CN1995061B - Cyclamin I and its preparation method and pharmaceutical composition - Google Patents
Cyclamin I and its preparation method and pharmaceutical composition Download PDFInfo
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- CN1995061B CN1995061B CN2006101387661A CN200610138766A CN1995061B CN 1995061 B CN1995061 B CN 1995061B CN 2006101387661 A CN2006101387661 A CN 2006101387661A CN 200610138766 A CN200610138766 A CN 200610138766A CN 1995061 B CN1995061 B CN 1995061B
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- 0 CC(C)(C1CC2)[C@@](C[C@@](C(C3O)O[C@@](C(C4O)O)OC(CO)[C@]4O)OC[C@@]3O[C@@]3OC(CO)([C@](C4O)O)C34O[C@@](C3O)OC(*4)[C@]4C3O)CC[C@]1(C)C(CC1)[C@]2(C)[C@](C)(C2)[C@]1(C1C[C@](C)(CC3)C=O)OC[C@@]13[C@@]2O Chemical compound CC(C)(C1CC2)[C@@](C[C@@](C(C3O)O[C@@](C(C4O)O)OC(CO)[C@]4O)OC[C@@]3O[C@@]3OC(CO)([C@](C4O)O)C34O[C@@](C3O)OC(*4)[C@]4C3O)CC[C@]1(C)C(CC1)[C@]2(C)[C@](C)(C2)[C@]1(C1C[C@](C)(CC3)C=O)OC[C@@]13[C@@]2O 0.000 description 1
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Abstract
The invention discloses a novel Cyclamen A, its preparing process and pharmaceutical compositions, as well as a group of compounds of formula I, wherein each group is defined in the specification. These compounds possesses good anticancer and anti-inflammatory actions. The invention also relates to the medicinal compositions containing these compounds, and their use in treating tumor and inflammatory diseases.
Description
Technical field
The invention belongs to the new pharmaceutical field.The present invention relates to new compound Cyclamin I compounds, contain the pharmaceutical composition that is used to treat cancer or inflammation of this compounds, and the application of this compound in preparing anticancer or anti-inflammatory drug.
Background technology
Red hair root is that (formal name used at school: Ardisia mamillata Hance), it is considered to have clearing away heat-damp and promoting diuresis to Myrsinacea Ardisa plant in traditional Chinese medicine, the effect with the stasis of blood of invigorating blood circulation.According to record in " Chinese medicine voluminous dictionary ", this plant can be used for treating diseases such as pain, wound, hemoptysis, sore furuncle pain.
Up to the present, still do not see the report that this type chemical ingredients has anticancer, anti-inflammatory, analgesic activities.
Summary of the invention
The contriver has found that through screening widely one type of new compound has good anticancer and anti-inflammatory analgesic action.
The present invention relates to the compounds of formula I, as follows.
Formula I
Wherein R1, R2 and R3 are hydrogen, hydroxyl, aldehyde radical, carboxyl, halogen atom, C1-C4 alkyl or are selected from the substituted C1-C4 alkyl of hydroxyl, halogen atom, C2-C4 alkenyl, C3-C8 naphthenic base and phenyl by 1-3;
The invention still further relates to the pharmaceutical composition of a compounds that contains above-mentioned formula I, especially for the pharmaceutical composition of treatment cancer or inflammation.
Embodiment
Accompanying drawing 1 is the extraction process schema of new compound Cyclamin I.
The present invention provides in the as above defined formula I compounds, and the C1-C4 alkyl refers to contain the straight or branched alkyl of 1 to 4 carbon atom, for example methyl, ethyl, propyl group, sec.-propyl, butyl, isobutyl-etc.
The C2-C4 alkenyl is meant the straight or branched thiazolinyl that contains 2 to 4 carbon atoms, for example vinyl, propenyl, allyl group, crotonyl, isobutenyl etc.
The C3-C8 naphthenic base is meant the naphthenic base that contains 3 to 8 carbon atoms, for example cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, suberyl and ring octyl group.
Halogen atom is meant fluorine, chlorine, bromine or iodine, is preferably fluorine or chlorine.
In a preferred version of the present invention, said compound is that R1 is the formula I compound of hydrogen or methyl or hydroxyl or carboxyl.
In another preferred version of the present invention, said compound is that R2 is the formula I compound of hydrogen or aldehyde radical or methyl or carboxyl.
In another preferred version of the present invention, said compound is that R3 is the formula I compound of hydrogen or methyl or aldehyde radical or carboxyl.
