CN104370969A - Ruthenium compound as well as preparation method and application thereof - Google Patents
Ruthenium compound as well as preparation method and application thereof Download PDFInfo
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- 150000003304 ruthenium compounds Chemical class 0.000 title claims abstract description 41
- 238000002360 preparation method Methods 0.000 title claims abstract description 19
- 239000000126 substance Substances 0.000 claims abstract description 10
- 239000003814 drug Substances 0.000 claims abstract description 7
- 201000007270 liver cancer Diseases 0.000 claims abstract description 7
- 208000014018 liver neoplasm Diseases 0.000 claims abstract description 7
- 208000005718 Stomach Neoplasms Diseases 0.000 claims abstract description 4
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 claims description 27
- 229910052707 ruthenium Inorganic materials 0.000 claims description 26
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 18
- HFPZCAJZSCWRBC-UHFFFAOYSA-N p-cymene Chemical compound CC(C)C1=CC=C(C)C=C1 HFPZCAJZSCWRBC-UHFFFAOYSA-N 0.000 claims description 17
- YKFLAYDHMOASIY-UHFFFAOYSA-N γ-terpinene Chemical compound CC(C)C1=CCC(C)=CC1 YKFLAYDHMOASIY-UHFFFAOYSA-N 0.000 claims description 16
- BIXNGBXQRRXPLM-UHFFFAOYSA-K ruthenium(3+);trichloride;hydrate Chemical compound O.Cl[Ru](Cl)Cl BIXNGBXQRRXPLM-UHFFFAOYSA-K 0.000 claims description 14
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 12
- 229960000935 dehydrated alcohol Drugs 0.000 claims description 12
- JKWMSGQKBLHBQQ-UHFFFAOYSA-N diboron trioxide Chemical compound O=BOB=O JKWMSGQKBLHBQQ-UHFFFAOYSA-N 0.000 claims description 12
- 238000001556 precipitation Methods 0.000 claims description 12
- 150000001875 compounds Chemical class 0.000 claims description 9
- 239000000843 powder Substances 0.000 claims description 9
- 238000010992 reflux Methods 0.000 claims description 9
- 238000003756 stirring Methods 0.000 claims description 8
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 6
- 239000000460 chlorine Substances 0.000 claims description 6
- 229910052801 chlorine Inorganic materials 0.000 claims description 6
- 230000008020 evaporation Effects 0.000 claims description 6
- 238000001704 evaporation Methods 0.000 claims description 6
- 239000012467 final product Substances 0.000 claims description 6
- 239000007788 liquid Substances 0.000 claims description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 6
- 229910052757 nitrogen Inorganic materials 0.000 claims description 6
- 201000000498 stomach carcinoma Diseases 0.000 claims description 3
- 238000006243 chemical reaction Methods 0.000 claims description 2
- GBNHFLHKILCBGT-UHFFFAOYSA-N C(C)(=O)[Ru].[O] Chemical compound C(C)(=O)[Ru].[O] GBNHFLHKILCBGT-UHFFFAOYSA-N 0.000 claims 1
- 206010028980 Neoplasm Diseases 0.000 abstract description 5
- 239000002775 capsule Substances 0.000 abstract description 2
- 229940079593 drug Drugs 0.000 abstract description 2
- 239000000839 emulsion Substances 0.000 abstract description 2
- 230000002401 inhibitory effect Effects 0.000 abstract description 2
- 238000002347 injection Methods 0.000 abstract description 2
- 239000007924 injection Substances 0.000 abstract description 2
- 239000006187 pill Substances 0.000 abstract description 2
- 239000002994 raw material Substances 0.000 abstract description 2
- 239000000375 suspending agent Substances 0.000 abstract description 2
- 239000003826 tablet Substances 0.000 abstract description 2
- 206010017758 gastric cancer Diseases 0.000 abstract 1
- 201000011549 stomach cancer Diseases 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 10
- VFLDPWHFBUODDF-FCXRPNKRSA-N Curcumin Natural products C1=C(O)C(OC)=CC(\C=C\C(=O)CC(=O)\C=C\C=2C=C(OC)C(O)=CC=2)=C1 VFLDPWHFBUODDF-FCXRPNKRSA-N 0.000 description 7
- 210000004027 cell Anatomy 0.000 description 7
- -1 Curcumin chemical compounds Chemical class 0.000 description 5
- 230000000259 anti-tumor effect Effects 0.000 description 5
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Substances [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 5
- 238000013019 agitation Methods 0.000 description 4
- 229940109262 curcumin Drugs 0.000 description 4
- 235000012754 curcumin Nutrition 0.000 description 4
- 239000004148 curcumin Substances 0.000 description 4
- VFLDPWHFBUODDF-UHFFFAOYSA-N diferuloylmethane Natural products C1=C(O)C(OC)=CC(C=CC(=O)CC(=O)C=CC=2C=C(OC)C(O)=CC=2)=C1 VFLDPWHFBUODDF-UHFFFAOYSA-N 0.000 description 4
- 229910052751 metal Inorganic materials 0.000 description 4
- 239000002184 metal Substances 0.000 description 4
- 229910052697 platinum Inorganic materials 0.000 description 4
- 230000000694 effects Effects 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
- 210000004881 tumor cell Anatomy 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- 206010034133 Pathogen resistance Diseases 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 206010051779 Bone marrow toxicity Diseases 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical class C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000000118 anti-neoplastic effect Effects 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 231100000366 bone marrow toxicity Toxicity 0.000 description 1
- 230000025084 cell cycle arrest Effects 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 239000002895 emetic Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 238000002649 immunization Methods 0.000 description 1
- 230000003053 immunization Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 231100000417 nephrotoxicity Toxicity 0.000 description 1
- 210000000578 peripheral nerve Anatomy 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 230000000452 restraining effect Effects 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000005760 tumorsuppression Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F15/00—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table
- C07F15/0006—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table compounds of the platinum group
- C07F15/0046—Ruthenium compounds
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a ruthenium compound with a structural formula (I) in the specification as well as a preparation method and application thereof. The chemical name of the ruthenium compound is monochloromono(1E,6E)-1,7-bis(3-methoxy-4-hydroxyphenyl)-4-carboxymethyl-1,6-heptanetriene-3,5-dione-methyl isopropyl benzene ruthenium. The ruthenium compound shows good inhibitory activities towards gastric cancer SGC-7901 cell lines and liver cancer BEL-7404 cell lines, can be used for preparing medicines for treating cancers and can be prepared into the forms, such as injections, tablets, pills, capsules, suspending agents or emulsion for use. The preparation method of the ruthenium compound is simple, is accessible in raw materials and has the advantage of low cost.
Description
Technical field
The present invention relates to field of compound preparation, be specifically related to a kind of ruthenium compound and its production and use.
Background technology
At present, cis-platinum has become and has been used for the treatment of cancer one of 3 kinds of medicines the most widely in the world, reaches nearly 500,000,000 dollars in the annual sales amount of the U.S..But the use of cis-platinum also has certain deficiency, it does not have restraining effect to some tumour, and easily and other platinum preparations produce cross resistance.In addition, cis-platinum has multiple side effect, as renal toxicity, peripheral nerve toxicity, bone marrow toxicity, haematics toxicity and emetic etc.Therefore, find efficient, low toxicity and be the study hotspot of researcher always without the new type antineoplastic medicine of cross resistance.
Curcumin chemical compounds is numerous due to its hapto, is easy to form title complex with metal with multiple coordination mode.Recently, because multiple curcumin title complex is found to have wide spectrum pharmacological activity---make one notice as characteristics such as antitumor, anti-inflammatories.With curcumin chemical compounds for main part prepares organometallic ruthenium compound, due to the synergy of metal Ru and curcumin part, its anti-tumor activity can be strengthened.
Summary of the invention
The object of the invention is to the synergistic research according to existing metal Ru and curcumin part, a kind of ruthenium compound and its production and use is provided.
Technical scheme provided by the invention is:
A kind of ruthenium compound,
1) chemical name of this ruthenium compound is that chlorine one (1E, 6E)-1,7-bis-(3-methoxyl group-4-hydroxy phenyl)-4-carboxymethyl-1,6-heptadiene-3, a 5-diketone monomethyl isopropyl benzene closes ruthenium;
2) its structural formula is formula (I):
A preparation method for ruthenium compound, wherein, comprises the following steps:
Step one, the hydrate ruthenium trichloride of 0.2-0.5g and the γ-terpinene of 2-6ml are dissolved in 5-15ml dehydrated alcohol, reflux stirs 4-8 hour, standing precipitation obtains the compound with formula (III), and namely dichloride-two-cymene closes two rutheniums (II);
Step 2, take the 3-carboxymethyl-2 of 0.05-0.15g, 3-methoxyl group-4 hydroxy benzaldehyde of 4-diacetylmethane, 0.05-0.2g and the boron trioxide of 0.02-0.08g are dissolved in 5-15ml dimethyl formamide solution jointly, under nitrogen protection, 70-90 DEG C of reaction is after 2-6 hour, add the hydrochloric acid of 0.1-0.2g, standing precipitation obtains the compound with formula (IV), i.e. (1E, 6E)-1,7-bis-(3-methoxyl group-4-hydroxy phenyl)-4-carboxymethyl-1,6-heptadiene-3,5-diketone monomethyl isopropyl benzene closes ruthenium;
Step 3, by (the 1E of 15-25mg, 6E)-1,7-bis-(3-methoxyl group-4-hydroxy phenyl)-4-carboxymethyl-1, dichloride-two-cymene that 6-heptadiene-3,5-diketone monomethyl isopropyl benzene closes ruthenium and 28-35mg closes the dehydrated alcohol that two rutheniums (II) are dissolved in 5-12ml, heated and stirred backflow 4-8 hour, react rear and solution evaporation has been remained 1-3ml liquid, add the normal hexane of 25-35ml, separate out orange red powder, to obtain final product.
Preferably, in the preparation method of described ruthenium compound, hydrate ruthenium trichloride described in step one is the hydrate ruthenium trichloride of ruthenium weight content 30%-40%; The purity of described γ-terpinene is 80%-99%.
Preferably, in the preparation method of described ruthenium compound, hydrate ruthenium trichloride described in step one is the hydrate ruthenium trichloride of ruthenium weight content 37%; The purity of described γ-terpinene is 95%.
A purposes for ruthenium compound, described ruthenium compound is for the preparation of the application for the treatment of cancer of the stomach and liver-cancer medicine.
The present invention has following beneficial effect: first, ruthenium compound of the present invention closes two rutheniums and the coordination of carboxymethyl curcumin chemical compounds by dichloride-two-cymene, ruthenium compound energy inhibition tumor cell with carboxymethyl is bred, can 51% be reached to tumor control rate, 28% is improve, with cell-cycle arrest after the ruthenium compound of carboxymethyl at G relative to its inhibiting rate of Benzazole compounds
1phase, apoptosis of tumor cells obviously increases, and tumor suppression and immunization strengthen.Secondly, can be used for the medicine preparing Therapeutic cancer, the form that can be made into injection, tablet, pill, capsule, suspension agent or emulsion uses.The preparation method of ruthenium compound of the present invention is simple, and raw material is easy to get, and has the advantage that cost is low.Ruthenium compound of the present invention shows stronger inhibit activities to SGC-7901 cell strain and liver cancer BEL-7404 cell strain, shows that the present invention has strong anti-tumor activity.
Embodiment
Below in conjunction with embodiment, the present invention is described in further detail, can implement according to this with reference to specification sheets word to make those skilled in the art.
A kind of ruthenium compound,
1) chemical name of this ruthenium compound is that chlorine one (1E, 6E)-1,7-bis-(3-methoxyl group-4-hydroxy phenyl)-4-carboxymethyl-1,6-heptadiene-3, a 5-diketone monomethyl isopropyl benzene closes ruthenium;
2) its structural formula is formula (I):
A preparation method for ruthenium compound, wherein, comprises the following steps:
Step one, the γ-terpinene being 95% by the hydrate ruthenium trichloride of 0.2-0.5g ruthenium weight content 37% and 2-6ml purity are dissolved in 5-15ml dehydrated alcohol, put into three-necked bottle, add magneton and carry out magnetic agitation, oil bath is heated, thermostatic control is at 70-90 DEG C, reflux stirs 4-8 hour, and standing precipitation obtains the compound with formula (III), and namely dichloride-two-cymene closes two rutheniums (II);
Step 2, take the 3-carboxymethyl-2 of 0.05-0.15g, 4-diacetylmethane, 3-methoxyl group-4 hydroxy benzaldehyde of 0.05-0.2g and the boron trioxide of 0.02-0.08g are placed in three-necked bottle, add 5-15ml dimethyl formamide solution again, constantly nitrogen protection is passed in three-necked bottle, react 2-6 hour at 70-90 DEG C after, add the hydrochloric acid of 0.1-0.2g, standing precipitation obtains the compound with formula (IV), i.e. (1E, 6E)-1, 7-bis-(3-methoxyl group-4-hydroxy phenyl)-4-carboxymethyl-1, 6-heptan two rare-3, 5 diketone monomethyl isopropyl benzenes close ruthenium,
Step 3, by (the 1E of 15-25mg, 6E)-1,7-bis-(3-methoxyl group-4-hydroxy phenyl)-4-carboxymethyl-1,6-heptadiene-3, dichloride-two-cymene that 5-bis--one monomethyl isopropyl benzene closes ruthenium and 28-35mg closes the dehydrated alcohol that two rutheniums (II) are dissolved in 5-12ml, heated and stirred backflow 4-8 hour, has reacted rear and solution evaporation has been remained 1-3ml liquid, added the normal hexane of 25-35ml, stir, separate out orange red powder, to obtain final product.
A purposes for ruthenium compound, described ruthenium compound is for the preparation of the application for the treatment of cancer of the stomach and liver-cancer medicine.
Embodiment 1:
A kind of ruthenium compound of the present invention, its chemical name is that chlorine one (1E, 6E)-1,7-bis-(3-methoxyl group-4-hydroxy phenyl)-4-carboxymethyl-1,6-heptadiene-3, a 5-diketone monomethyl isopropyl benzene closes ruthenium;
Its physico-chemical property is: orange red powder, soluble in water and organic solvent.
The preparation method of ruthenium compound of the present invention, its concrete steps are as follows:
Step one, the γ-terpinene being 95% by the hydrate ruthenium trichloride of 0.2g ruthenium weight content 37% and 2ml purity are dissolved in 5ml dehydrated alcohol, put into three-necked bottle, add magneton and carry out magnetic agitation, oil bath is heated, thermostatic control is at 70 DEG C, reflux stirs 4 hours, and standing precipitation obtains dichloride-two-cymene and closes two rutheniums (II);
Step 2, take the 3-carboxymethyl-2 of 0.05g, 3-methoxyl group-4 hydroxy benzaldehyde of 4-diacetylmethane, 0.05g and the boron trioxide of 0.02g are placed in three-necked bottle, add 5ml dimethyl formamide solution again, constantly nitrogen protection is passed in three-necked bottle, react at 70 DEG C after 2 hours, add the hydrochloric acid of 0.1g, standing precipitation obtains (1E, 6E)-1,7-bis-(3-methoxyl group-4-hydroxy phenyl)-4-carboxymethyl-1,6-heptadiene-3,5-bis--one monomethyl isopropyl benzene closes ruthenium;
Step 3, by (the 1E of 15mg, 6E)-1, dichloride-two-cymene that 7-bis-(3-methoxyl group-4-hydroxy phenyl)-4-carboxymethyl-1,6-heptadiene-3,5-diketone monomethyl isopropyl benzene closes ruthenium and 28mg closes the dehydrated alcohol that two rutheniums (II) are dissolved in 5ml, heated and stirred refluxes 4 hours, react rear and solution evaporation has been remained 1ml liquid, added the normal hexane of 25ml, stirred, separate out orange red powder, to obtain final product.
Embodiment 2:
A kind of ruthenium compound of the present invention, its chemical name is that chlorine one (1E, 6E)-1,7-bis-(3-methoxyl group-4-hydroxy phenyl)-4-carboxymethyl-1,6-heptadiene-3, a 5-diketone monomethyl isopropyl benzene closes ruthenium;
Its physico-chemical property is: orange red powder, soluble in water and organic solvent.
The preparation method of ruthenium compound of the present invention, its concrete steps are as follows:
Step one, the γ-terpinene being 95% by the hydrate ruthenium trichloride of 0.5g ruthenium weight content 37% and 6ml purity are dissolved in 15ml dehydrated alcohol, put into three-necked bottle, add magneton and carry out magnetic agitation, oil bath is heated, thermostatic control is at 90 DEG C, reflux stirs 8 hours, and standing precipitation obtains dichloride-two-cymene and closes two rutheniums (II);
Step 2, take the 3-carboxymethyl-2 of 0.15g, 3-methoxyl group-4 hydroxy benzaldehyde of 4-diacetylmethane, 0.2g and the boron trioxide of 0.08g are placed in three-necked bottle, add 15ml dimethyl formamide solution again, constantly nitrogen protection is passed in three-necked bottle, react at 90 DEG C after 6 hours, add the hydrochloric acid of 0.2g, standing precipitation obtains (1E, 6E)-1,7-bis-(3-methoxyl group-4-hydroxy phenyl)-4-carboxymethyl-1,6-heptadiene-3,5-diketone monomethyl isopropyl benzene closes ruthenium;
Step 3, by (the 1E of 25mg, 6E)-1, dichloride-two-cymene that 7-bis-(3-methoxyl group-4-hydroxy phenyl)-4-carboxymethyl-1,6-heptadiene-3,5-diketone monomethyl isopropyl benzene closes ruthenium and 35mg closes the dehydrated alcohol that two rutheniums (II) are dissolved in 12ml, heated and stirred refluxes 8 hours, react rear and solution evaporation has been remained 3ml liquid, added the normal hexane of 35ml, stirred, separate out orange red powder, to obtain final product.
Embodiment 3:
A kind of ruthenium compound,
A kind of ruthenium compound of the present invention, its chemical name is that chlorine one (1E, 6E)-1,7-bis-(3-methoxyl group-4-hydroxy phenyl)-4-carboxymethyl-1,6-heptadiene-3, a 5-diketone monomethyl isopropyl benzene closes ruthenium;
Its physico-chemical property is: orange red powder, soluble in water and organic solvent.
The preparation method of ruthenium compound of the present invention, its concrete steps are as follows:
Step one, the γ-terpinene being 95% by the hydrate ruthenium trichloride of 0.366g ruthenium weight content 37% and 3ml purity are dissolved in 10m1 dehydrated alcohol, put into three-necked bottle, add magneton and carry out magnetic agitation, oil bath is heated, thermostatic control is at 80 DEG C, reflux stirs 6 hours, and standing precipitation obtains dichloride-two-cymene and closes two rutheniums (II);
Step 2, take the 3-carboxymethyl-2 of 0.088g, 3-methoxyl group-4 hydroxy benzaldehyde of 4-diacetylmethane, 0.12g and the boron trioxide of 0.07g are placed in three-necked bottle, add 10ml dimethyl formamide solution again, constantly nitrogen protection is passed in three-necked bottle, react at 80 DEG C after 4 hours, add the hydrochloric acid of 0.146g, standing precipitation obtains (1E, 6E)-1,7-bis-(3-methoxyl group-4-hydroxy phenyl)-4-carboxymethyl-1,6-heptadiene-3,5-diketone monomethyl isopropyl benzene closes ruthenium;
Step 3, by (the 1E of 20mg, 6E)-1,7-bis-(3-methoxyl group-4-hydroxy phenyl)-4-carboxymethyl-1,6-heptadiene-3, dichloride-two-cymene that 5-diketone monomethyl isopropyl benzene closes ruthenium and 32mg closes the dehydrated alcohol that two rutheniums (II) are dissolved in 8ml, heated and stirred refluxes 6 hours, has reacted rear and solution evaporation is remained 2ml liquid, added the normal hexane of 30ml, stir, separate out orange red powder, to obtain final product.
Its hydrogen nuclear magnetic resonance modal data is
1h NMR:(ppm, CDCl
3) δ=1.400 (6H, d, J=6.9Hz), 2.350 (3H, s), 2.98 (1H, m, J=6.9Hz), 5.30 (2H, d, J=6.3Hz), 5.57 (2H, d, J=6.3Hz), 3.68 (s, 2H), 7.08 (d, 2H, J=15.1Hz), 7.66 (d, 2H, J=15.1Hz), 7.24 (d, 2H, J=1.6Hz), 6.82 (d, 2H, J=8.2Hz), 7.13 (dd, 2H, J=1.6Hz, J=8.2Hz), 3.91 (s, 6H).
Its pharmaceutical activity and application thereof is further illustrated below by pharmacodynamic experiment.
Experiment one: anti tumor activity in vitro is tested:
Adopt MTT method, carry out vitro cytotoxicity mensuration.The ruthenium compound obtain embodiment 3 and SGC-7901 cell strain and liver cancer BEL-7404 cell strain 72 hours action time respectively, result is as shown in table 1.
Table 1 ruthenium compound is to the IC of tumor cell line
50
| Cell strain | SGC-7901 | BEL-7404 |
| IC 50(umol/mL) | 2.5±1.3 | 5.5±1.8 |
As shown in Table 1, ruthenium compound of the present invention shows through anticancer experiment in vitro, acts on after 72 hours, the IC of described SGC-7901 cell strain
50be 2.5 ± 1.3, well below the 503nhibiting concentration of conventional Organic metal ruthenium ion pair compound, and the IC of liver cancer BEL-7404 cell strain
50reach 5.5 ± 1.8, illustrate that this compound has strong anti-tumor activity.Wherein said IC
50for medium effective concentration.The present invention is that the new antitumor drug of research and development provides new thinking.
Although embodiment of the present invention are open as above, but it is not restricted to listed in specification sheets and embodiment utilization, it can be applied to various applicable the field of the invention completely, for those skilled in the art, can easily realize other amendment, therefore do not deviating under the universal that claim and equivalency range limit, the present invention is not limited to specific details.
Claims (5)
1. a ruthenium compound, is characterized in that:
1) chemical name of this ruthenium compound is that chlorine one (1E, 6E)-1,7-bis-(3-methoxyl group-4-hydroxy phenyl)-4-carboxymethyl-1,6-heptadiene-3, a 5-diketone monomethyl isopropyl benzene closes ruthenium;
2) its structural formula is formula (I):
2. a preparation method for ruthenium compound as claimed in claim 1, is characterized in that, comprises the following steps:
Step one, the hydrate ruthenium trichloride of 0.2-0.5g and the γ-terpinene of 2-6ml are dissolved in 5-15ml dehydrated alcohol, reflux stirs 4-8 hour, standing precipitation obtains the compound with formula (III), and namely dichloride-two-cymene closes two rutheniums (II);
Step 2, take the 3-carboxymethyl-2 of 0.05-0.15g, 3-methoxyl group-4 hydroxy benzaldehyde of 4-diacetylmethane, 0.05-0.2g and the boron trioxide of 0.02-0.08g are dissolved in 5-15ml dimethyl formamide solution jointly, under nitrogen protection, 70-90 DEG C of reaction is after 2-6 hour, add the hydrochloric acid of 0.1-0.2g, standing precipitation obtains the compound with formula (IV), i.e. (1E, 6E)-1,7-bis-(3-methoxyl group-4-hydroxy phenyl)-4-carboxymethyl-1,6-heptadiene-3,5-diketone monomethyl isopropyl benzene closes ruthenium;
Step 3, by (the 1E of 15-25mg, 6E)-1,7-bis-(3-methoxyl group-4-hydroxy phenyl)-4-carboxymethyl-1, dichloride-two-cymene that 6-heptadiene-3,5-diketone monomethyl isopropyl benzene closes ruthenium and 28-35mg closes the dehydrated alcohol that two rutheniums (II) are dissolved in 5-12ml, heated and stirred backflow 4-8 hour, react rear and solution evaporation has been remained 1-3ml liquid, add the normal hexane of 25-35ml, separate out orange red powder, to obtain final product.
3. the preparation method of tertiary fourth oxygen ethanoyl ruthenium compound as claimed in claim 2, it is characterized in that, hydrate ruthenium trichloride described in step one is the hydrate ruthenium trichloride of ruthenium weight content 30%-40%; The purity of described Y-terpinene is 80%-99%.
4. the preparation method of ruthenium compound as claimed in claim 3, it is characterized in that, hydrate ruthenium trichloride described in step one is the hydrate ruthenium trichloride of ruthenium weight content 37%; The purity of described Y-terpinene is 95%.
5. a purposes for ruthenium compound as claimed in claim 1, is characterized in that, described ruthenium compound is for the preparation of the application for the treatment of cancer of the stomach and liver-cancer medicine.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105504959A (en) * | 2015-12-28 | 2016-04-20 | 广西师范学院 | Beta-cyclodextrin and carboxymethyl ruthenium compound and application of compound in microcontact printing technology |
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| ERIKA FERRARI ET AL.: "Newly Synthesized Curcumin Derivatives: Crosstalk between Chemico-physical Properties and Biological Activity", 《J. MED. CHEM.》 * |
| LAURA BONFILI ET AL.: "Arene–RuII Complexes of Curcumin Exert Antitumor Activity via Proteasome Inhibition and Apoptosis Induction", 《CHEMMEDCHEM》 * |
| 张磊等: "姜黄素衍生物生物活性的研究进展", 《沈阳药科大学学报》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105504959A (en) * | 2015-12-28 | 2016-04-20 | 广西师范学院 | Beta-cyclodextrin and carboxymethyl ruthenium compound and application of compound in microcontact printing technology |
| CN105504959B (en) * | 2015-12-28 | 2018-10-12 | 广西师范学院 | Beta-cyclodextrin and carboxymethyl ruthenium compound and its application in microcontact printing techniques |
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