CN1089945A - Anti-cancer medicine inula helianthus-aquatica lactone - Google Patents
Anti-cancer medicine inula helianthus-aquatica lactone Download PDFInfo
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- CN1089945A CN1089945A CN 93100687 CN93100687A CN1089945A CN 1089945 A CN1089945 A CN 1089945A CN 93100687 CN93100687 CN 93100687 CN 93100687 A CN93100687 A CN 93100687A CN 1089945 A CN1089945 A CN 1089945A
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- lactone
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- sunflower
- chloroform
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Abstract
Anti-cancer medicine inula helianthus-aquatica lactone.This medicine is a kind of white, needle-shaped crystals, 187-189 ℃ of fusing points, molecular formula C
17H
22O
5, molecular weight 306 is soluble in chloroform, is slightly soluble in ether, in sherwood oil and the alcohol.This medicine all has tangible lethal effect and growth-inhibiting effect to cancer cells such as people's lung, stomach, intestines, uterine neck, nasopharynx, bladder and leukemia cell.Aquatic-sunflower lactone provided by the invention is the PTS of international initiative, has to have good stability, and cancer suppressing action is strong, and toxicity is little, can try out in clinical, is a kind of cancer therapy drug with fine DEVELOPMENT PROSPECT.
Description
The present invention relates to a kind of chemical ingredients of medicine, specifically is a kind of chemical ingredients of cancer therapy drug.
Cancer is the fiendish enemy who threatens the human life, and people are seeking effective medicine always for a long time, but do not search out good effect as yet and the little medicine of side effect so far.
The object of the present invention is to provide a kind of curative effect height, cancer therapy drug safe in utilization.
Cancer therapy drug name provided by the invention is called flower of Aquatic-sunflower Inula lactones (abbreviation compd A), and its chemical structure is:
This medicine is a kind of white, needle-shaped crystals, fusing point 187-189 ℃, and molecular formula C
17H
22O
5Molecular weight 306 is soluble in chloroform, is dissolved in ether, sherwood oil and the alcohol of heat slightly soluble when cold.Be dissolved in alkali lye, add acid out and go out, Lei Mengde (Raymond) reagent is purple.Salt acid amide reacting positive.210nm has maximum absorption in ultraviolet.Infrared have ester and lactone and cyclopentanone absorption peak (1785,1735,1710,1670Cm
-1).HNMR reaches
13C NMR DEPT spectrum shows 17 carbon and 22 hydrogen atom signals, by three methyl (one is acyl group), four methylene radical (one of them is terminal thiazolinyl); five methynes (wherein two combine with oxygen); and five quaternary carbons (a ketone carbon, two ester carbon, an olefinic carbon) are formed.Mass spectrum has provided 306 molecular weight, and pointing out this medicine is the sesqui terpene lactones.
1, the position of ethanoyl
After hydrolysis, the hydrolyzate Aa that gets deacetylate checks not had the acetyl base peak and hydroxyl peak (3490-3380 is strong) occurred through IR figure with compound.The nucleus magnetic resonance figure of Aa and A is found that relatively σ 5.51Hd moves to σ 4.15ppm to High-Field, and appearance can be by the hydroxyl peak σ 4.71HBr of heavy water conversion.Through the test of uncoupling, when irradiation σ 5.51HD peak, simplifying appears in σ 3.05ppm peak.When irradiation 3.05 peaks, changing all appears in peaks such as σ 4.5,5.5,5.9,6.15, thereby determines that ethanoyl is positioned at the C6 position, and the terminal thiazolinyl of σ 5.9,6.15 is positioned on the lactone ring C11 position.From C6 position hydrogen peak shape be the d peak as can be known the C5 position be quaternary carbon.
2, the position of ketone group
13C NMR spectrum has provided the ketone carbon peak of σ-218.2, IR(1735Cm
-1) prompting has cyclopentanone in the molecule, therefore ketone group should be on the A ring, unimodal and coupling relation and the complexity supposition ketone group that splits branch be on the C3 position from the no 2H of hydrogen spectrum, and may be positioned on C2 or the C4, tests from uncoupling and know that the chemical shift of A ring hydrogen is all between σ 1.25-σ 2.23.When shining the methyl peak of σ 1.17, change all appears simplifying in peaks such as σ 1.5,1.7,2.3.And during the σ 5.5 of irradiation C8 position, do not have change substantially with the superiors.Compare A and approximate thing (1. chemical journal 41(3) again: 254,1983; 2.J, arg, chem 39(14): 2013,1974; 3.J, arg, chem 46:1356,1981:4.C.A 81:63800d, 1974) carbon spectrum find that the chemical shift of compd A C5 position by low field, is σ 56.06.Show C5 except that being subjected to C6 position hydroxyl influences, neighbouring also have the group that influence is bigger.And the chemical shift of C1 position is σ 46.66, and therefore the compound displaced phase of not having a replacement with the C2 position seemingly think that ketone group is positioned at the C4 position.
