCl3) data are shown in Table 4.
17 white powder of compound；(c=0.345 methanol), IR (KBr) νmax cm-1：3450,2962,
1734,1678,1461,1374,1249,1143,1117,1039cm-1,UVλmax(methanol) nm (log ε):213(3.80),HR-
ESI-MS(positive)m/z:585.3033(calcd for C31H46O9Na, 585.3040), molecular formula C31H46O9；1H-
NMR(600MHz,Pyridine-d5) and13C-NMR(150MHz,Pyridine-d5) data are shown in Table 5.
18 white powder of compound；(c=0.075, methanol)；IR(KBr)νmax cm-1：3433,2942,
1712,1640,1458,1376,1250,1115,1076,1043；ESI-TOF-MS(Positive)：m/z：584.3435
(calcd.for C30H50O10N 584.3435), molecular formula C30H46O10；1H-NMR(600MHz,Pyridine-d5) and13C-
NMR(150MHz,Pyridine-d5) data are shown in Table 5.
Embodiment 3：Antitumor activity of compound detection
Using MTT method, Activity determination is carried out to compound disclosed in this invention, with Human Prostate Cancer Cells (C4-2B
And 22Rvl), human renal carcinoma cell (786-0, A-498, Caki-2, ACHN), human melanoma cell (A375 and A375-S2) is
Example.
Take the 100 μ L of above-mentioned cell in logarithmic growth phase, every hole 2 × 104It is inoculated in 96 orifice plates, sets CO2Incubator
(37 DEG C, 5%CO2, saturated humidity) and culture.10 hole μ L/ of dosing after 12 hours, the working solution of sample are diluted to dense eventually with culture medium
Degree is respectively 10,5,2.5,1.25,0.625,0.3125,0.15625 μM, and sample-adding group and blank group are all provided with 3 multiple holes.Continue to train
After supporting 72 hours, MTT working solution is added, 20 holes μ L/ after 3 hours, discard culture medium, 150 hole μ L/ DMSO is added, and plate shakes
500rpm is shaked 3 minutes on bed, and the OD value in each hole is measured with microplate reader, and measurement wavelength is 490nm, calculates cell inhibitory effect
Rate, cell proliferation inhibition rate=(blank control group OD value-administration group OD value)/blank control group OD value × 100%.The above experiment
It is repeated three times, Activity Results (IC50) it is shown in Table 6.
The hydrogen spectrum and carbon modal data of 1 compound 1-4 of table
Note：Above compound used test solvent is deuterated pyridine；The hydrogen spectrum test of compound 1-4 is 600MHz, carbon spectrum
Test is 150MHz；* the data of 26S configurational isomer in a pair of of tautomer are expressed as.
The hydrogen spectrum and carbon modal data of 2 compound 5-8 of table
Note：5 used test solvent of above compound is deuterated chloroform, and 6,7 used test solvent of compound is deuterated pyridine,
8 used test solvent of compound is deuterated methanol；The hydrogen spectrum test of compound 5,6 is 600MHz, and the hydrogen spectrum test of compound 7 is
400MHz, the hydrogen spectrum test of compound 8 are 300MHz, and the carbon spectrum test of compound 5-7 is 150MHz, and the carbon of compound 8, which is composed, to be surveyed
Examination is 75MHz；* the data of 26S configurational isomer in a pair of of tautomer are expressed as.
The hydrogen spectrum and carbon modal data of 3 compound 9-12 of table
Note：Above compound 9-11 used test solvent is deuterated chloroform, and 12 used test solvent of compound is deuterated pyrrole
Pyridine；The hydrogen spectrum test of compound 9-12 is 600MHz, and the carbon spectrum test of compound 9 is 75MHz, and the carbon of compound 10-12, which is composed, to be surveyed
Examination is 150MHz；* the data of 26S configurational isomer in a pair of of tautomer are expressed as.
The hydrogen spectrum and carbon modal data of 4 compound 13-16 of table
Note：Above compound 13,14 used test solvents are deuterated pyridine, and compound 15,16 used test solvents are deuterium
For chloroform；The hydrogen spectrum test of compound 13,14,16 is 600MHz, and the carbon spectrum test of compound 15 is 75MHz, compound 14
Carbon spectrum test is 100MHz, and the carbon spectrum test of compound 13,16 is 150MHz；* it is expressed as 26S configuration in a pair of of tautomer
The data of isomers.
The hydrogen spectrum and carbon modal data of 5 compound 17-18 of table
Note：Above compound 17,18 used test solvents are deuterated pyridine；The hydrogen spectrum of compound 17,18, which is tested, is
The carbon spectrum test of 600MHz, compound 17,18 are 150MHz；* it is expressed as the number of 26S configurational isomer in a pair of of tautomer
According to.
