CN107050015B - Ovum South America chrysanthemum element is as the application in preparation anti-lung cancer, liver cancer and colon cancer drug - Google Patents

Ovum South America chrysanthemum element is as the application in preparation anti-lung cancer, liver cancer and colon cancer drug Download PDF

Info

Publication number
CN107050015B
CN107050015B CN201610921609.1A CN201610921609A CN107050015B CN 107050015 B CN107050015 B CN 107050015B CN 201610921609 A CN201610921609 A CN 201610921609A CN 107050015 B CN107050015 B CN 107050015B
Authority
CN
China
Prior art keywords
ovum
south america
chrysanthemum element
chrysanthemum
cancer
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.)
Active
Application number
CN201610921609.1A
Other languages
Chinese (zh)
Other versions
CN107050015A (en
Inventor
安熙强
张涛
程江南
范丽丽
赵婷婷
郭君婷
茹仙古丽·依明
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.)
INST OF PHARMACOLOGY XINJIANG UYGUR AUTONOMOUS REGIONS
Original Assignee
INST OF PHARMACOLOGY XINJIANG UYGUR AUTONOMOUS REGIONS
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 INST OF PHARMACOLOGY XINJIANG UYGUR AUTONOMOUS REGIONS filed Critical INST OF PHARMACOLOGY XINJIANG UYGUR AUTONOMOUS REGIONS
Priority to CN201610921609.1A priority Critical patent/CN107050015B/en
Publication of CN107050015A publication Critical patent/CN107050015A/en
Application granted granted Critical
Publication of CN107050015B publication Critical patent/CN107050015B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/335Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/365Lactones

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

Abstract

It is a kind of ovum South America chrysanthemum element as the application in preparation anti-lung cancer, liver cancer and colon cancer drug the present invention relates to pharmaceutical technology field;Present invention firstly provides ovum South America chrysanthemum elements to have different degrees of inhibiting effect to the growth of tri- kinds of human lung carcinoma cell line A549, Human Hepatic Carcinoma Cell Line BEL-7402 and human colon cancer cell strain HT-29 cell strains;And ovum South America chrysanthemum element is substantially better than positive drug TPT(topotecan hydrochloride to the growth in vitro inhibitory action of Human Hepatic Carcinoma Cell Line BEL-7402 and human colon cancer cell strain two kinds of cell strains of HT-29), to growth in vitro inhibitory action and the positive drug TPT(topotecan hydrochloride of human lung carcinoma cell line A549) effect it is more close;Illustrate that ovum South America chrysanthemum element has apparent antitumor action to external lung carcinoma cell, liver cancer cells and colon cancer cell, there is preferable prospect in medicine.

