CN101889998A - Composition and application thereof as TR3 receptor inducer - Google Patents
Composition and application thereof as TR3 receptor inducer Download PDFInfo
- Publication number
- CN101889998A CN101889998A CN2010101914717A CN201010191471A CN101889998A CN 101889998 A CN101889998 A CN 101889998A CN 2010101914717 A CN2010101914717 A CN 2010101914717A CN 201010191471 A CN201010191471 A CN 201010191471A CN 101889998 A CN101889998 A CN 101889998A
- Authority
- CN
- China
- Prior art keywords
- nmr
- benzene
- substituted radical
- benzene pyrrones
- och
- 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.)
- Granted
Links
Images
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a composition, a preparation method and application thereof as a TR3 receptor inducer, and belongs to the field of medicaments and foods. The composition serving as the TR3 receptor inducer is applied to preparing the foods or medicaments for preventing or treating cancer, hepatitis or atherosclerosis, and can be prepared into powder, tablets, capsules, pills, suppositories, dropping pills, enteric-coated preparations, injection, syrups, emulsion, suspension, tinctures, plaster or spray. Based on the mechanism that TR3 can be an ideal molecule target spot for screening medicaments for resisting tumors and cardiovascular and cerebrovascular diseases, the composition has practical significance for the discovery and development of compounds which can selectively regulate the expression way of the TR3 or medicinal compositions with the advanced treatment characteristic.
Description
Technical field
The invention belongs to pharmaceuticals and field of food, particularly a kind of compositions and the application in preparation TR3 receptor inducer thereof.
Background technology
TR3 (Nur77) is the nuclear receptor by upright early gene NR4A1 coding.It is after cytoplasm is synthetic, enter in the nuclear as transcription factor, by its central DNA in conjunction with territory and specific DNA eight aggressiveness sequences---Nur77/NGFI-B association reaction element interacts, or form heterodimer with retinol receptor RXR, be attached on the DNA response element, the transcriptional activity of regulation and control target gene plays a significant role at cell growth, differentiation and apoptotic process.TR3 family member's structure all has the transcriptional activation domain AF1 of the typical characteristic of nuclear receptor: N end, the DNA land of high conservative, and C holds ligand binding domain.Many outer signals, comprise that various somatomedin (as nerve growth factor, epidermal growth factor, fibroblast growth factor, serum somatomedin), Calcium ionophore, KCl, Buddhist ripple ester, tretinoin family, Tax albumen etc. can both irritation cells, induce or suppress the expression of TR3.TR3 not only can mediate the apoptosis of various human tumor cell, and relevant with multiple cancer.TR3 also is one of target molecule of virus protein effect, and virus protein is for the interference of TR3 transcription factor protein normal regulating function, with the generation development of chronic viral hepatitis, hepatic fibrosis, hepatocarcinoma substantial connection is arranged.In addition, TR3 subfamily member may promote incidence of atherosclerosis at the blood vessel wall high expressed, and Nur77 controlling gene transcriptional activation participates in what vascular smooth muscle cell increment of macrophage inflammatory reaction; Can infer that Nur77 is positioned at nucleus may promote atherosclerosis, transcriptional activation function is suppressed when being positioned at outside the nucleus, may suppress the atherosclerotic lesion progress.Therefore, regulate and control nuclear receptor TR 3 expressed chemical compound, may in prevention and treatment of diseases such as the relevant cancer of nuclear receptor TR 3, hepatitis, atherosclerosis, demonstrate wide prospect.
Summary of the invention
In order to solve deficiency and the shortcoming that above-mentioned prior art exists, primary and foremost purpose of the present invention is to provide a kind of two benzene pyrrones compound compositions that comprise.
Another object of the present invention is to provide the purposes of above-mentioned composition as preparation TR3 receptor inducer.
Purpose of the present invention is achieved through the following technical solutions: a kind of compositions, said composition comprise the two benzene pyrrones chemical compounds that have suc as formula (I) described structure:
R wherein
1Be OH or OCH
3R
2Be H, OCH
3Or substituted radical D; R
3Be H, OH or OCH
3R
4Be H, OH, substituted radical D, substituted radical E or substituted radical F; R
5Be H, OH, OCH
3Or substituted radical F, R
6Be H, OH or OCH
3, R
7Be H, OH or OCH
3, R
8Be H, OH, OCH
3, substituted radical C, substituted radical D or substituted radical F, and R
2And R
3Between connect substituted radical A, R
3And R
4Between connect substituted radical B,
Described pair of benzene pyrrones chemical compound is 1,6,7-trihydroxy-2-(3-methyl but-2-ene)-3-methoxyl group-8-(3-hydroxy-3-methyl butyl)-two benzene pyrrones (1,6,7-trihydroxy-2-(3-methylbut-2-enyl)-3-methoxy-8-(3-hydroxyl-3-methylbutyl)-xanthone, CF-1, as shown in Equation 1), 1,3,7-trihydroxy-2-(3-methyl but-2-ene)-8-(3,7-dimethyl-octa-2, the 5-diene)-and two benzene pyrrones (1,3,7-trihydroxy-2-(3-methylbut-2-enyl)-8-(3,7-dimethylocta-2,5-dienyl)-and xanthone, CF-2, as shown in Equation 2), 1,2-methoxyl group-3,7, and 8-trihydroxy-two benzene pyrrones (1,2-dimethoxy-3,7,8-trihydroxy-xanthone, CF-3, as shown in Equation 3) and 1,7-dihydroxy-4-(3,7-dimethyl-octa-2, the 6-diene)-5 '-(1-hydroxyl-1-Methylethyl)-4 ', 5 '-dihydrofuran [2 ', 3 ': 3,2]-two benzene pyrrones (1, and 7-dihydroxy-4-(3,7-dimethylocta-2,6-dienyl)-5 '-(1-hydroxy-1-methylethyl)-4 ', 5 '-dihydrofuro[2 ', 3 ': 3,2]-xanthone, CC-1, in more than one as shown in Equation 4).
The preparation method of described pair of benzene pyrrones chemical compound is by following operating procedure: the dry stem of Guttiferae cattle fogfruit cattle wood (Cratoxylum cochinchinense) or red bud wood (Cratoxylum formosum subsp.pruniflorum) is ground into coarse powder, immerse to extract in the solvent cold extraction or heating and refluxing extraction in extracting solvent, filter or the centrifugal insoluble matter of removing, again gained is extracted solution and carry out concentrating under reduced pressure, separate the two benzene pyrrones chemical compounds that obtain suc as formula (I) described structure.
Described extraction solvent is that volume fraction is 60% ethanol; Described extracting method is a reflux, extract,, and described extraction time is 6 hours; Described separation is to adopt chromatography method and/or extraction to separate.
The quality percentage composition of two benzene pyrrones chemical compounds is 3.3-16.7% in the described compositions.
The application of above-mentioned compositions in preparation TR3 receptor inducer.
Above-mentioned compositions can be applicable to preparation prevention or treatment cancer, hepatitis or atherosclerotic food or pharmaceuticals as the TR3 receptor inducer.
Described TR3 receptor inducer and pharmaceutically acceptable carrier are mixed and made into powder, tablet, capsule, pill, suppository, drop pill, enteric agents, injection, syrup, Emulsion, suspensoid, tincture, unguentum or spray.
Two benzene pyrrones chemical compounds or the wherein any two or more chemical compounds of selection suc as formula (I) described structure make up in varing proportions, make it to combine with suitable excipient, dosage forms such as the powder of making according to conventional method, tablet, capsule, pill, suppository, drop pill, enteric agents, injection, syrup, Emulsion, suspensoid, tincture, unguentum, spray, be used to prepare TR3 receptor inducer and preparation prevention or treatment TR3 relevant disease, as the food or the pharmaceuticals of angiopathy, cancer or diabetes.
When oral administration is made common formulations such as tablet, powder, granule, capsule, can select starch, lactose, sucrose, mannose, hydroxy methocel etc. as excipient.Except that excipient, can also use sodium laurylsulfate, magnesium stearate, Pulvis Talci etc. as lubricant, dextrin, crystalline cellulose, corn starch, gelatin, polyvinylpyrrolidone, arabic gum etc. are as binding agent, and potato starch, hydroxyl hexyl cellulose are as disintegrating agent.In addition, can also make syrup, Emulsion, suspensoid etc.For these dosage forms, can add correctives.
Exterior-applied formulation comprises suppository, ointment, external pulvis, spray, enema, Emulsion etc.Here employed solid or liquid additive often use in the present technique field.For ointment, select for use the hydrophobic base formed by water, fatty oil, lanoline, vaseline, glycerol, Cera Flava, paraffin, resin, higher alcohol, surfactant or hydrophilic matrix etc. at interior additive.
When making injection, generally be with distilled water for injection, normal saline, D/W, injection vegetable oil, propylene glycol, Polyethylene Glycol etc.In case of necessity, can add suitable isotonic agent, cosolvent, antioxidant, antiseptic etc.