Among the present invention most preferably among the formula I R1 be hydroxyl, R2 is an aldehyde radical, R3 is the compound of methyl.Its Chinese systematic name is: 3 β-O-{ β-D-Glucopyranose-(1 → 2)-[α-L-pyrans rhamnosyl-(1 → 2)-β-D-Glucopyranose-(1 → 4)]-β-L-arabopyranose }-16-hydroxyl-Cericlamine A; Its english system is by name: 3 β-O-{ β-D-glucopyranosyl-(1 → 2)-[α-L-rhamnopyranosyl-(1 → 2)-β-D-glucopyranosyl-(1 → 4)]-β-L-arabinopyranoside}-16-hydroxy-cyclamiretin A; Name and be Cyclamin I, shown in II.
Cyclamin I of the present invention can obtain according to the conventional method extraction of vegetable chemistry from the red hair root of Myrsinacea plant (Ardisia mamillata Hance).Its extraction process flow process is seen Figure of description Fig. 1.
Formula II
Inventing used organic solvent is water, methyl alcohol, ethanol, propyl alcohol, butanols etc., or their mixture;
The used macroporous resin of the present invention is D4006, AB-8 etc. (Chemical Plant of Nankai Univ.'s production); The filler of the used pillar chromatography of the present invention is sorbent materials such as silica gel and aluminum oxide.The used eluent of the present invention is separately wash-out or liquid mixture prepared according to a certain percentage such as methyl alcohol, ethanol, propyl alcohol, butanols, methylene dichloride, chloroform, ETHYLE ACETATE, acetone, benzene.
Other compounds of the present invention can be the methodology of organic synthesis acquisition of initiator by routine with suitable aglucon.The aglucon initiator can be known natural aglucon, also can obtain by conventional methodology of organic synthesis from these natural aglucons.
The present invention proves, and Cyclamin I of the present invention has good anticancer and anti-inflammatory, analgesic activity.
Therefore, compound of the present invention can be used for treating and/or preventing relative diseases such as cancer, inflammatory diseases or treatment pain.The present invention provides a kind of method of treating the patient of cancer or inflammatory diseases, comprises the above-mentioned formula I verivate that gives this patient treatment significant quantity.
Can compound of the present invention be used to prepare medicine, especially for the medicine of treatment cancer, inflammatory diseases or pain.Therefore, the present invention relates to formula I compound, particularly be used for treating the application of the medicine of cancer, inflammatory diseases or pain in preparation in the purposes of preparation in the medicine.
Further describe the present invention through following examples, but scope of the present invention is not limited to these embodiment.
Preparation embodiment
The preparation of Cyclamin I
Red hair root herb 1kg is pulverized, and extraction using alcohol is used 4 liters of ethanol at every turn; Extract 4 times, extracting solution merges, and filters; Be concentrated into proportion D=1.2, last AB-8 macroporous resin 1200g post (post bed: φ 50 * 200) carries out gradient elution with 10%-70% ethanol; Eluting liquid merges evaporate to dryness, obtains the total saponin 41g of extract.Total saponin is also gone up appearance to silica gel 2000g post (post bed: φ 150 * 1500), use propyl carbinol: acetic acid: water=7: 1: 2 mixed solvent wash-outs.Obtain Cyclamin I 18.23g.
Cyclamin I is a white powder.10%EtOH-H
2SO
4Check is reddish black (heating), and showing has sugar to exist.FAB-MS mass spectrum (m/z [M+H]
+) confirm that its molecular weight is 1074.It is M/Z455 that the positive ion fast atom bombardment MS provides glucoside unit mistake hydroxyl peak, has M/Z133 (pectinose dehydration) simultaneously, 147 (rhamnosyl dehydrations) and 163 (gluconate dehydratase) peak.Through gas chromatography (GC) and standard substance comparison, show and contain pectinose, rhamnosyl and glucose in the molecule that its mol ratio is 1: 1: 2.Its molecular structure warp
13C-NMR,
1H-NMR obtains conclusive evidence, and its data are seen table one, two.
Table one Cyclamin I's
13C-NMR data (δ ppm, DMSO-d
6, 150MHz)
| C 23 | 27.47 | C 2 | 73.82 |
| C 24 | 16.25 | C 3 | 72.52 |
| C 25 | 15.35 | C 4 | 76.13 |
| C 26 | 17.58 | C 5 | 68.12 |
| C 27 | 19.62 | C 6 | 17.85 |
| C 28 | 76.35 | ? | ? |
| C 29 | 23.82 | ? | ? |
| C 30 | 207.47 | ? | ? |
Table two. Cyclamin I's
1H NMR data (δ ppm DMSO-d
6, 600MHz)
| H28α | 2.87，d | ? | ? |
| H28β | 3.24，d | ? | ? |
| H29 | 0.89，3H，s | ? | ? |
| H30 | 9.38，1H，s | ? | ? |
Test example 1
The anti-tumor activity of Cyclamin I
Tumor cell extracorporeal growth suppresses experiment (mtt assay) and shows that Cyclamin I of the present invention has the good restraining effect to human stomach cancer cell line (Kato-III), human leukemia cell line knurl (K562), human oophoroma cell line (OVCA2780), mouse lymph leukemia cell line (L1210), human lung carcinoma cell line (A549) etc.See table three, table four.Show in the table that K562, L1210 are comparatively responsive to Cyclamin I of the present invention.In this experiment, Cyclamin I is at 10 μ g.mL
-1During concentration, the growth of tumour cell inhibiting rate reaches 50%, and the inhibiting rate of positive control drug cis-platinum is 35.7%.
