CN1298731C - Antineoplastic comound, Preparation and medicine composition with compound as active ingredient - Google Patents
Antineoplastic comound, Preparation and medicine composition with compound as active ingredient Download PDFInfo
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- CN1298731C CN1298731C CN 200410040506 CN200410040506A CN1298731C CN 1298731 C CN1298731 C CN 1298731C CN 200410040506 CN200410040506 CN 200410040506 CN 200410040506 A CN200410040506 A CN 200410040506A CN 1298731 C CN1298731 C CN 1298731C
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Abstract
The present invention relates to novel 2'-O-acetylcimigenol-3-O- alpha -L-arabinopyranoside and 25-O-diacetyleimigenol-3-O-a-L-arabinopyranoside, a preraration method thereof, a medical composition which uses the compound as active constituents and the application in medicine for treating ascitic tumors, gastric cancer and breast cancer.
Description
Technical field:
The present invention relates to novel cimigenol-3-O-α-L-(2 '-O-acetyl) arabopyranose glucoside (2 '-O-acetylcimigenol-3-O-α-L-arabinopyranoside) and 25-acetyl-cimigenol-3-O-α-L-(2 '-O-acetyl) arabopyranose glucoside (2 ', 25-O-diacetylcimigenol-3-O-α-L-arabinopyranoside), its preparation method, with this compound is the pharmaceutical composition of activeconstituents, and their application in the medicine of treatment ascitic tumor, cancer of the stomach, mammary cancer.
Background technology:
Rattletop is a famous Chinese medicine very commonly used, is mainly the dry rhizome of ranunculaceae plant three leaf rattletop Cimicifugaheracleifolia Kom, the rattletop C.dahurica Maxim of Xingan, rattletop or RHIIZOMA CIMICIFUGAE C.foetida L..Rattletop has the promoting eruption of delivering, and is clearing heat and detoxicating, the effect of elevate a turnable ladder yang-energy; Often be used to headache due to pathogenic wind-heat, dentalgia, aphtha, swelling and pain in the throat, measles without adequate eruption, the sun poison is sent out spot, prolapse of the anus, illnesss such as uterine prolapse.Rattletop Cimicifuga foetida L. mainly originates in ground such as Yunnan, Guizhou, Sichuan, Hubei, is the conventional Chinese medicine material of a large amount of cultivations.So far, do not see in the prior art novel cimigenol-3-O-α-L-(2 '-O-acetyl) arabopyranose glucoside is arranged (2 '-O-acetylcimigenol-3-O-α-L-arabinopyranoside) and 25-acetyl-cimigenol-3-O-α-L-(2 '-O-acetyl) arabopyranose glucoside (2 ', the report of compound of 25-O-diacetylcimigenol-3-O-α-L-arabinopyranoside) does not see that more having with this compound is the report of the pharmaceutical composition of activeconstituents.
Summary of the invention:
The object of the present invention is to provide a class have on new the novelty of pharmaceutical use cimigenol-3-O-α-L-(2 '-O-acetyl) arabopyranose glucoside (2 '-O-acetylcimigenol-3-O-α-L-arabinopyranoside) and 25-acetyl-cimigenol-3-O-α-L-(2 '-O-acetyl) arabopyranose glucoside (2 ', the compound of 25-O-diacetylcimigenol-3-O-α-L-arabinopyranoside).
Another object of the present invention provides a kind of method of extracting The compounds of this invention from the rattletop plant.
Further aim of the present invention provides a kind of pharmaceutical composition for the treatment of ascitic tumor, cancer of the stomach, mammary cancer.
Another object of the present invention provides above-claimed cpd and the purposes of composition aspect the medicine of preparation treatment ascitic tumor, cancer of the stomach, mammary cancer.