The relative prior art of the present invention, have following advantage and beneficial effect: the invention provides a kind of two benzene pyrrones compound compositions that comprised, said composition has the effect of inducing the TR3 expression of receptor, can be used as the TR3 receptor inducer, and the food or the pharmaceuticals that can be used for preparing prevention or treat diseases such as cancer, hepatitis or atherosclerosis, or truly have the chemical compound of associated uses, extract to mix above-mentioned composition and other, be used to prepare the food or the pharmaceuticals of prevention or diseases such as treatment cancer, hepatitis or atherosclerosis.
Description of drawings
Fig. 1 is the TR3 transcriptional activity figure of Compound C F-1～CF-16 in the red bud wood (10 μ M).
Fig. 2 is the TR3 transcriptional activity figure of the Compound C C-1～CC-5 (10 μ M) in the cattle wood.
Fig. 3 is the TR3 transcriptional activity figure of Compound C F-1～CF-3, CF-5～CF-8 in the red bud wood, CF-10, CF-13, CF-14, CF-16 (1 μ M).
The specific embodiment
Below in conjunction with embodiment and accompanying drawing, the present invention is described in further detail, but embodiment of the present invention is not limited thereto.
Embodiment 1: the two benzene pyrrones chemical compounds of extraction separation from red bud wood
Get the dry stem 5.0kg of red bud wood (Cratoxylum formosum subsp.pruniflorum), after the coarse crushing, with 8 times of amount 60% (V/V) alcohol-water reflux, extract, twice, each two hours, merge extractive liquid, obtained total extractum (675.0g) behind the concentrating under reduced pressure.Get the total extractum (600g) of red bud wood and be dissolved in the suitable quantity of water, filter, get filtrate through the open column chromatography of macroporous resin HP-20, alcohol-water gradient elution.Reclaim under reduced pressure respectively, water elution part (157.3g), 40% (v/v) alcohol-water eluting part (257.0g), and 90% (v/v) alcohol-water eluting part, this part be the total two benzene pyrrone positions of red bud wood (CF, 157.0g).
Get 90% (v/v) alcohol-water eluting portion C F (117.0g), adopt the open column chromatography of silica gel, cyclohexane extraction-ethyl acetate gradient elution obtains 8 fractions.Fraction Fr.4 (cyclohexane extraction-ethyl acetate v/v, 9: 1 eluting parts, 4.0g), through Sephadex LH-20 column chromatography, behind chloroform-methanol (4: the 1) eluting, again through the open column chromatography of silica gel, cyclohexane extraction-acetone (8: 2) eluting obtains 8 sub-fractions (Fr.4-1～Fr.4-8).Sub-fraction Fr.4-5 and Fr.4-6 are respectively through the SephadexLH-20 column chromatography, and chloroform-methanol (4: 1) and chloroform-methanol (1: 1) eluting obtain Compound C F-12 (14.2mg) and CF-5 (12.8mg).Sub-fraction Fr.4-7 is through Sephadex LH-20 column chromatography, cyclohexane extraction-dichloromethane (1: 1) eluting, and the open column chromatography of silica gel, chloroform-methanol eluting and recrystallization obtain Compound C F-10 (15.6mg), CF-9 (12.6mg), CF-15 (11.6mg), CF-11 (22.5mg), CF-2 (15.3mg) CF-16 (10.3mg) and CF-8 (11.7mg).Sub-fraction Fr.4-8 is through Sephadex LH-20 column chromatography, chloroform-methanol (1: 1) eluting, obtain Compound C F-4 (26.6mg) fraction Fr.6 (cyclohexane extraction-ethyl acetate v/v, 8: 2 eluting parts, 8.0g), through the open column chromatography of silica gel, cyclohexane extraction-ethyl acetate gradient elution obtains 8 sub-fractions (Fr.6-1～Fr.6-8).Sub-fraction Fr.6-3 (9: 1 eluting parts) is through Sephadex LH-20 column chromatography, and cyclohexane extraction-dichloromethane (1: 1) eluting obtains Compound C F-1 (180.0mg).Sub-fraction Fr.6-4 (8: 2 eluting parts) is through Sephadex LH-20 column chromatography, chloroform-methanol (3: 2) eluting, and the open column chromatography of silica gel, the chloroform eluting obtains Compound C F-6 (31.5mg), CF-13 (21.6mg), sub-fraction Fr.6-7 (8: 2 eluting parts) is through Sephadex LH-20 column chromatography, chloroform-methanol (3: 2) eluting, and the open column chromatography of silica gel, chloroform-methanol (100: 0,100: 1) eluting, obtain Compound C F-3 (9.4mg) and CF-14 (13.2mg).Sub-fraction Fr.6-8 (eluent ethyl acetate part) is through Sephadex LH-20 column chromatography, and chloroform-methanol (3: 2) eluting obtains Compound C F-7 (14.7mg).
By physicochemical constant and modern Wave Spectrum means (MS, NMR), in conjunction with the document related data, identified their structure, as follows.
Annotate: have
*The person is a noval chemical compound.
Compound C F-1, yellow powder, the ferric chloride colour developing is positive, and prompting has phenolic hydroxyl group to exist.UV (MeOH) λ
Max(log ε) 206 (4.73), 235 (4.57), 263 (4.59), 321 (4.34), 374 (4.15) nm; IR (KBr) v
Max3349 (OH), 2914,1618 (C=O), 1481,1292,808cm
-1, HR-ESI-MS provides m/z 427.1748[M-H]
-(calcd for C
24H
27O
7, 427.1762), infer molecular formula C
24H
28O
7, calculating degree of unsaturation is 11.
1H-NMR (400MHz, in acetone-d
6) in the collection of illustrative plates, δ
H13.75 (1H, s 1-OH) prompt for the hydroxyl hydrogen signal of hydrogen bond association, δ
H6.80 (H-5), 6.46 (1H, s H-4) are two fragrant hydrogen signals, δ for 1H, s
H3.96 (3H, s, 3-OCH
3) be one group of methoxyl group hydrogen signal, one group of hydrogen signal δ
H(3.31 2H, d, J=7.2Hz, H-1 '), 5.22 (1H, t, J=7.2Hz H-2 '), 1.64 (3H, s, H-4 '), 1.78 (3H, s, H-5 ') prompt for one group of isopentene group substituent group.Another group hydrogen signal δ
H3.48 (2H, t, J=7.2Hz, H-1 "), 1.88 (2H, t, J=7.2Hz, H-2 "), 1.30 (6H, s, H-4 ", H-5 ") prompts for a 3-hydroxy-3-methyl-butyl substituent group.
13C-NMR (100MHz, in acetone-d
6) show 23 spectral lines altogether in the collection of illustrative plates, wherein one from being the overlapping of two carbon signals highly as can be known, in conjunction with DEPT135 as can be known, comprises 1 carbonyl carbon signal (δ
C183.1), 11 sp
2Hydridization quaternary carbon signal (δ
C164.4,160.5,156.2,154.0,153.4,141.4,131.4,131.1,112.0,111.5,104.3), 3 sp
2Hydridization tertiary carbon signal (δ
C123.4,101.1,89.7), 1 oxygen quaternary carbon signal (δ of company
C71.2), 3 mesomethylene carbon signal (δ
C44.1,22.5,21.9) and 4 methyl carbon signal (δ
C29.6 * 2,25.8,17.8), 1 methoxyl group signal (δ
C56.4).
Comprehensive above UV, IR,
1H-NMR,
13C-NMR data, molecular formula and degree of unsaturation infer that this chemical compound is two benzene pyrrones chemical compounds.Contain 3 hydroxyl substituents and two C-5 unit substituent groups in the structure, and a methoxyl group substituent group.
In the HMBC collection of illustrative plates, association hydroxyl hydrogen signal δ
H13.75 (1-OH) with carbon signal δ
C160.5 (C-1), 111.5 (C-2), 104.3 (C-9a) are relevant, and the methylene hydrogen signal δ of isopentene group
H(3.31 H-1 ') and carbon signal C-1, C-2,164.4 (C-3) are relevant, determine that this isopentene group is connected the C-2 position.Methoxyl group hydrogen signal δ
H3.96 (3-OCH
3) relevant with C-3, determine that this methoxyl group is connected the C-3 position.Fragrance hydrogen signal δ
H6.46 (H-4) and C-3, C-2, C-9a, 156.2 (C-4a) are relevant, determine that it is connected the C-4 position.Six remaining aromatic carbon signal (δ
C154.0,153.4,141.4,131.1,112.0,101.1) and be the carbon signal on another phenyl ring.Methylene hydrogen signal δ
H3.48 (H-1 "), 1.88 (H-2 ") and carbon signal δ
C131.1 (C-8) relevant, fragrant hydrogen signal δ
H6.80 (H-5) with carbon signal δ
C154.0 (C-10a), 153.4 (C-6), 141.4 (C-7), 112.0 (C-8a) determine that this fragrance hydrogen H-5 is positioned at carbon signal δ
C131.1 the chemical displacement value of H-5 is considered in para-position (C-8), determines that it is connected the C-5 position.So this chemical compound is accredited as 1,6,7-trihydroxy-2-(3-methyl but-2-ene)-3-methoxyl group-8-(3-hydroxy-3-methyl butyl)-two benzene pyrrones through the SciFinder network retrieval, does not find relevant report, shows that this is a noval chemical compound.