Table three MTT development process detects the external antitumour activity (n=12) of Cyclamin I
The numeral of annotating in (1) bracket is the percentage that the OD value accounts for solvent control group
(2) compare with solvent control group ###P＜0.001
(3)
*P＜0.01, P＜0.001
* *Compare with solvent control group
(4) Kato-III is a human stomach cancer cell line
(5) K562 is a human leukemia cell line
(6) OVCA2780 is the human oophoroma cell line
Table four MTT colourimetry detects the external antitumour activity (n=10) of Cyclamin I
The numeral of annotating in (1) bracket is the percentage that the OD value accounts for solvent control group
(2) the positive contrast medicine of ### cis-platinum (DDP) compares P＜0.001 with solvent control group
(3)
* *Experimental group and solvent control group be P＜0.001 relatively
(4) L1210 mouse lymph leukemia cell line
(5) A549 human lung carcinoma cell line
Test example 2
The anti-inflammatory analgesic test of Cyclamin I
70 mouse are divided into 7 groups at random, in caused by dimethylbenzene xylene scorching preceding 1 hour, the animal of 6 groups respectively the Cyclamin I of oral following dosage (6.25,12.5,25,50,100mg.kg
-1), an other treated animal is accepted isopyknic solvent.Cause scorching back 30 minutes and get the both sides auricle, try to achieve the swelling degree.Table five result shows that Cyclamin I p-Xylol causes mouse ear oedema has certain restraining effect, wherein 25mg.kg
-1Dosage down effect is the most remarkable, inhibiting rate reaches 89.9%.
Table five Cyclamin I p-Xylol brings out the restraining effect (n=10, ig administration) of mouse ear oedema
Claims (4)
1. the compound of formula I,
Formula I.
2. a pharmaceutical composition is characterized by the formula I compound and the pharmaceutical carrier thereof that contain claim 1, as the medicine of treatment cancer or inflammation.
3. the purposes of formula I compound as claimed in claim 1 in preparation treatment cancer or inflammation medicine.
4. the purposes of pharmaceutical composition as claimed in claim 2 in preparation treatment cancer or inflammation medicine.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2006101387661A CN1995061B (en) | 2006-10-18 | 2006-11-15 | Cyclamin I and its preparation method and pharmaceutical composition |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200610150271 | 2006-10-18 | ||
| CN200610150271.0 | 2006-10-18 | ||
| CN2006101387661A CN1995061B (en) | 2006-10-18 | 2006-11-15 | Cyclamin I and its preparation method and pharmaceutical composition |
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| Publication Number | Publication Date |
|---|---|
| CN1995061A CN1995061A (en) | 2007-07-11 |
| CN1995061B true CN1995061B (en) | 2012-03-21 |
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|---|---|---|---|
| CN2006101387661A Expired - Fee Related CN1995061B (en) | 2006-10-18 | 2006-11-15 | Cyclamin I and its preparation method and pharmaceutical composition |
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Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103923160B (en) * | 2014-05-05 | 2016-04-20 | 中国人民解放军军事医学科学院毒物药物研究所 | Herba Ardisiae Mamillatae glycosides and medicinal use thereof |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1243012C (en) * | 2003-02-27 | 2006-02-22 | 北京瑞康医药技术有限公司 | Sekolamin saponin compound |
-
2006
- 2006-11-15 CN CN2006101387661A patent/CN1995061B/en not_active Expired - Fee Related
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1243012C (en) * | 2003-02-27 | 2006-02-22 | 北京瑞康医药技术有限公司 | Sekolamin saponin compound |
Non-Patent Citations (4)
| Title |
|---|
| Rao, G. Subha等.Antiviral activity of triterpenoid saponins containing acylated β-amyrin aglycones.《Journal of Pharmaceutical Sciences》.1974,第63卷(第3期),471-3. * |
| 赵贞贞.CA与STN记录1.《CA与STN记录1》.2010, * |
| 赵贞贞.CA与STN记录1.《CA与STN记录3》.2010, * |
| 赵贞贞.CA与STN记录2.《CA与STN记录2》.2010, * |
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| CN1995061A (en) | 2007-07-11 |
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Granted publication date: 20120321 Termination date: 20171115 |