Description

Ovum South America chrysanthemum element is as the application in preparation anti-lung cancer, liver cancer and colon cancer drug
Technical field
It is a kind of ovum South America chrysanthemum element as preparation anti-lung cancer, liver cancer and colon cancer medicine the present invention relates to pharmaceutical technology field Application in object.
Background technique
Cancer seriously threatens human health.The disease incidence of cancer persistently rises in recent years, becomes and is only second to cardiovascular and cerebrovascular disease The second largest fatal disease of disease.With the progress of medicine, a large amount of anti-tumor drugs are clinically emerged.But chemotherapeutics Toxic side effect makes its clinical application receive very big limitation, excavates small, the cheap chemotherapeutics of toxic side effect and has become doctor A medicine worker big project urgently to be resolved.
Tumour is body under the effect of various carcinogenic factors, some cell of local organization loses pair at the genetic level Its normal regulation grown leads to its clonal abnormality hyperplasia and the abnormality that is formed.The neoplastic disease number of cases in China is quite huge Greatly, there is data to show and account for the 55% of whole world case load.
Husky Inula britannica chinensis (Inulasalsoloides (Turcz.) Ostenf.) is composite family Inula, and perennial herb is planted Object.It is mainly distributed on Xinjiang of China, Gansu, Shaanxi, the Inner Mongol, Hebei, North Qinghai and east, North of Shanxi and western Liaoning Province Equal areas.Also known as twist maggot and climb (" Inner Mongol Chinese herbal medicine "), bald woman's grass, yellow lama, artemisia annua, the plain (" soft science in China of knotweed Medicinal plant "), I is smooth by leaflet inular flower, E Lesen-- all Ursula (covering name), sand ground Inula britannica chinensis, Huang Penghua, small Inula britannica chinensis, Leopard cat eye.
The structure of natural products has the characteristics that novel and multifarious.The bioactive natural product of structure novel is guide's chemical combination One of important sources of object, discovery not only will push the progress of chemistry with study of pharmacy, it is also possible to lead to drug new target drone It was found that.It is directly or indirectly from natural products, such as anti-tumor drug Japanese yew more than 60% in currently used anti-tumor drug Pure and mild vinca alkaloids etc..Lead compound with anti-tumor activity is found from traditional Chinese medicine and medicinal plant, is studied Its mechanism of action, to develop the hot spot that antineoplaston drug is current research.
For husky Inula britannica chinensis main chemical compositions compared with horn of plenty, sesquiterpenoids is its characteristic constituents.In addition, the plant is also Contain a small amount of triterpenes components.Sesquiterpenoids is the main active of husky Inula britannica chinensis, according to its carbon skeleton type Inula britannica chinensis The sesquiterpenoids reported in platymiscium is broadly divided into acyclic sesquiterpene;Driffractive ring eucalyptus type;Olive alkane type;Germacrane and more wound The wooden alkane type.In addition, Inulaplants also contain a small amount of diterpene-kind compound;Flavone compound and steroid compound.I The chemical constitution study of system has been carried out to the husky Inula britannica chinensis for picking up from hotan area and has done anti tumor activity in vitro inspection It surveys, to therefrom isolated compound with anti-tumor activity.
Ovum South America chrysanthemum element is the extract of husky Inula britannica chinensis, belongs to natural products, is germacrane sequiterpene.Ovum South America chrysanthemum Element has significant supression to act on human mouth epidermoid carcinoma cell KB and mouse lymphocyte leukaemia cell P-388, in Document (Gopalakrishna E.M., Watson W.H..Ovatifolin, asesquiterpene lactone [J] .J.Cryst.Mol.Struct..1977,7:49-57. report in).But not yet have been reported that related ovum South America chrysanthemum element is right so far The supression effect of lung, liver, colon-cancer cell.As what chemistry and biology of the people to it was studied gos deep into, molecular mechanism of action It will gradually define, this will further push the modifying for chemical structure and structure activity study of such compound, and help to improve The medical value of husky Inula britannica chinensis.
Summary of the invention
The present invention provides a kind of ovum South America chrysanthemum elements as the application in preparation anti-lung cancer, liver cancer and colon cancer drug, gram The deficiency for having taken the above-mentioned prior art can effectively solve and not yet have been reported that related ovum South America chrysanthemum element is thin to lung, liver, intestinal cancer so far The problem of supression effect of born of the same parents.