In order to realize above-mentioned purpose of the present invention, the invention provides following technical scheme:
Antineoplastic compound cimigenol-3-O-α-L-(2 '-O-acetyl) arabopyranose glucoside shown in the following structural formula (2 '-O-acetylcimigenol-3-O-α-L-arabinopyranoside) and 25-acetyl-cimigenol-3-O-α-L-(2 '-O-acetyl) arabopyranose glucoside (2 ', 25-O-diacetylcimigenol-3-O-α-L-arabinopyranoside)
The chemical structure of cimigenol-3-O-α-L-(2 '-O-acetyl) arabopyranose glucoside compound:
R＝2′-O-acetyl-O-arabinoyl
The chemical structure of 25-acetyl-cimigenol-3-O-α-L-(2 '-O-acetyl) arabopyranose glucoside compound:
R＝2′-O-acetyl-O-arabinoyl
The preparation method of The compounds of this invention comprises and gets rattletop Cimicifuga foetida L. rhizome, pulverizes the back with methanol extraction three times, each about 4 hours; After methanol extract liquid removes by filter the dregs of a decoction, be evaporated to steaming and do not go out methyl alcohol; Add again after a certain amount of water dilution, use petroleum ether extraction 2-3 time, behind the recovery sherwood oil, concentrate and obtain the Petroleum ether extraction position; Water layer is used ethyl acetate extraction 2-3 time more then, reclaim ethyl acetate, concentrate and obtain the ethyl acetate extraction position, separate with silica gel column chromatography at ethyl acetate extraction position (2-5 time) repeatedly, the elutriant chloroform: methyl alcohol (or chloroform/acetone) gradient elution, wash-out obtain compound cimigenol-3-O-α-L-(2 '-O-acetyl) arabopyranose glucoside; From the separated part close,, obtain compound 25-acetyl-cimigenol-3-O-α-L-(2 '-O-acetyl) arabopyranose glucoside again through the ODS column chromatography for separation with compound cimigenol-3-O-α-L-(2 '-O-acetyl) arabopyranose glucoside polarity.
The compounds of this invention cimigenol-3-O-α-L-(2 '-O-acetyl) arabopyranose glucoside (hereinafter to be referred as K-5) has the activity of very significant anti-mouse ehrlich ascites tumor cell strain (EAC), IC
50Be 0.35 μ g/mL; Compound 25-acetyl-cimigenol-3-O-α-L-(2 '-O-acetyl) arabopyranose glucoside (hereinafter to be referred as K-6) has the activity of very significant anti-mouse ehrlich ascites tumor cell strain (EAC), IC equally
50Be 0.14 μ g/mL; Particularly the cytotoxic activity of compound K-6 has surpassed positive control cancer therapy drug cis-platinum commonly used, and cis-platinum also has remarkable activity, IC to mouse ehrlich ascites tumor cell strain (EAC)
50Be 0.31 μ g/mL.
The pharmaceutical composition that is used for the treatment of ascitic tumor, cancer of the stomach, mammary cancer of the present invention contains claim 1 compound and the pharmaceutically acceptable carrier for the treatment of significant quantity.
Compound of the present invention and composition can be used for preparing the medicine of treatment ascitic tumor, cancer of the stomach, mammary cancer.
Pharmaceutically acceptable carrier mentioned above is meant the pharmaceutical carrier of pharmaceutical field routine, for example: thinner, vehicle such as water etc., weighting agent such as starch, sucrose etc.; Tamanori such as derivatived cellulose, alginate, gelatin and polyvinylpyrrolidone; Wetting agent such as glycerine; Disintegrating agent such as agar, lime carbonate and sodium bicarbonate; Absorption enhancer such as quaternary ammonium compound; Tensio-active agent such as cetyl alcohol; Absorption carrier such as kaolin and soap clay; Lubricant such as talcum powder, calcium stearate and magnesium and and polyoxyethylene glycol etc.Can also in composition, add other assistant agents such as flavouring agent, sweeting agent etc. in addition.
The compounds of this invention can composition form by oral, snuffing is gone into, the mode of rectum or administered parenterally is applied to the patient who needs this treatment.Be used for when oral, can be made into conventional solid preparation such as tablet, pulvis, granula, capsule etc., make liquid preparation such as water or oil-suspending agent or other liquid preparations such as syrup, elixir etc.; When being used for administered parenterally, can be made into solution, water or the oiliness suspension agent etc. of injection.Preferred form is tablet, capsule and injection.
The various formulations of pharmaceutical composition of the present invention can be according to the conventional production method preparation of pharmaceutical field.Activeconstituents is mixed with one or more carriers, be made into required formulation then.
It is 0.1%～99.5% activeconstituents that pharmaceutical composition of the present invention preferably contains weight ratio, most preferably contains weight ratio and be 0.5%～95% activeconstituents.
The amount of application of The compounds of this invention can be according to variations such as the type of route of administration, patient's age, body weight, the disease of being treated and severity, and its per daily dose can be 0.01～10mg/kg body weight, preferred 0.1～5mg/kg body weight.Can use by one or many.
