CN103288881B - Dual-core organic metal ruthenium compound with anti-tumor activity - Google Patents
Dual-core organic metal ruthenium compound with anti-tumor activity Download PDFInfo
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- CN103288881B CN103288881B CN201310274321.6A CN201310274321A CN103288881B CN 103288881 B CN103288881 B CN 103288881B CN 201310274321 A CN201310274321 A CN 201310274321A CN 103288881 B CN103288881 B CN 103288881B
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Abstract
The invention discloses a dual-core organic metal ruthenium compound with anti-tumor activity. The chemical name of the dual-core organic metal ruthenium compound is bis-hexafluorophosphate phenylacetaldehyde dibenzene-N4-methyl-thiosemicarbazide dimethyl isopropyl benzene ruthenium (II). A preparation method of the dual-core organic metal ruthenium compound comprises the following steps of: 1) preparing a product A; 2) preparing phenylacetaldehyde benzene-N4-methyl-thiosemicarbazide; 3) dissolving the phenylacetaldehyde benzene-N4-methyl-thiosemicarbazide (19mg, 0.1mmol) and the product A (32mg, 0.05mmol) into 6ml of acetone, stirring at normal temperature for 12 hours, to form red transparent solution, then adding 16.3mg (0.1mmol) ammonium hexafluorophosphate, capping a bottle cap, standing for 12 hours to have a great deal of particulate red crystals, namely products. Proved by the in-vitro anti-tumor experiments, the dual-core organic metal ruthenium compound has obvious inhibition effect on liver cancer BEL7404 tumor cell strains.
Description
Technical field
The invention belongs to a kind of title complex with anti-tumor activity.Specifically a kind of Dual-core organic metal ruthenium compound with anti-tumor activity.
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.
One of them important Research Thinking is, replaces platinum as the central metal of title complex, reduce the toxicity of metal complexes with other metallic elements.Because ruthenium and platinum belong to VIII race together in periodictable, chemical property is more similar, so the antitumor character research of researcher to ruthenium complexe is also comparatively active.Research shows, metal Ru can be imitated ferro element and is combined with biomacromolecules such as serum proteins, and this makes ruthenium complexe relative to platinum medicine, and its toxicity significantly reduces.Therefore ruthenium complexe is also considered to one of the most promising antitumor drug.
Thiosemicarbazide is numerous due to its hapto, is easy to form title complex with metal with multiple coordination mode.Recently, because multiple thiosemicarbazide title complex is found to have wide spectrum pharmacological activity, as antitumor, anti-malarial, the characteristic such as antimycotic and making one notice.The present invention with amido thiocarbamide for main part prepares a kind of binuclear organometallic ruthenium compound, there is comparatively powerful antitumor activity, having no relevant report at present.
Summary of the invention
The object of this invention is to provide a kind of Dual-core organic metal ruthenium compound with anti-tumor activity.
The technical scheme that the present invention solves the problems of the technologies described above is as follows:
1. a Dual-core organic metal ruthenium compound:
(1) chemical name of this Dual-core organic metal ruthenium compound is two-hexafluoro-phosphate radicalization two phenyl aldehyde contracting-N
4-Methyl-amino thiocarbamide dimethylisopropyl benzene closes two rutheniums (II).
(2) structural formula:
Molecular formula: [(η
6-p-MeC
6h
4pr
i) Ru (μ
2-S-L)]
2(PF
6)
2
Relative molecular weight: 1145.0265
(3) physico-chemical property: be red crystals, soluble in water and organic solvent.Its hydrogen nuclear magnetic resonance modal data is
1h NMR (CDCl
3solvent): δ=8.74 (d, 2H, NH-CH
3, J=4.8Hz), 7.94 (d, 4H,-phenyl), 7.54 (s, 2H ,-CH=N-), 7.48 (m, 6H ,-phenyl), 6.326,6.233 (2d, 2 × 2H, cymene-phenyl, J=6.0Hz), 6.279,6.270 (dd, 2 × 2H, cymene-phenyl, J=6.3Hzand 14.6Hz), 3.18 (s, 3H, NH-CH
3), 2.82 (m, 1H, cymene-CH (CH
3)
2, J=6.9Hz), 2.80 (d, 3H, NH-CH
3, J=4.8Hz), 2.36 (s, 3H, cymene-CH
3), 1.22,1.20 (2d, 6H, cymene-CH (CH
3)
2, J=6.9Hz) and ppm.
2. prepare a method for binuclear organometallic ruthenium compound, the method comprises the steps:
1) by the RuCl of 0.366g ruthenium content 37%
3xH
2the γ-terpinene of O and 3ml purity 95% is dissolved in 10ml ethanol, and reflux stirs 6 hours.Standing precipitation obtains product A.
2) 0.109g N is taken
4-Methyl-amino thiocarbamide and 0.12ml phenyl aldehyde are dissolved in the ethanolic soln of 10ml50% jointly, are heated to 80 DEG C, and after 4 hours, standing precipitation obtains phenyl aldehyde contracting-N
4-Methyl-amino thiocarbamide.
3) by phenyl aldehyde contracting-N
4-Methyl-amino thiocarbamide (19mg, 0.1mmol) with product A (32mg, 0.05mmol) be dissolved in 6ml acetone, stirring at normal temperature 12 hours, forms clear red solution, then adds ammonium hexafluorophosphate 16.3mg (0.1mmol), cover bottle cap, leave standstill 12 hours, occur a large amount of granular crystals red crystals, be product.
Product magnetic resonance detection, its hydrogen nuclear magnetic resonance modal data is
1h NMR (CDCl
3solvent): δ=8.74 (d, 2H, NH-CH
3, J=4.8Hz), 7.94 (d, 4H,-phenyl), 7.54 (s, 2H ,-CH=N-), 7.48 (m, 6H ,-phenyl), 6.326,6.233 (2d, 2 × 2H, cymene-phenyl, J=6.0Hz), 6.279,6.270 (dd, 2 × 2H, cymene-phenyl, J=6.3Hz and 14.6Hz), 3.18 (s, 3H, NH-CH
3), 2.82 (m, 1H, cymene-CH (CH
3)
2, J=6.9Hz), 2.80 (d, 3H, NH-CH
3, J=4.8Hz), 2.36 (s, 3H, cymene-CH
3), 1.22,1.20 (2d, 6H, cymene-CH (CH
3)
2, J=6.9Hz) and ppm.
3. a purposes for Dual-core organic metal ruthenium compound, two-hexafluoro-phosphate radicalization two phenyl aldehyde contracting-N of the present invention
4-Methyl-amino thiocarbamide dimethylisopropyl benzene closes two rutheniums (II) and shows to have significant restraining effect to liver cancer BEL7404 tumor cell line by the experiment of tumor cell in vitro inhibit activities
Beneficial effect of the present invention is:
1. binuclear organometallic ruthenium compound of the present invention can be used for the medicine preparing Therapeutic cancer, and the form that can be made into injection, tablet, pill, capsule, suspension agent or emulsion uses.
2. the preparation method of binuclear organometallic ruthenium compound of the present invention is simple, and raw material is easy to get, and has the advantage that cost is low.
Accompanying drawing explanation
Fig. 1 is that product of the present invention is at CDCl
3hydrogen nuclear magnetic resonance spectrogram.
In figure: δ=8.74 (d, 2H, NH-CH
3, J=4.8Hz), 7.94 (d, 4H,-phenyl), 7.54 (s, 2H ,-CH=N-), 7.48 (m, 6H ,-phenyl), 6.326,6.233 (2d, 2 × 2H, cymene-phenyl, J=6.0Hz), 6.279,6.270 (dd, 2 × 2H, cymene-phenyl, J=6.3Hz and 14.6Hz), 3.18 (s, 3H, NH-CH
3), 2.82 (m, 1H, cymene-CH (CH
3)
2, J=6.9Hz), 2.80 (d, 3H, NH-CH
3, J=4.8Hz), 2.36 (s, 3H, cymene-CH
3), 1.22,1.20 (2d, 6H, cymene-CH (CH
3)
2, J=6.9Hz) and ppm.
Embodiment
Embodiment 1
The preparation of binuclear organometallic ruthenium compound
The preparation of binuclear organometallic ruthenium compound, its concrete steps are as follows:
By the RuCl of 0.366g purity 37%
3xH
2the γ-terpinene of O and 3ml purity 95% is dissolved in 10ml ethanol, and reflux stirs 6 hours.Standing precipitation obtains product A.Take 0.109gN
4-Methyl-amino thiocarbamide and 0.12ml phenyl aldehyde are dissolved in the ethanolic soln of 10ml50% jointly, are heated to 80 DEG C, and after 4 hours, standing precipitation obtains phenyl aldehyde contracting-N
4-Methyl-amino thiocarbamide.By phenyl aldehyde contracting-N
4-Methyl-amino thiocarbamide (21mg, 0.1mmol) with product A (32mg, 0.05mmol) be dissolved in 6ml acetone, stirring at normal temperature 12 hours, forms clear red solution, then adds ammonium hexafluorophosphate 16.3mg (0.1mmol), cover bottle cap, leave standstill 12 hours, occur a large amount of granular crystals red crystals, be product.
Embodiment 2
Anti tumor activity in vitro is tested
Adopt MTT method, carry out vitro cytotoxicity mensuration.Binuclear organometallic ruthenium compound embodiment 1 obtained and liver cancer BEL7404 cell strain distinguish 72 hours action time, and result is as shown in table 2.
Table 2 binuclear organometallic ruthenium compound is to the medium effective concentration (IC of tumor cell line
50)
| Cell strain | BEL7404 |
| IC 50(umol/mL) | 32 |
As can be seen from the result of embodiment 2, binuclear organometallic ruthenium compound of the present invention shows through anticancer experiment in vitro, and this ruthenium complexe has strong anti-tumor activity.The present invention is that the new antitumor drug of research and development provides new thinking.
Claims (2)
1. a Dual-core organic metal ruthenium compound, is characterized in that:
Its structural formula is:
2. the preparation method of Dual-core organic metal ruthenium compound as claimed in claim 1, the method comprises the steps:
1) by the RuCl of 0.366g ruthenium content 37%
3xH
2the γ-terpinene of O and 3ml purity 95% is dissolved in 10ml ethanol, and reflux stirs 6 hours, and standing precipitation obtains product A;
2) 0.109g N is taken
4-Methyl-amino thiocarbamide and 0.12ml phenyl aldehyde are dissolved in the ethanolic soln of 10ml 50% jointly, are heated to 80 DEG C, and after 4 hours, standing precipitation obtains phenyl aldehyde contracting-N
4-Methyl-amino thiocarbamide;
3) by 19mg phenyl aldehyde contracting-N
4-Methyl-amino thiocarbamide and 32mg product A are dissolved in 6ml acetone, stirring at normal temperature 12 hours, form clear red solution, then add 16.3mg ammonium hexafluorophosphate, cover bottle cap, leave standstill 12 hours, occur a large amount of particulate state red crystals, be product.
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| CN104262409B (en) * | 2014-09-29 | 2017-02-01 | 广西中医药大学 | Organic compound used for treating liver cancers as well as preparation method and application thereof |
| CN105462340B (en) * | 2015-12-28 | 2018-12-11 | 广西师范学院 | Gamma-cyclodextrin and ruthenium complex and its application in microcontact printing techniques |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102964386A (en) * | 2012-11-30 | 2013-03-13 | 广西师范学院 | Dinuclear organic metal ruthenium compound and preparation method and application thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN102964386A (en) * | 2012-11-30 | 2013-03-13 | 广西师范学院 | Dinuclear organic metal ruthenium compound and preparation method and application thereof |
Non-Patent Citations (3)
| Title |
|---|
| Potential Mechanism of the Anti-trypanosomal Activity of Organoruthenium Complexes with Bioactive Thiosemicarbazones;Bruno Demoro等,;《Biological Trace Element Research》;20130407;第371-381页+参考文献36, 尤其摘要、第7132页方案1和右栏第3段、第7133-7134页2.1部分和表1以及参考文献36第1535页图1和右栏最后一段、第1538页表2 * |
| Screening organometallic binuclear thiosemicarbazone ruthenium complexes as potential anti-tumour agents: cytotoxic activity and human serum albumin binding mechanism;Bruno Demoro等,;《Dalton Trans.》;20130301;第7131-7146页 * |
| Synthesis, crystal and electronic structure, anticancer activity of ruthenium(II) arene complexes with thiosemicarbazones;Wei Su等,;《Appl. Organometal. Chem.》;20130411;第307-312页, 尤其是摘要、第309页图1、第311页表3和图6 * |
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