The technical scheme is that being realized by following measures: a kind of ovum South America chrysanthemum element as preparation anti-lung cancer, Application in liver cancer and colon cancer drug.
Here is the further optimization and/or improvements to invention technology described above scheme:
Above-mentioned ovum South America chrysanthemum element is to extract from husky Inula britannica chinensis or other Inulaplants, purified isolated; Or, ovum South America chrysanthemum element obtains for chemical synthesis process.
The dosage form of above-mentioned ovum South America chrysanthemum element is tablet, sugar coated tablet, film coated tablet, enteric coated tablet, capsule, ebonite One of wafer, soft capsule, oral solution, mouth containing agent, granule, electuary, pill, powder, injection, powder-injection.
The chemical structural formula of above-mentioned ovum South America chrysanthemum element are as follows:
Present invention firstly provides ovum South America chrysanthemum elements to human lung carcinoma cell line A549, Human Hepatic Carcinoma Cell Line BEL-7402 and people The growth of tri- kinds of cell strains of colon cancer cell line HT-29 has different degrees of inhibiting effect;And ovum South America chrysanthemum element is to human liver cancer The growth in vitro inhibitory action of cell strain BEL-7402 and human colon cancer cell strain two kinds of cell strains of HT-29 is substantially better than positive drug TPT (topotecan hydrochloride), to growth in vitro inhibitory action and the positive drug TPT of human lung carcinoma cell line A549, (hydrochloric acid topology is replaced Health) effect it is more close;It is apparent anti-to illustrate that ovum South America chrysanthemum element has external lung carcinoma cell, liver cancer cells and colon cancer cell Function of tumor has preferable prospect in medicine.
Detailed description of the invention
Attached drawing 1 is compound ovum South America chrysanthemum element structural formula.
Attached drawing 2 is compound ovum South America chrysanthemum element1H-NMR。
Attached drawing 3 is compound ovum South America chrysanthemum element13C-NMR。
Attached drawing 4 is the one-dimensional NOE of compound ovum South America chrysanthemum element.
Attached drawing 5 is compound ovum South America chrysanthemum element two dimension HMBC spectrum.
Attached drawing 6 is compound ovum South America chrysanthemum element two dimension1H-1HCOSY spectrum.
Attached drawing 7 is compound ovum South America chrysanthemum element high resolution mass spectrum.
Attached drawing 8 is the crucial COSY (thick line) and HMBC (arrow) signal graph of ovum South America chrysanthemum element.
Specific embodiment
The present invention is not limited by the following examples, can determine according to the technique and scheme of the present invention with actual conditions specific Embodiment.
Embodiment 1, the ovum South America chrysanthemum element is as the application in preparation anti-lung cancer, liver cancer and colon cancer drug.
Embodiment 2, as the optimization of above-described embodiment, ovum South America chrysanthemum element is to plant from husky Inula britannica chinensis or other Inulas It is extracted in object, it is purified isolated;Or, ovum South America chrysanthemum element obtains for chemical synthesis process.
Embodiment 3, as the optimization of above-described embodiment, the dosage form of ovum South America chrysanthemum element is tablet, sugar coated tablet, Film coated tablets Agent, enteric coated tablet, capsule, hard capsule, soft capsule, oral solution, mouth containing agent, granule, electuary, pill, powder, note Penetrate one of liquid, powder-injection.
Embodiment 4, as the optimization of above-described embodiment, the chemical structural formula of ovum South America chrysanthemum element are as follows:
Application of the above-mentioned ovum South America chrysanthemum element in preparation anti-lung cancer, liver cancer and colon cancer drug is as follows:
One, the preparation of ovum South America chrysanthemum element
Ovum South America chrysanthemum element can obtain for chemical synthesis process;Ovum South America chrysanthemum element can also be for from husky Inula britannica chinensis or other are sheathed Extract, can be extracted by existing method in flower plant, a) by husky Inula britannica chinensis (pick up from hotan area, plant sample by Nationality, Inst. of Pharmacology, Xinjiang Uygur Autonomous Regions drug research department researcher Yang Wei person of outstanding talent identification, and keep sample in Xinjiang Uygur certainly Food research sensing chamber, the institute of materia medica Zhi Qu, marked as S.X.F.0001) herb 80kg is 50% to 95% with volume fraction Ethyl alcohol soak extraction impregnates 5 times that the ethyl alcohol volume used is husky Inula britannica chinensis quality of medicinal material to be extracted, altogether soak extraction every time 3 times, every time 24 hours;Merge ethyl alcohol soaked extracting solution, is concentrated under reduced pressure into no ethanol flavor;It adopts and concentrate 3 is extracted with ethyl acetate It is secondary, every time for 24 hours, acetic acid ethyl acetate extract is concentrated under reduced pressure and obtains medicinal extract;