Embodiment:
The following examples can make those skilled in the art more fully understand the present invention, but do not limit the present invention in any way.
Embodiment 1:
Cimigenol-3-O-α-L-(2 '-O-acetyl) arabopyranose glucoside (2 '-O-acetylcimigenol-3-O-α-L-arabinopyranoside) preparation of (K-5)
The dry rhizome 2.5Kg of rattletop Cimicifuga foetida L. is pulverized back methanol extraction three times, each about 4 hours; After methanol extract liquid removes by filter the dregs of a decoction, be evaporated to steaming and do not go out methyl alcohol; Add again after a certain amount of water dilution, use petroleum ether extraction three times, behind the recovery sherwood oil, concentrate and obtain 187g Petroleum ether extraction position; Water layer is used ethyl acetate extraction three times more then, reclaims ethyl acetate, concentrates and obtains 214.5g ethyl acetate extraction position.214.5g separate with the 1000g silica gel column chromatography at the ethyl acetate extraction position, the elutriant chloroform: methyl alcohol was from 100: 0; 100: 1; 50: 1; 20: 1 to 1: 1 gradient elutions, the heavily about 13.5g of position Fr.3 that obtains by 50: 1 elutriant wash-outs of chloroform/methanol.This separated part 13.5g Fr.3 separates once more with the 300g silica gel column chromatography, and continue with the elutriant chloroform: methyl alcohol was from 80: 1; 60: 1; 50: 1 gradient elutions, by chloroform: the part that 80: 1 elutriant wash-outs of methyl alcohol obtain obtains the heavily about 124mg of separated part Fr.3.1 after concentrating.This separated part 124mg Fr.3.1 separates once more with the 80g silica gel column chromatography, and continue with the elutriant chloroform: methyl alcohol obtains two compound Ks-5 (21mg) successively from 90: 1 wash-outs, K-7 (80mg).
K-5 compound: C
37H
58O
10, white powder, mp 143-145 ℃, [α]
D=25.0 ° (c 0.80, MeOH).High resolution mass spectrum (HRFABMS) is 661.3944[M-H-OAc (m/z)]
-(calculated value C
35H
55O
9, 619.3846).
Hydrogen nuclear magnetic resonance spectrum data δ (ppm): 4.31 (1H, m, 15-H), 3.44 (1H, dd, J=9.3,3.5Hz, 3-H), 2.25 (2H, m) 1.86 (1H, dd, J=2.8,10.7Hz) (2-H); 2.07 (1H, m) 1.02 (1H, m) (11-H); 1.67 (1H, m) 1.56 (1H, m) (12-H); 1.66 (1H, m) 0.70 (1H, dd, J=9.6,10.2Hz) (6-H); 1.65 (1H, m, 20-H), 1.64 (1H, m, 8-H), 1.53 (1H, m) 1.16 (1H, m) (1-H); 1.52 (1H, m) 1.12 (1H, m) 7-H); 1.50 (1H, m, 17-H), 1.28 (1H, dd, J=3.5,9.3Hz, 5-H); 1.12 (3H, s, 18-H), 0.46 (1H, d, J=2.8Hz) 0.22 (1H, d, J=3.1Hz) (19-H); 0.85 (3H, d, J=5.1Hz, 21-H), 1.44 (3H, s, 26-H), 1.47 (3H, s, 27-H), 1.18 (3H, s, 28-H), 1.05 (3H, s, 29-H), 0.93 (3H, s, 30-H).COCH
3Part: 2.11 (3H, s, 2 '-COCH
3).Pectinose part: 4.73 (1H, d, J=6.2Hz, 1 '-H), 5.90 (1H, t, J=6.7Hz, 2 '-H), 4.17 (1H, dd, J=2.7,7.6Hz, 3 '-H), 4.26 (1H, m, 4 '-H), 3.74 (2H, m, 5 '-H).