1H-NMR and
13The C-NMR data see Table 1.Its structural formula is as follows:
Compound C F-2, yellow powder, the ferric chloride colour developing is positive, and prompting has phenolic hydroxyl group to exist.UV (MeOH) λ
Max(log ε) 205 (4.55), 241 (4.54), 265 (4.48), 316 (4.24), 379 (3.77) nm; IR (KBr) v
Max3414,2923,1645,1458,1167,820cm
-1HR-ESI-Q-TOF-MS provides m/z 447.2184[M-H]
-(cacled forC
28H
31O
5, 447.2177), infer molecular formula C
28H
32O
5, calculating degree of unsaturation is 13.
1H-NMR (400MHz, in CDCl
3) in the collection of illustrative plates, δ
H13.65 (1H, s 1-OH) prompt for the hydroxyl hydrogen signal of hydrogen bond association, two fragrant hydrogen signal δ that intercouple
H7.13 (1H, d, J=8.8Hz, H-6), 7.08 (1H, d, J=8.8Hz,, H-5) there is another fragrant hydrogen signal δ in the quaternary phenyl ring in ortho position of prompting
H6.22 (H-4) there is one group of hydrogen signal δ in one five phenyl ring that replaces of prompting for 1H, s
H(3.41 2H, d, J=7.0Hz, H-1 '), 5.29 (1H, t, J=7.0Hz, H-2 '), 1.74 (3H, s, H-4 '), 1.83 (3H, s, H-5 ') prompt for one group of isopentene group substituent group.Another group hydrogen signal δ
H4.24 (2H, d, J=6.6Hz, H-1 "), 5.27 (1H; t, J=6.6Hz, H-2 "), 2.06 (2H, m, H-4 "), 2.09 (2H, m, H-5 "), 5.04 (1H, t, J=6.4Hz, H-6 ") 1.64 (3H, s, H-8 "), 1.86 (3H, s, H-9 "), 1.57 (3H; s, H-10 ") prompt for one 3,7-dimethyl-octa-2,6-dialkylene substituent group.
13C-NMR (100MHz, in CDCl
3) show 28 spectral lines altogether in the collection of illustrative plates, in conjunction with DEPT135 as can be known, comprise 1 carbonyl carbon signal (δ
C183.2), 12 sp
2Hydridization quaternary carbon signal (δ
C161.9,160.4,154.9,151.7,150.9,138.1,134.4,131.8,127.2,118.3,108.9,103.8), 6 sp
2Hydridization tertiary carbon signal (δ
C123.9,123.4,121.7,121.6,116.4,93.0), 4 mesomethylene carbon signal (δ
C39.7,26.4,25.7,21.4), 5 methyl carbon signal (δ
C25.7,25.5,17.8,17.6,16.3), comprehensive above UV, IR,
1H-NMR,
13C-NMR data, molecular formula and degree of unsaturation infer that this chemical compound is two benzene pyrrones chemical compounds.Contain 3 hydroxyl substituents in the structure, a C-5 unit substituent group, and a C-10 unit substituent group.
In the HMBC collection of illustrative plates, association hydroxyl hydrogen signal δ
H13.65 (1-OH) with carbon signal δ
C160.4 (C-1), 108.9 (C-2), 103.8 (C-9a) are relevant, and the methylene hydrogen signal δ of isopentene group
H(3.41 H-1 ') and carbon signal C-1, C-2,161.9 (C-3) are relevant, determine that this isopentene group is connected the C-2 position.Fragrance hydrogen signal δ
H6.22 (H-4) with carbon signal C-3,155.0 (C-4a), 108.9 (C-2), C-9a is relevant, determines that it is connected the C-4 position.Methylene hydrogen signal δ
H4.24 (H-1 ") points out 3 significantly to low field displacement, 7-dimethyl-octa-2, the 6-dialkylene may be connected the C-8 position, by H-1 " and with carbon signal 150.9 (C-7), 120.2 (C-8), the HMBC of 118.3 (C-8a) is relevant also can to prove conclusively.Fragrance hydrogen signal δ
H7.13 (H-6) with carbon signal C-7, C-8 is relevant, determines that it is connected the C-6 position.So this chemical compound is accredited as 1,3,7-trihydroxy-2-(3-methyl but-2-ene)-8-(3,7-dimethyl-octa-2,5-diene)-two benzene pyrrones through the SciFinder network retrieval, does not find relevant report, shows that this is a noval chemical compound.
1H-NMR and
13The C-NMR data see Table 1.Its structural formula is as follows:
Table 1 NMR Data of CF-1and CF-2 (400MHz for
1H NMR)
aMeasured?in.acetone-d
6?
bMeasured?in?chloroform-d
1.
c?Siganls?may?be?interchangeable?in?each?column.
Compound C F-3, yellow powder, the ferric chloride colour developing is positive, and prompting has the existence of phenolic hydroxyl group.UV (MeOH) λ
Max(log ε) 205 (4.78), 238 (4.50), 269 (4.41), 281 (4.09), 309 (4.23), 372 (4.23) nm; IR (KBr) v
Max3435,1619,1473,1293,1081,782cm
-1HR-ESI-Q-TOF-MS provides m/z 303.0509[M-H]
-(cacled for C
15H
11O
7, 303.0510), infer molecular formula C
15H
12O
7, calculating degree of unsaturation is 10.
1H-NMR composes (400MHz, in acetone-d
6) in, δ
H13.26 (1H, s 8-OH) prompt for the hydroxyl hydrogen signal of hydrogen bond association, two fragrant hydrogen signal δ that intercouple
H7.24,6.79 (1H, each, d, J=8.8Hz, H-6and H-5), point out one 1,2,3, the existence of 4-four substituted benzene rings, another one fragrance hydrogen signal δ
H6.73 (H-4) there is δ in one five phenyl ring that replaces of prompting for 1H, s
H3.97,3.90 (3H, each, s, 3-OCH
3) be two methoxyl group hydrogen signals.
In the HMBC collection of illustrative plates, association hydroxyl hydrogen signal δ
H13.26 (8-OH) with carbon signal δ
C148.9 (C-8), 141.0 (C-7), 109.5 (C-8a) are relevant, and fragrant hydrogen signal δ
H7.24 (H-6) with carbon signal C-8, C-7 is relevant, determines that fragrant hydrogen signal H-6 and 6.79 (H-5) base of intercoupling are connected C-6, the C-5 position.Two methoxyl group δ
H3.97,3.90 (3H, each, s, 3-OCH
3) the carbon geochemistry displacement be respectively δ 62.1,61.6, infer that all there is substituent group at their ortho position, simultaneously according to the chemical displacement value of H-4 (δ 6.73), determine that finally this structure is 1,2-methoxyl group-3,7,8-trihydroxy-two benzene pyrrones.
1H-NMR and
13The C-NMR data see Table 2, and its structural formula is as follows:
Table 2 NMR Data (400MHz for
1H, in acetone-d
6)
Compound C F-4, pale brown toner end, the ferric chloride demonstration is positive, and prompting has phenolic hydroxyl group to exist.ESI-MS (negative) provides m/z 363[M-H]
-, the prompting molecular weight is 364.In conjunction with
1H-NMR and
13The C-NMR data infer that its molecular formula is C
23H
24O
4, calculating degree of unsaturation is 12.With document (Phytochemistry, 1992,31 (1), the data in 313-316) relatively, basically identical is 1,3 so identify this chemical compound, 5-trihydroxy-4-(3,7-dimethyl-octa-2,5-diene)-two benzene pyrrones.
1H-NMR and
13The C-NMR data see Table 3.Its structural formula is as follows:
Table 3 NMR Data (400MHz for
1H, in CDCl
3+ CD
3OD)
Compound C F-5, yellow powder, the ferric chloride demonstration is positive, and prompting has phenolic hydroxyl group to exist.ESI-MS (negative) provides m/z 395[M-H]
-, the prompting molecular weight is 396.In conjunction with
1H-NMR and
13The C-NMR data infer that its molecular formula is C
23H
24O
6, calculating degree of unsaturation is 12.With document (Bioorganic ﹠amp; Medicinal Chemistry, 2004,12,1947-1953) data in compare, and basically identical is 1,3,6 so identify this chemical compound, 7-four-hydroxyl-2,4-two (3-methyl butyl-2-alkene)-two benzene pyrrones.