B) gradient elution is carried out by the mixed solution that the volume ratio of 1:0~0:1 is formed with petroleum ether and ethyl acetate, into one Step optimization is detected in the eluent that the volume ratio of petroleum ether and ethyl acetate is 7:3 by thin-layer chromatography, and petroleum ether and second are collected Under acetoacetic ester expansion system, Rf value about 0.6, sulfuric acid-ethyl alcohol shows the component of purple, after being concentrated under reduced pressure under the conditions of lower than 60 DEG C Mass crystallization is precipitated, crystallization obtains ovum South America chrysanthemum element through dehydrated alcohol recrystallization is primary again.
Ovum South America chrysanthemum element is white powder crystallization, and ESI/MS provides quasi-molecule peak m/z329.1342 [M+Na]+, 345.1291[M+K]+, in conjunction with carbon spectrum, hydrogen spectrum, one-dimensional NOE, two dimension HMBC, two dimension1H-1HCOSY determines that molecular formula is C17H22O5。 The compound spectrum (Jeske F., Huneck S., Jakupovic J..Further sesquiterpene lactones from Inulasalsoloides.Pergamon.1996.41(6):1539-
1542.) report is almost the same, therefore determines that it is ovatifolin, is named as ovum South America chrysanthemum element.
The Structural Identification data of ovum South America chrysanthemum element are as follows:
HRESI-MS:329.1342[M+Na]+,345.1291[M+K]+
[α]20D (c=0.10, MeOH): -61.0 ° (c=0.10, MeOH);
UV(MeOH):λmax(logε):206(3.6)nm;
IRnmax:3452,1739,1730,1717,1662,1652,1653cm-1
1H-NMR(400MHz in CDCl3)、13C-NMR100MHz in CDCl3) and HMBC spectral data be shown in Table 1; Fig. 1 is compound ovum South America chrysanthemum element structural formula;Fig. 2 is compound ovum South America chrysanthemum element1H-NMR;Fig. 3 is compound ovum South America chrysanthemum Element13C-NMR;Fig. 4 is the one-dimensional NOE of compound ovum South America chrysanthemum element;Fig. 5 is compound ovum South America chrysanthemum element two dimension HMBC spectrum;Fig. 6 is to change Close object ovum South America chrysanthemum element two dimension1H-1HCOSY spectrum;Fig. 7 is compound ovum South America chrysanthemum element high resolution mass spectrum;Fig. 8 is ovum South America chrysanthemum element Crucial COSY (thick line) and HMBC (arrow) signal graph.
Ovum South America chrysanthemum element Structural Identification process
Ovum South America chrysanthemum element is colourless crystallization, is soluble in chloroform.HR-ESI-MS provides its quasi-molecular ion peak [M+Na]+m/ z329.1342(calcd for C17H22O5Na, 329.1359), releasing its molecular formula is C17H22O5, calculate its degree of unsaturation It is 7,1H H NMR spectroscopy (table 1, Fig. 2-3) shows a methyl signals in δH1.64 (s, 15-CH3), an acetonyl signal δH2.17 (s ,-CH3), 4 alkene hydrogen signals 6.37 (1H, d, J=4.0Hz, H-13a), 5.58 (1H, d, J=4.0Hz, H- 13b), 5.14 (1H, dd, J=12.0,4.4Hz, H-1), 4.86 (1H, t, J=18.4,9.6Hz, H-5).Carbon spectrum provides 17 Carbon signal, including three ethylene linkage carbon signal δC136.7 (C-1), 142.2 (C-4), 127.9 (C-5), 133.2 (C-10), 138.5 (C-11), 120.6 (C-13);Two ester group carbon signal δC170.2 (C-12), 170.8 (- Ac) and three oxygen-containing carbon Signal δC75.0 (C-6), 70.2 (C-8) and 63.2 (C-14).The nuclear magnetic data for analyzing the compound can be seen that in addition to acetyl Base, the compound parent nucleus have 15 carbon, deduct three double bonds, 5 degrees of unsaturation of two carbonyls, there are also 2 degrees of unsaturation, tables Bright SX-1 is dicyclic compound, and in conjunction with its source of students, which may be bicyclic sesquiterpenoids.Comprehensive analysis two-dimensional nucleus Magnetic data can release the planar structure (Fig. 1) of the compound.?1H-1There are two spin system (H- for the display of H COSY (Fig. 6) spectrum 1/H-2/H-3/, H-5/H-6/H-7/H-8/H-9), therefore there are two segment (segment I:C-1-C-2-C-3, segments for the compound II:C-5-C-6-C7-C-8-C-9) see Fig. 8.In HMBC spectrum (Fig. 5), δH4.80ppm, 4.57ppm (H-14) and 136.7ppm (C-1), 42.5ppm (C-9) and 170.8ppm (acetyl carbonyl) is related;Show that acetyl group connects on 14 carbon, C-14 connects in C- On 10 olefinic carbons;δH1.64ppm (15-CH3) and 39.2ppm (C-3), 142.2ppm (C-4), 127.9ppm (C-5) are related, say Bright 15-CH3 connects on 4 olefinic carbons;δH2.44,2.39ppm (H-2), 2.40,2.18ppm (H-3), 4.86ppm (H-5), 5.24ppm (H-6) is related to 142.4ppm (C-4), δH2.40,2.18ppm (H-3), 5.24ppm (H-6), 2.76ppm (H- 7) related to 127.9ppm (C-5), show that the head of the tail end and segment II of segment I passes through4,5△ is connected;C-10 and δH 5.14ppm (H-1), 2.4ppm (H-2), 4.60ppm (H-8), 2.96,2.31ppm (H-9) prompt the head and segment II of segment I Tail portion pass through1,10△ is connected, i.e. the first of SX-1 ring is one containing there are two 10 member rings of ethylene linkage.