Nuclear magnetic resonance of carbon spectrum data δ (ppm): 112.0 (s, 16-C), 90.2 (d, 24-C), 88.3 (d, 3-C), 80.3 (d, 15-C), 71.3 (d, 23-C), 71.0 (s, 25-C), 59.6 (d, 17-C), 48.7 (d, 8-C), 47.5 (d, 5-H), 47.4 (s, 14-C), 41.9 (s, 13-C), 41.1 (s, 4-C), 38.2 (t, 22-C), 34.2 (t, 12-C), 32.3 (t, 1-C), 30.8 (t, 19-C), 30.0 (t, 2-C), 27.2 (q, 26-C), 26.6 (s, 10-C), 26.5 (t, 7-C), 26.3 (t, 11-C), 25.4 (q, 27-C), 25.4 (q, 29-C), 24.1 (d, 20-C), 21.1 (t, 6-C), 20.1 (s, 9-C), 19.6 (q, 18-C), 19.6 (q, 21-C), 15.3 (q, 30-C), 11.8 (q, 28-C).2 '-COCH3 part: 170.2 (s, CO), 21.4 (q, COCH3).Pectinose part: 104.5 (s, 1 '-C), 74.4 (d, 2 '-C), 72.5 (d, 3 '-C), 69.8 (d, 4 '-C), 67.3 (t, 5 '-C).
Ir data IR (KBr) υ max:3443; 2963,2934,2870,1739,1735,1457,1239,1070cm
-1
The chemical structure of K-5 compound:
R＝2′-O-acetyl-O-arabinoyl
The chemical structure of compound K-5 is: cimigenol-3-O-α-L-(2 '-O-acetyl) arabopyranose glucoside (2 '-O-acetylcimigenol-3-O-α-L-arabinopyranoside)
Embodiment 2
25-acetyl-cimigenol-3-O-α-L-(2 '-O-acetyl) arabopyranose glucoside (2 ', the 25-O-diacetylcimigenol-3-O-α-L-arabinopyranoside) preparation of (K-6)
The dry rhizome 2.5Kg of rattletop Cimicifuga foetida L. is pulverized back methanol extraction three times, each about 4 hours; After methanol extract liquid removes by filter the dregs of a decoction, be evaporated to steaming and do not go out methyl alcohol; Add again after a certain amount of water dilution, use petroleum ether extraction three times, behind the recovery sherwood oil, concentrate and obtain 187g Petroleum ether extraction position; Water layer is used ethyl acetate extraction three times more then, reclaims ethyl acetate, concentrates and obtains 214.5g ethyl acetate extraction position.214.5g separate with the 1000g silica gel column chromatography at the ethyl acetate extraction position, the elutriant chloroform: methyl alcohol was from 100: 0; 100: 1; 50: 1; 20: 1 to 1: 1 gradient elutions, the heavily about 13.5g of position Fr.3 that obtains by 50: 1 elutriant wash-outs of chloroform/methanol.R.3, this separated part 13.5g F separates once more with the 300g silica gel column chromatography, and continue with the elutriant chloroform: methyl alcohol was from 80: 1; 60: 1; 50: 1 gradient elutions, by chloroform: the part that 80: 1 elutriant wash-outs of methyl alcohol obtain obtains the heavily about 124mg of separated part Fr.3.1 after concentrating.This separated part 124mg Fr.3.1 separates once more with the 80g silica gel column chromatography, and continue with the elutriant chloroform: methyl alcohol obtains two compound Ks-5 (21mg) successively from 90: 1 wash-outs, K-7 (80mg).By chloroform: the part that 60: 1 elutriant wash-outs of methyl alcohol obtain obtains the heavily about g of separated part Fr.3.2 after concentrating.By chloroform: the part that 50: 1 elutriant wash-outs of methyl alcohol obtain obtains the r.3.3 heavily about 221mg of separated part F after concentrating.Separated part 221mg Fr.3.3 separates once more with the 30gODS reversed-phase silica gel column chromatography, uses methyl alcohol: 80: 20 wash-outs of water obtain compound K-6 (17mg), and K-14 (70mg).
