CN105294775B - A kind of platinum complex with antitumor activity - Google Patents
A kind of platinum complex with antitumor activity Download PDFInfo
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- CN105294775B CN105294775B CN201510817121.XA CN201510817121A CN105294775B CN 105294775 B CN105294775 B CN 105294775B CN 201510817121 A CN201510817121 A CN 201510817121A CN 105294775 B CN105294775 B CN 105294775B
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- complex
- platinum
- platinum complex
- carboplatin
- antitumor activity
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- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 title claims abstract description 48
- 229910052697 platinum Inorganic materials 0.000 title claims abstract description 22
- 230000000259 anti-tumor effect Effects 0.000 title claims abstract description 11
- 150000001336 alkenes Chemical class 0.000 claims abstract description 4
- TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 claims abstract description 4
- DVQHYTBCTGYNNN-UHFFFAOYSA-N azane;cyclobutane-1,1-dicarboxylic acid;platinum Chemical compound N.N.[Pt].OC(=O)C1(C(O)=O)CCC1 DVQHYTBCTGYNNN-UHFFFAOYSA-N 0.000 abstract description 13
- 229960004562 carboplatin Drugs 0.000 abstract description 12
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 abstract description 7
- 238000000338 in vitro Methods 0.000 abstract description 4
- -1 octane ion Chemical class 0.000 abstract description 3
- 229910021529 ammonia Inorganic materials 0.000 abstract description 2
- 239000003446 ligand Substances 0.000 abstract description 2
- 150000001991 dicarboxylic acids Chemical class 0.000 abstract 1
- 239000003814 drug Substances 0.000 description 11
- 229940079593 drug Drugs 0.000 description 9
- 206010028980 Neoplasm Diseases 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 210000004027 cell Anatomy 0.000 description 6
- 201000011510 cancer Diseases 0.000 description 5
- 238000004458 analytical method Methods 0.000 description 4
- 230000002401 inhibitory effect Effects 0.000 description 4
- 230000001093 anti-cancer Effects 0.000 description 3
- KLNFSAOEKUDMFA-UHFFFAOYSA-N azanide;2-hydroxyacetic acid;platinum(2+) Chemical compound [NH2-].[NH2-].[Pt+2].OCC(O)=O KLNFSAOEKUDMFA-UHFFFAOYSA-N 0.000 description 3
- 238000002512 chemotherapy Methods 0.000 description 3
- 230000012010 growth Effects 0.000 description 3
- 229950008991 lobaplatin Drugs 0.000 description 3
- 229950007221 nedaplatin Drugs 0.000 description 3
- 229910000069 nitrogen hydride Inorganic materials 0.000 description 3
- 238000011275 oncology therapy Methods 0.000 description 3
- 229960001756 oxaliplatin Drugs 0.000 description 3
- DWAFYCQODLXJNR-BNTLRKBRSA-L oxaliplatin Chemical compound O1C(=O)C(=O)O[Pt]11N[C@@H]2CCCC[C@H]2N1 DWAFYCQODLXJNR-BNTLRKBRSA-L 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- XJXKGUZINMNEDK-GPJOBVNKSA-L [(4r,5r)-5-(aminomethyl)-2-propan-2-yl-1,3-dioxolan-4-yl]methanamine;platinum(2+);propanedioate Chemical compound [Pt+2].[O-]C(=O)CC([O-])=O.CC(C)C1O[C@H](CN)[C@@H](CN)O1 XJXKGUZINMNEDK-GPJOBVNKSA-L 0.000 description 2
- XSMVECZRZBFTIZ-UHFFFAOYSA-M [2-(aminomethyl)cyclobutyl]methanamine;2-oxidopropanoate;platinum(4+) Chemical compound [Pt+4].CC([O-])C([O-])=O.NCC1CCC1CN XSMVECZRZBFTIZ-UHFFFAOYSA-M 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 229950006835 eptaplatin Drugs 0.000 description 2
- 239000012452 mother liquor Substances 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 238000012827 research and development Methods 0.000 description 2
- SQGYOTSLMSWVJD-UHFFFAOYSA-N silver(I) nitrate Inorganic materials [Ag+].[O-]N(=O)=O SQGYOTSLMSWVJD-UHFFFAOYSA-N 0.000 description 2
- 238000011282 treatment Methods 0.000 description 2
- 101710134784 Agnoprotein Proteins 0.000 description 1
- IAJNCFRZTUTEAU-UHFFFAOYSA-N CC(C(C1C(O)=O)C(O)=O)=CC=C1C=C Chemical compound CC(C(C1C(O)=O)C(O)=O)=CC=C1C=C IAJNCFRZTUTEAU-UHFFFAOYSA-N 0.000 description 1
- 206010013786 Dry skin Diseases 0.000 description 1
- 0 N*(NC(C(C12)=C3C=CC1=CC3)O)(N=I)OC2=N Chemical compound N*(NC(C(C12)=C3C=CC1=CC3)O)(N=I)OC2=N 0.000 description 1
- 230000000118 anti-neoplastic effect Effects 0.000 description 1
- 239000003005 anticarcinogenic agent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229960004316 cisplatin Drugs 0.000 description 1
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 1
- 238000004737 colorimetric analysis Methods 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000003912 environmental pollution Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000002075 main ingredient Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 229940126532 prescription medicine Drugs 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000000682 scanning probe acoustic microscopy Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
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- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The invention discloses a kind of platinum complex with antitumor activity.Complex Chinese of the present invention is：The ammino platinum of 2,3 dicarboxylic acids, 5 alkene two ring [2,2,2] octane two, molecular formula are：C10H16N2O4Pt, molecular weight are：423, for the complex with 2,3 dicarboxyl, 5 alkene two ring [2,2,2] octane ion for part, ammonia is carrier ligand.Preliminary anti tumor activity in vitro, which is studied, to be shown, the half-inhibition concentration IC of platinum complex of the invention to A549 and KB cell lines50Respectively 3.4 and 7.9.Half-inhibition concentration IC with carboplatin to A549 and KB cell lines50Compare, its anti tumor activity in vitro is better than carboplatin.