3, mass spectrum, ultraviolet, infrared, it is as shown in the table for the nuclear-magnetism test data:
Table 1, ultra-violet absorption spectrum absorption peak and parsing tabulation
Table 2, infrared absorption spectrum absorption peak and parsing tabulation
| Absorption peak wave number Cm -1 | Absorption peak strength | Group and resonance-type | Remarks |
| 1765 1735 1710 1670 1460 1410 1280 1252 | Strong strong and weak weak strong | The two key gamma lactone OAC of gamma lactone cyclopentanone OAC | KBr |
Table 3 hydrolyzate Aa infrared absorption spectrum absorption peak and parsing tabulation
| Absorption peak wave number Cm -1 | Absorption peak strength | Group and resonance-type | Remarks |
| 3540－3300 1765 1730 1625 1455 1400 1260 1240 | Qiang Qiangqiang is strong | OH gamma lactone cyclopentanone | KBr |
The absorption peak of table 4, hydrolyzate Aa ultra-violet absorption spectrum and parsing tabulation
Table 5, hydrolyzate Aa's
13C nucleus magnetic resonance resolution table (400MHz heavy hydrogen pyridine)
The proton nmr spectra resolution table of table 6, compd A
Instrument: Bruker-400 solvent: chloroform
The mass-spectrometric data of table 7, compd A and resolution table
Table 8, hydrolyzate Aa mass-spectrometric data and resolution table
Table 9, compd A
13C nucleus magnetic resonance resolution table (400MHz chloroform)
| The carbonatoms of compound | Chemical shift σ ppm | The DEPT spectrum | Relevant hydrogen atom |
| 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 | 46.66 24.49 44.40 218.2 56.06 74.84 52.77 76.24 37.85 30.08 137.46 169.26 121.94 18.42 19.95 169.49 21.05 | CH CH 2CH 2C?=?0 C CH CH CH CH 2CH C C?=?0 CH 2CH 3CH 3C?=?0 CH 3 | 1-H 2-H 23-H 6-H 7-H 8-H 9-H 210-H 13α-H,13β-H 14-Me 15-Me 17-Me |
Table 10, hydrolyzate Aa proton nmr spectra resolution table
Instrument: Bruker-400 solvent: heavy hydrogen pyridine
Embodiment: this compound can extract with following method:
With flower of Aquatic-sunflower Inula grass 1Kg(Inula helianthus Aquatica C ' Y ' Uu ex ling) put in the apparatus,Soxhlet's, add sherwood oil (60-90 ℃) 2Kg, heat on the water-bath, refluxing extraction, there is crystallization to separate out when cold, filter,, promptly get the aquatic-sunflower lactone constituents through methyl alcohol recrystallization repeatedly, again through silica gel column layer (sample: silica gel=1: 200, the chloroform wash-out, the silica gel G thin-layer chromatography is checked (developping agent: chloroform, developer: Lei Mengde-Raymond reagent), merge same section, methanol crystallization can be got the aquatic-sunflower lactone that accounts for upper column quantity 90%, and the lactone yield can reach 3-5 ‰.
Pharmacodynamic study proves, in vitro tests: cancer cells such as people's lung, stomach, intestines, uterine neck, nasopharynx, bladder and leukemia cell are all had tangible lethal effect and growth-inhibiting effect, and ID30 is 0.1mg/kg, and ID50 is 1mg/kg, and ID90 is 4mg/kg.Recommending clinical consumption is 1mg/kg, and normal cell is not had obvious damaging action.In vivo test: to mouse interior tumor, as ehrlich carcinoma, S180, U14, liver cancer, kinds of tumors such as carcinoma of the pancreas are all effective in cure, to ascites carcinoma curative effect P＜0.01, solid tumor curative effect P＜0.05.Administrations such as abdominal cavity, filling stomach, intramuscular injection are all effective, and effective dose iP is 30mg/kg, and im is 30mg/kg, and Po is 200mg/kg.
Safety research: toxicologic study proves, mouse LD50ip is 270mg/kg, po is 1400mg/kg, acute chronic toxicity and the long term toxicity test of rat and dog are not seen blood picture, the heart, liver, renal function and marrow, the toxic reaction of brain etc. can cause blood pressure drops for the quick intravenous injection of dog, but available metaraminol and ephedrine is prevented and treated effectively, wherein three dogs respectively repeat three tests, each one month at interval, 10 times of at every turn testing dosage (in a day) intelligent's dosage, off-test is for the third time put to death, core, liver, spleen, kidney, organs and tissues paraffin wax cut sections for microscopic examination such as lung, no abnormality seen changes, and result of study proves that aquatic-sunflower lactone provided by the invention is the PTS of international initiative, have and have good stability, have cancer suppressing action, and toxicity is little, can try out in clinical.It is a kind of cancer therapy drug with fine DEVELOPMENT PROSPECT.
Claims (3)
1, a kind of medicine for the treatment of human body diseases is characterized in that the chemical structure of this medicine is,
This medicine is a kind of white, needle-shaped crystals, fusing point 187-189 ℃, and molecular formula C
17H
22O
5, molecular weight 306 is soluble in chloroform, is dissolved in the ether of heat, in sherwood oil and the alcohol, and slightly soluble when cold.