K-6 compound: C
39H
60O
11, white powder, mp 157-159 ℃, [α]
D=41.1 ° (c 0.75, MeOH).High resolution mass spectrum (HRFABMS) is 661.3944[M-H-OAc (m/z)]
-(calculated value C
37H
57O
10,
661.3951)。
Hydrogen nuclear magnetic resonance spectrum data δ (ppm): 4.26 (1H, m, 15-H), 3.36 (1H, dd, J=9.3,3.5Hz, 3-H), 2.24 (2H, and m) 1.85 (1H, m, 10.7Hz, 2-H), 2.11 (1H, m) 1.17 (1H, m) (11-H); 1.67 (1H, m) 1.56 (1H, m) (12-H); 1.66 (1H, m) 0.70 (1H, dd, J=9.6,10.2Hz) (6-H); 1.67 (1H, m, 20-H), 1.67 (1H, m, 8-H), 1.50 (1H, m) 1.20 (1H, m) (1-H); 2.08 (1H, m) 1.16 (1H, m) (7-H); 1.44 (1H, d, J=11.0Hz, 17-H), 1.28 (1H, dd, J=3.8,12.1Hz, 5-H); 1.13 (3H, s, 18-H), 0.46 (1H, d, J=3.4Hz) 0.22 (1H, d, J=3.8Hz) (19-H).COCH
3Part: 2.09 (3H, s, 2 '-COCH
3), 1.95 (3H, s, 25-COCH
3); 0.84 (3H, d, J=6.4Hz, 21-H), 1.67 (3H, s, 26-H), 1.65 (3H, s, 27-H), 1.17 (3H, s, 28-H), 1.07 (3H, s, 29-H), 0.95 (3H, s, 30-H).Pectinose part: 5.16 (1H, d, J=7.7Hz, 1 '-H), 5.89 (1H, dd, J=7.8,9.2Hz, 2 '-H), 4.16 (1H, dd, J=3.2,12.7Hz, 3 '-H), 4.27 (1H, m, 4 '-H), 4.25 (2H, m, 5 '-H).
Nuclear magnetic resonance of carbon spectrum data δ (ppm): 112.5 (s, 16-C), 86.8 (d, 24-C), 88.7 (d, 3-C), 80.2 (d, 15-C), 71.7 (d, 23-C), 83.2 (s, 25-C), 59.4 (d, 17-C), 48.7 (d, 8-C), 47.5 (d, 5-H), 47.2 (s, 14-C), 41.8 (s, 13-C), 41.8 (s, 4-C), 37.9 (t, 22-C), 34.0 (t, 12-C), 32.3 (t, 1-C), 30.9 (t, 19-C), 30.9 (t, 2-C), 24.0 (q, 26-C), 26.3 (s, 10-C), 26.6 (t, 7-C), 26.5 (t, 11-C), 21.5 (q, 27-C), 22.3 (q, 29-C), 23.4 (d, 20-C), 21.4 (t, 6-C), 20.1 (s, 9-C), 19.6 (q, 18-C), 19.6 (q, 21-C), 15.3 (q, 30-C), 11.9 (q, 28-C).COCH3 part: 170.2 (s, 2 '-CO), 21.4 (q, 2 ' COCH
3), 170.1 (s, 5-CO), 22.3 (q, 25-COCH
3).Pectinose part: 104.5 (s, 1 '-C), 74.4 (d, 2 '-C), 72.5 (d, 3 '-C), 69.8 (d, 4 '-C), 67.3 (t, 5 '-C).
Ir data IR (KBr) ν max:3444,2961,2936,1739,1313,1200,1166,604cm
-1
The chemical structure of K-6 compound:
R＝2′-O-acetyl-O-arabinoyl
The chemical structure of compound K-6 is: 25-acetyl-cimigenol-3-O-α-L-(2 '-O-acetyl) arabopyranose glucoside (2 ', 25-O-diacetylcimigenol-3-O-α-L-arabinopyranoside)
Embodiment 3
Tablet: activeconstituents 10mg lactose 180mg starch 55mg Magnesium Stearate 5mg
The preparation method: activeconstituents, lactose and starch are mixed, and water is evenly moistening, the mixture after moistening is sieved and drying, after sieve, adds Magnesium Stearate, then with the mixture compressing tablet, and every heavy 250mg, active component content is 10mg.
Embodiment 4
Ampulla: activeconstituents 2mg sodium-chlor 10mg
Preparation method: activeconstituents and sodium-chlor are dissolved in the proper amount of water for injection, filter gained solution, in the ampoule of under aseptic condition, packing into.
Embodiment 5
Capsule: activeconstituents 10mg lactose 187mg Magnesium Stearate 3mg
The preparation method: activeconstituents is mixed with auxiliary agent, sieve, uniform mixing, the mixture that the obtains hard gelatin capsule of packing into, the heavy 200mg of each capsule, active component content is 10mg.
