CN1128138C - Carbazole alkaloid derivative and its prepn and use - Google Patents

Carbazole alkaloid derivative and its prepn and use Download PDF

Info

Publication number
CN1128138C
CN1128138C CN 01123987 CN01123987A CN1128138C CN 1128138 C CN1128138 C CN 1128138C CN 01123987 CN01123987 CN 01123987 CN 01123987 A CN01123987 A CN 01123987A CN 1128138 C CN1128138 C CN 1128138C
Authority
CN
China
Prior art keywords
compound
carbazole alkaloid
hydrogen
carbazole
preparation
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.)
Expired - Fee Related
Application number
CN 01123987
Other languages
Chinese (zh)
Other versions
CN1332157A (en
Inventor
崔承彬
蔡兵
阎少羽
姚新生
Original Assignee
崔承彬
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by 崔承彬 filed Critical 崔承彬
Priority to CN 01123987 priority Critical patent/CN1128138C/en
Publication of CN1332157A publication Critical patent/CN1332157A/en
Application granted granted Critical
Publication of CN1128138C publication Critical patent/CN1128138C/en
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

Links

Images

Landscapes

  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines Containing Plant Substances (AREA)

Abstract

The present invention relates to a novel carbazole alkaloid derivative or salt thereof, a preparing method thereof and an application of the compound for preparing cell cycle inhibitor or apoptosis inducer. The present invention separates carbazole alkaloid derivatives with three kinds of structure types from the wampee of a black fruit and the derivatives or salt thereof can be used for preparing anti-cancer drugs or the cell cycle inhibitor or the apoptosis inducer. The novel carbazole alkaloid derivative of the present invention comprises simple replacemuet carbazole in a formula (I) and carbazole dimer in formulas (II), (III). The preparing method of the carbazole alkaloid derivative comprises the steps that dry bark or leaves are extracted from the wampee of the black fruit by alcohol or aqueous alcohol to obtain crude extract; active components in the extract is extracted by organic solvent and is separated through repeated column chromatography, silica gel thin-layer chromatography preparation, reversed phase HPLC preparation, recrystallization, etc.