Description
Technical field
The present invention relates to a kind of platinum complex field, is to be related to a kind of platinum with antitumor activity to match somebody with somebody in particular
Compound.
Background technology
Cancer the health of the mankind as the 2nd big cause of death in disease, serious threat, and the whole world there are about 700 every year
Ten thousand people die from cancer.In recent years, the bad life habits because of people and environmental pollution, the morbidity and mortality of cancer drastically on
Rise, it has also become the problem that the mankind urgently capture.Chemotherapy is one of 3 big means of current clinical anticancer.Therefore, countries in the world
The annual research and development for all putting into a large amount of human and material resources and financial resources progress chemotherapy cancer therapy drug, achieve many achievements, control cancer
The efficient raising for the treatment of, time course of progression extend, and patient's total life cycle and quality of life etc. are significantly improved.Platinum medicine
It is the novel inorganic anticarcinogen of exploitation the 1960s.The research and development of nearly 30 years is experienced, has successfully been developed in succession suitable
Platinum (Cisplatin), carboplatin (Carboplatin), Nedaplatin (Nedaplatin), oxaliplatin (Oxaliplatin), Eptaplatin
(Sunpla) and lobaplatin (Lobaplatin), for clinical anticancer.Particularly cis-platinum and carboplatin are clinically to use at present
One of most wide cancer therapy drug, it is the choice drug for treating many tumours.According to recent statistics, the combined chemotherapy side of existing Clinical practice
In case, the scheme that has 85% is using cis-platinum or carboplatin as main ingredient, or has them to participate in coordination.Cis-platinum and carboplatin just entered in 1996
Enter the row of 10 leading big cancer therapy drugs of global marketing volume, respectively ranking the 8th and the 5th.Carboplatin in 1999 enters the whole world again
Best-selling 150 kinds of prescription medicine ranking lists, the 66th is ranked, the only annual sales amount of U.S. Bristol-Squibb companies 2002 just reaches
600000000 dollars, turn into " cookle " of antineoplastic.Such as oxaliplatin, Nedaplatin, Eptaplatin and lobaplatin platinum class anticancer simultaneously
Medicine is just gradually obtaining the understanding of doctor and patient, also by as the important drugs for the treatment of cancer.
The content of the invention
It is an object of the invention to provide a kind of platinum complex with more preferable antitumor activity.
The present invention has the platinum complex of antitumor activity, and the complex Chinese is：The ring of 2,3- dicarboxylic acids -5- alkene two
The ammino platinum of [2,2,2] octane two, molecular formula are：C10H16N2O4Pt, molecular weight are：423, the complex is with 2,3- dicarboxyls -5-
The ring of alkene two [2,2,2] octane ion is part (structural formula I), and ammonia is carrier ligand, the complex concrete structure such as following formula (II).
Using SRB colorimetric methods, from A549 and KB cell lines, with carboplatin (English abbreviation CBDCA) for positive control drug, make
It it is 72 hours with the time.Drug concentration is respectively 8 groups of 100,50,10,5,1,0.5,0.1,0.05 (μ g/ml), is commented according to curative effect
Valency calculates inhibiting rate, observes suppression situation of the medicine to growth of tumour cell under various concentrations.Inhibiting rate=(control class value-
Medication class value)/control class value × 100%.Preliminary anti tumor activity in vitro research shows that platinum complex of the invention is to A549
And the half-inhibition concentration IC of KB cell lines50Respectively 3.4 and 7.9.Dense is suppressed to the half of A549 and KB cell lines with carboplatin
Spend IC50Compare, its anti tumor activity in vitro is better than carboplatin.The platinum complex of the present invention presses down to the half of A549 and KB cell lines
Concentration IC processed50And its 1 and table 2. are shown in Table respectively with the comparative result of carboplatin
Inhibiting rate (%) of 1. platinum complex of the present invention of table to A549 cell strain growths
Inhibiting rate (%) of 2. platinum complex of the present invention of table to KB cell strain growths
Embodiment
With reference to specific embodiment, the present invention will be further described.
Complex preparation method of the present invention is as follows：
Agents useful for same：Analyze pure Pt (NH3)2I2, the pure AgNO of analysis3, the pure NaOH of analysis.
Preparation process：
Weigh 10 grams of Pt (NH3)2I2It is dissolved in 100mL distilled water, 50mL is added under stirring condition and contains 6.8 grams of AgNO3Water
Solution, react 3 hours, filtering AgI precipitations, mother liquor is poured into clean flask.
By Pt (NH3)2I2Molten metering, excessive about 10% 2,3- dicarboxylic acids -5- alkene two ring [2,2,2] octane is weighed, added
In above-mentioned mother liquor, pH value is adjusted between 7~9 with 20% NaOH solution, 1 hour existing white precipitate of reaction produces, and continues
Reaction 2 hours, white precipitate is filtered, with water and ethanol, respectively washing three times, 70 DEG C of dryings and drying, obtains 5.78 grams of product respectively,
Yield 66%.
Elementary analysis (being analyzed using ICP Atomic Emission Spectrometer AESs), elementary analysis result are carried out to the said goods
(%)：C (28.3), H (3.8), N (6.6), O (15.1), Pt (46.2).Its results of IR (cm-1)：C-H(2955,
2837), N-H (3225,3062), C=C (1089), C-C (1195,1172,1123), C=O (1655), P-N (462), P-O
(426).Above-mentioned as shown by data, prepared compound are consistent with goal of the invention platinum complex result.
Claims (1)
1. a kind of platinum complex with antitumor activity, it is characterized in that, the complex Chinese is：2,3- dicarboxylic acids -5-
The ammino platinum of the ring of alkene two [2,2,2] octane two, molecular formula are：C10H16N2O4Pt, molecular weight are：423, specific body structural formula is as follows：
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510817121.XA CN105294775B (en) | 2015-11-23 | 2015-11-23 | A kind of platinum complex with antitumor activity |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510817121.XA CN105294775B (en) | 2015-11-23 | 2015-11-23 | A kind of platinum complex with antitumor activity |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN105294775A CN105294775A (en) | 2016-02-03 |
| CN105294775B true CN105294775B (en) | 2018-04-03 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510817121.XA Active CN105294775B (en) | 2015-11-23 | 2015-11-23 | A kind of platinum complex with antitumor activity |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105294775B (en) |
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2015
- 2015-11-23 CN CN201510817121.XA patent/CN105294775B/en active Active
Non-Patent Citations (5)
| Title |
|---|
| DNA damage induced by novel demethylcantharidin-integrated platinum anticancer complexes;Siu-Kwong Pang等;《Biochemical and Biophysical Research Communications》;ELSEVIER;20070907;第363卷;第235-240页 * |
| Organic Cation Transporters Are Determinants of Oxaliplatin Cytotoxicity;Shuzhong Zhang等;《Cancer Res.》;20060901;第66卷(第17期);第8847-8857页 * |
| Pharmacokinetics and tissue distribution of novel traditional Chinese medicine-platinum anticancer agents in rats;Xinning Wang等;《Journal of Inorganic Biochemistry》;ELSEVIER;20070304;第101卷;第909-917页 * |
| Protein phosphatase 2A inhibition and circumvention of cisplatin cross-resistance by novel TCM-platinum anticancer agents containing demethylcantharidin;Kenneth K. W. To等;《Bioorganic & Medicinal Chemistry》;ELSEVIER;20040729;第12卷;第4565-4573页 * |
| The Platinum Benzoic Acid Blues-a New Class of Blue Platinum Compounds;T. Ramstad等;《Transition Met. Chem.》;19850430;第10卷;第153-155页 * |
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| Publication number | Publication date |
|---|---|
| CN105294775A (en) | 2016-02-03 |
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Effective date of registration: 20190528 Address after: Room 311, 866 Harley Road, China (Shanghai) Free Trade Pilot Area, Pudong New Area, Shanghai, 200120 Patentee after: Heplatin Pharmaceutical (Shanghai) Co., Ltd. Address before: Tianjin highway 300134 East Tianjin District of Beichen City Patentee before: Tianjin University Of Commerce |