Embodiment 6
The anti-tumor biological effect of embodiment 1 and embodiment 2 compounds
The anti-tumor biological measuring method:
The MMT method of improvement is adopted in the evaluation of anti-tumor activity.The MMT method is a kind of external antitumour activity evaluation method that comes into one's own day by day, and this method objectivity is strong, can realize semi-automation, and it is easy to participate in method than isotropic substance nucleic acid precursor.But this fado as lysate, made the reduzate of MMT with acidifying Virahol equal solvent in the past--the dissolving of-Jia Za and protein precipitation etc. is very incomplete, causes steps such as changing nutrient solution and violent jolting loaded down with trivial details, and result's reliability also decreases.Zhou Jianjuns etc. are at some defectives of MMT method, done further improvement, Zhou JJ, Yue XF, Han JX et al.ImprovedMTT assay for activity of antitumor agents.Chin J Pharm (Chinese Journal of Pharmaceuticals) 1993,24 (10): 455-457.The MMT method of improvement has adopted three strong lysates of solvency action, can not resemble in the original method, add before the MMT, need the nutrient solution that suction is abandoned or centrifugal removal replacing is original, reach and remove wherein composition such as serum protein in order to avoid cause interference, also needn't be after adding MMT generation Jia Za, thermal agitation culture plate hydrotropy.So not only operate loaded down with trivial detailsly, change the cell that nutrient solution will lose 20-30%.The modification method of Zhou Jianjun etc. has been simplified operation, has also improved reliability, is more suitable for in-vitro screening and drug sensitive detection in the significant antitumor medicine.Thereby the MMT method of improvement is adopted in the experiment of the anti-tumor activity in this patent.
Material and method
Prepare before the test
Sample is dissolved into 10 milligrams every milliliter concentration and is preserved as stock solution and under 4 degrees centigrade of dark with methyl-sulphoxide.The stock solution of sample is diluted to experimental concentration with non-immune salt solution before use.
Cell is arranged and is cultivated
Mouse ehrlich ascites tumor cell strain, human stomach cancer cell line and human breast cancer cell strain are to collect the center from the US mode bacterial classification.All cells are grown in the RPMI-1640 medium, add the immune serum of the non-activity of 10% thermal inactivation, and 2 receive the L-glutaminate that rubs, 100 penicillin of tiring, the HEPES that 10 millis of the Streptomycin sulphate of 100ug/ml and PH7.4 rub.Cell is stored under 37 degrees centigrade, the moist 5%CO that contains
2Incubator in.
Cell growth-inhibiting method
Sample is cultivated the tetrazolium analytical method to the growth-inhibiting of tumour cell by trace and is measured, and has only less adjustment.Simply, the adherent tumour cell is seeded the micro-culture dish in 96 holes, makes its adhesion 24 hours before adding medicament, and suspension cell is sowing before medicine adds.Each tumour cell be listed in different steps (adhesive cell is 72 hours, and suspension cell is 48 hours) add 5 concentration (0.01,0.1,1,10, sample 100mg/ml), and each concentration triplicate.Join the MTT of 5mg/ml in each hole the latter stage after adding sample, and culture dish is placed under 37 degrees centigrade the condition and cultivated 4 hours, and then adding three-phase mixing solutions (10% SDS, the hydrochloric acid that 5% Virahol and 0.012 rubs), again culture dish being placed on 37 degrees centigrade cultivated 12-20 hour down.On the sensitization mirror of 570 nanometers, read optical density(OD).Sample is to use IC to the cytotoxicity of tumour
50Value is expressed, and calculates with the LOGIT method.
Table 1 compound K-5, K-6 sample are to the inhibiting rate of tumour cell:
EAC: mouse ehrlich ascites tumor cell strain;
SGC-7901: human stomach cancer cell line;
A231: human breast cancer cell strain.
The measurement result of anti-tumor biological:
Table 2 compound K-5, K-6 is to the cytotoxic activity of mouse ehrlich ascites tumor cell strain (EAC), human stomach cancer cell line (SGC7901) and human breast cancer cell strain (A231)
| Test compound | Molecular weight (MW) | IC 50(μg/mL) EAC | SGC7901 | A231 |
| Compound K-5 compound K-6 cis-platin (positive control, cis-platinum) | 662 704 | 0.35 0.14 0.31 | 10～100 10～100 0.17 | 4.46 7.19 0.87 |
From table 1 and table 2 as can be seen compound K-5 have the activity of very significant anti-mouse ehrlich ascites tumor cell strain (EAC), IC
50Be 0.35 μ g/mL; Compound K-6 has the activity of very significant anti-mouse ehrlich ascites tumor cell strain (EAC), IC equally
50Be 0.14 μ g/mL; Particularly the cytotoxic activity of compound K-6 has surpassed positive control cancer therapy drug cis-platinum commonly used, and cis-platinum also has remarkable activity, IC to mouse ehrlich ascites tumor cell strain (EAC)
50Be 0.31 μ g/mL.But the cytotoxic activity of compound K-5, compound K-6 pair human stomach cancer cell line (SGC7901) and human breast cancer cell strain (A231) then than a little less than the commonly used cancer therapy drug cis-platinum of positive control some.Thus can compound K-5, the anti-tumor activity of K-6 has certain singularity on target spot, be very significant antineoplastic compound.
