CN100432092C - Synthesis of rutin platinum - Google Patents
Synthesis of rutin platinum Download PDFInfo
- Publication number
- CN100432092C CN100432092C CNB2006101069207A CN200610106920A CN100432092C CN 100432092 C CN100432092 C CN 100432092C CN B2006101069207 A CNB2006101069207 A CN B2006101069207A CN 200610106920 A CN200610106920 A CN 200610106920A CN 100432092 C CN100432092 C CN 100432092C
- Authority
- CN
- China
- Prior art keywords
- rutin
- platinum
- compound
- synthetic method
- filtering
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
Rutin platinum is prepared through dissolving rutin in alcohol solvent, adding platinum compound, regulating pH value to 5-9 with ammonia water, heating reflux for 2-8 hr, distilling until reaching 2/3 reduced volume, hot suction filtering, recovering filter residue, cooling the filtrate to separate out precipitate, filtering to obtain the solid matter, dissolving, column chromatographic separating, collecting the eluted liquid, concentrating and filtering to obtain rutin platinum product. Rutin platinum is water soluble, and extracorporeal anticancer experiment shows that it has relatively high anticancer effect. Rutin platinum is hopeful in developing anticancer compound with flexible administration way.
Description
Technical field
The invention belongs to a kind of synthetic method of new compound.The method of synthesizing the rutin platinum title complex specifically by rutin.
Background technology
Rutin is a kind of widely distributed flavonoid compound, mainly is present in the plants such as the sophora bud, buckwheat, eucalyptus leaves, and is wherein the highest with content in the sophora bud, buckwheat, the eucalyptus leaves, can be used as the raw material that extracts rutin.Rutin is a main raw material of producing medicines such as rutin tablets and troxerutin.
Rutin and derivative thereof have pharmacologically active widely, and toxicity is low, are mainly used in control hematencephalon, hypertension, retinal hemorrhage, purpura, acute hemorrhage nephritis, chronic bronchitis, analgesia, radioprotective and antifatigue etc. clinically.In recent years, domestic and foreign literature reports that also rutin has antitumous effect.
Rutin itself is nontoxic, and intramolecularly has big π key conjugated system, is good chelating ligand, can form stable chelate with many metal ions.Domestic and international research shows that many organic molecule parts cooperate the formation title complex with metal after, its drug effect obviously strengthens.Organic molecule is the carrier of metal ion, and metal ion is again the guiding of organic molecule, and metallic element has its special biological property, and depends on its residing minute subenvironment to a great extent.So the research of rutin metal complexes in recent years is a focus in the study of pharmacy always, littler in the hope of obtaining toxicity, pharmacological action is more obvious, the drug effect better medicament.Totally 21 kinds of rutin metal complexess such as Mg, Al, Cr, Fe, Co, Ni, Cu, Zn, Ga, Mn, Cd, Mo, Sn, Au, Bi, La, Pr, Nd, Sm, Gd and Tb have been synthesized at present both at home and abroad.Some pharmacological action is obvious in these synthetic rutin metal complexess, and some biological activity is remarkable, and some has entered clinical experiment.
Since nineteen sixty-five Rosenberg after Scince has delivered cis-platinum antitumous effect has been arranged, platinum class anticancer compound is one of research focus of pharmacy, medical science always.Present international and domestic more than the 9000 kind of Pt that synthesized altogether
2+And Pt
4+Title complex, found the not platinum complex of rare antitumour activity, wherein some has been applied to clinical.So far 1055 platinum complexes have screened in the state-run cancer research of U.S. institute, and the person has 190 wherein to have the antitumour activity, accounts for 18%.The institute of materia medica, Shanghai has worked out the 3-hydroxyl carboplatin with independent intellectual property right recently, and antitumour activity is remarkable.
Cancer is the arch enemy of man, the annual life that seizes nearly ten million people in the whole world.Therefore, exploitation has the PTS of clinical treatment value to have great importance.20 years in the past, the platinum kind anti-cancer drugs became topmost chemotherapeutics, and worldwide sales volume had surpassed 2,200,000,000 dollars in 2004.The platinum complexes of present clinical use has that antitumor spectrum is narrow, resistance, the water-soluble low and strong untoward reaction of toxic side effect.
Existing platinum kind anti-cancer drugs and most of other classification antitumor drugs, because solubility, therapeutic modality is based on injection, and orally active very few, brings great misery to patient.
Consider that metal platinum complex has antitumour activity widely, rutin has good curative effect and cancer resistance to multiple inflammation.After rutin and the platinic compound reaction, can generate the rutin platinum title complex under certain condition.The present invention has introduced the method for synthetic rutin platinum.
By Chinese patent Information Network, china academia periodical net, Chinese outstanding Bo Shuoshixueweilunwenku and CAS search inquiry, the document of relevant rutin platinum does not appear in the newspapers.