1H-NMR and
13The C-NMR data see Table 4.Its structural formula is as follows:
Table 4 NMR Data (400MHz for
1H, in acetone-d
6)
Compound C F-6, yellow powder, the ferric chloride demonstration is positive, and prompting has phenolic hydroxyl group to exist.ESI-MS (negative) provides m/z 395[M-H]
-, the prompting molecular weight is 396.In conjunction with
1H-NMR and
13The C-NMR data infer that its molecular formula is C
23H
24O
6, calculating degree of unsaturation is 12.With document (Food and Chemical Toxicology, 2008,46, the data in 688-693) relatively, basically identical is 1,3,6 so identify this chemical compound, 7-tetrahydroxy-2,8-two (3-methyl butyl-2-alkene)-two benzene pyrrones.
1H-NMR and
13The C-NMR data see Table 5.Its structural formula is as follows:
Table 5 NMR Data (400MHz for
1H, in acetone-d
6)
Compound C F-7, pale yellow powder, the ferric chloride demonstration is positive, and prompting has phenolic hydroxyl group to exist.ESI-MS (negative) provides m/z 341[M-H]
-, ESI-MS (positve) provides m/z 343[M+H]
+, the prompting molecular weight is 342.In conjunction with
1H-NMR and
13The C-NMR data infer that its molecular formula is C
19H
18O
6, calculating degree of unsaturation is 11.With document (Phytochemistry, 1996,43 (2), the data in 513-520) relatively, basically identical is 1 so identify this chemical compound, 6-dihydroxy-5-methoxyl group-4,5-dihydro-4,4,5-trimethyl furan [2 ', 3 ': 3,4]-two benzene pyrrones.
1H-NMR and
13The C-NMR data see Table 6.Its structural formula is as follows:
Compound C F-8, yellow powder, the ferric chloride demonstration is positive, and prompting has phenolic hydroxyl group to exist.ESI-MS (negative) provides m/z 341[M-H]
-, the prompting molecular weight is 342.In conjunction with
1H-NMR and
13The C-NMR data infer that its molecular formula is C
19H
18O
6, calculating degree of unsaturation is 11.With document (Phytochemistry, 1972,11 (6), the data in 2089-2092.) relatively, basically identical is 1,5 so identify this chemical compound, 6-trihydroxy-3-methoxyl group-4-(2-methyl butyl-3-alkene-2-yl)-two benzene pyrrones,
1H-NMR and
13The C-NMR data see Table 6.Its structural formula is as follows:
Table 6 NMR Data of CF-7and (400MHz for
1H NMR, in acetone-d
6)
a：Measured?in?Acetone-d
6，
b：Measured?in?CDCl
3+CD
3OD
Compound C F-9, yellow powder, the ferric chloride demonstration is positive, and prompting has phenolic hydroxyl group to exist.ESI-MS (negative) provides m/z 257[M-H]
-, the prompting molecular weight is 258.In conjunction with
1H-NMR and
13The C-NMR data infer that its molecular formula is C
14H
10O
5, calculating degree of unsaturation is 10.With document (Phytochemistry, 1998,49 (7), the data in 2159-2162) relatively, basically identical is 1 so identify this chemical compound, 7-dihydroxy-8-methoxyl group-two benzene pyrrones.
1H-NMR and
13The C-NMR data see Table 7.Its structural formula is as follows:
Compound C F-10, yellow powder, the ferric chloride demonstration is positive, and prompting has phenolic hydroxyl group to exist.ESI-MS (negative) provides m/z 258[M-H]
-, 515[2M-H]
-, the prompting molecular weight is 258.In conjunction with
1H-NMR and
13The C-NMR data infer that its molecular formula is C
14H
10O
5, calculating degree of unsaturation is 10.With document (Planta Medica, 1999, the data in 65:368-371) relatively, basically identical is 1 so identify this chemical compound, 6-dihydroxy-5-methoxyl group-two benzene pyrrones.
1H-NMR and
13The C-NMR data see Table 7.Its structural formula is as follows:
Table 7 NMR Data of CF-9and CF-10 (400MHz for
1H NMR)
a：Measured?in?CDCl
3，
b：Measured?in?DMSO-d
6.
Compound C F-11, yellow powder, the ferric chloride demonstration is positive, and prompting has phenolic hydroxyl group to exist.ESI-MS (negative) provides m/z 273[M-H]
-, the prompting molecular weight is 274.In conjunction with
1H-NMR and
13The C-NMR data infer that its molecular formula is C
14H
10O
6, calculating degree of unsaturation is 10.With document (Phytochemistry, 1996,42 (4), the data in 1195-1198) relatively, basically identical is 1,4 so identify this chemical compound, 7-trihydroxy-8-methoxyl group-two benzene pyrrones.
1H-NMR and
13The C-NMR data see Table 8.Its structural formula is as follows:
Compound C F-12, yellow powder, the ferric chloride demonstration is positive, and prompting has phenolic hydroxyl group to exist.ESI-MS (negative) provides m/z 287[M-H]
-, the prompting molecular weight is 288.In conjunction with
1H-NMR and
13The C-NMR data infer that its molecular formula is C
15H
12O
6, calculating degree of unsaturation is 10.(Phytochemistry 1993,33, and 809-812) data in compare, and basically identical is 1 so identify this chemical compound, 6-dihydroxy-7,8-dimethoxy-two benzene pyrrones with document.
1H-NMR and
13The C-NMR data see Table 8.Its structural formula is as follows:
Table 8 NMR Data of CF-11 and CF-12 (400MHz for
1H NMR)
a：Measured?in?Acetone-d
6，
b：Measured?in?CDCl
3+CD
3OD.
Compound C F-13, yellow powder, the ferric chloride colour developing is positive, and prompting has phenolic hydroxyl group to exist.ESI-MS (negative) provides m/z 273[M-H]
-, the prompting molecular weight is 274.In conjunction with
1H-NMR and
13The C-NMR data infer that its molecular formula is C
14H
10O
6, calculating degree of unsaturation is 10.With document (Planta Medica, 2002,68, the data in 49-54) relatively, basically identical is 1,3 so identify this chemical compound, 6-trihydroxy-5-methoxyl group-two benzene pyrrones.
1H-NMR and
13The C-NMR data see Table 9.Its structural formula is as follows:
Compound C F-14, yellow powder, the ferric chloride colour developing is positive, and prompting has phenolic hydroxyl group to exist.ESI-MS (negative) provides m/z 257[M-H]
-, the prompting molecular weight is 258.In conjunction with
1H-NMR and
13The C-NMR data infer that its molecular formula is C
14H
10O
5, calculating degree of unsaturation is 10.With document (Acta Chemica Scandinavica SeriesB:Organic Chemistry and Biochemistry 1987, B41 (3), 210-212) data in compare, basically identical, so identify that this chemical compound is 1,5-dihydroxy-6-methoxyl group-two benzene pyrrones.
1H-NMR and
13The C-NMR data see Table 9.Its structural formula is as follows:
Table 9 NMR Data of CF-13and CF-14 (400MHz for
1H)
a：Measured?in?DMSO-d
6，
b：Measured?in?Acetone-d
6.
Compound C F-15, yellow powder, the ferric chloride demonstration is positive, and prompting has phenolic hydroxyl group to exist.ESI-MS (negative) provides m/z 227[M-H]
-, 455[2M-H]
-, the prompting molecular weight is 228.In conjunction with
1H-NMR and
13The C-NMR data infer that its molecular formula is C
13H
8O
4, calculating degree of unsaturation is 10.With document (Journal of ChemicalCrystallography, 2005,35 (1), the data in 23-25) relatively, basically identical is 1 so identify this chemical compound, 7-dihydroxy-two benzene pyrrones.
1H-NMR and
13The C-NMR data see Table 10.Its structural formula is as follows:
Compound C F-16, yellow powder, the ferric chloride demonstration is positive, and prompting has phenolic hydroxyl group to exist.ESI-MS (negative) provides m/z 243[M-H]
-, the prompting molecular weight is 244.In conjunction with
1H-NMR and
13The C-NMR data infer that its molecular formula is C
13H
8O
5, calculating degree of unsaturation is 10.(Phytochemistry, 1996,42 (4): the data 1195-1198) compare, and basically identical is 1,4 so identify this chemical compound, 7-trihydroxy-two benzene pyrrones with document.
1H-NMR and
13The C-NMR data see Table 10.Its structural formula is as follows:
Table 10 NMR Data of CF-15and CF-16 (, 400MHz for
1H)
a：Measured?in?CDCl
3+CD
3OD，
b：Measured?in?Acetone-d
6.