2, a kind of medicine according to claim 1, it is characterized in that this medicine can extract with following method, with flower of Aquatic-sunflower Inula grass 1Kg(Inula helianthus Aquatica C ' Y ' Uu ex ling) put in the apparatus,Soxhlet's, add sherwood oil (60-90 ℃) 2Kg, heat on the water-bath, refluxing extraction, there is crystallization to separate out when cold, filter,, promptly get the aquatic-sunflower lactone constituents through the methyl alcohol periodic crystallisation, again through silica gel column layer (sample: silica gel=1: 200, the chloroform wash-out, the silica gel G thin-layer chromatography is checked (developping agent: chloroform, developer: Lei Mengde-Raymond reagent), merge same section, methanol crystallization can be got the aquatic-sunflower lactone that accounts for upper column quantity 90%, and the lactone yield can reach 3-5 ‰.
3, a kind of medicine for the treatment of human body diseases is characterized in that cancer cells such as lung, stomach, intestines, uterine neck, nasopharynx, bladder and the leukemia cell to the people all has tangible lethal effect and growth-inhibiting effect.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN93100687A CN1056142C (en) | 1993-01-04 | 1993-01-04 | Anti-cancer medicine inula helianthus-aquatica lactone |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN93100687A CN1056142C (en) | 1993-01-04 | 1993-01-04 | Anti-cancer medicine inula helianthus-aquatica lactone |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 99108173 Division CN1112182C (en) | 1999-06-11 | 1999-06-11 | Medical application of aquatic-sunflower lactone |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1089945A true CN1089945A (en) | 1994-07-27 |
| CN1056142C CN1056142C (en) | 2000-09-06 |
Family
ID=4983179
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN93100687A Expired - Fee Related CN1056142C (en) | 1993-01-04 | 1993-01-04 | Anti-cancer medicine inula helianthus-aquatica lactone |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1056142C (en) |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1062866C (en) * | 1997-10-31 | 2001-03-07 | 中国人民解放军第二军医大学药学院 | Bryostatin as anti-cancer active compound |
| CN1067552C (en) * | 1994-12-06 | 2001-06-27 | 大连医科大学 | Method for extracting lipid anti-cancer medicine from liver |
| EP1381378A4 (en) * | 2001-02-21 | 2004-07-28 | Univ Rutgers | Compositions and methods for cancer prevention and treatment derived from inula britannica |
| CN101890065A (en) * | 2010-06-17 | 2010-11-24 | 昆明医学院第一附属医院 | Inula flower injection and preparation method thereof |
| CN102000066A (en) * | 2010-09-26 | 2011-04-06 | 中国科学院昆明植物研究所 | Inula helianthus-aquatica extract, anti-tumor medicament using same as active ingredient, preparation method and application thereof |
| CN110563679A (en) * | 2019-08-21 | 2019-12-13 | 中山大学 | sesquiterpene lactone compound, preparation method thereof and application of sesquiterpene lactone compound in preparation of medicine for preventing and treating nasopharyngeal carcinoma |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5549369A (en) * | 1978-10-04 | 1980-04-09 | Nippon Kayaku Co Ltd | Antitumorigenic substance |
| CA1270843A (en) * | 1982-05-19 | 1990-06-26 | Edward Stewart Johnson | Sesquiterpene lactones |
| JPS617201A (en) * | 1984-06-20 | 1986-01-13 | Sumitomo Chem Co Ltd | Fungicide |
-
1993
- 1993-01-04 CN CN93100687A patent/CN1056142C/en not_active Expired - Fee Related
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1067552C (en) * | 1994-12-06 | 2001-06-27 | 大连医科大学 | Method for extracting lipid anti-cancer medicine from liver |
| CN1062866C (en) * | 1997-10-31 | 2001-03-07 | 中国人民解放军第二军医大学药学院 | Bryostatin as anti-cancer active compound |
| EP1381378A4 (en) * | 2001-02-21 | 2004-07-28 | Univ Rutgers | Compositions and methods for cancer prevention and treatment derived from inula britannica |
| CN101890065A (en) * | 2010-06-17 | 2010-11-24 | 昆明医学院第一附属医院 | Inula flower injection and preparation method thereof |
| CN101890065B (en) * | 2010-06-17 | 2013-04-17 | 昆明医科大学第一附属医院 | Inula flower injection and preparation method thereof |
| CN102000066A (en) * | 2010-09-26 | 2011-04-06 | 中国科学院昆明植物研究所 | Inula helianthus-aquatica extract, anti-tumor medicament using same as active ingredient, preparation method and application thereof |
| CN102000066B (en) * | 2010-09-26 | 2012-07-25 | 中国科学院昆明植物研究所 | Inula helianthus-aquatica extract, anti-tumor medicament using same as active ingredient, preparation method and application thereof |
| CN110563679A (en) * | 2019-08-21 | 2019-12-13 | 中山大学 | sesquiterpene lactone compound, preparation method thereof and application of sesquiterpene lactone compound in preparation of medicine for preventing and treating nasopharyngeal carcinoma |
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| Publication number | Publication date |
|---|---|
| CN1056142C (en) | 2000-09-06 |
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Granted publication date: 20000906 Termination date: 20110104 |