Summary of the invention
As lead compound, it is carried out structural modification or transformation with rutin, can be made into a series of derivatives with related activity.Because the rutin structure has higher superdelocalizability, complete big π key conjugated system, strong coordination Sauerstoffatom and suitable sterie configuration can be used as the good chelating ligand of metal ion.Rutin has 3 ', 4 ' dihydroxyl and 4-carbonyl-5-hydroxyl, but becomes stable five-ring or six-ring with the metal ion chelating.
Platinum is positioned at the 6th cycle of periodictable, group VIII, with iron, cobalt, nickel be same gang.Outermost electron is arranged and is 5d
96s
1, become Pt when losing 4 electronics
4+The time, outermost electron is arranged and is 5d
6, outermost layer has unoccupied orbital, and the not share electron pair that is easy to accept ligand forms stable inner orbital coordination compound.Under certain condition, platinic compound and rutin reaction back just can form stable rutin platinum title complex.
Get rutin behind the purifying in alcoholic solution, used alcoholic solution is a methyl alcohol, or ethanol, or propyl alcohol, or butanol solution.Add platinic compound, platinic compound is a platinum dichloride, or Tetrachloroplatinum, or platinichloride.Rutin and platinic compound reaction are 1 in molar ratio: the ratio of 0.1-3 adds, and transfers pH=5-9 with ammoniacal liquor, reflux 2-8 hour.Change distillation, steam 2/3 o'clock of whole volumes, suction filtration while hot, filter residue reclaims, and precipitation is separated out in the filtrate cooling, filters, and must precipitate.Resolution of precipitate, column chromatography is collected elutriant.Concentrate, filter, get rutin platinum.
Rutin platinum has higher water-soluble, from external cancer resistance experiment preliminary observation, reasonable effect is arranged.Be expected to develop class route of administration anticancer new compound more flexibly.
Embodiment
Embodiment one
Get the rutin 1.329g (0.002mol) behind the purifying, add in the 50ml ethanol, add Tetrachloroplatinum 1.348g (0.004mol), stir and make dissolving fully.After treating dissolving fully, add strong aqua and transfer pH=8.2, reflux 6h changes distillation.When steaming 35ml ethanol, stop distillation, suction filtration while hot, filter residue reclaims, and precipitation is separated out in the filtrate cooling.Filter, must precipitate.Precipitation is dissolved in propyl alcohol, dress chromatography column chromatography.Water, formic acid and butanone are made eluent, and proportioning is: water: formic acid: butanone=1: 2: 5.Collect elutriant.Concentrate, filter, get rutin platinum.
Rutin platinum is light grey powdery substance, and is soluble in water and pure, is insoluble in acetone and benzene etc.
The toxicity of rutin platinum (experimentizing) by " technical requirements of new drug pharmacology, toxicological study " in " provisions for new drugs approval ":
Prove oral rutin platinum LD through the animal acute toxicological experiment
50(its mouse oral clothes medium lethal dose) is 410mg/kg.According to the toxicology acute toxicity grading criteria, rutin platinum belongs to lower toxicity.To the toxicity of each system of body, remain further experiment to be identified during concrete life-time service.
Anti-tumor experiment:
Mtt assay detects rutin platinum to mouse tumor cell S180, H22, EAC and human liver cancer cell HepG2 growth in vitro restraining effect, and the result shows that rutin platinum can suppress the growth of tumour cell, and inhibiting rate is respectively: 41.3%, 34.6%, 50.4%, 31.7%.
Reference
1. flavone chromium and production method and purposes ZL00118913.1 such as Liu Gang
2. Melim sulfate compound ZL 98116970.8 such as wooden Quan Zhang
3. rutin ester compound CN 200410016489.8 such as Chen Yi front yard
4.DE：2201123
5.GB：815877
Claims (4)
1. the synthetic method of a rutin platinum is characterized in that rutin and platinic compound react, and transfer pH=5-9 with ammoniacal liquor in alcoholic solution, reflux 2-8 hour, change distillation, steam 2/3 o'clock of whole volumes, suction filtration while hot, filter residue reclaims, the filtrate cooling, separate out precipitation, filter, must precipitate, resolution of precipitate, column chromatography is collected elutriant, concentrate, filter, get rutin platinum.
2. synthetic method according to claim 1 is characterized in that platinic compound is a platinum dichloride, or Tetrachloroplatinum, or platinichloride.
3. synthetic method according to claim 1 is characterized in that the alcoholic solution that reacts used is a methyl alcohol, or ethanol, or propyl alcohol, or butanol solution.