Claims (4)
1, the cimigenol of the antineoplastic compound shown in the following structural formula-3-O-α-L-(2 '-O-acetyl) arabopyranose glucoside and 25-acetyl-cimigenol-3-O-α-L-(2 '-O-acetyl) arabopyranose glucoside:
The chemical structure of cimigenol-3-O-α-L-(2 '-O-acetyl) arabopyranose glucoside compound:
R=2 '-ethanoyl-arabopyranose base
The chemical structure of 25-acetyl-cimigenol-3-O-α-L-(2 '-O-acetyl) arabopyranose glucoside compound:
R=2 '-ethanoyl-arabopyranose base.
2, the preparation method of claim 1 compound, this method comprise and get rattletop Cimicifuga foetida L. rhizome, pulverizes the back with methanol extraction three times, each 4 hours; After methanol extract liquid removes by filter the dregs of a decoction, be evaporated to steaming and do not go out methyl alcohol; Add again after a certain amount of water dilution, use petroleum ether extraction 2-3 time, behind the recovery sherwood oil, concentrate and obtain the Petroleum ether extraction position; Water layer is used ethyl acetate extraction 2-3 time more then, reclaims ethyl acetate, concentrate and obtain the ethyl acetate extraction position, the ethyl acetate extraction position repeatedly 2-5 time with the silica gel column chromatography separation, the elutriant chloroform: methyl alcohol was from 100: 0; 100: 1; 50: 1; 20: 1 to 1: 1 gradient elutions, by chloroform: separate once more with silica gel column chromatography at the position that 50: 1 wash-outs of methyl alcohol obtain, and continue to use chloroform: methyl alcohol was from 80: 1; 60: 1; 50: 1 gradient elutions, by chloroform: the part that 80: 1 wash-outs of methyl alcohol obtain is separated once more with silica gel column chromatography, and continue use chloroform: 90: 1 wash-outs of methyl alcohol must compound K-5 be cimigenol-3-O-α-L-(2 '-O-acetyl) arabopyranose glucoside; From the separated part close with compound cimigenol-3-O-α-L-(2 '-O-acetyl) arabopyranose glucoside polarity, through reversed material ODS column chromatography for separation, getting compound K-7 is 25-acetyl-cimigenol-3-O-α-L-(2 '-O-acetyl) arabopyranose glucoside again.
3, the pharmaceutical composition that is used for the treatment of ascitic tumor, cancer of the stomach, mammary cancer wherein contains claim 1 compound and the pharmaceutically acceptable carrier for the treatment of significant quantity.
4, the application of claim 1 compound in the medicine of preparation treatment ascitic tumor, cancer of the stomach, mammary cancer.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410040506 CN1298731C (en) | 2004-08-19 | 2004-08-19 | Antineoplastic comound, Preparation and medicine composition with compound as active ingredient |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410040506 CN1298731C (en) | 2004-08-19 | 2004-08-19 | Antineoplastic comound, Preparation and medicine composition with compound as active ingredient |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1613867A CN1613867A (en) | 2005-05-11 |
| CN1298731C true CN1298731C (en) | 2007-02-07 |
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| Application Number | Title | Priority Date | Filing Date |
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| CN 200410040506 Expired - Fee Related CN1298731C (en) | 2004-08-19 | 2004-08-19 | Antineoplastic comound, Preparation and medicine composition with compound as active ingredient |
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| Country | Link |
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| CN (1) | CN1298731C (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101570563B (en) * | 2009-06-05 | 2011-11-23 | 中国科学院昆明植物研究所 | Altin alkyl-type triterpenoids, pharmaceutical composition, preparation method and application thereof |
| CN102614208B (en) * | 2012-02-25 | 2013-09-18 | 中国科学院昆明植物研究所 | Application of compound (20R,24R)-24,25-16,23-23,27-triepoxy-12-acetoxyl-9,19-cyclolanostanol-3-O-beta-D xylopyranoside in pharmacy |
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2004
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