Description

Carbazole alkaloid derivative and preparation method thereof and purposes
Technical field:
The present invention relates to new carbazole alkaloid analog derivative or its salt, the application in preparation cell cycle inhibitor or cell death inducer of its preparation method and this compounds.
Background technology:
The carbazole alkaloid compounds has some reports, as document Tian-Shung Wu, et al, Carbazole alkaloidsfrom Clausena excavata and their biological activity:Phytoehemistry, Vol.43.No.l.pp133-140,1996 and document A.Chakraborty, et al, Carbazole alkaloid with antimicrobial activityfrom Clausena heptaphylla:Phytochemistry, Vol.38.No.3.pp787-789,1995.Natural Bicyclomahanimbine multi-source is in Rutaceae (Rutaceae) Clausena (Clausena) plant.This platymiscium main chemical compositions is Bicyclomahanimbine and coumarin kind compound.The black fruit of congener Calusena lansium Clausena dunniana Levl is the cancer that is used for the treatment of among the people in China partial area, but its chemical ingredients is not particularly appeared in the newspapers so far about the research of this botanical anticancer activeconstituents.
Summary of the invention:
The present invention isolates the new carbazole alkaloid analog derivative of three kinds of structure types from black fruit Calusena lansium, they have cell cycle inhibition and apoptosis-inducing effect, and these carbazole alkaloid derivatives or their salt can be used for preparing cell cycle inhibitor or cell death inducer.
New carbazole alkaloid derivative of the present invention comprises the simple substituted carbazole of formula (I) and formula (II), (III) carbazole two amount bodies, and its chemical structure is as follows:
Figure C0112398700031
Formula (I) formula (II) formula (III)
Wherein, R 1Be hydrogen, alkoxyl group or hydroxyl; R 2Be alkoxyl group, alkoxyalkyl or acyl group; R 3Be hydrogen or alkoxyl group; R 4Be hydrogen or alkyl;
In the preferred formula (I), R 1Be hydrogen, methoxyl group or hydroxyl; R 2Be methoxyl methyl or formyl radical; R 3Be hydrogen or methoxyl group; R 4Be hydrogen or dimethyl-allyl.
The preparation method of above-claimed cpd extracts black fruit Calusena lansium exsiccant stem skin or branches and leaves with ethanol or aqueous ethanol solution, gets crude extract, with organic solvent extraction gained crude extract, obtains extract.Above-mentioned extractive with organic solvent is separated purification process through repeatedly silica gel with Sephadex LH-20 column chromatography, preparation silica gel thin-layer chromatography repeatedly, anti-phase preparation HPLC and recrystallization etc., isolate each activeconstituents in the medicinal extract, obtain new carbazolyl alkaloid reactive monomer.
The present invention adopts flow cytometry and is equipped with cell microscopic morphology observation of characteristics and method such as fluorescence microscopy karyomorphism observation of characteristics, being screening and the test job that leading indicator has been carried out antitumour activity to the cell cycle inhibition of tsFT210 mouse mastopathy cell, apoptosis-inducing and to the direct killing effect of this cancer cells.
The biological action feature of new carbazolyl alkaloid of the present invention is: the perhaps cell cycle of anticancer turnover, and perhaps inducing cancer cell generation apoptosis, perhaps direct killing cancer cells, and bring into play antitumous effect thus.
Add the acceptable acid of medicine in the Bicyclomahanimbine of the present invention and can be made into salt.In carbazole alkaloid derivative of the present invention or its salt, add the medicine acceptable auxiliary and can be made into cancer therapy drug, cell cycle inhibitor or cell death inducer.
Description of drawings:
Fig. 1 is the UV spectrum of compound 1 in methyl alcohol, and Fig. 2 is the infrared spectra (KBr) of compound 1, and Fig. 3 is that compound 1 is in deuterated acetone 1H nuclear magnetic resonance spectrum, Fig. 4 are that compound 1 is in deuterated acetone 13The C nuclear magnetic resonance spectrum;
Fig. 5 is the UV spectrum of compound 2 in methyl alcohol, and Fig. 6 is the infrared spectra (KBr) of compound 2, and Fig. 7 is that compound 2 is in deuterated acetone 1H nuclear magnetic resonance spectrum, Fig. 8 are that compound 2 is in deuterated acetone 13The C nuclear magnetic resonance spectrum;
Fig. 9 is the UV spectrum of compound 3 in methyl alcohol, and Figure 10 is the infrared spectra (KBr) of compound 3, and Figure 11 is that compound 3 is in deuterated acetone 1H nuclear magnetic resonance spectrum, Figure 12 are that compound 3 is in deuterated acetone 13The C nuclear magnetic resonance spectrum;
Figure 13 is the UV spectrum of compound 4 in methyl alcohol, and Figure 14 is the infrared spectra (KBr) of compound 4, and Figure 15 is that compound 4 is in deuterated acetone 1H nuclear magnetic resonance spectrum, Figure 16 are that compound 4 is in deuterated acetone 13The C nuclear magnetic resonance spectrum;
Figure 17 is the UV spectrum of compound 5 in methyl alcohol, and Figure 18 is the infrared spectra (KBr) of compound 5, and Figure 19 is that compound 5 is in deuterated acetone 1H nuclear magnetic resonance spectrum, Figure 20 are that compound 5 is in deuterated acetone 13The C nuclear magnetic resonance spectrum;
Figure 21 is the UV spectrum of compound 6 in methyl alcohol, and Figure 22 is the infrared spectra (KBr) of compound 6, and Figure 23 is that compound 6 is in deuterated dimethyl sulfoxide 1H nuclear magnetic resonance spectrum, Figure 24 are that compound 6 is in deuterated dimethyl sulfoxide 13The C nuclear magnetic resonance spectrum.
Embodiment:
The separation preparation of carbazole alkaloid in the black fruit of the example I Calusena lansium stem skin
1. the preparation of thick extracted extract and chloroform extract
The alcohol reflux of 5 kilograms of usefulness 70% of dry fragment of black fruit Calusena lansium stem skin, each 15L refluxed 4 hours, extracted altogether three times.United extraction liquid, concentrating under reduced pressure, vacuum-drying get thick extracted extract 300 grams.
Get these medicinal extract 280 grams and be scattered in the 2L distilled water, extract respectively three times with isopyknic sherwood oil and chloroform successively.Extraction liquid is concentrate drying respectively, obtains activated chloroform extract 30 grams.
2. the separation of activeconstituents in the chloroform extract
Chloroform extract 30 grams with the post that reduces pressure on the 300 gram silica gel 60H dry method, with the segmentation of petrol ether/ethyl acetate mixed solvent gradient elution, obtain 24 stream parts after 35 gram silica gel G are mixed sample.With final concentration is each stream of 50 μ g/ml test part activity, in conjunction with the thin layer check result, merges into B (5.0g), C (4.0g), D (0.65g) and four active constituents of E (1.35g) and A (1.0g), two non-activity components of F (17g).Sephadex LH-20 column chromatography for separation is gone up at D, E position respectively, and each stream part is merged into 11 components according to active testing and thin layer check result, Fr.1 (80mg), Fr.2 (90mg), Fr3 (170mg), Fr.4 (160mg), Fr.5 (140mg), Fr.6 (70mg), Fr.7 (170mg), Fr.8 (120mg), Fr.9 (130mg), Fr.10 (160mg), Fr.11 (500mg).
Fr.1 (80mg) is dissolved in and goes up Sephadex LH-20 post in the methyl alcohol, obtains compound 1 (1.5mg) with methanol-eluted fractions; Fr.2 (90mg) separates [normal hexane-acetone (97: 3) expansion] through the preparation silica gel tlc, gets compound 2 (3.2mg); Fr.5 (140mg) separates through Sephadex LH-20 column chromatography (methanol-eluted fractions), and purifying gets compound 3 (2.7mg); Fr.6 (70mg) prepares HPLC[methanol-water (7: 3) wash-out through ODS] separation and purification gets compound 4 (2.2mg); Fr.8 (120mg) prepares HPLC[methanol-water (7: 3) wash-out through ODS] separation and purification, get compound 5 (9.0mg).
The chemical structure of separating the carbazole alkaloid derivative for preparing in the black fruit Calusena lansium stem skin is as follows.
Figure C0112398700051
Figure C0112398700052
1：R 1＝R 3＝R 4＝H，R 2＝CH 2OCH 3
2：R 1＝OCH 3，R 2＝CH 2OCH 3，R 3＝R 4＝H
3：R 1＝OH，R 2＝CHO，R 3＝OCH 3，R 4＝H
4：R 1＝OH，R 2＝CHO，R 3＝OCH 3，
R 4＝CH 2CH＝C(CH 3) 2
The chemical structure of separating the carbazole alkaloid derivative of preparation in the black fruit Calusena lansium stem skin
Compound 1 is the incarnadine prism, and 182～183 ℃ of fusing points are positive with the Dragendorff reagent react, and molecular formula is C 14H 13NO, ESI-MS m/z:212[M+H] +, HR-EI-MS m/z (M +): measured value 211.0990 (calculated value 211.0992).UV λ MaxNm (log ε) in MeOH:338 (3.71), 324 (3.80), 295 (4.45), 259 (4.64), 236 (4.92) .IR ν MaxCm -1(KBr): 3289 (NH), 2924,2853 (CH 3), 1609,1498 (phenyl ring), 1454,1245,1092,812. 1H NMR δ in CD 3COCD 3: 10.32br s (NH), and 8.11d (J=7.0Hz, 5-H), 8.06d (J=1.0Hz, 4-H), and 7.49d (J=7.0Hz, 8-H), 7.47d (J=7.0Hz, 1-H), 7.37d (J=7.0Hz, 2-H), 7.35dd (J=7.0,7.0Hz, 7-H), 7.16dd (J=7.0,7.0Hz, 6-H), 4.56s (2H, CH 2OCH 3), 3.33s (3H, CH 2OCH 3). 13C NMRδin CD 3COCD 3：139.9(C-8a)，137.8(C-9a)，128.8(C-3)，127.2(C-7)，125.7(C-4a)，123.6(C-4a)，123.3(C-4b)，120.2(C-5)，120.2(C-4)，119.3(C-6)，110.6(C-8)，110.2(C-1)，75.6(CH 2OCH 3)，57.5(CH 2OCH 3)。
Compound 2 brown oil are positive with the Dragendorff reagent react, and molecular formula is C 15H 15NO 2, ESI-MSm/z:242[M+H] +, HR-EI-MS m/z (M +):: measured value 241.1102 (calculated value 241.1103).UV λ MaxNm (log ε) in MeOH:324 (3.82), 290 (4.22), 259 (4.61), 252 (4.61), 241 (4.90), 226 (4.76) .IR ν MaxCm -1(KBr): 3415,3285 (NH), 2934,2849 (CH 3), 1588,1503 (phenyl ring), 1453,1231,847. 1H NMR δ inCD 3COCD 3: 10.21br s (NH), and 7.94d (J=7.0 Hz, 5-H), 7.53d (J=1.0Hz, 4-H), 7.43d (J=7.0Hz, 8-H), and 7.24dd (J=7.0,7.0Hz, 7-H), 7.03dd (J=7.0,7.0Hz, 6-H), and 6.84d (J=1.0Hz, 2-H), 4.43s (2H, CH 2OCH 3), 3.87s (3H, OCH 3), 3.21s (3H, CH 2OCH 3). 13C NMRδin CD 3OCD 3：145.9(C-1)，140.2(C-8a)，130.1(C-3)，129.6(C-9a)，125.3(C-7)，123.7(C-4a)，123.4(C-4b)，120.1(C-5)，118.8(C-6)，112.1(C-4)，111.4(C-8)，106.2(C-2)，75.1(CH 2OCH 3)，56.8(CH 2OCH 3)，55.0(OCH 3).
Compound 3 faint yellow unformed powder are positive with the Dragendorff reagent react, and molecular formula is C 14H 11NO 3, ESI-MS m/z:242[M+H] +, HR-EI-MS (M +): measured value 241.0735 (calculated value 241.0733).UV λ MaxNm (log ε) in MeOH:340 (4.44), 285 (4.84), 242 (4.85), 203 (4.64) .IR ν MaxCm -1(KBr): 3409 (NH ﹠amp; OH), 2927,2841 (CH 3), 1671,1655 (C=O), 1618,1581 (phenyl ring), 1491,1347,1158. 1HNMR δ in CD 3COCD 3: 10.65br s (NH), 9.97s (CHO), 8.13d (J=1.5Hz, 4-H), 8.04d (J=7.5Hz, 5-H), 7.35d (J=1.5Hz, 2-H), 7.14d (J=2.0Hz, 8-H), 6.88dd (J=7.5,2.0Hz, 6-H), 3.88s (3H, OCH 3). 13C NMR δ in CD 3COCD 3: 191.9 (CHO), 160.6 (C-7), 144.1 (C-1), 142.8 (C-8a), 134.6 (C-9a), 131.3 (C-3), 125.4 (C-4a), 122.0 (C-5), 118.2 (C-4b), 118.1 (C-4), 110.1 (C-6), 107.8 (C-2), 96.1 (C-8), 55.8 (OCH 3).
Compound 4 faint yellow prisms, fusing point 197-198 ℃, be positive with the Dragendorff reagent react, molecular formula is C 19H 19NO 3, ESI-MS m/z:310[M+H] +, HR-EI-MS (M +): measured value 309.1365 (calculated value 309.1365).UV λ MaxNm (log ε) in MeOH:343 (4.41), 288 (4.78), 254 (4.63), 243 (4.79). ν MaxCm -1(KBr): 3433,3318 (NH ﹠amp; OH), 2929,2837 (CH 3), 1667 (C=O), 1618,1578 (phenyl ring), 1486,1241,791. 1H NMR δ in CD 3COCD 3: 10.05brs (NH), 9.85s (CHO), 8.01d (J=1.5Hz 4-H), 7.86d (J=7.0Hz, 5-H), 7.22d (J=1.5Hz2-H), 6.89d (J=7.0Hz, 6-H), 5.21d (J=5.5Hz, 11-H), 3.61d (J=5.5Hz, 2H, 10- H 2), 3.81s (3H, OCH 3), 1.71s (3H, 13- H 3), 1.54s (3H, 14- H 3). 13C NMR δ inCD 3COCD 3: 191.8 (CHO), 157.3 (C-7), 144.1 (C-1), 141.5 (C-8a), 135.0 (C-9a), 132.2 (C-12), 131.2 (C-3), 126.0 (C-4a), 123.5 (C-11), 119.4 (C-5), 119.0 (C-4b), 118.0 (C-4), 113.4 (C-8), 108.3 (C-2), 106.5 (C-6), 56.8 (OCH 3), 25.8 (C-14), 24.4 (C-10), 18.0 (C-13).
Compound 5 brown unformed powder are positive with the Dragendorff reagent react, and molecular formula is C 26H 18N 2O 3, ESI-MS m/z:407[M+H] +, HR-EI-MS m/z (M +): measured value 406.1304 (calculated value 406.1311) .UV λ MaxNm (log ε) in MeOH:345 (4.28), 332 (4.27), 292 (4.62), 245 (5.15), 225 (5.26) .IR ν MaxCm -1(KBr): 3388 (NH ﹠amp; OH) 2921,2858 (CH 3), 1638 (C=O), 1589,1536 (phenyl ring), 1469,1396,1230,747. 1H NMR δ in CD 3COCD 3: 11.5br s (OH), and 8.16d (J=7.0Hz, 5-H), 7.28dd (J=7.0,6.0Hz, 6-H), 7.34dd (J=6.0,7.0Hz, 7-H), 7.56d (J=7.0Hz, 8-H), 1.74s (3H, 3-C H 3), 6.77s (4 '-H), 7.63d (J=7.0Hz, 5 '-H), 6.79dd (J=7.0,6.5Hz, 6 '-H), 7.14dd (J=6.5,7.0Hz, 7 '-H), 7.41d (J=7.0Hz, 8 '-H), 2.10s (3H, 3 '-C H 3) .13C NMR δ in CD 3COCD 3: 184.0 (C-4), 180.0 (C-1), 146.4 (C-3), 143.5 (C-1 '), 143.0 (C-2), 141.3 (C-8a '), 138.8 (C-8a), 137.1 (C-9a), 129.0 (C-9a '), 128.9 (C-7 '), 127.6 (C-3 '), 127.3 (C-7), 125.1 (C-4b), 124.6 (C-6), 123.8 (C-4b '), 123.3 (C-4a '), 123.2 (C-5), 121.6 (C-5 '), 119.6 (C-6 '), 119.4 (C-2 '), 117.3 (C-4a), 114.4 (C-8), 113.2 (C-4 '), 112.2 (C-8 '), 19.2 (3 '- CH 3), 13.5 (3- CH 3).
The separation preparation (preparation of compound 6) of carbazole alkaloid in the embodiment 2 black fruit Calusena lansium branches and leaves
1. the extraction of medicinal extract preparation
Get the dry branches and leaves of 4 kilograms of black fruit Calusena lansium, the medical ethanol room temperature lixiviate with 95%, each 20L, lixiviate seven days is extracted three times altogether.United extraction liquid, concentrating under reduced pressure, vacuum-drying gets crude extract 280 grams.
Get branches and leaves extract 250 grams and mix sample,,, obtain 40 stream parts with the segmentation of petrol ether/ethyl acetate mixed solvent gradient elution with the post that reduces pressure on the 1000 gram silica gel 60H dry method through 300 gram silica gel G.With final concentration is the activity of each stream part of 50 μ g/ml test, and in conjunction with the thin layer check result, merging into B (15g), C (30g), E (15g) and four of F (20g) has reactive site and A (10g), D (20g) and three non-activity positions of G (50g).
2. the separation of compound 6 preparation
Get F position 10 gram, last ODS post, with methanol-water (8: 2) wash-out, two active constituents, after Sephadex LH-20 post on the active constituent that elutes, use methanol-eluted fractions, get compound 6 crude products, through preparing HPLC[ODS, MeOH-H 2O (8: 2) is a moving phase]] refining, obtain compound 6 pure product 150mg.
The chemical structure of separating the carbazole alkaloid compound 6 for preparing in the black fruit Calusena lansium branches and leaves is as follows:
The chemical structure of separating the carbazole alkaloid compound 6 of preparation in the black fruit Calusena lansium branches and leaves
Compound 6 is brown unformed powder, is positive molecular formula C with the Dragendorff reagent react 38H 38N 2O 6, ESI-MS m/z:617[M+H] +, HR-EI-MS (M +): measured value 616.2574 (calculated value 616.2573) .UV λ MaxNm (log ε) in MeOH:344 (4.78), 300 (5.10), 225 (5.30) .IR ν MaxCm -1(KBr): 3500,3465 (NH ﹠amp; OH), 2972,2934,2854 (CH 3), 1642 (C=C), 1610,1459 (phenyl ring), 1284,1202,748. 1H NMR δ inDMSO-d 6: 9.82br s (2H, N-H ﹠amp; N '-H), 7.99br s (2H, 7,7 '-OH), 7.61s (2H, 4,4 '-H), 7.55s (2H, 5,5 '-H), 7.05d (2H, J=9.5Hz, 10,10 '-H), 5.56d (2H, J=9.5Hz, 11,11 '-H), 3.93s (6H, 8,8 '-OCH 3), 1.36s (6H, 13,13 '-CH 3), 1.35s (6H, 14,14 '-CH 3).13C NMRδin DMSO-d 6：147.2(C-2，2’)，143.3(C-7，7’)，142.6(C-8，8’)，134.9(C-8a，8a’)，134.7(C-9a，9a’)，127.7(C-11，11’)，119.4(C-4，4’)，119.1(C-10，10’)，117.5(C-4a，4a’)，115.4(C-3，3’)，113.6(C-4b，4b’)，104.9(C-6，6’)，104.5(C-1，1’)，101.2(C-5，5’)，74.8(C-12，12’)，56.4(8，8’-O CH 3)，27.4(C-13，13’)，27.0(C-14，14’)，15.9(3，3’- CH 3).
3 cell cycles of embodiment suppress and the apoptosis-inducing active testing
1. laboratory sample and experimental technique
Laboratory sample is 3-methoxymethylcarbazole (1), Clausine-X (2), and Clausine-Y (3), Clausine-Z (4), Clausenamine-B (5) and Bikoenigine (6) are mixed with the solution of desired concn respectively with methyl alcohol, for using.
Temperature sensitive type mouse breast cancer tsFT210 cell is with containing the RPMI-1640 substratum of 10%FBS, 32 ℃, feed succeeding transfer culture in the incubator of 5% carbonic acid gas.During active testing, the tsFT210 cell in the vegetative period of taking the logarithm, being mixed with density with fresh substratum is 2 * 10 5The cell suspension of cells/ml adds in 24 orifice plates by 0.5ml/well respectively, and every hole adds the sample methanol solution of 5 μ l different concns, cultivates 17h down for 32 ℃.Get it filled under the thing effect cell after cultivating, at first under opticmicroscope, observe the morphological change that drug treating causes, judge the morphological feature that has or not apoptosis or necrocytosis, then cell is transferred to the 1.5ml Eppendorf centrifuge tube from 24 orifice plates respectively, 4 ℃ of centrifugal 3min of following 3000rpm, supernatant liquor is removed in suction, add 0.5 μ l phosphate buffer solution concussion washing once, collecting cell under the same terms, add 150 μ l propidium iodide (PI) aqueous solution (5mgPI, 100mg Sodium citrate and 200mg NP-40in 100mlH 2O), behind 4 ℃ of 30min that dye down, measure the content distribution of DNA in the cell with flow cytometry analysis.In addition, cell after the thing of getting it filled is in case of necessity handled, with cell dyeing, the morphological feature of observation of cell nuclear chromatin changes under fluorescent microscope with Hoechst 33258 fluorescent reagents, judges to have or not apoptotic morphological feature or cell cycle to be suppressed in the G2 phase or in the M phase.
2. experimental result
Observe under opticmicroscope: after handling with various carbazole alkaloid derivatives of the present invention, the tsFI210 cancer cells is various typical morphological change, and the cell that the cell cycle is suppressed in the G2/M phase evenly becomes big and form is full; By apoptosis-induced cell generation shrinkage, sprout or form apoptotic body; When medicine had cytotoxicity, cell expanded, forms lighttight black vesica, presented the representative configuration feature of non-viable non-apoptotic cell.In conjunction with above-mentioned morphological observation result, be summarized as follows table with flow cytometry mensuration and through the relevant result that the Wincycle software analysis obtains.
The minimal effective concentration (MIC) of 1～6 pair of tsFT210 cell of compound
Compound MIC(μg/ml)
The apoptosis-inducing effect The G2/M restraining effect Cytotoxic activity
Taxol DCC
1 2 3 4 5 6 50 ＞200 50 12.5 50 12.5 12.5 25＜MIC＜＝50 25＜MIC＜＝50 6.25＜MIC＜＝12.5 25＜MIC＜＝50 6.25＜MIC＜＝12.5 6.25＜MIC＜＝12.5 1.56 ＞200 12.5 50 25 12.5 0.78＜MIC＜＝1.56 6.25＜MIC＜＝12.5 25＜MIC＜＝50 12.5＜MIC＜＝25 6.25＜MIC＜＝12.5 ＞200 100 100 100 50 50 50＜MIC＜＝100 50＜MIC＜＝100 50＜MIC＜＝100 25＜MIC＜＝50 25＜MIC＜＝50
The above results shows that test-compound has the cell cycle inhibition, apoptosis-inducing reaches the direct killing effect to cancer cells.

Claims (4)

1. following carbazole alkaloid derivative:
Figure C0112398700021
Formula (I) formula (II) formula (III)
Wherein, R 1Be hydrogen, alkoxyl group or hydroxyl; R 2Be alkoxyl group, alkoxyalkyl or acyl group; R 3Be hydrogen or alkoxyl group; R 4Be hydrogen or alkyl;
2. the described carbazole alkaloid derivative of claim 1, R 1Be hydrogen, methoxyl group or hydroxyl; R 2Be methoxyl methyl or formyl radical; R 3Be hydrogen or methoxyl group; R 4Be hydrogen or dimethyl-allyl.
3. the described carbazole alkaloid derivative of claim 1 or its salt application in preparation cell cycle inhibitor or cell death inducer.
4. the preparation method of the described carbazole alkaloid derivative of claim 1 is characterized by stem skin or branches and leaves with the black fruit of the extraction using alcohol Calusena lansium of ethanol or 60-70%, gets crude extract; With this medicinal extract of organic solvent extraction, obtain extract; This extract through repeatedly silica gel and Sephadex LH20 column chromatography, preparation silica gel thin-layer chromatography repeatedly, anti-phase preparation HPLC and recrystallization, is isolated the activeconstituents in the medicinal extract.
CN 01123987 2001-08-10 2001-08-10 Carbazole alkaloid derivative and its prepn and use Expired - Fee Related CN1128138C (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN 01123987 CN1128138C (en) 2001-08-10 2001-08-10 Carbazole alkaloid derivative and its prepn and use

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN 01123987 CN1128138C (en) 2001-08-10 2001-08-10 Carbazole alkaloid derivative and its prepn and use

Publications (2)

Publication Number Publication Date
CN1332157A CN1332157A (en) 2002-01-23
CN1128138C true CN1128138C (en) 2003-11-19

Family

ID=4665418

Family Applications (1)

Application Number Title Priority Date Filing Date
CN 01123987 Expired - Fee Related CN1128138C (en) 2001-08-10 2001-08-10 Carbazole alkaloid derivative and its prepn and use

Country Status (1)

Country Link
CN (1) CN1128138C (en)

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1298722C (en) * 2005-03-07 2007-02-07 中国海洋大学 Indole carbazole alkaloid and its preparing method and use
CN103012417B (en) * 2013-01-08 2015-01-07 中国科学院昆明植物研究所 Carbazole alkaloids in clausena plants, medicine composition with carbazole alkaloids as anti-tumor active component, and preparation method and application of carbazole alkaloids
CN102988356B (en) * 2013-01-08 2014-08-27 中国科学院昆明植物研究所 Medicine composition with carbazole alkaloid in clausena plants as antineoplastic activity ingredient and preparation method and application thereof
CN110776456B (en) * 2019-10-15 2023-04-07 云南大学 Carbazole compound, preparation method thereof and application of carbazole compound in anti-HIV (human immunodeficiency virus) medicines

Also Published As

Publication number Publication date
CN1332157A (en) 2002-01-23

Similar Documents

Publication Publication Date Title
Elkousy et al. Antiviral activity of castor oil plant (Ricinus communis) leaf extracts
CN104945360B (en) Preparation method and application of phenylpropanoid compound in tobacco
CN101244129A (en) Lhasa rhubarb extract, preparation method, and application in preparing preparation for treating cardiovascular and cerebrovascular diseases
CN101647850B (en) New application of chemical component of eucommia bark used as plant estrogen
CN104370871B (en) The mouth diphenylene ketone oxide class separated from Swertia punicea Hemsl. and the application of suppression hepatitis B virus
CN112159378A (en) Gilmane type sesquiterpene lactone compound and preparation method and application thereof
CN111184713A (en) Application of eudesmane type sesquiterpene lactone epimer in preparation of anti-breast cancer medicine
CN113321618B (en) Three alkaloid compounds in purslane and extraction and separation method thereof
CN1128138C (en) Carbazole alkaloid derivative and its prepn and use
RU2123005C1 (en) Alkaloid compounds, method of their preparing, pharmaceutical composition
CN113735918B (en) Labdane diterpene glycoside compound and preparation method thereof
CN112898357B (en) Diterpene glycoside novel compound in trollius chinensis bunge and separation and purification method and application thereof
CN112920151B (en) Isopentene-based flavonoid compound and preparation method and application thereof
Belofsky et al. Investigation of Dalea parryi (Fabaceae) metabolites for anthelmintic activity against the human pathogenic hookworm Ancylostoma ceylanicum
Abeysekera et al. Studies on the composition and standardization of" Bakuchi oil", an Ayurvedic medicinal oil prepared from Psoralea corylifolia L. used in the treatment of vitiligo.
CN111150739B (en) Application of polygonin and method for extracting polygonin from polygonum bulbiferum
CN100434419C (en) Compound of monocyclic polysubstitution saturated cyclohexanones, prepartion method and usage
CN104861010B (en) A kind of new laudanum alkane type diterpene glycoside compound and its production and use
WO2012061954A1 (en) Preparative method and use of zingiberensis saponin extracted from dioscorea zingiberensis with antitumor activity
CN106220587A (en) New alkaloids compound and extraction separation method thereof in Herba Portulacae
CN110559307A (en) albizzia julibrissin new lignan compound and new application thereof
US10501472B2 (en) Method to isolate inoscavin a from Fulviformes fastuosus and medicinal preparation thereof to treat rhabdomyosarcoma cancer conditions
CN112300185B (en) Alkaloid compound with reduced hepatotoxicity, and preparation method and application thereof
CN116496332B (en) Labdane diterpenoid glycoside compound and preparation method thereof
CN109705183A (en) Smelly seven secondary metabolites and its pharmaceutical composition and preparation method and its application

Legal Events

Date Code Title Description
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
C06 Publication
PB01 Publication
C14 Grant of patent or utility model
GR01 Patent grant
C19 Lapse of patent right due to non-payment of the annual fee
CF01 Termination of patent right due to non-payment of annual fee