CN107200769B - A kind of rotundic acid derivative with prevention and treatment metastasis effect - Google Patents
A kind of rotundic acid derivative with prevention and treatment metastasis effect Download PDFInfo
- Publication number
- CN107200769B CN107200769B CN201710514649.9A CN201710514649A CN107200769B CN 107200769 B CN107200769 B CN 107200769B CN 201710514649 A CN201710514649 A CN 201710514649A CN 107200769 B CN107200769 B CN 107200769B
- Authority
- CN
- China
- Prior art keywords
- rotundic acid
- derivative
- cell
- rotundic
- present
- 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
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J63/00—Steroids in which the cyclopenta(a)hydrophenanthrene skeleton has been modified by expansion of only one ring by one or two atoms
- C07J63/008—Expansion of ring D by one atom, e.g. D homo steroids
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The present invention provides a kind of rotundic acid derivatives to prevent and treat the application in tumor metastasis medicine in preparation.Show that rotundic acid derivative of the invention has significant inhibiting effect to the proliferation of tumour cell, adherency, migration etc. by experiment in vitro；And to human normal cell's safety and low toxicity.Interior animal experiment shows that it can effectively reduce the experimental lung metastasis of mouse B16-F10 melanoma, prompts it with preferable inhibiting effect on tumor metastasis.Rotundic acid derivative of the invention can be applied in the prophylactic agent of metastases, rotundic acid derivative is opened up in the new application of tumor prevention and treatment, postoperative retransfer for preventing malignant tumour to develop the rebirth medicine of metastases provides new selection.And derivative of the present invention has more obvious pharmacological activity compared with rotundic acid.
Description
Technical field
The present invention relates to prevention malignant tumour postoperative metastasis drug, specifically rotundic acid derivative prevention and
The application in tumor metastasis medicine is treated, field of medicaments is belonged to.
Background technique
Malignant tumour is to seriously endanger one of the major disease of human health, and the tumor patient cause of death is mostly pernicious swollen
Caused by the transfer of tumor advanced stage.Metastases refer to that tumour cell is free from primary tumor, enter cyclic system to surrounding tissue infiltration, invasion
It unites and shifts in vivo therewith, and form the processes such as metastatic tumor with endothelial cell adherency infiltration.Metastases are that tumour is difficult to
One of the main reason for curing and recurring, and lead to the key factor of tumor patient death.Clinical diagnosis is the results show that about
60% or more first visit tumor patient has occurred and that transfer, and survival rate is less than 20% within 5 years.Currently, the tumour of only only a few
Transfer patient can effectively be treated by operation, and other clinical treatment mode effects are very limited.Therefore, metastases
Prevention and treatment be faced with very stern challenge, how to block the infiltration metastasis of tumour is that improve oncotherapy horizontal and cure tumour
Key.
Number is chemotherapeutics to clinical use anti-tumor drug greatly absolutely at present, and it is numerous that these drugs can act on growth of tumour cell
In the different links grown, inhibit or kill tumour cell.Chemotherapeutics kills normal tissue while killing tumor cell
Cell, especially vigorous blood, the lymphocyte etc. of growth and development in killing human body, and these cells and tissue are people
The immune defense system that weight is wanted destroys the immune system of human body, and cancer may rapidly develop, and causes serious consequence.Change
It treats drug and lacks selectivity mostly, widely distributed in vivo, Yi Yinfa toxic side effect causes patient not to be resistant to, and reduces drug and treats
Effect.Therefore, people have been devoted to the research of new type antineoplastic medicine in recent years, wherein effectively inhibiting the medicine of Nasopharyngeal neoplasms
Object is a new drug development direction.
Rotundic acid is primarily present in Chinese medicine iron holly bark (Ilicis routundae cortex), has extensive medicine
Reason effect, such as it is anticancer, liver protection, anti-inflammatory, antiviral, anti-oxidant.In recent years, the feature that rotundic acid is especially efficient with its low toxicity
And diversified mechanism of anticancer action is increasingly subject to people's attention, before showing biggish clinical application potentiality and good application
Scape.But rotundic acid is insoluble in water, leads to problems such as the preparation of its preparation difficult and vivo biodistribution is using low, therefore by rescuing
The structure of acid must be answered to be modified, to improve the solubility of slightly solubility rotundic acid, so that its anticancer activity is further increased, and
It is effectively improved its bioavilability, is increasingly becoming the hot and difficult issue of researcher research.
Our research has been proven that rotundic acid has the pharmacological activity (patent for preventing and treating cardiovascular and cerebrovascular disease
Publication number: CN101856357A), while there is the pharmacological actions such as reducing blood lipid (patent publication No.: CN101849950A)；In addition,
The present inventor research demonstrate rotundic acid amino acid derivativges with antineoplastic action (patent publication No.:
CN102391352B)；Rotundic acid acylated derivatives have antineoplastic action (patent publication No.: CN102127142B)；This
Inventor also study demonstrate rotundic acid reacted with succinic anhydride generate derivative have the function of prevention and cure of cardiovascular disease
(patent publication No.: CN102140126B).These rotundic acid derivatives with respect to rotundic acid parent itself, though to tumour cell
Anticancer activity improves, but is not directed to the research to normal cell toxicity and its in terms of anti-tumor metastasis；This project
Group has found the compound of the present invention on the basis of early-stage study, can obviously improve the solubility of rotundic acid, chemical combination physics
Change property to stablize；Furthermore it is compared with rotundic acid, more significant inhibited proliferation is all had to variety classes tumour cell,
And it is lower to normal cell toxicity, prompt it to have the characteristics that safe and efficient and less toxic, it is expected to be applied to metastases
In early prevention and treatment.In consideration of it, it is swollen in prevention and treatment to inquire into it using rotundic acid derivative of the present invention as research object
Application in terms of tumor metastasis.Its main advantage of the rotundic acid derivative of inventor's synthesis is:
1) derivative of the present invention can further improve the solubility of rotundic acid, have in terms of physicochemical property and druggability
More preferable advantage；
2) derivative of the present invention is substantially better than rotundic acid parent to the anticancer activity of various tumour cells, to normal cell
Safety and low toxicity are a kind of anti-tumor metastasis drug candidates of potential high-efficiency low-toxicity.Therefore, inventor answers derivative of the present invention
Tumour is prevented and treated for preventing and treating tumor metastasis medicine research, and by inside and outside experiment discussion derivative of the present invention
The effect and mechanism of transfer.
Before the present invention completes, in addition to the present inventor's research, there are no the derivatives of document report rotundic acid to have
The effect for preventing and treating metastases does not find that the derivative of rotundic acid prevents and treats tumor metastasis medicine in preparation yet
The report of application.
Summary of the invention
The purpose of the present invention is to the defects of the above-mentioned prior art, provide rotundic acid derivative and are preventing and controlling
Treat the application in tumor metastasis medicine.
The purpose of the present invention is be achieved by the following technical programs:
A kind of rotundic acid derivative with prevention and treatment metastasis effect, structural formula are as follows:
A kind of rotundic acid derivative with prevention and treatment metastasis effect as described above is obtained by following methods
It arrives:
1, ethyl alcohol extract Chinese medicine iron holly bark (Ilicis routundae cortex), it is purified, separation, alkaline degradation and obtain
The rotundic acid obtained.
2, rotundic acid is dissolved in DMF, under the catalysis of Anhydrous potassium carbonate, is reacted with 1,2- dichloroethanes, is carried out silicon
Rubber column gel column separation, obtains compound rotundic acid-(2- chlorine) ethyl ester.
3, it takes compound rotundic acid-(2- chlorine) ethyl ester to be dissolved in DMF, Anhydrous potassium carbonate is added, potassium iodide is made, triethylamine
It for catalyst, is reacted with piperazine hexahydrate, silica gel post separation, obtains compound rotundic acid-(2- piperazine) ethyl ester.