Embodiment 2: the two benzene pyrrones chemical compounds of extraction separation from cattle wood
The dry stem (6Kg) of Guttiferae cattle fogfruit cattle wood (Cratoxylum cochinchinense), with 60% (V/V) alcohol-water heating and refluxing extraction, concentrated extract, adopt ethyl acetate respectively, n-butyl alcohol carries out equal-volume extraction 3 times, ethyl acetate extraction part, be the total two benzene pyrrone positions (142.5g) of cattle wood, through silica gel column chromatography, (98: 2-0: 100) gradient elution obtains 10 sub-fractions (Fr.1～Fr.10) to cyclohexane extraction-acetone.From sub-fraction Fr.2 (95: 5 eluting parts, 1.9g), in separate out crystallization, after the filtration, in cyclohexane extraction-acetone, obtain Compound C C-5 (187mg) through recrystallization.Sub-fraction Fr.4 (9: 1 eluting parts, 17.5g), Fr.5 (85:15 eluting part, 9.6g) and Fr.6 in insoluble matter recrystallization in methanol obtain Compound C C-3 (210mg), CC-4 (830mg) and CC-2 (145mg).(9: 1 eluting parts, 14.7g) through silica gel mesolow column chromatography, (9: 1-7: 1) gradient elution obtains 9 sub-fractions (Fr.3-1～Fr.3-9) to cyclohexane extraction-acetone to sub-fraction Fr.3.(7: 1 eluting parts are separated out crystallization in 630mg) to sub-fraction Fr.3-7, obtain Compound C C-1 (67mg) after the filtration.
By physicochemical constant and modern Wave Spectrum means (MS, NMR), in conjunction with the document related data, identified their structure, as follows.
Annotate: have
*The person is a noval chemical compound.
Compound C C-1, yellow powder,
(c 0.568, acetone).UV (CH
3OH) λ
Max(log ε): 378 (3.68), 323 (4.08), 266 (4.40), 241 (4.36), 231 (4.39), 204 (4.38); IR (KBr) v
Max3283cm
-1There is hydroxyl to have 1668cm in the prompting structure
-1There is carbonyl to exist in the prompting structure.ESI-MS (positive), provide m/z487[M+Na]
+, ESI-MS (negative) provides m/z 463[M-H]
-, releasing compound molecular weight is 464.HR-TOF-MS provides m/z 487.2083 ([M+Na]
+, value of calculation is 487.2097), determine that the compound molecule formula is C
28H
32O
6, calculating its degree of unsaturation is 13.
1H-NMR (400MHz, in DMSO-d
6) show 32 hydrogen signals, in conjunction with the HSQC collection of illustrative plates, confirm wherein to contain 1 association close phenolic hydroxyl group hydrogen signal δ 12.96 (1H, s), 1 phenolic hydroxyl group hydrogen signal δ 9.91 (1H, s), 1 hydroxyl hydrogen signal δ 4.68 (1H, s), 3 fragrant hydrogen signals [δ 7.38 (1H, d, J=9.0Hz), 7.38 (1H, d, J=3.0Hz), 7.25 (1H, dd, J=9.0,3.0Hz)], and 2 alkene methine hydrogen signals [δ 5.20 (1H, brt), δ 4.94 (1H, brt)], 1 oxygen methine hydrogen signal [δ 4.70 (1H, m)] even, 4 groups of methylene hydrogen signals [δ 3.30 (2H, m), 3.07 (2H, m), 1.95 (2H, m), 1.89 (2H, m)], 5 groups of methyl hydrogen signal [δ 1.77 (3H, s), and δ 1.46 (3H, s), δ 1.43 (3H, s), 1.17 (3H, s), δ 1.10 (3H, s)].
13C-NMR (100MHz, in DMSO-d
6) collection of illustrative plates shows 28 spectral lines altogether, comprises 1 carbonyl carbon signal (δ 179.9), 11 sp as can be known in conjunction with DEPT135 and HSQC collection of illustrative plates
2Hydridization quaternary carbon signal (δ 165.4,154.7,154.2,153.8,148.9,134.6,130.5,120.0,107.1,102.7,101.1), wherein 5 is to connect oxygen quaternary carbon, 5 sp
2Hydridization tertiary carbon signal (δ 124.2,123.9, and 121.5,118.7,107.8), 1 company's oxygen quaternary carbon signal (δ 70.1), 1 company's oxygen tertiary carbon signal (δ 91.1), (δ 38.9,26.2 for 4 mesomethylene carbon signals, 25.9,21.4) 5 methyl carbon signals (δ 26.1,25.2, and 24.0,17.3,15.8).Comprehensively
1H-NMR,
13C-NMR data, molecular formula and degree of unsaturation can infer that this chemical compound for two benzene pyrrones chemical compounds, contains three hydroxyls in the structure.
1In the H-NMR collection of illustrative plates δ 12.96 (1H, s 1-OH) locate to exist an association hydroxyl signal, δ 9.91 (1H, s 7-OH) locate to exist a free phenolic hydroxyl group signal, δ 9.91/C-6 in the HMBC spectrum, C-7, the relevant of C-8 proved that it is connected on the C-7.δ 7.38 (1H, d, J=9.0Hz, H-5), 7.25 (1H, dd, J=9.0,3.0Hz, H-6) and 7.38 (J=3.0Hz H-8) locates three fragrant proton signals and shows that a phenyl ring in the structure has ABX coupling system for 1H, d.δ 7.38/C-6 in the HMBC spectrum, C-7, C-8a, C-10a, 7.25/C-7, C-8, C-10a, 7.38/C-6, C-7, C-9, C-8a, C-10a relevant proved that they should belong to and has been H-5, H-6 and H-8.
1H and
13δ in the C-NMR collection of illustrative plates
H(3.07 2H, m, H-4 ')/
C(26.2 C-4 '), 4.70 (1H, m, H-5 ')/91.1 (C-5 '), 1.17 (3H, s, H-7 ')/26.1 (C-7 '), 1.10 (3H, s, H-8 ')/24.0 (C-8 '), δ
C(70.1 C-6 '), δ
H4.68 (1H, s, 6 '-OH) show in the structure and to have one five carbon unit.Visible following relevant in the HMBC spectrum: H-4 '/C-2, C-6 ', H-5 '/C-3, H-7 '/C-5 ', C-6 ', C-8 ', H-8 '/C-5 ', C-6 ', C-7 ' and 6 '-OH/C-6 ' deducibility thus go out this five carbon unit and are one and are being connected the 1-hydroxyl-substituent dihydrofuran ring plate of 1-Methylethyl section, the dihydrofuran ring is connected on the C-2 and C-3 of two benzene pyrrone parent nucleus, and 1-hydroxyl-1-Methylethyl is connected on the C-2 ' of dihydropyran ring.
1H and
13δ in the C-NMR collection of illustrative plates
H3.30 (2H, m, H-1 ")/δ
C21.4 (C-1 "), 5.20 (1H, br t, H-2 ")/121.5 (C-2 "); 1.89 (2H, m, H-4 ")/38.9 (C-4 "), 1.95 (2H; m, H-5 ")/25.9 (C-5 "), 4.94 (1H, br t; H-6 ")/123.9 (C-6 "), 1.46 (3H, s, H-8 ")/25.2 (C-8 "); 1.77 (3H, s, H-9 ")/15.8 (C-9 "), 1.43 (3H; s, and H-10 ")/17.3 (C-10 "), δ
C134.6 (C-3 "), 130.5 (C-7 ") shows in the structure and to have one 3,7-dimethyl-octa-2,6-dialkylene substituent group.And according to H-1 in the HMBC spectrum " and C-3, it is connected the relevant deduction with C-4a of C-4 on the C-4.
Comprehensive HSQC and HMBC collection of illustrative plates belong to the whole carbon signals and the hydrogen signal of this chemical compound.Through the SciFinder network retrieval, do not find relevant report, show that this is new two benzene pyrrones chemical compounds, called after 1,7-dihydroxy-4-(3,7-dimethyl-octa-2,6-diene)-5 '-(1-hydroxyl-1-Methylethyl)-4 ', 5 ' dihydrofuran [2 ', 3 ': 3,2]-two benzene pyrrones
1H-NMR and
13The C-NMR data see Table 11, and its structural formula is as follows:
Compound C C-2, yellow solid.
366，322，259，243，203。IR (KBr) v
Max3349cm
-1There is hydroxyl to have 1645cm in the prompting structure
-1There is carbonyl to exist in the prompting structure.ESI-MS (positive) provides m/z 465[M+H]
+, ESI-MS (negative) provides m/z 463[M-H]
-, releasing compound molecular weight is 464.In conjunction with
1H-NMR and
13The C-NMR data determine that the compound molecule formula is C
28H
32O
6, calculating its degree of unsaturation is 13.With document (Phytochemistry, 2006,67,470-474) Bao Dao data compare, basically identical.So this chemical compound is accredited as passeris montani saturati cage wood ketone B, cochinchinone B.
1H-NMR and
13The C-NMR data see Table 11, and its structural formula is as follows:
Table 11 NMR data of CC-1and CC-2 (400MHz for
1H NMR)
aMeasured?in?DMSO-d
6，
bMeasured?in?acetone-d
6.
