CN103804472A - Taxane medicinal precursor - Google Patents
Taxane medicinal precursor Download PDFInfo
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- CN103804472A CN103804472A CN201410031867.3A CN201410031867A CN103804472A CN 103804472 A CN103804472 A CN 103804472A CN 201410031867 A CN201410031867 A CN 201410031867A CN 103804472 A CN103804472 A CN 103804472A
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Abstract
The invention discloses a taxane medicinal precursor, which is a conjugate formed by bonding a hydroxyl group at C-2' or C-7 position of a taxane compound and water-soluble targeting peptide through a conjugation bridge, wherein the conjugation bridge contains at least one of an ester bond, a carbonic ester bond, a urea bond and a disulfide bond. Compared with the taxane compound, the medicinal precursor has the advantages that the medicinal precursor has extremely high water solubility capable of reaching 2mg/ml, so that the problem that the taxane compound can only be dissolved by using an unsafe substance such as an organic solvent and tween 80 in the prior art is solved; due to the adoption of a covalent coupling mode, the taxane medicinal precursor is ensured to have high stability when being stored in vitro, and the taxane compound can be rapidly released to achieve medicinal effects after the taxane medicinal precursor enters cells; the taxane compound can be carried to a specific tumor cell through the targeting peptide to reduce killing ability to normal cells; a decomposed product of the targeting peptide in the cells is amino acid, so that high biocompatibility is ensured.
Description
Technical field
The present invention relates to a kind of taxone precursor, be specifically related to a kind of taxone precursor.
Background technology
Taxone mainly comprises taxol and Docetaxel, is one of effective antitumour medicine clinically at present.Taxol (paclitaxel) is from the bark of Ramulus et folium taxi cuspidatae of the Pacific Ocean, to separate a kind of tetracyclic diterpene compound obtaining, and molecular formula is C
47h
51o
14n, molecular weight is 853.9, water insoluble.U.S. FDA approval listing in 1992, its mechanism of action is and cell tubulin binding that promotion tubulin polymerization, to resist depolymerization, blocking-up mitotic division, thereby suppresses tumor growth, inducing apoptosis of tumour cell.Clinical study is verified taxol, at the multiple noumenal tumour for the treatment of, comprises the aspects such as mammary cancer, advanced ovarian cancer, lung cancer, brain and tumor colli and acute leukemia, has significant effect.Docetaxel (docetaxel) is that the non-cell toxicity precursor compound 10-deacylated tRNA base Tetraol II of extracting from european yew obtains through semi-synthetic, within 1998, obtains U.S. FDA approval listing.The mechanism of action of Docetaxel is similar to taxol, but anti-tumor activity is the doubly a lot of of taxol, and the cancer such as mammary cancer, nonsmall-cell lung cancer is had to obvious result for the treatment of.
Due to water-soluble lower (approximately 1～10 μ g/mL) of taxone, the paclitaxel injection that therefore used clinically and Docetaxol injection all need to use respectively surfactant polyoxyethylene Viscotrol C (Cremophor EL) and polysorbate 80 (tween 80) and solubility promoter ethanol to reach the object of dissolved substance.
The paclitaxel injection (commodity are called " PTX ") of existing listing, take polyoxyethylenated castor oil (Cremophor EL): ethanol=1: 1 as solvent, concentration is 6mg/mL, when clinical application, dilute 5～20 times by physiological saline or dextran, once quiet note 3h, dosage is 135mg/m
2.Polyoxyethylenated castor oil has been proved to be and can have caused serious anaphylaxis, neurotoxicity, renal toxicity and ypotension etc.In addition, polyoxyethylenated castor oil also can form molecule parcel taxol molecule in blood, affects drug molecule to diffusion between tissue, reduces antitumous effect.
Similarly, the Docetaxel injection (commodity are called " taxotere ") of listing at present, adopt the double solvent of tween 80 and dehydrated alcohol to be prepared from, but the use of tween 80 easily causes the anaphylaxis of serious patient, before chemotherapy, patient often needs to take in advance or injects Claritin (corticoid and bisfentidine), in infusion process, also need to connect millipore filter and enter the patient blood recycle system to prevent the crystal fine grain that medicine produces in dilution, these all bring great risk and inconvenience to clinical application.
For these reasons, people have developed a series of taxone in recent years derivative or new formulation overcome its water-soluble problem.As by chemical coupling method, introduce water soluble group and obtain water-soluble larger D51-7059 C-2 ' of taxol parent nucleus or the hydroxyl of C-7 position.In addition the method that, taxol is imported to liposome, micella or make emulsion also can reach the effect of solubilising.But these current technology often can only improve the water-soluble of taxone, the targeting problem of medicine can not be improved.By coupling, some soluble small molecular polypeptide that possess tumour cell targeting are prepared the prodrug of taxone, not only can solve solubility problem, and can give the medicine target ability to tumour cell in vivo, there is very good market outlook and clinical value.
Summary of the invention
The invention provides a kind of taxone precursor, this taxone precursor is covalent coupling small molecules targeting peptides in bearing taxanes molecule, has greatly improved the targeting of medicine and water-soluble.
A kind of taxone precursor, C-2 ' that described taxone precursor is bearing taxanes position or C-7 position hydroxyl and water-soluble targeting peptides are combined the conjugate of formation by cross structure, comprise at least one in ester bond, carbonic acid ester bond, urea key and disulfide linkage in described cross structure.
By connect water-soluble targeting peptides on C-2 ' position or C-7 position hydroxyl, water-soluble and the tumor-targeting of bearing taxanes is improved greatly, when use, only need, by water dissolution, no longer need organic cosolvent, greatly reduce the toxicity producing in drug use process.
As preferably, C-2 ' the position hydroxyl that described taxone precursor is bearing taxanes and water-soluble targeting peptides are combined the conjugate of formation by cross structure.Compared with C-2 ' position, the chemosynthesis difficulty at C-7 position place is larger.
As preferably, described covalent linkage is at least one in ester bond, carbonic acid ester bond, urea key, disulfide linkage.
As preferably, described targeting peptides is liver cancer cell targeting peptides.As further preferred, the aminoacid sequence of described liver cancer cell targeting peptides is: SFSIIHTPILPL.Coupling can occur in the N end of this aminoacid sequence, also can occur in C end.As preferably, in one end that coupling occurs, on described targeting peptides, also with connection peptides, connection peptides is preferably made up of 2～4 glycine, and connection peptides can avoid bearing taxanes to affect the combination of targeting peptides and tumour cell.
In the present invention, described bearing taxanes is taxol or Docetaxel.
As preferably, the structural formula of described taxone precursor is as shown in formula I or formula II:
Or, as shown in formula III or formula IV:
Wherein, X is water-soluble amino acids, and the number n of water-soluble amino acids is 0～5.
For further improving the water-soluble of described taxone precursor, at one end of targeting peptides and bearing taxanes coupling (N end or C end) introducing water-soluble amino acids, as preferably, the number n of water-soluble amino acids is 2～5.Described water-soluble amino acids is preferably arginine, Methionin, aspartic acid or L-glutamic acid, more preferably arginine or Methionin.
And, utilize sulfydryl and the bearing taxanes of halfcystine to carry out coupling, sulfydryl is not only easy to reaction, preparation condition gentleness, multiple couplings site can also be provided, and coupling can occur in the sulfydryl of C end (leucic carboxyl), N end (amino of halfcystine) or the halfcystine of targeting peptides, there is coupling on sulfydryl time, can also form stable disulfide linkage, guarantee that described taxone front body structure is stable.
Between hydroxyl on taxol or Docetaxel C-2 ' position of formula I or formula II and the cysteine sulfydryl of targeting peptides, introduce carbonic acid ester bond and disulfide linkage; Formula III or formula IV are introduced ester bond and urea key between the hydroxyl on taxol or Docetaxel C-2 ' position and the cysteine sulfydryl of targeting peptides.
As further preferred, the structural formula of described taxone precursor is suc as formula shown in (V) or formula VI:
Or, shown in (VII) or formula (VIII):
In formula (V), (VI), (VII), (VIII), glycine (G
m) as connection peptides, the number m of glycine is preferably 2～4, more preferably 2.
The preparation method of described taxone precursor comprises: first introduce corresponding group, the derivative of synthesizing taxone compound at C-2 ' position or the C-7 position hydroxyl of bearing taxanes; Then this derivative is mixed with targeting peptides, under stirring at room temperature, carry out coupling, obtain described taxone precursor.
The present invention also provides described taxone precursor in the application of preparing in medicines resistant to liver cancer.Described taxone precursor can use separately after freeze-drying, also can add different vehicle post-treatment to become any formulation, comprises tablet, pill, capsule, granule, oral liquid and for intravenous aqueous injection or powder injection.
Compared with prior art, beneficial effect of the present invention is embodied in:
(1) compared with bearing taxanes, taxone precursor of the present invention has fabulous water-soluble, solubleness can reach 1.8mg/ml, and having solved in prior art can only be with an organic solvent and the dangerous material such as the tween 80 problem of dissolving bearing taxanes; The taxone precursor obtaining, preparation cost is low, and stability is high, and security is good, meets the requirement of clinical application, meets the requirement of scale operation, possesses good market outlook;
(2) targeting peptides can be transported to bearing taxanes specific tumour cell, reduces Normocellular lethality, and targeting peptides is amino acid at intracellular degraded product, therefore has higher biocompatibility.
Accompanying drawing explanation
Fig. 1 is the synthetic route chart of SP94-taxol in embodiment 1;
Fig. 2 is taxol C '-2 bit derivant in Fig. 1
1h-NMR nuclear magnetic spectrum;
Fig. 3 is taxol maleimide derivatives in Fig. 1
1h-NMR nuclear magnetic spectrum;
Fig. 4 is the ESI mass spectrum of SP94-taxol in Fig. 1;
Fig. 5 is the synthetic route chart of SP94-Docetaxel in embodiment 2;
Fig. 6 is Docetaxel derivative in Fig. 5
1h-NMR nuclear magnetic spectrum;
Fig. 7 is the ESI mass spectrum of SP94-Docetaxel;
Fig. 8 is the anti tumor activity in vitro MTT measurement result figure of SP94-taxol and taxol.
Embodiment
Utilize taxol and hepatoma-targeting peptide SP94 coupling to prepare taxone precursor, its synthetic route as shown in Figure 1, comprises the following steps:
(1) taxol C '-2 bit derivant 2 is synthetic
In dry reaction flask, add taxol 1(300mg, 0.35mmol), with anhydrous pyridine 2ml dissolving; In reaction solution, add Succinic anhydried (105mg, 1.05mmol) and DMAP DMAP(4.3mg, 0.035mmol).Stirring at room temperature 2 hours, TLC shows that reaction finishes rear termination reaction, vacuum rotary steam is removed pyridine; Normal phase silicagel column (methylene dichloride: methyl alcohol=20:1) separates and obtains white solid, and product yield is 91%.Utilize
1h-NMR(Fig. 2) confirmation target product 2.
(2) taxol maleimide derivatives 3 is synthetic
Get compound 2(100mg, 0.105mmol) be dissolved in 2ml dry DMF, in reaction solution, add N-(2-amino-ethyl) maleimide trifluoroacetate (28mg, 0.11mmol), HOBt(15.6mg, 0.115mmol), HBTU(43.7mg, 0.115mmol) and DIPEA(69.3mg, 0.42mmol); Stirring at room temperature 4 hours, the reaction of TLC detection display finishes rear termination reaction, and vacuum rotary steam is removed DMF; Solid is washed with saturated sodium bicarbonate aqueous solution, 5% citric acid and saturated aqueous common salt after being dissolved in methylene dichloride successively, and after anhydrous sodium sulfate drying, vacuum rotary steam is removed methylene dichloride; Normal phase silicagel column (methylene dichloride: methyl alcohol=20:1) separates and obtains solid, and product yield is 80%.Utilize
1h-NMR(Fig. 3) confirmation target product 3.
(4) prodrug of SP94 polypeptide coupling taxol synthesizes and high performance liquid phase separation
Get compound 3(10mg, 8.4 μ mol) and SP94 polypeptide (13mg, 8.4 μ mol) (aminoacid sequence is as shown in SEQ ID No.1) be dissolved in DMF and Tris damping fluid (pH8.0), stirring at room temperature 2 hours, TLC shows that reaction finishes rear the termination reaction, (CH of high performance liquid phase for reaction solution
3cN:H
2o=10:90 (0min) → 90:10 (30min)) separate and obtain 18mg white solid.Product yield is 78%, and the ESI mass spectrum of target product 4 is shown in as Fig. 4.The water-soluble 2mg/ml that is about of target product 4.
Embodiment 2 Docetaxels are by the preparation of carbonic acid ester bond and disulfide linkage and hepatoma-targeting polypeptide SP94 coupling prodrug
Utilize Docetaxel and hepatoma-targeting peptide SP94 coupling to prepare taxone precursor, its synthetic route as shown in Figure 5, comprises the following steps:
(1) compound 9 is synthetic
According to document (E.A.Dubikovskaya et al., Overcoming multidrug resistance of small-molecule therapeutics through conjugation with releasable octaarginine transporters, Proceedings of the National Academy of Sciences, 2008,105 (34): 12128-12133.), synthetic compound 9.
(2) Docetaxel derivative 11 is synthetic
Get Docetaxel 10(40mg, 49.5 μ mol) be dissolved in the anhydrous DCM of 2ml, in reaction solution, add compound 9(22mg, 59.4 μ mol), DMAP(7.3mg, 59.4 μ mol); Stirring at room temperature 4 hours, TLC shows that reaction finishes rear termination reaction; In reaction solution, add DCM50ml again, then, successively with saturated sodium bicarbonate aqueous solution, saturated aqueous common salt washing, after anhydrous sodium sulfate drying, vacuum rotary steam is removed methylene dichloride; Normal phase silicagel column (methylene dichloride: methyl alcohol=20:1) separates and obtains solid 60mg, and product yield is 85%.Utilize
1h-NMR(Fig. 6) confirmation target product 11.
(3) prodrug of SP94 polypeptide coupling Docetaxel synthesizes and high performance liquid phase separation
Get compound 11(10mg, 9.7 μ mol) and SP94 polypeptide (15mg, 9.7 μ mol) be dissolved in 2ml DMF and Tris damping fluid (pH8.0), stirring at room temperature 4 hours, TLC shows that reaction finishes rear termination reaction, and reaction solution separates and obtains 15mg white solid with high performance liquid phase.Product yield is 60%, and the ESI mass spectrum of target product 12 is shown in Fig. 7.The water-soluble 1.8mg/ml that is about of target product 12.
The antitumor drug effect evaluation of embodiment 3
The target product 4(SP94-PTX obtaining for Evaluation operation example 1) kill capability to tumour cell, take hepatoma cell line 7721 as example, adopt mtt assay to carry out evaluating drug effect, and with taxol in contrast.SP94-PTX4 the results are shown in Figure 8 to the cytotoxicity of liver cancer 7721.As seen from Figure 8, water-soluble SP94-PTX and co-culture of cells be after 72 hours, and its In Vitro Anti liver cancer efficacy shows, SP94-PTX has the cytotoxicity identical with PTX.
Claims (9)
1. a taxone precursor, it is characterized in that, C-2 ' that described taxone precursor is bearing taxanes position or C-7 position hydroxyl and water-soluble targeting peptides are combined the conjugate of formation by cross structure, comprise at least one in ester bond, carbonic acid ester bond, urea key and disulfide linkage in described cross structure.
2. taxone precursor as claimed in claim 1, is characterized in that, described water-soluble targeting peptides is liver cancer cell targeting peptides.
3. taxone precursor as claimed in claim 2, is characterized in that, the aminoacid sequence of described liver cancer cell targeting peptides is: SFSIIHTPILPL.
4. taxone precursor as claimed in claim 1, is characterized in that, described bearing taxanes is taxol or Docetaxel.
5. taxone precursor as claimed in claim 1, is characterized in that, structural formula is as shown in formula I or formula II:
Wherein, X is water-soluble amino acids, and the number n of water-soluble amino acids is 0～5.
6. taxone precursor as claimed in claim 1, is characterized in that, structural formula is as shown in formula III or formula IV:
Wherein, X is water-soluble amino acids, and the number n of water-soluble amino acids is 0～5.
7. the taxone precursor as described in claim 5 or 6, is characterized in that, described water-soluble amino acids is arginine, Methionin, aspartic acid or L-glutamic acid.
8. taxone precursor as claimed in claim 7, is characterized in that, described water-soluble amino acids is arginine or Methionin.
9. the taxone precursor as described in claim 5 or 6, is characterized in that, the number n of water-soluble amino acids is 2～5.
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Cited By (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104667292A (en) * | 2015-02-02 | 2015-06-03 | 北京大学 | Preparation of reducing response type drug conjugate nanoparticle and application of reducing response type drug conjugate nanoparticle |
| CN104667290A (en) * | 2014-10-25 | 2015-06-03 | 中国科学技术大学 | Targeting peptide-modified gold nanoparticle and preparation method thereof as well as application of targeting peptide-modified gold nanoparticle as platinic pro-drug carrier |
| WO2015196944A1 (en) * | 2014-06-26 | 2015-12-30 | 中国人民解放军军事医学科学院毒物药物研究所 | Gnrh analog-cytotoxic molecule conjugate and preparation method and use thereof |
| CN105396141A (en) * | 2015-12-10 | 2016-03-16 | 浙江大学 | iRGD-anticancer medicine conjugates, preparing method thereof and applications of the conjugates |
| CN106806905A (en) * | 2017-01-03 | 2017-06-09 | 浙江大学 | It is a kind of to collect the fluorescence imaging rare earth upconversion nano pharmaceutical carrier integrated with medicine is carried and its application |
| CN106806906A (en) * | 2017-01-03 | 2017-06-09 | 浙江大学 | A kind of preparation method for collecting the fluorescence imaging rare earth upconversion nano pharmaceutical carrier integrated with medicine is carried |
| CN109422799A (en) * | 2017-08-22 | 2019-03-05 | 复旦大学 | Docetaxel anti-liver cancer and anti-targeted prodrug and its pharmaceutical usage |
| CN109420179A (en) * | 2017-08-22 | 2019-03-05 | 复旦大学 | Polyenoid taxane targeted prodrug and its inhibitor against colon carcinoma cells pharmaceutical usage |
| CN110075314A (en) * | 2019-05-20 | 2019-08-02 | 上海交通大学 | A kind of amphipathic medicine medicine conjugate and its nanoparticle formulations preparation method |
| CN115960116A (en) * | 2022-12-19 | 2023-04-14 | 中国药科大学 | Coupled prodrug, nanoparticle, pharmaceutical composition, preparation method and application |
| CN116251195A (en) * | 2022-12-27 | 2023-06-13 | 哈尔滨吉象隆生物技术有限公司 | Paclitaxel targeting peptide conjugate and application thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7550609B2 (en) * | 1999-11-24 | 2009-06-23 | Immunogen Inc. | Cytotoxic agents comprising taxanes and their therapeutic use |
| TW200935055A (en) * | 2007-11-20 | 2009-08-16 | Academia Sinica | Peptides specific for hepatocellular carcinoma cells and applications thereof |
| CN101791409A (en) * | 2003-04-22 | 2010-08-04 | 研究及应用科学协会股份有限公司 | peptide vectors |
-
2014
- 2014-01-23 CN CN201410031867.3A patent/CN103804472B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7550609B2 (en) * | 1999-11-24 | 2009-06-23 | Immunogen Inc. | Cytotoxic agents comprising taxanes and their therapeutic use |
| CN101791409A (en) * | 2003-04-22 | 2010-08-04 | 研究及应用科学协会股份有限公司 | peptide vectors |
| TW200935055A (en) * | 2007-11-20 | 2009-08-16 | Academia Sinica | Peptides specific for hepatocellular carcinoma cells and applications thereof |
Non-Patent Citations (1)
| Title |
|---|
| 杨恩慈等: "改善紫杉醇水溶性方法的研究进展", 《中南药学》 * |
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| WO2015196944A1 (en) * | 2014-06-26 | 2015-12-30 | 中国人民解放军军事医学科学院毒物药物研究所 | Gnrh analog-cytotoxic molecule conjugate and preparation method and use thereof |
| CN104667290A (en) * | 2014-10-25 | 2015-06-03 | 中国科学技术大学 | Targeting peptide-modified gold nanoparticle and preparation method thereof as well as application of targeting peptide-modified gold nanoparticle as platinic pro-drug carrier |
| CN104667292B (en) * | 2015-02-02 | 2017-09-05 | 北京大学 | A kind of preparation and its application for reducing response type drug conjugates nanoparticle |
| CN104667292A (en) * | 2015-02-02 | 2015-06-03 | 北京大学 | Preparation of reducing response type drug conjugate nanoparticle and application of reducing response type drug conjugate nanoparticle |
| CN105396141A (en) * | 2015-12-10 | 2016-03-16 | 浙江大学 | iRGD-anticancer medicine conjugates, preparing method thereof and applications of the conjugates |
| CN105396141B (en) * | 2015-12-10 | 2018-08-24 | 浙江大学 | IRGD- anticancer drug conjugates and its preparation method and application |
| CN106806905B (en) * | 2017-01-03 | 2020-05-19 | 浙江大学 | Rare earth up-conversion nano-drug carrier integrating fluorescence imaging and drug loading and application thereof |
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| CN106806906B (en) * | 2017-01-03 | 2020-05-19 | 浙江大学 | Preparation method of rare earth up-conversion nano-drug carrier integrating fluorescence imaging and drug loading |
| CN106806905A (en) * | 2017-01-03 | 2017-06-09 | 浙江大学 | It is a kind of to collect the fluorescence imaging rare earth upconversion nano pharmaceutical carrier integrated with medicine is carried and its application |
| CN109422799A (en) * | 2017-08-22 | 2019-03-05 | 复旦大学 | Docetaxel anti-liver cancer and anti-targeted prodrug and its pharmaceutical usage |
| CN109420179A (en) * | 2017-08-22 | 2019-03-05 | 复旦大学 | Polyenoid taxane targeted prodrug and its inhibitor against colon carcinoma cells pharmaceutical usage |
| CN109422799B (en) * | 2017-08-22 | 2022-07-29 | 复旦大学 | Docetaxel liver cancer-resisting targeted prodrug and medicinal application thereof |
| CN109420179B (en) * | 2017-08-22 | 2022-08-26 | 复旦大学 | Docetaxel targeted prodrug and anti-colon cancer medicinal application thereof |
| CN110075314A (en) * | 2019-05-20 | 2019-08-02 | 上海交通大学 | A kind of amphipathic medicine medicine conjugate and its nanoparticle formulations preparation method |
| CN115960116A (en) * | 2022-12-19 | 2023-04-14 | 中国药科大学 | Coupled prodrug, nanoparticle, pharmaceutical composition, preparation method and application |
| CN116251195A (en) * | 2022-12-27 | 2023-06-13 | 哈尔滨吉象隆生物技术有限公司 | Paclitaxel targeting peptide conjugate and application thereof |
| CN116251195B (en) * | 2022-12-27 | 2023-12-05 | 哈尔滨吉象隆生物技术有限公司 | Paclitaxel targeting peptide conjugate and application thereof |
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