δH 5.24ppm(H-6) With 138.5ppm (C-11), 170.2ppm (C-12) is related, 2.76ppm (H-7) and 138.5ppm (C-11), 170.2ppm (C- 12), 120.6ppm (C-13) is related, prompts 6,7 and is connected to a lactone ring five membered, because there are two alkene hydrogen to believe on the carbon of 120.6ppm Numbers 6.37,5.58ppm, so have an exocyclic double bond, and H-7 is related to 120.6ppm, so double bond exists11,13△;δH 5.24ppm (H-6), 2.76ppm (H-7) and 2.96,2.31ppm (H-9) is related to 71.4ppm, and hydroxyl should connect at 8.So far, Obtain the planar structure (Fig. 1) of the compound.Literature survey discovery, the compound are identical as structure reported in the literature.(Jeske, F,Huneck S,Jakupovic J,et
al.Furthersesquiterpene lactones from Inulasalsoloides.Phytochemist ry.1996;41(6):1539-1542.)(GneccoS,Philip-PoyserJ,SilvaM.Sesquiterpene lactones from Podanthusovatifolius.Phytochemistry.1973;12(10):2469-2477.) (Gopalakrishna EM,Watson WH.Ovatifolin,asesquiterpene lactone.JCrystMolStruct.1977;7:49-57.) compound is determined as ovum South America chrysanthemum element.
Two, anti-tumor activity is verified using MTS colorimetric method
Two, anti-tumor activity is verified using MTS colorimetric method
Cell strain processing
A549 human lung carcinoma cell line, BEL-7402 human hepatoma cell strain, HT-29 human colon cancer cell strain, in 37 DEG C, 5% It is incubated under CO2 and saturated humidity environment containing 10% fetal calf serum McCoy ' s5A culture medium, RPMI1640 culture medium, DMEM/F- In 12 culture mediums, cell is passed on when increasing in logarithm, adjustment cell concentration to 1 × 104A/mL is inoculated in the culture of 96 holes 190 μ L are added in plate, every hole, are incubated for 18h to carrying out subsequent experimental for 24 hours.
Model preparation
Tumor cell line is grouped at random: 1. Normal group (control): the McCoy ' to contain 10% fetal calf serum S5A culture medium or 1640 culture mediums or DMEM/F-12 culture medium continue to cultivate, and final volume is supplemented to 200 μ L (replenisher and samples Solution is identical);2. screening sample group (sample): 10 μ L of test sample is added in every hole, and for final volume up to 200 μ L, compound is dense eventually Degree is 5 μ g/mL, and sample and tumor cell line are incubated for 72h jointly and carry out coherent detection;3. positive drug group (positive): using Five concentration gradients are arranged in a clinical line anti-tumor drug topotecan hydrochloride (TPT, MW:393.91), and positive drug is added in every hole 10 μ L, for final volume up to 200 μ L, final concentration is followed successively by 5 μM, 1 μM, 0.2 μM, 0.04 μM, 0.008 μM, positive drug and tumour cell The common 72h that is incubated for of strain carries out coherent detection.
Activity determination
At the end of prepared by model, 100 μ L MTS mixed liquors are added in every hole, continue to cultivate 4h colour developing, in microplate reader 490nm wave Strong point detects the absorbance value in each hole.
Selection primary dcreening operation Tumor growth inhibition effect be more than 50% sample carry out secondary screening (activity revalues), sample to be sieved and The concentration gradient that cell is incubated for jointly is set as the 1/10 to 1/3 of primary dcreening operation final concentration, and 3 to 5 gradients are arranged, and other methods are same On, IC is calculated after measuring light absorption value50
Calculation method
Every group of cell detects light absorption value with MTS method, and sample is calculated after measurement to the inhibiting rate of growth of tumour cell.With sample The logarithm of product various dose maps to growth of tumour cell inhibiting rate, and dose-effect curve can be obtained, therefrom find out the sample 50 3nhibitory dose IC50
Sample inhibiting rate (%)=
[(ODcontrol-ODblank)-(ODsample-ODblank)]/(ODcontrol-ODblank) × 100%
ODsample: sample treatment group light absorption value;ODcontrol: Normal group light absorption value;ODblank: culture plate blank well (cell-free) light absorption value.
Experimental result
This experiment has carried out growth of tumour cell using the human tumor cells of in vitro culture as research object, to ovum South America chrysanthemum element Inhibitory activity evaluation.
1, to the growth inhibition effect of human lung carcinoma cell line A549
Ovum South America chrysanthemum element can significantly inhibit human lung carcinoma cell line A549 growth in 5 μ g/mL of primary dcreening operation dosage, and inhibiting rate is 44.11%.Above-mentioned sample setting dose gradient is revalued, ovum South America chrysanthemum element presses down the growth of human lung carcinoma cell line A549 Production presentation dose dependent, IC50For 1.53 μ g/mL.The IC of positive drug TPT (topotecan hydrochloride)50For 0.13 μ g/mL. Ovum South America chrysanthemum element is suitable with positive drug TPT (topotecan hydrochloride) effect to the growth inhibition effect of human lung carcinoma cell line A549.
2, to the growth inhibition effect of Human Hepatic Carcinoma Cell Line BEL-7402
5 μ g/mL ovum South America chrysanthemum elements obviously can inhibit Human Hepatic Carcinoma Cell Line BEL-7402 to grow, inhibiting rate 81.39%.It is right Above-mentioned sample setting dose gradient is revalued, growth inhibition effect of the ovum South America chrysanthemum element to Human Hepatic Carcinoma Cell Line BEL-7402 Dose dependent, IC is presented50For 3.10 μ g/mL.The IC of positive drug TPT (topotecan hydrochloride)50For 30.82 μ g/mL.Ovum south U.S. chrysanthemum element is all remarkably higher than positive drug TPT (topotecan hydrochloride) to the growth inhibition effect of Human Hepatic Carcinoma Cell Line BEL-7402.
3, to the growth inhibition effect of human colon cancer cell strain HT-29
5 μ g/mL ovum South America chrysanthemum elements can obviously inhibit human colon cancer cell strain HT-29 to grow, inhibiting rate 82.69%.It is right It is arranged dose gradient and is revalued, and the growth inhibition effect of human colon cancer cell strain HT-29 is presented in ovum South America chrysanthemum element Dose dependent, IC50For 3.66 μ g/mL.The IC of positive drug TPT (topotecan hydrochloride)50For 13.26 μ g/mL.Ovum South America chrysanthemum Element is all remarkably higher than positive drug TPT (topotecan hydrochloride) to the growth inhibition effect of human colon cancer cell strain HT-29.
Activity rating conclusion: the evaluation of sample extracorporeal anti-tumor function is shown in Table 2, as can be seen from Table 2:
1, ovum South America chrysanthemum element is to human lung carcinoma cell line A549, Human Hepatic Carcinoma Cell Line BEL-7402 and human colon cancer cell strain The growth of tri- kinds of cell strains of HT-29 has different degrees of inhibiting effect.Positive drug TPT is to A549, BEL-7402, HT-29 body The IC that outgrowth inhibits50It is 0.13 μ g/mL, 30.82 μ g/mL, 13.26 μ g/mL.
2, ovum South America chrysanthemum element shows preferable extracorporeal anti-tumor function, thin to human lung carcinoma cell line A549, human liver cancer The growth inhibition IC of born of the same parents' strain tri- kinds of cell strains of BEL-7402 and human colon cancer cell strain HT-2950It is 1.53 μ g/mL, 3.10 μ g/ mL,3.66μg/mL.And ovum South America chrysanthemum element is to two kinds of cells of Human Hepatic Carcinoma Cell Line BEL-7402 and human colon cancer cell strain HT-29 The growth in vitro inhibitory action of strain is substantially better than positive drug TPT (topotecan hydrochloride) (IC50For 30.82 μ g/mL and 13.26 μ g/ ML), the growth in vitro inhibitory action of human lung carcinoma cell line A549 is acted on positive drug TPT (topotecan hydrochloride) more close (IC50: 0.13 μ g/mL).Ovum South America chrysanthemum element has apparent antitumor action to tumor cell in vitro.
3, ovum South America chrysanthemum element has apparent antitumor action;It can be seen that: ovum South America chrysanthemum element of the present invention is to external swollen Oncocyte has significant anti-tumor activity, it is expected to anti-tumor medicinal preparation is used to prepare as active constituent, before medicinal Scape.
In conclusion present invention firstly provides ovum South America chrysanthemum elements to human lung carcinoma cell line A549, human hepatoma cell strain The growth of tri- kinds of cell strains of BEL-7402 and human colon cancer cell strain HT-29 has different degrees of inhibiting effect;And ovum South America Chrysanthemum element is bright to the growth in vitro inhibitory action of Human Hepatic Carcinoma Cell Line BEL-7402 and human colon cancer cell strain two kinds of cell strains of HT-29 It is aobvious to be better than positive drug TPT (topotecan hydrochloride), to the growth in vitro inhibitory action and positive drug TPT of human lung carcinoma cell line A549 (topotecan hydrochloride) effect is more close;Illustrate ovum South America chrysanthemum element to external lung carcinoma cell, liver cancer cells and colon cancer cell With apparent antitumor action, there is preferable prospect in medicine.
The above technical features constitute embodiments of the present invention, can basis with stronger adaptability and implementation result Actual needs increases and decreases non-essential technical characteristic, to meet the needs of different situations.
1 ovum South America chrysanthemum element of table1H-NMR、13C-NMR and HMBC spectral data
The evaluation of 2 sample extracorporeal anti-tumor function of table

Claims (9)

1. a kind of ovum South America chrysanthemum element is as the application in preparation anti-lung cancer, liver cancer and colon cancer drug.
2. ovum South America chrysanthemum element according to claim 1 is as the application in preparation anti-lung cancer, liver cancer and colon cancer drug, It is characterized in that ovum South America chrysanthemum element is to extract from husky Inula britannica chinensis or other Inulaplants, it is purified isolated;Or, ovum South America chrysanthemum element obtains for chemical synthesis process.
3. ovum South America chrysanthemum element according to claim 1 or 2 is as answering in preparation anti-lung cancer, liver cancer and colon cancer drug With, it is characterised in that the dosage form of ovum South America chrysanthemum element is tablet, capsule, oral solution, mouth containing agent, granule, electuary, pill, dissipates One of agent, injection, powder-injection.
4. ovum South America chrysanthemum element according to claim 3 is as the application in preparation anti-lung cancer, liver cancer and colon cancer drug, The tablet for being characterized in that ovum South America chrysanthemum element is one of sugar coated tablet, film coated tablet, enteric coated tablet.
5. ovum South America chrysanthemum element according to claim 3 is as the application in preparation anti-lung cancer, liver cancer and colon cancer drug, The capsule for being characterized in that ovum South America chrysanthemum element is one of hard capsule, soft capsule.
6. ovum South America chrysanthemum element according to claim 1 or 2 is as answering in preparation anti-lung cancer, liver cancer and colon cancer drug With, it is characterised in that the chemical structural formula of ovum South America chrysanthemum element are as follows:
7. ovum South America chrysanthemum element according to claim 3 is as the application in preparation anti-lung cancer, liver cancer and colon cancer drug, It is characterized in that the chemical structural formula of ovum South America chrysanthemum element are as follows:
8. ovum South America chrysanthemum element according to claim 4 is as the application in preparation anti-lung cancer, liver cancer and colon cancer drug, It is characterized in that the chemical structural formula of ovum South America chrysanthemum element are as follows:
9. ovum South America chrysanthemum element according to claim 5 is as the application in preparation anti-lung cancer, liver cancer and colon cancer drug, It is characterized in that the chemical structural formula of ovum South America chrysanthemum element are as follows:
CN201610921609.1A 2016-10-21 2016-10-21 Ovum South America chrysanthemum element is as the application in preparation anti-lung cancer, liver cancer and colon cancer drug Active CN107050015B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201610921609.1A CN107050015B (en) 2016-10-21 2016-10-21 Ovum South America chrysanthemum element is as the application in preparation anti-lung cancer, liver cancer and colon cancer drug

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201610921609.1A CN107050015B (en) 2016-10-21 2016-10-21 Ovum South America chrysanthemum element is as the application in preparation anti-lung cancer, liver cancer and colon cancer drug

Publications (2)

Publication Number Publication Date
CN107050015A CN107050015A (en) 2017-08-18
CN107050015B true CN107050015B (en) 2019-08-27

Family

ID=59616950

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201610921609.1A Active CN107050015B (en) 2016-10-21 2016-10-21 Ovum South America chrysanthemum element is as the application in preparation anti-lung cancer, liver cancer and colon cancer drug

Country Status (1)

Country Link
CN (1) CN107050015B (en)

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
Comparative Study of Ovatifolin Antioxidant and Growth Inhibition Activities;C. L. Cespedes et al;《J. Agric. Food Chem.》;20011231;第49卷;4243-4251 *
Study of Chromatographic Retention of Natural Terpenoids by Chemoinformatic Tools;Tiago B. Oliveira et al;《J. Chem. Inf. Model》;20141217;第55卷;26?38 *

Also Published As

Publication number Publication date
CN107050015A (en) 2017-08-18

Similar Documents

Publication Publication Date Title
Shen et al. Bioactive constituents of Clausena lansium and a method for discrimination of aldose enantiomers
CN101531644B (en) New daphnane diterpene compounds in Daphne genkwa as well as preparation method and application of same
CN108084060B (en) Alkaloid oleraurea in purslane and extraction and separation method thereof
CN109824568A (en) Two kinds of indoles new alkaloids compounds and its extraction separation method and application in purslane
CN110272342A (en) A kind of naphthoic acid compound and its extraction separation method and purposes in purslane
CN106008502A (en) Alkaloid compounds with novel skeletons in purslane and extraction and separation method thereof
CN108864004A (en) The purposes of the rich volt lactone of hydroxyl dihydro and its derivative in purslane
Zhu et al. Tinopanoids KT, clerodane diterpenoids with anti-inflammatory activity from Tinospora crispa
CN113717866A (en) An endophytic fungus of Hibiscus Adhatoda fruit and its application in preparing antineoplastic active compound
CN106279305A (en) Amide alkaloid compound and extraction separation method thereof in Herba Portulacae
CN107050015B (en) Ovum South America chrysanthemum element is as the application in preparation anti-lung cancer, liver cancer and colon cancer drug
CN114213375B (en) Sesquiterpene lactone compound and preparation method and application thereof
CN113735918B (en) Labdane diterpene glycoside compound and preparation method thereof
CN106083556A (en) Azulene structure noval chemical compound and extraction separation method thereof in Herba Portulacae
CN114369022B (en) Organic acid compound in purslane and extraction and separation method thereof
CN106619611B (en) Application of eupatorium lactone in preparing medicine for resisting liver cancer and colon cancer
KR101134796B1 (en) A Composition comprising pseurotin D as an active ingredient for treating and preventing cancer disease
CN103610682A (en) Preparation method of 3(alpha)-hydroxyl-30-olive-12,20(29)-diene-28-acid and application in preparing anti-tumor drug
KR20110087397A (en) A composition comprising isodihydroauroglaucin as an active ingredient for treating and preventing cancer disease
CN110305094A (en) Two kinds of flavone compounds and its extraction separation method and purposes in purslane
CN109045012A (en) The application of new skeleton loop coil sesquiterpene dimers compound
CN116496332B (en) Labdane diterpenoid glycoside compound and preparation method thereof
CN104083348A (en) Applications of four kaurane diterpene compounds in preparation of glycosidase inhibitor medicines
CN116496333B (en) Carbon-reducing labdane diterpenoid glycoside compound and preparation method thereof
CN115536532B (en) Crotonane diterpenoid compound, preparation method, pharmaceutical composition and application thereof

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant