CN101177434A - Meletin ammino platinum anti-cancer drugs and method for making same - Google Patents
Meletin ammino platinum anti-cancer drugs and method for making same Download PDFInfo
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- CN101177434A CN101177434A CNA200710179415XA CN200710179415A CN101177434A CN 101177434 A CN101177434 A CN 101177434A CN A200710179415X A CNA200710179415X A CN A200710179415XA CN 200710179415 A CN200710179415 A CN 200710179415A CN 101177434 A CN101177434 A CN 101177434A
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- quercetin
- ammino platinum
- platinum
- ammino
- diiodo
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Abstract
The invention discloses a quercetin combined ammino platinum with antineoplastic activity, belonging to medication technical field, the chemical structural formula is as follows: the invention prepares complex compound from the quercetin and the platinum-based antineoplastic medicine, which not only has synergic anti-tumor effectiveness, but also can reduce the toxic and side effects of the platinum-based antineoplastic medicine and avoid drugfastness. The invention also discloses the preparation method of quercetin combined ammino platinum anticancer drugs.
Description
Technical field
The present invention relates to medical technical field, it is a kind of Quercetin-platinum-containing anticancer drug with anti-tumor activity, comprises its preparation method in definite saying.
Background technology
Malignant tumour is one of topmost disease that threatens at present the human life.According to statistics, in the whole world 5,800,000,000 populations in 1996, because of tumour dead have 630 surplus ten thousand people, wherein nearly 60% dies from lung cancer, cancer of the stomach, mammary cancer, colorectal carcinoma, oral carcinoma, liver cancer, cervical cancer, die from tumour person and account for more than 12% of death toll, for being only second to the second largest cause of the death of cardiovascular disorder.In China, cancer also is the second largest cause of the death of population.China human mortality's who announced in 1997 reason, the sample survey result shows, China's the nineties population tumor mortality rate is 124.4610 ten thousand, its percentage that accounts for total cause of the death rises to 17.64% from 12.57% of the seventies, wherein the mortality ratio of cancer of the stomach, liver cancer, lung cancer, these four kinds of cancers of the esophageal carcinoma is 92.06/10 ten thousand, accounts for 73.97% of whole cancer mortalities.This year, along with the deterioration of environment and a large amount of uses of hormone, the trend that cancer morbidity more becomes to rise.Therefore, the exploitation cancer therapy drug, the spectrum anticarcinogen that especially can treat the high cancer of the stomach of sickness rate (accounting for cancer general mortality rate 21.76%), liver cancer (17.83%), lung cancer (11.19%), the esophageal carcinoma (15.02%) has good society and economic benefit undoubtedly.
Since it is found that cis-platinum had antitumour activity in 1967, the application of platinum metals cancer therapy drug and research have obtained rapidly development, today, cis-platinum, carboplatin and heptan platinum-containing anticancer drug such as platinum become indispensable medicine in the cancer chemotherapy.The mechanism of action of platinum series antineoplastic medicament, the significant feature target spot is positioned at DNA, can be crosslinked in the DNA chain, interchain linkage, DNA-protein cross by forming, destroy duplicating and suppressing the growth that cell fission etc. is used for suppressing tumour cell of DNA.But there is self inherent shortcoming in this class medicine: toxic side effect is big, can cause pernicious, vomiting, alopecia, bone marrow depression etc., exists cross resistance and anticancer spectrum narrow etc. each other.In order to reduce the toxic side effect of this class medicine, be the complex compound (license number be CN1039588C) of leavings group as the complex compound that carries group (license number be CN1039588C), demethyl spot huge legendary turtle acid group or selenate radical and release one after another with the antitumor drug of salicylate for the ylidene ligands (patent publication No. is CN1557822A) of dissociating with diamino or cyclohexanediamine.
Quercetin (Quercetin Que) is modal Flavonoid substances, extensively is present in vegetables, fruit and the herbal medicine.The Quercetin pharmacological action is extensive, has many-sided effect such as coronary artery dilator, reducing blood-fat, platelet aggregation-against, anti-diabetic complication.
Summary of the invention
(1) technical problem that will solve
Not only toxic side effect is strong for heavy dose of platinum medicine, and is easy to generate resistance.About the anticancer mechanism of action of Quercetin is to suppress carcinogenic, carcinogenic promoting agent by mechanism such as Green Tea Extracts, and Quercetin is effective free-radical scavengers and antioxidant.Can prevent the destruction of lipid peroxidation pair cell effectively, prevent the generation of canceration.Quercetin can also be by suppressing the formation of carcinogens and dna adduct, influence the metabolic enzyme relevant forcefully with carcinogen, suppress carcinogen, the carcinogenic and short cancer effect of carcinogenic promoting agent (" Quercetin Antitumor Effects progress " Sichuan medical science (the 20th volume) the 1st phase in 1999).The present invention has kept such characteristics according to these characteristics of Quercetin, has inserted the platinum ammonia complex with antitumous effect, has improved the anticancer property of medicine greatly, has reduced the toxic side effect of medicine.
(2) technical scheme
The present invention relates to a kind of Quercetin and close ammino platinum medicine with anti-tumor activity.
The present invention relates to the preparation method that a kind of Quercetin with anti-tumor activity closes ammino platinum medicine.
Described potassium chloroplatinite can obtain or obtain through commercial sources by technique known is synthetic.
Described Quercetin can extract from vegetables, fruit or Chinese medicine and obtain, also can make or obtain or obtain through commercial sources by microbial process by known common synthetic technology, be known about extraction, the synthetic method of Quercetin to those of ordinary skills.
The present invention has two kinds of synthesis paths as follows:
(1), closes ammino platinum with the synthetic Quercetin of Quercetin more earlier with potassium chloroplatinite synthetic intermediate diiodo-two ammino platinum.
(2), closing ammino platinum with the synthetic Quercetin of Quercetin salt earlier with potassium chloroplatinite synthetic intermediate diiodo-two ammino platinum.
Embodiment
Further set forth the present invention below in conjunction with specific embodiment.Should be understood that these embodiment only are used to illustrate the present invention, and be not used for limiting the scope of the invention.
Embodiment 1
(1) earlier with potassium chloroplatinite synthetic intermediate diiodo-two ammino platinum, concrete synthesis path and chemical equation are as follows:
(2) again synthetic diiodo-two ammino platinum and the synthetic Quercetin of Quercetin are closed ammino platinum, concrete synthesis path and chemical equation are as follows:
The concrete steps of diiodo-two ammino platinum preparation:
Measure 20ml and contain 20g potassium chloroplatinite (K
2(PtCl
4), the 0.048mmol) aqueous solution mixes with 3.3g KI saturated solution, heating in water bath 5min, reaction soln becomes black, adds 1.5ml (1: 1) aqua ammonia, forms pitch black yellow crystal, solution is colourless solution, filter, use cold water washing, again with ice-cold ethanol and ether washing, dry air obtains diiodo-two ammino platinum (Pt (NH
3)
2I
2) 22g.
Quercetin closes the concrete steps of ammino platinum preparation:
Add 12.5g diiodo-two ammino platinum (Pt (NH successively
3)
2I
2, 0.02mmol), 4.6gAgNO
3, remove by filter AgI.Add the 2.0g Quercetin in filtrate, lucifuge stirred 10 hours for 50 ± 5 ℃, and reaction mixture gets solution after silica gel algae soil layer filters, be evaporated to 150ml, and filter and obtain the brownish black solid, a small amount of washing, the lucifuge dry air obtains Quercetin and closes ammino platinum.
Embodiment 2
(1) earlier with potassium chloroplatinite synthetic intermediate diiodo-two ammino platinum, concrete synthesis path and chemical equation are as follows:
(2) again synthetic diiodo-two ammino platinum and the synthetic Quercetin of Quercetin sylvite are closed ammino platinum, concrete synthesis path and chemical equation are as follows:
The concrete steps of diiodo-two ammino platinum preparation:
Measure 20ml and contain 20g potassium chloroplatinite (K
2(PtCl
4), the 0.048mmol) aqueous solution mixes with 3.3g KI saturated solution, heating in water bath 10min, reaction soln becomes black, adds 1.5ml (1: 1) aqua ammonia, forms pitch black yellow crystal, solution is colourless solution, filter, use cold water washing, again with ice-cold ethanol and ether washing, dry air obtains diiodo-two ammino platinum (Pt (NH
3)
2I
2) 22g.
Quercetin closes the concrete steps of ammino platinum preparation:
Add 12.5g diiodo-two ammino platinum (Pt (NH successively
3)
2I
2, 0.02mmol), 4.6gAgNO
3, remove by filter AgI.Add 2.0g Quercetin sylvite in filtrate, lucifuge stirred 20 hours for 60 ℃, and reaction mixture gets solution after silica gel algae soil layer filters, be evaporated to 150ml, and filter and obtain the brownish black solid, a small amount of washing, the lucifuge dry air obtains Quercetin and closes ammino platinum.
Embodiment 3
(1) earlier with potassium chloroplatinite synthetic intermediate diiodo-two ammino platinum, concrete synthesis path and chemical equation are as follows:
(2) again synthetic diiodo-two ammino platinum and the synthetic Quercetin of Quercetin are closed ammino platinum, concrete synthesis path and chemical equation are as follows:
The concrete steps of diiodo-two ammino platinum preparation:
Measure 20ml and contain 20g potassium chloroplatinite (K
2(PtCl
4), the 0.048mmol) aqueous solution mixes with the 3.3gKI saturated solution, heating in water bath 5min, reaction soln becomes black, adds 1.5ml (1: 1) aqua ammonia, forms pitch black yellow crystal, solution is colourless solution, filter, use cold water washing, again with ice-cold ethanol and ether washing, dry air obtains diiodo-two ammino platinum (Pt (NH
3)
2I
2) 22g.
Quercetin closes the concrete steps of ammino platinum preparation:
Add 0.02mmol 12.5g diiodo-two ammino platinum (Pt (NH successively
3)
2I
2), 4.6g Ag
2O removes by filter AgI.Add 2.0g Quercetin sylvite in filtrate, lucifuge stirred 10 hours for 50 ℃, and reaction mixture gets solution after silica gel algae soil layer filters, be evaporated to 150ml, and filter and obtain the brownish black solid, a small amount of washing, the lucifuge dry air obtains Quercetin and closes ammino platinum.
Embodiment 4
(1) earlier with potassium chloroplatinite synthetic intermediate diiodo-two ammino platinum, concrete synthesis path and chemical equation are as follows:
(2) again synthetic diiodo-two ammino platinum and the synthetic Quercetin of Quercetin sylvite are closed ammino platinum, concrete synthesis path and chemical equation are as follows:
The concrete steps of diiodo-two ammino platinum preparation:
Measure 20ml and contain 20g potassium chloroplatinite (K
2(PtCl
4)) aqueous solution, mix with 3.3g KI saturated solution, heating in water bath 5min, reaction soln becomes black, add 1.5ml (1: 1) aqua ammonia, form pitch black yellow crystal, solution is colourless solution, filters, use cold water washing, with ice-cold ethanol and ether washing, dry air obtains diiodo-two ammino platinum (Pt (NH again
3)
2I
2) 22g.
Quercetin closes the concrete steps of ammino platinum preparation:
Add 0.02mmol 12.5g diiodo-two ammino platinum (Pt (NH successively
3)
2I
2), 5.2gAg
2O removes by filter AgI.Add 2.0g Quercetin sylvite in filtrate, lucifuge stirred 20 hours for 60 ℃, and reaction mixture gets solution after silica gel algae soil layer filters, be evaporated to 150ml, and filter and obtain the brownish black solid, a small amount of washing, the lucifuge dry air obtains Quercetin and closes ammino platinum.
Experimental example 1
Ultimate analysis (%) result: C 34.12, N 5.08, and H 2.59, and O 18.23, and Pt 36.51.Theoretical value (%): C 34.03, and N 5.29, and H 2.65, and O 18.15, and Pt 36.86.
Experimental example 2
Through Infrared spectroscopy:
| Stretching vibration peak | ν Pt-O | ν C＝O | ν C2-C3 | δ COH | δ COH | ν C-O |
| Cm - | 532 VW | 1593 S | 1324 S | 1308 m | 1318 S | 1293 S |
Experimental example 3
The intravenous injection Quercetin closes ammino platinum and cis-platinum to the contrast of the anti-tumor activity of murine sarcoma S-180 knurl strain, sees Table 1.
Table 1 intravenous injection Quercetin closes ammino platinum, the cis-platinum anti-tumor activity to the strain of murine sarcoma S-180 knurl
| Medicine name | Size of animal (only) | Dosage/(mg/kg) | Tumour inhibiting rate/% |
| Quercetin closes ammino platinum | 15 | 4.5 | 86.4 |
| Cis-platinum | 15 | 4.5 | 48.5 |
Claims (2)
1. the Quercetin with anti-tumor activity closes ammino platinum, it is characterized in that its structural formula is:
2. preparation method that the Quercetin with anti-tumor activity closes ammino platinum is characterized in that:
(1), closes ammino platinum with the synthetic Quercetin of Quercetin more earlier with potassium chloroplatinite synthetic intermediate diiodo-two ammino platinum.
(2), closing ammino platinum with the synthetic Quercetin of Quercetin salt earlier with potassium chloroplatinite synthetic intermediate diiodo-two ammino platinum.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA200710179415XA CN101177434A (en) | 2007-12-13 | 2007-12-13 | Meletin ammino platinum anti-cancer drugs and method for making same |
| CN 200810183126 CN101475596B (en) | 2007-12-13 | 2008-12-12 | Platinum complexes of quercetin and derivatives thereof, as well as preparation and use thereof |
Applications Claiming Priority (1)
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|---|---|---|---|
| CNA200710179415XA CN101177434A (en) | 2007-12-13 | 2007-12-13 | Meletin ammino platinum anti-cancer drugs and method for making same |
Publications (1)
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|---|---|
| CN101177434A true CN101177434A (en) | 2008-05-14 |
Family
ID=39403876
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|---|---|---|---|
| CNA200710179415XA Pending CN101177434A (en) | 2007-12-13 | 2007-12-13 | Meletin ammino platinum anti-cancer drugs and method for making same |
| CN 200810183126 Expired - Fee Related CN101475596B (en) | 2007-12-13 | 2008-12-12 | Platinum complexes of quercetin and derivatives thereof, as well as preparation and use thereof |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101353339B (en) * | 2008-09-16 | 2012-06-27 | 郑州大学 | Synthesis of quercetin platinum |
| CN106854223A (en) * | 2017-01-05 | 2017-06-16 | 石家庄学院 | Mustargen quercetin derivative and its production and use |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101953805B (en) * | 2010-09-29 | 2012-05-30 | 贵州益佰制药股份有限公司 | Method for preparing antitumor medical preparation |
| CN111569868A (en) * | 2020-06-10 | 2020-08-25 | 上海济平新能源科技有限公司 | Method for preparing catalyst loaded on carbon |
| CN114870025B (en) * | 2022-04-28 | 2023-06-30 | 云南大学 | Responsive slow-release polydopamine-Zn-natural polyphenol coordination nano-drug and preparation method thereof |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100441590C (en) * | 2006-03-10 | 2008-12-10 | 中山大学 | Compounds like quercetol and metal complex of their glycosides and uses |
-
2007
- 2007-12-13 CN CNA200710179415XA patent/CN101177434A/en active Pending
-
2008
- 2008-12-12 CN CN 200810183126 patent/CN101475596B/en not_active Expired - Fee Related
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101353339B (en) * | 2008-09-16 | 2012-06-27 | 郑州大学 | Synthesis of quercetin platinum |
| CN106854223A (en) * | 2017-01-05 | 2017-06-16 | 石家庄学院 | Mustargen quercetin derivative and its production and use |
| CN106854223B (en) * | 2017-01-05 | 2019-03-29 | 石家庄学院 | Mustargen quercetin derivative and its preparation method and application |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101475596A (en) | 2009-07-08 |
| CN101475596B (en) | 2013-03-20 |
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