Compound C C-3, yellow needle,
383,381,317,267,235,202.IR (KBr) v
Max3282cm
-1There is hydroxyl to have 1644cm in the prompting structure
-1There is carbonyl to exist in the prompting structure.ESI-MS (positive) provides m/z 403[M+Na]
+, ESI-MS (negative) provides m/z 379[M-H]
-, releasing compound molecular weight is 380.In conjunction with
1H-NMR and
13The C-NMR data determine that the compound molecule formula is C
23H
24O
5, calculating its degree of unsaturation is 12.With document (Chemical and Pharmaceutical Bulletin, 1996,44,232-234) data of report relatively, basically identical, so this chemical compound is accredited as 1,3,7-trihydroxy-2,4-two (3-methyl butyl-2-alkene)-two benzene pyrrones.
1H-NMR and
13The C-NMR data see Table 12, and its structural formula is as follows:
Compound C C-4, yellow needle,
Nm:363,316,260,243,204.IR (KBr) v
Max3356cm
-1There is hydroxyl to have 1648cm in the prompting structure
-1There is carbonyl to exist in the prompting structure.ESI-MS (positive) provides m/z 433[M+Na]
+, ESI-MS (negative) provides m/z 409[M-H]
-, releasing compound molecular weight is 410.In conjunction with
1H-NMR and
13The C-NMR data determine that the compound molecule formula is C
24H
26O
6, calculating its degree of unsaturation is 12.With document (Natural Products Research, 2006,20,1332-1337) data of report relatively, basically identical is so this chemical compound is accredited as Indonesia Resina garciniae ketone B, dulcisxanthone B.
1H-NMR and
13The C-NMR data see Table 12, and its structural formula is as follows:
Table 12 NMR data of CC-3and CC-4 (400MHz for
1H NMR, in acetone-d
6).
Compound C C-5, yellow prismatic crystal, UV (CH
3OH) nm:314,258,243,204; IR (KBr) v
Max3402cm
-1There is hydroxyl to have 1600cm in the prompting structure
-1There is carbonyl to exist in the prompting structure.ESI-MS (positive) provides m/z 447[M+Na]
+, ESI-MS (negative) provides m/z 423[M-H]
-, releasing compound molecular weight is 424.In conjunction with
1H-NMR and
13The C-NMR data determine that the compound molecule formula is C
25H
28O
6, calculating its degree of unsaturation is 12.With document (Australian Journal of Chemistry, 1970,23,2539-2543) data of report relatively, basically identical, so this chemical compound is accredited as β-mangostin,
1H-NMR and
13The C-NMR data see Table 13, and its structural formula is as follows:
Table 13 NMR data of CC-5 (400MHz for
1H NMR, in acetone-d
6).
Embodiment 3: the influence that two benzene pyrrones chemical compounds of embodiment 1 gained are expressed TR3mRNA
Present embodiment adopts RT-PCR to analyze.The NIH-H460 lung carcinoma cell is inoculated in 6 orifice plates (5 * 10
5Cells/well), adhere-wall culture is spent the night, and behind the hungry 12h, dosing is cultivated.Press total RNA that the explanation of total RNA extraction reagent box is extracted and purifying cells is.And the mRNA of cell total rna is transcribed into cDNA according to reverse transcription test kit explanation.PCR condition: cDNA 4 μ L in the 20 μ L systems, 10 * PCR buffer, 25mmol/L MgCl
2, 10mmol/L dNTPs adds TR3 primer 10 μ mol/L at every turn, and Taq enzyme 1U is reflected in the PCR instrument and carries out.94 ℃ of 4min, 94 ℃ of 30sec, 56 ℃ of 30sec, 72 ℃ of 30sec, 35 circulations.The PCR primer sequence: TR3 upstream 5 '-TCA TGGACG GCT ACA CAG-3 ', downstream 5 '-GTA GGC ATG GAA TAG CTC-3 '; β-actin upstream 5 '-CTGGAG AAG AGC TAC GAG-3 ', downstream 5 '-TGA TGG AGT TGA AGG TAG-3 '.The two benzene pyrrones chemical compounds of experimental result demonstration can be induced the expression of TR3mRNA, and have certain dose-effect relationship.Fig. 1-the 3rd, the cardiac glycoside compounds of embodiment 1 gained influence figure to what the mRNA of TR3 expressed under variable concentrations.Wherein, Compound C F1, CF2, CF3, CF5, CF6, CF7, CF8, CF10, CF13, CF14, CF16 can induce TR3mRNA under 1 μ M concentration expression, activity intensity is suitable with positive control drug TPA, and pointing out above-mentioned pair of benzene pyrrones chemical compound is the derivant of TR3.
Embodiment 4: the two benzene pyrrones chemical compounds of the present invention are to the lethal effect of tumor cell
Present embodiment adopts the inhibitory action of mtt assay test compounds to tumor cell.Select degrees of fusion 80%, the cell of logarithmic (log) phase growth is used trypsinization, shifts, and is centrifugal, removes supernatant, with the DMEM culture fluid suspendible that contains 10%FBS (the calf fetal blood of deactivation is clear) of new preparation.Various cells are with 1.0 * 10
4/ hole is inoculated in 96 well culture plates and adds successively simultaneously all that 5 differences are dilution waits to sieve the sample medicinal liquid, and each dilution factor repeats 3 holes, simultaneously parallel solvent control of doing same concentrations, and the negative control of not dosing, cultivated 72 hours MTT dyeing for 37 ℃, OD is measured in the DMSO decolouring
570, calculate inhibition rate of tumor growth IR (%)=(blank OD meansigma methods-administration group OD meansigma methods)/blank OD meansigma methods * 100.Experimental result is referring to table 14.The result shows, red bud wood among embodiment 1 and the embodiment 2 and the total two benzene pyrrone positions of cattle wood and 13 pairs of benzene pyrrones chemical compounds are to 4 kinds of tumor cells of human body: breast cancer cell MCF-7; Non-small lung cancers cell H-460; Hepatoma carcinoma cell HepG2; The propagation of SMMC-7221 has inhibitory action in various degree.
Table 14: the external tumor experimental data that presses down of two benzene pyrrones chemical compounds
Embodiment 5: the preparation of the total two benzene pyrrone positions of red bud wood granule
Get the total two benzene pyrrone position 5g of the red bud wood of embodiment 1 gained and mix, add water and make soft material, cross 12 mesh sieves and carry out pelletize, obtain granule after the drying with starch 25g.In this granule, contain total two benzene pyrrone position 50mg among every 300mg.
Embodiment 6: the preparation of cattle wood and the total two benzene pyrrone position mixing tablets of red bud wood
Get wooden total two each 5g of benzene pyrrone position of total two benzene pyrrone positions of embodiment 2 gained cattlees wood and the red bud of embodiment 1 gained and mix with sodium carboxymethyl cellulose 36g and Pulvis Talci 4g, mixture breaks into diameter 6mm with single punch tablet machine, the sheet of weight 500mg.Every contains total two benzene pyrrone position 100mg in this tablet.
Embodiment 7:1,6, the preparation of 7-trihydroxy-2-(3-methyl but-2-ene)-3-methoxyl group-8-(3-hydroxy-3-methyl butyl)-two benzene pyrrones (CF-1) tablet
Get 1,6,7-trihydroxy-2-(3-methyl but-2-ene)-3-methoxyl group-8-(3-hydroxy-3-methyl butyl)-two benzene pyrrones (CF-1) 1g mixes with microcrystalline Cellulose 27g and magnesium stearate 2g, and mixture breaks into diameter 6mm with single punch tablet machine, the sheet of weight 300mg.Every contains 1,6 in this tablet, 7-trihydroxy-2-(3-methyl but-2-ene)-3-methoxyl group-8-(3-hydroxy-3-methyl butyl)-two benzene pyrrone 10mg.
Embodiment 8:1,7-dihydroxy-4-(3,7-dimethyl-octa-2,6-diene)-5 '-(1-hydroxyl-1-Methylethyl)-4 ', 5 '-dihydrofuran [2 ', 3 ': 3,2]-preparation of two benzene pyrrones (CC-1) capsule
Get 1,7-dihydroxy-4-(3,7-dimethyl-octa-2,6-diene)-5 '-(1-hydroxyl-1-Methylethyl)-4 ', 5 '-dihydrofuran [2 ', 3 ': 3,2]-two benzene pyrrones (CC-1) 1g mixes with lactose 27g, magnesium stearate 2g, with every 300mg filled capsules.
In this capsule, each capsule contains 1,7-dihydroxy-4-(3,7-dimethyl-octa-2,6-diene)-5 '-(1-hydroxyl-1-Methylethyl)-4 ', 5 '-dihydrofuran [2 ', 3 ': 3,2]-two benzene pyrrone 10mg.
Embodiment 9:1,3,7-trihydroxy-2-(3-methyl but-2-ene)-8-(3,7-dimethyl-octa-2,5-diene)-two benzene pyrrones (CF-2) and 1,2-methoxyl group-3,7, the preparation of 8-trihydroxy-two benzene pyrrones (CF-3) epoxy glue wafer
Get 1,3,7-trihydroxy-2-(3-methyl but-2-ene)-8-(3,7-dimethyl-octa-2, the 5-diene)-two benzene pyrrones (CF-2) and 1,2-methoxyl group-3,7,8-trihydroxy-each 1g of two benzene pyrrones (CF-3) mixes with lactose 25g, magnesium stearate 3g, with every 300mg filled capsules.In this capsule, each capsule contains two benzene pyrrones chemical compound 20mg.
Embodiment 10:1,2-methoxyl group-3,7,8-trihydroxy-two benzene pyrrones (CF-3) and 1,5, the preparation of 6-trihydroxy-3-methoxyl group-4-(2-methyl butyl-3-alkene-2-yl)-two benzene pyrrones (CF-8) compound recipe effervescent tablet
Get 1,2-methoxyl group-3,7,8-trihydroxy-two benzene pyrrones (CF-3) and 1,5,6-trihydroxy-3-methoxyl group-4-(2-methyl butyl-3-alkene-2-yl)-each 2g of two benzene pyrrones (CF-8) adds boric acid 6g, starch 10g, sodium bicarbonate 4g, microcrystalline Cellulose 12g and Pulvis Talci 4g mix, and mixture breaks into diameter 6mm with single punch tablet machine, the sheet of weight 400mg.Every contains 1 in this tablet, 2-methoxyl group-3,7,8-trihydroxy-two benzene pyrrones and 1,5,6-trihydroxy-3-methoxyl group-4-(2-methyl butyl-3-alkene-2-yl)-two benzene pyrrone 40mg.
Embodiment 11: the total two atherosclerotic experimentatioies of benzene pyrrone position CF Chinese People's Anti-Japanese Military and Political College Mus of red bud wood
(1) experimental animal: 50 of healthy cleaning level male SD rats, 8～10 ages in week, body weight 180～220g.
(2) feedstuff: machine-processed pellet, normal feedstuff prescription: flour 20% (quality percentage composition, down together), rice flour 2%, corn 20%, wheat bran 25%, bean material 20%, bone meal 2%, fish flour 2%; High lipid food prescription: 4% cholesterol, 10% Adeps Sus domestica, 0.2% methylthiouracil, 86% normal feedstuff.
(3) instrument and reagent FDAC 7060 type automatic clinical chemistry analyzers; LEO-1430VP scanning electron microscope difficult to understand in the Germany, cholesterol (going up seamount Pu chemical industry company limited, chemical pure); Triglyceride determination test kit, T-CHOL mensuration test kit, determine cholesterol with high density lipoprotein test kit, low-density lipoprotein cholesterol are measured test kit and are all built up the institute of biological products available from Nanjing.
(4) experimental technique
Animal grouping and administration experiment: get 12 rats from 50 SD rats at random, the normal feedstuff of feeding is as normal control group (A).Fed high lipid food after 1 month for all the other 38, stochastic sampling detects 2 rat aortas, to find that atheromatous plaque is the modeling success, all the other 36 the high lipid food rats of feeding are divided into 3 groups at random, every group 12, be hyperlipidemia model group (B), low dose group, 0.5g/kg (C), high dose group, 2g/kg (D).The medication group is irritated the medicine of stomach corresponding dosage, and model group and normal control group are all irritated stomach equivalent distilled water simultaneously.Irritating the stomach amount is every rat 0.5ml/d, totally 8 weeks.
Observation index: rat is injected 2% sodium pentobarbital 45mg/kg intraperitoneal anesthesia, cut neck portion from carotid artery, intubate is got blood 2.5mL, separation of serum, by the operational approach of each detection kit, measure T-CHOL (TC), triglyceride (TG), HDL-C (HDL-C), low-density lipoprotein cholesterol (LDL-C).
Aortic tissue is learned and is observed: open the thoracic cavity and separate aorta, peel off epicardial fat, cut big or small 1 of 5mm * 8mm from aortic arch, behind the clean surface of PBS buffer, drop into immediately in the 2.5% glutaraldehyde fixative, then with after the rinsing of PBS buffer, fix with 1% osmic acid, the abundant rinsing of reuse PBS buffer uses 50%, 70%, 90%, 100% (V/V) ethanol to dewater step by step then respectively totally 4 times, behind isoamyl acetate displacement ethanol, sample is moved into the liquid CO of critical point drying instrument
2Drying, behind the sample drying in ion sputtering instrument plated film, last scanning electron microscopic observation.
Statistical analysis: experimental result adopts (x ± represent that s) the SPSS10.0 statistical software carries out variance analysis.
(5) experimental result
Tested for the 8th weekend, high lipid food group (B group) serum TC, TG, LDL-C level are than the obvious rising of normal control group (A group), each medication group and high lipid food group (B group) are relatively, serum TC, TG, LDL-C content are reduced, and high dose group has apparent in view improvement effect, and effect is better than low dose group, when reducing TC, TG, LDL-C, rising HDL-C shows the effect (P＜0.01) that tangible accent blood fat is arranged, and the results are shown in Table 15.
Respectively organize rat fat relatively (mmol/L, x ± s) after table 15 treatment
Annotate: compare with the A group,
*Compare with the B group P＜0.01,
△P＜0.01
Each organizes rat scanning electron microscope result relatively, and normal group is seen the aortic tunica intima smooth surface, and is complete, and the vertical ridge of endotheliocyte is systematicness to be arranged, and directivity is arranged, and endotheliocyte does not have protuberance and strips off, and iuntercellular connects closely, surperficial deposit-free.Model group sees that many places, aortic tunica intima surface are rough; pathological changes is remarkable; be variation; cell is arranged and become irregular, and directivity changes, and connects between endotheliocyte to go to pot; the netted or worm-eaten sample of the visible pine in surface changes; there are a large amount of deposits on the surface, endotheliocyte atrophy, hypertrophy, swells, comes off, and the vertical ridge of formation is low flat.Add the total two benzene pyrrone positions (CF) of red bud wood high dose group and see that aortic tunica intima is the reparation state, the surface is more smooth, the vertical ridge that endotheliocyte is arranged is thicker, but than the model group rule, directivity is arranged, the endotheliocyte protuberance obviously, connect still tight, the accidental endotheliocyte that comes off, the visible a small amount of adherent granule in surface, but do not have a large amount of deposits, do not see the netted or worm-eaten sample change of pine yet.Low dose group sees that aortic tunica intima is rough, and the vertical ridge of endotheliocyte is scrambling to be arranged, non-directional, endotheliocyte is protuberance, hypertrophy, the deep mixed gully of formation, be changes such as Folium Salicis Babylonicae shape, botryoidalis, iuntercellular connects more loose, and there are a large amount of deposits on the surface.
The foregoing description is a preferred implementation of the present invention; but embodiments of the present invention are not restricted to the described embodiments; other any do not deviate from change, the modification done under spirit of the present invention and the principle, substitutes, combination, simplify; all should be the substitute mode of equivalence, be included within protection scope of the present invention.
Claims (8)
1. compositions, it is characterized in that: said composition comprises the two benzene pyrrones chemical compounds that have suc as formula (I) described structure:
R wherein
1Be OH or OCH
3R
2Be H, OCH
3Or substituted radical D; R
3Be H, OH or OCH
3R
4Be H, OH, substituted radical D, substituted radical E or substituted radical F; R
5Be H, OH, OCH
3Or substituted radical F, R
6Be H, OH or OCH
3, R
7Be H, OH or OCH
3, R
8Be H, OH, OCH
3, substituted radical C, substituted radical D or substituted radical F, and R
2And R
3Between connect substituted radical A, R
3And R
4Between connect substituted radical B,
2. compositions according to claim 1, it is characterized in that: described pair of benzene pyrrones chemical compound is 1,6,7-trihydroxy-2-(3-methyl but-2-ene)-3-methoxyl group-8-(3-hydroxy-3-methyl butyl)-two benzene pyrrones, 1,3, and 7-trihydroxy-2-(3-methyl but-2-ene)-8-(3,7-dimethyl-octa-2, the 5-diene)-two benzene pyrrones, 1,2-methoxyl group-3,7,8-trihydroxy-two benzene pyrrones and 1,7-dihydroxy-4-(3,7-dimethyl-octa-2, the 6-diene)-5 '-(1-hydroxyl-1-Methylethyl)-4 ', 5 '-dihydrofuran [2 ', 3 ': 3,2]-in two benzene pyrrones more than one.
3. compositions according to claim 1, it is characterized in that: the preparation method of described pair of benzene pyrrones chemical compound is by following operating procedure: the dry stem of Guttiferae cattle fogfruit cattle wood or red bud wood is ground into coarse powder, immerse to extract in the solvent cold extraction or heating and refluxing extraction in extracting solvent, filter or the centrifugal insoluble matter of removing, again gained is extracted solution and carry out concentrating under reduced pressure, separate the two benzene pyrrones chemical compounds that obtain suc as formula (I) described structure.
4. compositions according to claim 3 is characterized in that: described extraction solvent is that volume fraction is 60% ethanol; Described extracting method is a reflux, extract,, and described extraction time is 6 hours; Described separation is to adopt chromatography method and/or extraction to separate.
5. compositions according to claim 1 is characterized in that: the quality percentage composition of two benzene pyrrones chemical compounds is 3.3-16.7% in the described compositions.
6. the application of compositions according to claim 1 in preparation TR3 receptor inducer.
7. a compositions as claimed in claim 1 is applied to preparation prevention or treatment cancer, hepatitis or atherosclerotic food or pharmaceuticals as the TR3 receptor inducer.
8. application according to claim 7 is characterized in that: described TR3 receptor inducer and pharmaceutically acceptable carrier are mixed and made into powder, tablet, capsule, pill, suppository, drop pill, enteric agents, injection, syrup, Emulsion, suspensoid, tincture, unguentum or spray.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201010191471A CN101889998B (en) | 2010-05-28 | 2010-05-28 | Composition and application thereof as TR3 receptor inducer |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201010191471A CN101889998B (en) | 2010-05-28 | 2010-05-28 | Composition and application thereof as TR3 receptor inducer |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101889998A true CN101889998A (en) | 2010-11-24 |
| CN101889998B CN101889998B (en) | 2012-10-03 |
Family
ID=43099458
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201010191471A Expired - Fee Related CN101889998B (en) | 2010-05-28 | 2010-05-28 | Composition and application thereof as TR3 receptor inducer |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101889998B (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102552237A (en) * | 2010-12-22 | 2012-07-11 | 财团法人工业技术研究院 | Pharmaceutical composition and health food for preventing hepatic fibrosis or liver cirrhosis |
| WO2013036207A1 (en) * | 2011-09-08 | 2013-03-14 | Agency For Science, Technology And Research | Derivatives of xanthone compounds |
| CN103724313A (en) * | 2013-11-28 | 2014-04-16 | 江苏康缘药业股份有限公司 | Antineoplastic compound extracted from cambogia and preparation method and application of antineoplastic compound |
| WO2020162638A1 (en) * | 2019-02-08 | 2020-08-13 | 学校法人近畿大学 | Composition for ameliorating malignant tumor diseases |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1449399A (en) * | 2000-06-29 | 2003-10-15 | 拜奥马研究所有限公司 | Polycyclic xanthones as antibiotics |
| CN101278982A (en) * | 2007-05-24 | 2008-10-08 | 林隆金 | Chinese medicine compound preparation for curing acute or chronic hepatitis B and method of preparing the same |
-
2010
- 2010-05-28 CN CN201010191471A patent/CN101889998B/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1449399A (en) * | 2000-06-29 | 2003-10-15 | 拜奥马研究所有限公司 | Polycyclic xanthones as antibiotics |
| CN101278982A (en) * | 2007-05-24 | 2008-10-08 | 林隆金 | Chinese medicine compound preparation for curing acute or chronic hepatitis B and method of preparing the same |
Non-Patent Citations (7)
| Title |
|---|
| 《 Natural Product Research》 20061231 Preecha Phuwapraisirisan, et al 《Antioxidant xanthones from Cratoxylum cochinchinense, Preecha Phuwapraisirisan, et al》 摘要，第1334页 1-8 第20卷, 第14期 2 * |
| 《Bioorganic & Medicinal Chemistry》 20040415 Ying-Shu Zou，et al 《Cytotoxic isoprenylated xanthones from Cudrania tricuspidata》 摘要，第1949页 1-8 第12卷, 2 * |
| 《Chemical & Pharmaceutical Bulletin》 20061231 Lanphookhied S, et al 《Cytotoxic and antimalarial prenylated xanthones from Cratoxylum cochinchinense》 第745-747页 1-7 第54卷, 第5期 * |
| 《Food and Chemical Toxicology》 20080229 Lih-Greeng Chen, et al 《Anti-inflammatory activity of mangostins from Garcinia mangostana》 摘要，第689页 1-8 第46卷, 第2期 2 * |
| 《Journal of Natural Products》 20020213 Eun-Kyoung Seo, et al 《Cytotoxic Prenylated Xanthones and the Unusual Compounds Anthraquinobenzophenones from Cratoxylum sumatranum》 第299-305页 1-8 第65卷, 第3期 * |
| 《Journal of Natural Products》 20020213 Eun-Kyoung Seo, et al 《Cytotoxic Prenylated Xanthones and the Unusual Compounds Anthraquinobenzophenones from Cratoxylum sumatranum》 第299-305页 1-8 第65卷, 第3期 2 * |
| 《天然产物研究与开发》 20081231 林贵贤等 《黄牛木属植物的化学成分与生物活性研究进展》 第1114-1124页 1-8 第20卷, 2 * |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102552237A (en) * | 2010-12-22 | 2012-07-11 | 财团法人工业技术研究院 | Pharmaceutical composition and health food for preventing hepatic fibrosis or liver cirrhosis |
| WO2013036207A1 (en) * | 2011-09-08 | 2013-03-14 | Agency For Science, Technology And Research | Derivatives of xanthone compounds |
| CN104114547A (en) * | 2011-09-08 | 2014-10-22 | 新加坡科技研究局 | Derivatives of xanthone compounds |
| JP2014531431A (en) * | 2011-09-08 | 2014-11-27 | エージェンシー フォー サイエンス，テクノロジー アンド リサーチ | Derivatives of xanthone compounds |
| CN103724313A (en) * | 2013-11-28 | 2014-04-16 | 江苏康缘药业股份有限公司 | Antineoplastic compound extracted from cambogia and preparation method and application of antineoplastic compound |
| WO2020162638A1 (en) * | 2019-02-08 | 2020-08-13 | 学校法人近畿大学 | Composition for ameliorating malignant tumor diseases |
| JPWO2020162638A1 (en) * | 2019-02-08 | 2021-12-16 | 学校法人近畿大学 | Composition for improving malignant tumor |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101889998B (en) | 2012-10-03 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101904880B (en) | Mangosteen total xanthone extract and application thereof in preparation of TR3 receptor inducer | |
| CN109575099A (en) | Dammarane saponins member derivative and its preparation method and application | |
| CN101889998B (en) | Composition and application thereof as TR3 receptor inducer | |
| CN101434635A (en) | Water-soluble phenolic triterpenoid with antineoplastic activity and preparation thereof | |
| CN102030796A (en) | Several cardiac glycoside compounds separated from rosebay and applications thereof | |
| WO2013113294A1 (en) | Sterol derivative, preparation method therefor and use thereof | |
| CN111825735B (en) | Dammarane sapogenin and oleanane sapogenin derivatives, preparation and application thereof | |
| CN101856351B (en) | Composition and use thereof in preparation of RXR receptor transcription inhibitor | |
| Xiao et al. | Bioactive substances inhibiting COX-2 and cancer cells isolated from the fibrous roots of Alangium chinense (Lour.) Harms | |
| CN107674054B (en) | Novel skeleton heteroterpene compounds, preparation method, pharmaceutical composition and anti-tumor application thereof | |
| CN110218198A (en) | A kind of naphthoquinones and triazole core skeleton derivative compound and its preparation method and application | |
| CN101323634B (en) | Induced nuclear receptor TR3 expressed cardiac glycoside compounds and use thereof | |
| CN101628863B (en) | New compounds separated from leaves of rubus corchorifolius and preparation method and application thereof | |
| WO2008146989A1 (en) | A pharmaceutical composition containing daurinol for the prevention and treatment of cancers | |
| CN110551090B (en) | Method for extracting antitumor active ingredients in traditional Chinese medicine rhizoma cibotii by ultrasonic waves | |
| CN105837592A (en) | Phloroglucinolo abietane diterpenoid compound, preparation method thereof and medicinal application | |
| CN111544458A (en) | Extractive of maihua spruce, preparation method and application in pharmacy | |
| CN109206392A (en) | A kind of coumarin kind compound and the preparation method and application thereof | |
| CN111978309B (en) | Tripterygium wilfordii source compound, application and preparation method thereof, pharmaceutical composition and pesticide | |
| CN108864134A (en) | The preparation method and application of card Sa alkane forskolin and its extract containing the derivative | |
| CN111909119B (en) | Tripterygium wilfordii source compound and application and preparation method thereof, pharmaceutical composition and pesticide | |
| CN117447471B (en) | Indole diketopiperazine compound, preparation method thereof and application thereof in preparation of osteoclast differentiation inhibitor | |
| CN105796647A (en) | Cudrania tricuspidata extract and application thereof to preparation of RXR receptor transcription inhibitor | |
| Toussaint-Douhoré et al. | Liver cancer antiproliferative activity of a new nor-cucurbitacin from Mareya micrantha Müll. Arg. | |
| CN102850203B (en) | Juglone derivative and application thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20121003 |