Compound rotundic acid-(2- piperazine) ethyl ester is taken, is dissolved in dry methylene chloride, pyridine carboxylic acid, EDC is added
HCL, HOBT, room temperature reaction, silica gel post separation obtain derivative of the present invention.
Derivative experimental data of the present invention are as follows: molecular weight: 705.97, white powder, molecular formula C42H63N3O6；1H NMR
(400MHz, DMSO) δ: 8.58-8.56 (1H), 7.95-7.89 (1H), 7.56-7.54 (1H), 7.50-7.45 (1H), 5.16
(1H, 12-CH), 4.42-4.38 (1H, 19-OH), 4.16-4.14 (1H, 3-OH), 4.00 (2H, 1'-CH2), 3.86 (1H, 23-
OH), 3.62 (2H, piperazine, N-CH2), 3.47-3.35 (2H, piperazine, N-CH2), 3.31-3.30 (2H, 3-CH, 23-CH2),
3.09-3.04 (1H, 23-CH2), 2.59-2.55 (5H, 11-CH2, piperazine, N-CH2), 2.44-2.39 (3H, 2'-CH2, 18-
CH), 1.99-1.37 (14H), 1.29 (3H, 30-CH3), 1.24-1.13 (5H), 1.08 (3H, 27-CH3), 0.93-0.91
(1H), 0.85-0.83 (6H, 24-CH3, 29-CH3), 0.61 (3H, 26-CH3), 0.53 (3H, 25-CH3)；13C NMR
(100MHz, DMSO) δ: 176.83 (C-28), 166.55 (C-1 "), 154.00 (C-2 "), 148.30 (C-3 "), 138.32 (C-
13), 137.29 (C-5 "), 127.24 (C-12), 124.51 (C-4 "), 123.09 (C-6 "), 71.64 (C-03), 70.50 (C-
19), 64.66 (C-23), 61.53 (C-1'), 55.65 (C-2'), 53.29 (C-18), 52.98 (piperazine, N-C, overlappings),
52.43 (piperazine, N-C, overlappings), 47.43 (C-05), 46.68 (C-09), 46.53 (C-17), 41.83 (C-20), 41.60 (C-
14), 41.37 (C-08), 41.10 (C-01), 38.02 (C-04), 37.16 (C-22), 36.24 (C-10), 32.24 (C-07),
27.97 (C-15), 26.55 (C-21), 26.35 (C-29), 25.82 (C-02), 25.12 (C-16), 24.04 (C-27), 23.14
(C-11), 17.56 (C-06), 16.51 (C-25), 16.19 (C-26), 15.43 (C-30), 12.58 (C-24).
Rotundic acid derivative of the present invention has the function of prevention and treatment metastases, and tumour includes but is not limited to liver
Cancer, melanoma.
It is above-described a kind of with the rotundic acid derivative for preventing and treating metastasis effect, it can be used for preparing
The drug of metastases is prevented and treated, made preparation includes tablet, capsule, granule, oral solution, pill, injection
The dosage forms such as agent.
The invention has the characteristics that being chemically modified to the rotundic acid extracted from iron holly bark for lead compound, obtain
To derivative of the present invention, prove have and significantly inhibit to the transfer of tumour cell through pharmacological evaluation, and activity is bright
It is aobvious to be better than parent compound rotundic acid.And it is used for rotundic acid and rotundic acid derivative to prevent and treat tumour for the first time
Shift the application of aspect.
The beneficial effects of the present invention are:
(1) derivative of the present invention can further improve the solubility of rotundic acid, have in terms of physicochemical property and druggability
Have the advantages that more preferable；
(2) rotundic acid derivative of the present invention has preferable selectivity to the inhibiting effect of tumour cell, to normal cell
Safety and low toxicity are a kind of medicine for treating tumor metastasis of potential high-efficiency low-toxicity.
(3) rotundic acid derivative of the present invention can inhibit tumour cell extracellular matrix and Human umbilical vein endothelial cells
(HUVEC) adherency.
(4) rotundic acid derivative of the present invention can inhibit the movement transfer ability of tumour cell.
(5) rotundic acid derivative of the present invention can prevent and treat the transfer of mouse B16-F10 melanoma generation lung.
Specific embodiment
Below with reference to example, specific embodiments of the present invention will be described in further detail.Following instance is for saying
The bright present invention, but be not intended to limit the scope of the invention.
1 rotundic acid of embodiment and derivative are to the Proliferation Ability of hepatocellular carcinoma H22 and to normal liver cell LO2 toxicity
Research
Will be after logarithmic growth phase hepatocellular carcinoma H22 and Human normal hepatocyte LO2 digestion, cell density is adjusted to 1
×105A/mL, is inoculated in 96 orifice plates, and every 100 μ L of hole sets 37 DEG C, 5%CO2It is cultivated for 24 hours in incubator；Old culture medium is removed,
Test medicine (rotundic acid and derivative) is added with culture medium by test medicine storage liquid dilution, sets different concentration, often
100 μ L of hole separately sets blank control group, and every group sets 5 multiple holes.Drug effect for 24 hours after, inhale abandon pastille culture medium, in every Kong Zhongjia
Enter serum-free without 100 μ L of phenol red medium, add the 100 μ L of solution of 0.5mg/mL MTT, continues after being incubated for 4h, terminate training
It supports；It inhales and abandons supernatant in 96 orifice bores, 100 μ L DSMO are added in every hole, vibrate 10min, are in microplate reader in 570nm wavelength
It measures each hole absorbance value (OD value), calculates cell survival rate (%)=(medication group mean OD value/blank control group is averaged OD
Value) × 100%.Experimental result is shown in Table 1.
1 rotundic acid of table and derivative are to the Proliferation Ability of HepG2 and to LO2 toxicity test result
The experimental results showed that derivative of the present invention has significant Inhibit proliferaton effect to hepatocellular carcinoma H22, and have
Dosage is according to lazyness, and rotundic acid effect itself is unobvious；(0.25-5 μM) derivative of the present invention of low concentration is to liver cancer cells
There is certain inhibited proliferation, inhibiting rate 9.6%-61.8% after HepG2 effect for 24 hours；The LO2 of the concentration range
The survival rate of cell is all larger than 89%, smaller to normal liver cell LO2 toxicity.And with the raising of derivatives concentration of the present invention,
Inhibited proliferation of the compound to hepatocellular carcinoma H22 and the toxicity to normal liver cell LO2 significantly enhance.?
In 0.25-5 μM of concentration range, the anticancer activity of derivative of the present invention is apparently higher than rotundic acid itself, and derivative of the present invention
It is lower compared with toxicity of the rotundic acid to normal cell, the characteristics of having both safety and low toxicity.
2 rotundic acid of embodiment and derivative inhibit the adhesive attraction of hepatocellular carcinoma H22 extracellular matrix
The fibronectin FN (fibronectin) for being stored in -20 DEG C is statically placed in 37 DEG C of water-baths to melting completely, with no blood
Clear culture solution is configured as the FN working solution that concentration is 10 μ g/ml.96 holes are completely covered by using 100 hole μ L/ FN working solutions
Plate, left at room temperature over night gently suck liquid.Single cell suspension, cell concentration 5 is made in logarithmic growth phase HepG2 cell
×105/ ml mixes with the drug (0,0.25,0.5,1.0,2.5,5.0 μM) of various concentration, is inoculated in coated 96 orifice plate of FN
In.37 DEG C, after 5%CO2 is incubated for 2h, PBS is rinsed 3 times, and the 10 μ l of culture solution of MTT is added after draining, and continues to be incubated for 4h, in abandoning
Clearly, 100 μ l DMSO are added, the OD value at enzyme detector detection 570nm is used after dissolution.
Adhesion inhibition rate (%)=(1- medication group mean OD value/blank control group mean OD value) × 100%.
2 rotundic acid of table and derivative inhibit the adhesive attraction of hepatocellular carcinoma H22 extracellular matrix
Derivative of the present invention can obviously inhibit human liver cancer cell HepG2 to the adhesive capacity of FN glue, inhibiting rate as the result is shown
For 4.9%-51.4%, there is dose dependent；And rotundic acid only 5 μM of groups inhibitory effect (17.6%) compared with the control group
There are significant differences.
3 rotundic acid of embodiment and derivative inhibit the adhesion experiment of hepatocellular carcinoma H22 and HUVEC cell
Human umbilical vein endothelial cells are isolated from the umbilical vein of normal pregnant occasion childbirth, are cultivated.Logarithmic phase will be in
It is inoculated in 24 orifice plates after HUVEC cell dissociation, when the endothelial cell of above-mentioned 24 orifice plate covers with orifice plate, is cleaned two or three times with PBS,
Then it is added and contains endothelium stimulating factor IL-1 β, concentration is that the culture medium of 1ng/L is incubated under conditions of 5%CO2 at 37 DEG C
4h.Orifice plate is taken out after 4h, after being cleaned two or three times with PBS, logarithmic growth phase HepG2 cell is made 4 × 10 after fluorescent marker5/
ml-1Single cell suspension, and the RPM-1640 culture solution of various concentration derivative of the present invention is added, drug final concentration is respectively as follows: 0,
0.25,0.2,1.0,2.5,5.0 μM, every 500 μ l of hole.37 DEG C, 5%CO2 be incubated for 2h after, PBS rinse 3 times, nothing is added after draining
500 μ l of serum free culture system liquid.Then it takes pictures under fluorescence microscope, random clap takes 10 views after eye and record each eye that regards
Cell number calculates the rotundic acid and its derivative Human Umbilical Vein Endothelial Cells adhesion inhibition rate of various concentration.
Adhesion rate (%)=(medication group average cell number/blank control group average cell number) × 100%.
3 rotundic acid of table and derivative inhibit the adhesion experiment of hepatocellular carcinoma H22 and HUVEC cell
As shown in Table 3, compared with the control group, 0.25-5 μM of derivative of the present invention is thin with HUVEC to hepatoma Hep G 2 cells
The inhibiting rate of the adherency of born of the same parents is respectively 9.3%, 19.8%, 34.3%, 49.2%, 55.2%, significant difference.And 0.25-5 μM
Rotundic acid is unobvious to the inhibiting effect of hepatocellular carcinoma H22 and HUVEC cell adherence；5 μM of rotundic acid is thin to liver cancer
The inhibiting rate of born of the same parents HepG2 and HUVEC cell adherence is only 13.5%.
The influence that 4 rotundic acid of embodiment and derivative migrate human liver cancer cell HepG2
The HepG2 cell for choosing logarithmic growth phase, after trypsin digestion, adjustment cell concentration is 2 × 105/ ml, with
The hole 2ml/ is inoculated in 6 orifice plates, is placed in 37 DEG C, 5%CO2Incubator in cultivate 12h, when cell monolayer is paved with orifice plate；PBS is light
It washes 3 times, is separately added into (0,0.25,0.5,1.0,2.5,5.0 μM) measurement distance of rotundic acid and derivative, after culture for 24 hours, survey
Determine migration distance.Experiment calculates cell migration rate in triplicate.
Cell migration rate=(medication group 0h average distance-medication group for 24 hours average distance)/(control group 0h average distance-right
According to group average distance for 24 hours) × 100%
The influence that 4 rotundic acid of table and derivative migrate human liver cancer cell HepG2
Experimental result the result shows that: compared with the control group, 5 μM of rotundic acid is to the inhibition of metastasis rate of liver cancer cells
18.5%, it is unobvious to the inhibition of metastasis effect of hepatocellular carcinoma H22.The present composition of various concentration is to liver cancer cells
The inhibition of metastasis effect of HepG2 has dose dependent, and with the increase of concentration, the mobility of HepG2 cell is significantly reduced；5μ
After the derivative of the present invention of M acts on for 24 hours hepatoma Hep G 2 cells, the inhibition of metastasis rate of cell is up to 60.5%.
The inhibition that 5 rotundic acid of example and 0 manual cell's pulmonary metastases of Derivatives In Mice melanoma B16-F1 are formed
Effect
Logarithmic growth phase B16-F10 cell, PBS buffer solution adjust cell concentration to 1 × 10 ml-1.C57/BL6 mouse
Tail vein injection, every 0.2ml.It is randomly divided into totally 5 groups of physiological saline group, experimental group, every group 8.Control group gives physiology salt
Water, derivative of the present invention are divided into low middle high three dosage groups, dosage 10mgkg-1、20mg·kg-1、40mg·kg-1,
Rotundic acid (40mgkg-1) group.Next day is administered using stomach-filling mode after tumor inoculation, every single administration 0.2ml, and daily 1
It is secondary, successive administration 21d.Next day cervical dislocation puts to death mouse after administration, takes lung, and formalin fixer is fixed, and dissection is aobvious
Pulmonary metastases stove number is counted under micro mirror, and inhibiting rate is calculated as follows.
Inhibiting rate=(1- administration group mean transferred tumor stove number/physiological saline group mean transferred tumor stove number) × 100
The inhibition that 5 rotundic acid of table and 0 manual cell's pulmonary metastases of Derivatives In Mice melanoma B16-F1 are formed is made
With
The experimental results showed that after the derivative of the present invention administration of various dose, it, can different journeys compared with physiological saline group
The formation of the inhibition Pulmonary metastasis focuses of degree；Derivative high dose medication group of the present invention is high to the Lung metastases inhibiting rate of B16-F10 cell
Up to 63.6%；And with the rotundic acid medication group of dosage group, inhibiting rate is only 19.0%, and the Lung metastases of cell inhibit without apparent
Effect.
Claims (2)
1. a kind of rotundic acid derivative, structure feature are as follows:
2. rotundic acid derivative according to claim 1 answering in the drug that preparation prevents and treats metastases
With.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710514649.9A CN107200769B (en) | 2017-06-29 | 2017-06-29 | A kind of rotundic acid derivative with prevention and treatment metastasis effect |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710514649.9A CN107200769B (en) | 2017-06-29 | 2017-06-29 | A kind of rotundic acid derivative with prevention and treatment metastasis effect |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN107200769A CN107200769A (en) | 2017-09-26 |
| CN107200769B true CN107200769B (en) | 2019-03-05 |
Family
ID=59910477
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201710514649.9A Active CN107200769B (en) | 2017-06-29 | 2017-06-29 | A kind of rotundic acid derivative with prevention and treatment metastasis effect |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN107200769B (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111333694B (en) * | 2020-04-28 | 2022-04-26 | 吉林省中医药科学院（吉林省中医药科学院第一临床医院） | Application of hederagenin derivative in medicine for resisting myocardial anoxia reoxygenation injury |
| CN114558023B (en) * | 2022-03-18 | 2023-11-14 | 广西中医药大学 | Application of pedunculoside in preparation of medicines for inhibiting lung metastasis cancer |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102127142A (en) * | 2010-12-28 | 2011-07-20 | 赵全成 | Ilicis routundae cortex derivants and application thereof in preparing medicament capable of resisting tumors |
| CN102391352A (en) * | 2011-11-09 | 2012-03-28 | 赵全成 | Amino acid derivatives of rotundic acid and application of derivatives in preparation of antitumor medicines |
| CN105859823A (en) * | 2016-06-14 | 2016-08-17 | 吉林省中医药科学院 | Application of ilicis routundae cortex acid ester derivatives in preparation of anti-tumor drugs |
| CN106883282A (en) * | 2017-02-22 | 2017-06-23 | 吉林省中医药科学院（吉林省中医药科学院第临床医院） | Application of the rotundic acid derivative in anti-tumor drug is prepared |
-
2017
- 2017-06-29 CN CN201710514649.9A patent/CN107200769B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102127142A (en) * | 2010-12-28 | 2011-07-20 | 赵全成 | Ilicis routundae cortex derivants and application thereof in preparing medicament capable of resisting tumors |
| CN102391352A (en) * | 2011-11-09 | 2012-03-28 | 赵全成 | Amino acid derivatives of rotundic acid and application of derivatives in preparation of antitumor medicines |
| CN105859823A (en) * | 2016-06-14 | 2016-08-17 | 吉林省中医药科学院 | Application of ilicis routundae cortex acid ester derivatives in preparation of anti-tumor drugs |
| CN106883282A (en) * | 2017-02-22 | 2017-06-23 | 吉林省中医药科学院（吉林省中医药科学院第临床医院） | Application of the rotundic acid derivative in anti-tumor drug is prepared |
Non-Patent Citations (3)
| Title |
|---|
| Novel rotundic acid derivatives: Synthesis, structural characterization and in vitro antitumor activity;YU CHEN等;《INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE》;20131231;第31卷;353-360 * |
| Synthesis, Characterization and Cytotoxicity of New Rotundic Acid Derivatives;Yu-Fang He等;《Molecules》;20120131;第17卷;1278-1291 * |
| 救必应酸的制备及其衍生物的设计、合成和抗肿瘤活性研究;赫玉芳;《中国博士学位论文全文数据库 医药卫生科技辑》;20130815;E079-45 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN107200769A (en) | 2017-09-26 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102675401B (en) | Preparation of anti-tumor medicine LQC-Y and application thereof | |
| CN102675403A (en) | Synthesis of anti-hepatitis B medicine LQC-X and application thereof | |
| CN107200769B (en) | A kind of rotundic acid derivative with prevention and treatment metastasis effect | |
| CN106478569A (en) | Isoalantolactone derivative and its salt | |
| CN102311449A (en) | Application of gossypol derivative to preparing anti-tumor medicament | |
| CN110693872A (en) | Dihydromyricetin with broad-spectrum anti-tumor activity, derivative and application thereof | |
| CN106749089A (en) | The preparation of new fluoro thiazole hydrazone compounds and its application in antineoplastic | |
| US20200383989A1 (en) | Therapeutic Agent for Fatty Liver Diseases and Therapeutic Agent for Adiposity | |
| AU2014220455B2 (en) | Sugar-analog phosphorus-containing heterocycles having an anti-metastatic activity | |
| WO2021023016A1 (en) | Thiazolidone derivative of lovatinib acid and application thereof | |
| Huang et al. | Synthesis, characterization, and biological studies of diosgenyl analogs | |
| CN105412011A (en) | Amphiphilic micelle of carrier with anti-tumor and anti-metastasis activity | |
| CN103183719B (en) | Saponin derivative and uses thereof | |
| CN107188923B (en) | The double iron holly bark acid esters new medical uses of ethane -1,2- | |
| CN106748939A (en) | The new bromine phenol thiosemicarbazide compound of one class and its preparation and medicine and purposes | |
| CN101541717B (en) | A trans-cinnamic acid derivative, its preparation method and the use | |
| CN104151388A (en) | Preparation of anti-tumor drug LQC-Y and application thereof | |
| CN103351383B (en) | 5-fluorouracil nitroxyl-free-radical anti-tumor drug | |
| CN106749088A (en) | The new bromine phenol thiazole compound of one class and its preparation and medicine and purposes | |
| CN106496169A (en) | Alantolactone derivant and its salt | |
| CN107011406A (en) | A kind of compound with antitumor action and its preparation method and application | |
| CN104098646B (en) | Gracillin derivative and antitumor activity application thereof | |
| CN103880793B (en) | Containing furan imine compound and its production and use | |
| CN109251224A (en) | There is chemotherapy and the complex of iridium of phototherapy antitumor action and its preparation method and application simultaneously | |
| CN102838652B (en) | A kind of oleanolic acid derivate with anticarcinogenesis and its production and use |
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 |