4. synthetic method according to claim 1 is characterized in that the mol ratio of rutin and platinic compound reaction is 1: 0.1-3.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2006101069207A CN100432092C (en) | 2006-08-24 | 2006-08-24 | Synthesis of rutin platinum |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2006101069207A CN100432092C (en) | 2006-08-24 | 2006-08-24 | Synthesis of rutin platinum |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1911951A CN1911951A (en) | 2007-02-14 |
| CN100432092C true CN100432092C (en) | 2008-11-12 |
Family
ID=37721029
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB2006101069207A Expired - Fee Related CN100432092C (en) | 2006-08-24 | 2006-08-24 | Synthesis of rutin platinum |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN100432092C (en) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ITMI20131495A1 (en) | 2013-09-10 | 2015-03-11 | Ce R C Ar Di Paolo Maestri | USEFUL COMPOSITIONS FOR CHEMOTHERAPY-RESISTANT CANCER TREATMENT |
| BR112017000858A2 (en) | 2014-07-17 | 2017-12-05 | Probiotical Spa | compositions comprising melatonin and flavonoids for use in the treatment of chemotherapy resistant tumors |
| RU2017132516A (en) | 2015-03-05 | 2019-04-08 | Пробиотикал С.П.А | Compositions for Use in the Treatment of Chemotherapy Resistant Tumors |
| CN111454310A (en) * | 2020-03-26 | 2020-07-28 | 江苏派莘生物科技有限公司 | Preparation method of rutin metal complex |
-
2006
- 2006-08-24 CN CNB2006101069207A patent/CN100432092C/en not_active Expired - Fee Related
Non-Patent Citations (6)
| Title |
|---|
| 国内黄酮金属配合物的研究进展. 赵兵等.化学试剂，第28卷第3期. 2006 * |
| 芦丁及芦丁稀土配合物与DNA相互作用的研究. 曾红娟，全文，西北师范大学硕士学位论文. 2002 * |
| 芦丁配合物的合成、表征及其与DNA作用的电化学研究. 康敬万，苏碧泉等.西北师范大学学报（自然科学版），第42卷第1期. 2006 * |
| 芦丁金属配合物的合成、表征及与血清蛋白的相互作用. 杨美玲，全文，西北师范大学硕士学位论文. 2005 * |
| 黄酮类有机金属配合物及其生物构效和协同作用的研究. 李方，全文，四川大学博士学位论文. 2004 * |
| 黄酮类有机金属配合物及其生物构效和协同作用的研究. 李方，全文，四川大学博士学位论文. 2004 芦丁及芦丁稀土配合物与DNA相互作用的研究. 曾红娟，全文，西北师范大学硕士学位论文. 2002 芦丁金属配合物的合成、表征及与血清蛋白的相互作用. 杨美玲，全文，西北师范大学硕士学位论文. 2005 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1911951A (en) | 2007-02-14 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN100432092C (en) | Synthesis of rutin platinum | |
| CN100528886C (en) | Metal complex with liriodenine as ligand and its synthesis process and use | |
| CN101845060A (en) | Beta-carboline ruthenium compound as well as preparation method and application thereof | |
| CN111233958B (en) | Momordica grosvenori flavin metal zinc complex and preparation method thereof | |
| NO770122L (en) | NEW ANTHRA-CYCLING LYCOSIDES AND PROCEDURES FOR THE PREPARATION OF THIS. | |
| US20090175775A1 (en) | Metal complexes having vitamin b12 as a ligand | |
| JP2004518751A (en) | Method for producing Liangtoujian extract, pharmaceutical composition containing the extract and use thereof | |
| Mohapatra et al. | Monomeric copper (II) complexes with unsymmetrical salen environment: Synthesis, characterization and study of biological activities | |
| EP3988521A1 (en) | Cellular senescence-activating compounds | |
| EP1765826B1 (en) | Novel antiviral macrocycle derivatives and metal complexes, incorporating bridged macrocycles | |
| CN101456881B (en) | Luteolin and platinum complexes of derivatives thereof, preparation method and use thereof | |
| CN101787051A (en) | Water-soluble carboxyl-bridge dicaryon Pt (II) anti-tumor complex | |
| Savaraj et al. | Clinical kinetics of 1, 4‐dihydroxy‐5, 8‐bis [[2‐[(2‐hydroxyethyl) amino] ethyl] amino]‐9, 10‐anthracenedione | |
| CN114524853B (en) | All-trans retinoic acid-aryl metal complex, preparation method and application | |
| Zhong et al. | Synthesis, characterization, and antitumor activity of novel tumor‐targeted platinum (IV) complexes | |
| CN102875606B (en) | Copper diphosphonate complex and preparation method and application thereof | |
| WO2002066435A1 (en) | Metal complexes and therapeutic uses thereof | |
| CN112175014B (en) | Nitric oxide donor type tetravalent platinum derivative, preparation method and medical application thereof | |
| CN113735909A (en) | Lindqvist type tungsten vanadate trimethylolethane derivative and preparation method and application thereof | |
| CN101914117B (en) | Dichloroacetoxyl-containing platinum (II) anticancer coordination compound | |
| CN114075250A (en) | Preparation of platinum metal complex of oxafolium and application thereof in antitumor drugs | |
| CN101353339B (en) | Synthesis of quercetin platinum | |
| CN115160399B (en) | Soap-skin acid compound, preparation method and medical application thereof | |
| CN115417844B (en) | Cyclohexylethanol compound rengyolone and preparation method and application thereof | |
| CN101070273A (en) | Anti-tumor compound trans-4-[2-(3,5,-dimethoxyphenyl) vinyl]-1,2-xyyl alcohol and preparing method therefor |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| C17 | Cessation of patent right | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20081112 |