Anti-tumor activity result (the IC of 6 compound of table50,μM)
It can be seen from Table 6 that compound disclosed by the invention has very good suppression to kinds of tumor cells proliferation
System activity, IC50Value is minimum up to 0.17 μM.By Structure-activity analysis it is found that containing when in compound structure of the present invention
Alpha, beta-unsaturated ketone group (i.e. R1For carbonyl, 2-3 are double bond) and/or 5 β, 6 beta epoxide group (i.e. R5With R4It is combined into group
B), and 4 have hydroxyl to replace (i.e. R3For hydroxyl) when, anti-tumor activity is substantially better than the compound without above-mentioned group.
Effective functional group that above-mentioned structure-activity relationship is related to belongs to compound characteristic structure of the present invention, while illustrating this
Inventing the compound is one of the effective component that plant straw berry tomato plays drug effect.
Antitumoral compounds provided by the present invention, its extracting method and its application are described in detail above.This
Specific embodiment is applied in text, and principle and implementation of the present invention are described, and the explanation of above embodiments is only used
Method and its central idea of the invention are understood in help.It should be pointed out that for those of ordinary skill in the art, not
, can be with several improvements and modifications are made to the present invention under the premise of being detached from the principle of the invention, these improvement and modification are also fallen into
The protection of the claims in the present invention.
Claims (9)
1. the antitumoral compounds being shown below or its optical isomer：
Above-mentioned each compound is isolated from the drying cauline leaf and/or fruit of straw berry tomato.
2. a kind of extracting method of compound as described in claim 1, which is characterized in that include the following steps：
The drying cauline leaf and/or fruit for using straw berry tomato for raw material, with volume fraction be 1-99% ethyl alcohol or methanol it is water-soluble
Liquid refluxing extraction 1-3 times is extracted 1-48 hours every time, and merging obtains extracting solution, and extracting solution removal solvent is obtained total medicinal extract；
Total medicinal extract is extracted with organic solvent, organic extract liquid is obtained, obtains organic solvent after organic extract liquid is concentrated
Layer medicinal extract；The organic solvent is one of methanol, ethyl alcohol, acetone, ethyl acetate, chloroform, petroleum ether and n-butanol or several
Kind；
Organic solvent layer medicinal extract is separated by chromatography, obtains compound as described in claim 1.
3. compound application in preparation of anti-tumor drugs as described in claim 1.
4. application as claimed in claim 3, which is characterized in that the tumour includes：Lung cancer, bronchiolar carcinoma, liver cancer, ovary
Cancer, cervix cancer, bladder cancer, carcinoma of testis, clear-cell carcinoma, cancer of pancreas, gastric cancer, osteocarcinoma, cancer of the esophagus, colon cancer, cholangiocarcinoma, forefront
Gland cancer, choriocarcinoma, melanoma, spongiocytoma, neurofibroma, fibrosarcoma or lymphangioma.
5. a kind of vegetable hair Calyx seu fructus physalis extract comprising compound as described in claim 1.
6. vegetable hair Calyx seu fructus physalis extract application in preparation of anti-tumor drugs as claimed in claim 5, which is characterized in that institute
Stating tumour includes：Lung cancer, bronchiolar carcinoma, liver cancer, oophoroma, cervix cancer, bladder cancer, carcinoma of testis, clear-cell carcinoma, cancer of pancreas,
Gastric cancer, osteocarcinoma, cancer of the esophagus, colon cancer, cholangiocarcinoma, prostate cancer, choriocarcinoma, melanoma, spongiocytoma, nerve fibre
Tumor, fibrosarcoma or lymphangioma.
7. a kind of pharmaceutical composition, which is characterized in that including one or more of compound described in claim 1.
8. a kind of pharmaceutical composition, which is characterized in that comprising compound described in claim 1 or its is pharmaceutically acceptable
Salt and pharmaceutically acceptable carrier and/or excipient.
9. composition application in preparation of anti-tumor drugs as claimed in claim 7 or 8, which is characterized in that the tumour
Including：Lung cancer, bronchiolar carcinoma, liver cancer, oophoroma, cervix cancer, bladder cancer, carcinoma of testis, clear-cell carcinoma, cancer of pancreas, gastric cancer, bone
Cancer, cancer of the esophagus, colon cancer, cholangiocarcinoma, prostate cancer, choriocarcinoma, melanoma, spongiocytoma, neurofibroma, fiber
Sarcoma or lymphangioma.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510991855.XA CN105777839B (en) | 2015-12-25 | 2015-12-25 | A kind of antitumoral compounds, its extracting method and its application |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510991855.XA CN105777839B (en) | 2015-12-25 | 2015-12-25 | A kind of antitumoral compounds, its extracting method and its application |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN105777839A CN105777839A (en) | 2016-07-20 |
| CN105777839B true CN105777839B (en) | 2018-11-23 |
Family
ID=56389977
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510991855.XA Active CN105777839B (en) | 2015-12-25 | 2015-12-25 | A kind of antitumoral compounds, its extracting method and its application |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105777839B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108047298B (en) * | 2017-11-07 | 2020-07-10 | 天津中医药大学 | Physalis pubescens glycoside, and extraction method and application thereof |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102516344A (en) * | 2011-11-14 | 2012-06-27 | 浙江大学 | Compound with antitumor activity and preparation method and application thereof |
-
2015
- 2015-12-25 CN CN201510991855.XA patent/CN105777839B/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102516344A (en) * | 2011-11-14 | 2012-06-27 | 浙江大学 | Compound with antitumor activity and preparation method and application thereof |
Non-Patent Citations (3)
| Title |
|---|
| Insect inhibitory steroidal saccharide esters from physalis peruviana;Anthony C. Waiss JR. et al.;《J.Nat. Prod.》;19931231;第56卷(第8期);第1365-1372页 * |
| Physapubescin B Exhibits Potent Activity against Human Prostate Cancer In Vitro and In Vivo;Wanjing Ding et al.;《Journal of Agricultural and Food Chemistry》;20150929;第63卷;第9505-9506页 * |
| 两种酸浆属植物中活性迈克尔反应受体分子的发现及作用靶点;季龙;《中国优秀硕士学位论文全文数据库 医药卫生科技辑》;20130515(第5期);第15-16页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN105777839A (en) | 2016-07-20 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101035548B (en) | Steroidal saponin pharmaceutical composition, the preparation method and use thereof | |
| CN101190258A (en) | Total sesquiterpene lactone extract containing rich parthenolide and preparation method and application thereof | |
| CN105294720A (en) | Dimerization chromone alkaloid compound as well as preparation method and application thereof | |
| Amer et al. | Novel aminoalkaloids from European mistletoe (Viscum album L.) | |
| Niu et al. | Main iridoid glycosides and HPLC/DAD-Q-TOF-MS/MS profile of glycosides from the antioxidant extract of Eucommia ulmoides Oliver seeds | |
| CN105348192A (en) | Antiviral-activity isoquinoline alkaloid compound in Cassia alata L. and preparation method of antiviral-activity isoquinoline alkaloid compound | |
| CN108003214A (en) | A kind of saponin compound and its methods and applications extracted from the rhizoma bolbostemmae | |
| CN105294623A (en) | Sesquiterpene lactone compound, preparation method and application thereof | |
| CN104817432A (en) | Anti-tumor drug of diterpenoid compound, and preparation method and application thereof | |
| Cheng et al. | Bioactive triterpenoids from the leaves and twigs of Lithocarpus litseifolius and L. corneus | |
| CN102070485B (en) | Method for separating and purifying active component aurantiamide acetate from traditional Chinese medicine clematis terniflora | |
| Shu et al. | Two new triterpenoids from Psidium guajava | |
| CN108358921A (en) | A kind of new indole alkaloids compound and its preparation method and application | |
| CN105777839B (en) | A kind of antitumoral compounds, its extracting method and its application | |
| CN101190259A (en) | Southern magnolia total lactone extract and preparation method and application thereof | |
| Vidal-Gutiérrez et al. | Antiproliferative activity of standardized phytopreparations from Ibervillea sonorae (S. Watson) Greene | |
| CN103191143B (en) | New application of cardiac glycoside compound | |
| CN111329866B (en) | Application of pentacyclic triterpenoid in preparation of anti-migraine medicine | |
| CN109180632B (en) | A method for preparing compound separated from radix Tripterygii Wilfordii | |
| CN113968869A (en) | Guaiane sesquiterpene lactone compound Artemvulactone and preparation method and application thereof | |
| CN103509077B (en) | Triterpene saponin componds and its production and use | |
| CN108478619B (en) | Convolvulus arvensis total resin glucoside extract, preparation method and medical application thereof | |
| CN101851271A (en) | Glaucocalyxin D derivative, preparation method and application thereof | |
| RU2776898C1 (en) | Method for producing myricitrin from the bark of eastern black walnut, exhibiting neurotropic activity | |
| CN109970839A (en) | Triterpene saponin componds and preparation method thereof and medical usage |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |