CN104274429A - Application of cycloartane triterpenoid in preparation of anti-lung cancer medicine - Google Patents

Application of cycloartane triterpenoid in preparation of anti-lung cancer medicine Download PDF

Info

Publication number
CN104274429A
CN104274429A CN201410393799.5A CN201410393799A CN104274429A CN 104274429 A CN104274429 A CN 104274429A CN 201410393799 A CN201410393799 A CN 201410393799A CN 104274429 A CN104274429 A CN 104274429A
Authority
CN
China
Prior art keywords
lung cancer
cycloartane
triterpenoid
alkene
glycol
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
Application number
CN201410393799.5A
Other languages
Chinese (zh)
Other versions
CN104274429B (en
Inventor
谭成玉
孔亮
李敏晶
李伟
孟繁桐
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Dalian Ocean University
Original Assignee
Dalian Ocean University
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 Dalian Ocean University filed Critical Dalian Ocean University
Priority to CN201410393799.5A priority Critical patent/CN104274429B/en
Publication of CN104274429A publication Critical patent/CN104274429A/en
Application granted granted Critical
Publication of CN104274429B publication Critical patent/CN104274429B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/575—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines Containing Plant Substances (AREA)

Abstract

The invention discloses an application of cycloartane triterpenoid (23Z)-9,19-cycloartane-23-alkene-3alpha, 25-glycol in preparation of an anti-lung cancer medicine. The plant source of cycloartane triterpenoid is abundant; when the effective in vitro acting concentration of the prepared cycloartane triterpenoid (23Z)-9,19-cycloartane-23-alkene-3alpha, 25-glycol for a lung cancer cell strain is 5-20mu mol/L, the cycloartane triterpenoid has obvious proliferation inhibition action on the lung cancer cell strains H1299, H1944, H292 and H358 and the IC50 values are respectively 2.6mu mol/L, 7.8mu mol/L, 4.9mu mol/L and 8.7mu mol/L. The cycloartane triterpenoid can be applied to preparation of the anti-lung cancer medicine.

Description

Cycloartane type triterpene compound is preparing the application in anti-lung-cancer medicament
Technical field
The present invention relates to a kind of novelty teabag of Cycloartane type triterpene compound, especially a kind of Cycloartane type triterpene compound is preparing the application in anti-lung-cancer medicament.
Background technology
At present, mainly by inducing tumor cell differentiation, inducing apoptosis of tumour cell, inhibition tumor cell propagation, inhibition tumor cell telomere body enzymatic activity, reversing tumor cellular drug resistance, the sensitivity improving other antitumor drug, the migration path blocking tumor cell, Tumor suppression angiogenesis, raising immunity of organism level etc., (document 1. poplar passes mark, Xu Kecheng to the Antitumor Mechanism of Chinese herbal medicine.The antitumor action of Chinese medicine, international medical and health Leader, 2004,18:9-12).In existing clinical conventional antineoplastic agent, the medicine being directed to natural product or obtain through structural modification mainly contains paclitaxel, hydroxycamptothecin, matrine, cantharidin, vincaleucoblastine, vincristine, resveratrol, podophyllotoxin, arteannuin, Radix Ginseng etc., said medicine has the advantages such as determined curative effect, untoward reaction be less, becomes the leading role on antitumor drug market.
(23Z)-9,19-cyclic-ahltin-23-alkene-3 α, 25-diol compound is a kind of cyclic-ahltin type tetracyclic triterpenoid, and its structural formula is shown in following formula.The people such as Pi are separated and obtain (document 2. Hui-Fang Pi from Hupeh Fritillary Bulb, Peng Zhang, Han-Li Ruan, Yong-Hui Zhang, Han-Dong Sun and Ji-Zhou Wu.Two new triterpenoids from the leaves and stems of fritillaria hupehensis. Journal of Asian Natural Products Research, 2009,11 (9): 779-782).
But have no cyclic-ahltin type tetracyclic triterpenoid up to now, (23Z)-9,19-cyclic-ahltin-23-alkene-3 α, 25-glycol has the report of anti-lung cancer activity.
Summary of the invention
The present invention has found cyclic-ahltin type tetracyclic triterpenoid, (23Z)-9,19-cyclic-ahltin-23-alkene-3 α, 25-glycol has anti-lung cancer activity, thus invented Cycloartane type triterpene compound, (23Z)-9,19-cyclic-ahltin-23-alkene-3 α, 25-glycol is preparing the application in anti-lung-cancer medicament.
The present invention is first from the Cycloartane type triterpene compound (23Z)-9 that Echinops plant entire leaf Echinops latifolius aerial parts extracts, 19-cyclic-ahltin-23-alkene-3 α, 25-glycol, its plant origin enriches, prepared Cycloartane type triterpene compound (23Z)-9,19-cyclic-ahltin-23-alkene-3 α, when 25-glycol is 5 ~ 20 μm of ol/L to the useful effect concentration of lung cancer cell line in vitro, obvious Inhibit proliferaton effect is had, its IC to lung cancer cell line H1299, H1944, H292 and H358 50value is respectively 2.6,7.8,4.9 and 8.7 μm of ol/L, can be applicable to the medicine preparing anti-pulmonary carcinoma.
Accompanying drawing explanation
Fig. 1 is the hydrogen nuclear magnetic resonance spectrogram of embodiment of the present invention products therefrom.
Fig. 2 is the carbon-13 nmr spectra figure of embodiment of the present invention products therefrom.
Fig. 3 is embodiment of the present invention gained compound (23Z)-9,19-cyclic-ahltin-23-alkene-3 α, and 25-glycol is to the inhibitory action of four kinds of lung cancer cell lines.
Detailed description of the invention
Embodiment 1:
A. the entire leaf Echinops latifolius aerial parts of drying and crushing is got, employing volume fraction is ethanol or the methanol 6-10 times amount immersion post-heating reflux, extract, of 50 ~ 100%, each extraction time 2 ~ 3h, extraction time 2 ~ 3 times, merge extractive liquid, reclaim under reduced pressure extracting solution to determining alcohol lower than 5 %;
B. extracted 2 ~ 5 times through petroleum ether, normal hexane or cyclohexane extraction by the extracting solution of gained, the volume ratio of extractant and extracting solution is 1 ~ 3:3 ~ 1, combining extraction liquid, and recycling design obtains extract;
C. be separated through silica gel column chromatography by the extract obtained, with the mixed solvent gradient elution of petroleum ether, ethyl acetate, collection petroleum ether and ethyl acetate volume ratio are the eluting fraction of 100:6 ~ 8;
D. distilling under reduced pressure is except desolventizing, and through dichloromethane-ethyl acetate recrystallization, obtains this compound.
Pass through 1hNMR and 13c NMR analyzes its structure, and its spectrogram respectively as shown in Figure 1, 2.
1H?NMR(Pyridine-d 5，600MHz)：δ0.34(1H,?d,?J=3.96Hz,?H a-19)，0.58(1H,?d,?J=3.72Hz,?H b-19)，0.93(3H,?s,?28-CH 3)，0.98(3H,?d,?J=6.48Hz,?21-CH 3)，1.03(3H,?s,?18-CH 3)，1.10(3H,?s,?29-CH 3)，1.14(3H,?s,?30-CH 3)，1.34(3H,?m,?5,?15-H)，1.34(1H,?m,?H-7)，1.09(1H,?m,?H-7)，1.26(6H,?s,?26,?27-CH 3)，1.51(1H,?m,?20-H)，1.54(1H,?m,?8-H)，1.57(1H,?m,?H b-1)，1.27(1H,?m,?H a-1)，1.58(1H,?m,?17-H)，1.58(1H,?m,?H b-6)，1.82(1H,?m,?H a-6)，1.62(2H,?m,?12-H)，1.67(1H,?m,?H b-2)，1.54(1H,?m,?H a-2)，1.91(H,?m,?H b-16)，1.34(1H,?m,?H a-16)，2.01(1H,?m,?H b-11)，1.17(1H,?m,?H a-11)，2.31(1H,?m,?H b-22)，1.67(1H,?m,?H a-22)，3.56(1H,?brs,?3-H)；5.97(2H,?23,?24-H)；
13C?NMR(Pyridine-d 5，150MHz)：δ?32.8(C-1)，31.7(C-2)，78.3(C-3)，41.5(C?-4)，47.8(C-5)，21.8(C-6)，28.7(C-7)，48.5(C-8)，20.4(C-9)，26.7(C-10)，27.00(C-11)，36.2(C-12)，45.9(C-13)，49.5(C-14)，33.5(C-15)，27.0(C-16)，52.6(C-17)，18.8(C-18)，30.3(C-19)，37.2(C-20)，19.0(C-21)，40.00(C-22)，142.0(C-23)，125.0(C-24)，70.1(C-25)，31.3(C-26)，31.2(C-27)，20.0(C-28)，15.3(C-29)，26.6(C-30)。
Gained spectrogram and known compound wave spectrogram are compared, determines that products therefrom is cycloartane triterpenoids compounds (23Z)-9,19-cyclic-ahltin-23-alkene-3 α, 25-glycol, C 30h 50o 2, white, needle-shaped crystals, mp. 192-195 DEG C, unstressed configuration under ultraviolet, 10% H 2sO 4the colour developing of-EtOH solution is aubergine.
The mtt assay that utilizes that the present invention relates to measures this cycloartane triterpenoids compounds, (23Z)-9,19-cyclic-ahltin-23-alkene-3 α, and 25-glycol is to lung cancer cell line Inhibition test process:
Reference literature (Qianjiang tide, Wei Dongzhi, Chen Xiaolan, Zhang Siliang .MTT method measures the Drug resistance [J] of people's epidermal carcinoma cell. East China University of Science's journal. and 2000. 2 (26). 103-106.), process is as follows:
(1) inoculating cell: digestion is in three kinds of lung cancer cell lines (H1299, H292 and H1944) of exponential phase of growth respectively, is made into suspension by the RPMI1640 culture medium containing 10% calf serum.By lung cancer cell line with seed cell number 1.5 × 10 5individual/mL is inoculated in 96 well culture plates, and every hole adds 100 μ l, at 37 DEG C, and CO 224 h are cultivated in incubator.
(2) dosing: cell is diluted in culture medium by Concentraton gradient, testing compound is added DMSO and be made into certain density stock solution, be then the solution of 1 ~ 20 μm of ol/L with being made into respectively containing the RPMI1640 culture medium of 10% calf serum, be inoculated in 96 porocyte culture plates, at 37 DEG C, 5%-7%CO 248 h are cultivated in incubator.Blank does not add medicinal liquid, continues to cultivate 48h.
(3) stop cultivating: centrifugal, abandoning supernatant, every hole adds the MTT of 20 μ L, 37 ° of C, CO 2in incubator 4 hours, centrifugal, abandoning supernatant, and the DMSO adding 150 μ L, room temperature to place after 0.5h shaken well 10 minutes.Under 570nm, microplate reader measures OD value, calculates its suppression ratio.
Measure this compound by above-mentioned mtt assay to test lung cancer cell line Inhibition test step, result shows its inhibitory action IC to lung cancer cell line H1299 50value is 2.6 μm of ol/L.
Embodiment 2:
The cycloartane triterpenoids compounds (23Z)-9 obtained will be separated in embodiment 1,19-cyclic-ahltin-23-alkene-3 α, 25-glycol measures this compound by above-mentioned mtt assay and tests lung cancer cell line H1944 Inhibition test step, and result shows its inhibitory action IC to lung cancer cell line H1944 50value is 7.8 μm of ol/L.
Embodiment 3:
The cycloartane triterpenoids compounds (23Z)-9 obtained will be separated in embodiment 1,19-cyclic-ahltin-23-alkene-3 α, 25-glycol measures this compound by above-mentioned mtt assay and tests lung cancer cell line H292 Inhibition test step, records its Inhibit proliferaton effect IC to lung cancer cell line H292 50value is 4.9 μm of ol/L.
Measure this compound by above-mentioned mtt assay to test lung cancer cell line Inhibition test step, record its Inhibit proliferaton effect IC to lung cancer cell line H358 50value is 8.7 μm of ol/L.
Embodiment of the present invention gained compound (23Z)-9,19-cyclic-ahltin-23-alkene-3 α, 25-glycol to the inhibitory action effect of four kinds of lung cancer cell lines as shown in Figure 3.
Described compound is (23Z)-9,19-cyclic-ahltin-23-alkene-3 α, 25-glycol, when preparing anti-lung-cancer medicament, can be mixed to form various forms of powder, unguentum with acceptable excipient substance on materia medica, powder, injection, water preparation or injection; Described excipient substance is polyvinylpyrrolidone, micro-silica white etc.
Oral, subcutaneous, intravenous injection or anorectal administration can be taked in use; The use of injection can select arbitrarily normal saline, glucose, stabilizing agent, antiseptic, suspending agent or emulsifying agent etc.

Claims (1)

1. a cycloartane triterpenoids compounds, (23Z)-9,19-cyclic-ahltin-23-alkene-3 α, 25-glycol, is preparing the application in anti-lung-cancer medicament.
CN201410393799.5A 2014-08-12 2014-08-12 Cycloartane type triterpene compound application in preparing anti-lung-cancer medicament Active CN104274429B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201410393799.5A CN104274429B (en) 2014-08-12 2014-08-12 Cycloartane type triterpene compound application in preparing anti-lung-cancer medicament

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201410393799.5A CN104274429B (en) 2014-08-12 2014-08-12 Cycloartane type triterpene compound application in preparing anti-lung-cancer medicament

Publications (2)

Publication Number Publication Date
CN104274429A true CN104274429A (en) 2015-01-14
CN104274429B CN104274429B (en) 2016-08-24

Family

ID=52250096

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201410393799.5A Active CN104274429B (en) 2014-08-12 2014-08-12 Cycloartane type triterpene compound application in preparing anti-lung-cancer medicament

Country Status (1)

Country Link
CN (1) CN104274429B (en)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111337612A (en) * 2020-04-17 2020-06-26 合肥诺明药物安全研究有限公司 Quantitative analysis method for HYA13369 concentration in blood plasma and tissues
CN111808160A (en) * 2020-07-10 2020-10-23 山东省药学科学院 New cycloartane type saponin-9, 19-seco-9, 11-ene derivative and its preparing method and use

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
DONGDONG WANGA等: "Antitumor effects of Bulbus Fritillariae cirrhosae on Lewis lungcarcinoma cells in vitro and in vivo", 《INDUSTRIAL CROPS AND PRODUCTS》, no. 51, 31 January 2014 (2014-01-31), pages 92 - 101 *
HUI FANG PI等: "A new cycloartane triterpenoid from the leaves and stems of Fritillaria hupehensis", 《CHINESE CHEMICAL LETTERS》, no. 18, 31 December 2007 (2007-12-31), pages 418 - 420 *
HUI-FANG PI等: "Two new triterpenoids from the leaves and stems of Fritillaria hupehensis", 《JOURNAL OF ASIAN NATURAL PRODUCTS RESEARCH》, vol. 11, no. 0, 30 September 2009 (2009-09-30), pages 779 - 782 *

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111337612A (en) * 2020-04-17 2020-06-26 合肥诺明药物安全研究有限公司 Quantitative analysis method for HYA13369 concentration in blood plasma and tissues
CN111808160A (en) * 2020-07-10 2020-10-23 山东省药学科学院 New cycloartane type saponin-9, 19-seco-9, 11-ene derivative and its preparing method and use
CN111808160B (en) * 2020-07-10 2022-08-09 山东省药学科学院 New cycloartane type saponin-9, 19-seco-9, 11-ene derivative and its preparing method and use

Also Published As

Publication number Publication date
CN104274429B (en) 2016-08-24

Similar Documents

Publication Publication Date Title
CN101123880A (en) Anti-tumor compounds with angeloyl groups
CN109575099B (en) Dammarane sapogenin derivative and preparation method and application thereof
CN102940687B (en) A kind of Fructus Toosendan extract and uses thereof
CN106496171B (en) Polycyclic polyisocyanate pentenyl phloroglucinol derivatives compound, preparation method and application with anti-tumor activity
CN104311623B (en) A kind of Sasanguasaponin C by name 1with Sasanguasaponin C 2pentacyclic triterpenoid and preparation method thereof and application
CN104892713B (en) The preparation method of cucurbitacin C and the like and application
CN105687215B (en) Guava Leaf active component with antitumor action and its preparation method and application
CN104274429B (en) Cycloartane type triterpene compound application in preparing anti-lung-cancer medicament
CN104341376B (en) A kind of new sequiterpene quinones and its preparation method and application in arrowleaf abelmoschus root
CN105061545B (en) Triterpene saponin componds and its preparation method and application in shiny-leaved yellowhorn
CN104892714B (en) New ganoderma lucidum triterpene, preparation method and medicinal uses thereof
CN106317156A (en) Pentahydroxy diketone cucurbitane type triterpene as well as preparation method and application thereof
CN111825735A (en) Dammarane sapogenin and oleanane sapogenin derivatives, and preparation and application thereof
CN103610682B (en) The preparation method of 3 Alpha-hydroxy-30-olive-12,20 (29)-diene-28-acid and preparing the application in antitumor drug
CN105601693A (en) Preparation method and antitumor effect of ginsenoside F1
CN105418722B (en) A kind of entitled Sasanguasaponin C4And C5Pentacyclic triterpenoid preparation method
CN107474092A (en) A kind of straw mushroom fructification active component and its application
CN107474027A (en) The propionic acid of straw mushroom fructification active component 2 (5H) furanone 4 and application
CN113149820A (en) Monocyclic heteroterpene structural compound, preparation method and application thereof
CN107325069B (en) Extraction method of sesquiterpenoids
CN105037470A (en) Novel triterpenoid compound, preparation method and medical application thereof
CN104861010A (en) New labdane diterpene glycoside compound, preparation method therefor and applications
CN108299536A (en) A kind of triterpene and preparation method thereof with reverse multiple drug resistance of tumor effect
CN109180765B (en) Pregnane steroid alkaloid and preparation method and application thereof
CN103800308B (en) Cycloartane type falls triterpene and is preparing the purposes in antitumor drug

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