CN101148445A - Method for preparing o-dihydroxyflavone-selenium complexes and medical use - Google Patents
Method for preparing o-dihydroxyflavone-selenium complexes and medical use Download PDFInfo
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- CN101148445A CN101148445A CNA200710066974XA CN200710066974A CN101148445A CN 101148445 A CN101148445 A CN 101148445A CN A200710066974X A CNA200710066974X A CN A200710066974XA CN 200710066974 A CN200710066974 A CN 200710066974A CN 101148445 A CN101148445 A CN 101148445A
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- dihydroxyflavone
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Abstract
The present invention relates to synthesis process and medicinal use of o-dihydroxyflavone-selenium complex. The o-dihydroxyflavone-selenium complex in the structure as shown may be applied in preparing health product, pesticide, plant growth regulator, feed additive, immunomodulator, antitumor medicine, antibacterial medicine, etc.
Description
Technical field
The invention belongs to the synthetic and pharmacology technical field of crude drugization, medicine, be specifically related to synthetic flavones-selenium complexes, and this compound suppresses screening active ingredients to human body tumour cell growth.Can be used for preparing healthcare products, agricultural chemicals, sterilant, plant-growth regulator, fodder additives, immunomodulator, antitumor drug, antibacterials.
Background technology
Selenium has multiple special function to HUMAN HEALTH, current selenium has been confirmed as the trace element of needed by human by United Nations's health organization, diseases such as multiple disease such as tumour, aging, hypoimmunity are all relevant with the scarce selenium of body, and an amount of supplement selenium has great significance to enhance immunity power, inhibition aging, preventing disease.Organoselenium is compared with inorganic selenium, have characteristics such as bioavailability height, biological activity is strong, toxicity is low, environmental pollution is little, therefore seeking biological activity height and the low organic selenium compounds of toxicity just becomes the research of organic selenium compounds of a focus, particularly traditional Chinese medicine ingredients of present drug research.
Flavones has the function that reduces capillary permeability, can keep the normal osmotic pressure of blood vessel, helps to keep recovering the normal elasticity of capillary vessel, and multiple inflammation is also had good curative effect.Rutin is the representative of neighbour-dihydroxyflavone class material, and is the most common, selects its raw material as experiment for use.The synthetic existing report of some transition metal complex of rutin, but the synthetic of rutin-selenium complexes and anti-tumor activity research are not appeared in the newspapers as yet.By obtaining Quercetin to the rutin hydrolysis, find that in the recent period it also has antineoplastic effect, it is carried out the transformation of structure, can obtain better anti-tumor activity.
Summary of the invention
One of purpose of the present invention provides o-dihydroxyflavone-selenium complexes.
Two of purpose of the present invention provides the preparation method of o-dihydroxyflavone-selenium complexes.
These purposes of the present invention will further embody and set forth by following detailed description and explanation.
The objective of the invention is to realize by following technical proposals:
Of the present invention, be mainly neighbour-dihydroxyflavone class, its general structure following (seeing Figure of description 1):
Fig. 1 neighbour-dihydroxyflavone
R wherein
1, R
3Can be hydroxyl, hydrogen or methoxyl group, R
2Can be hydroxyl, monoglycosides, polysaccharide glycosides, rutinoside.
Embodiment
1. instrument and reagent
The all cpds fusing point of this experiment XRC-1 type micro melting point apparatus, temperature is not proofreaied and correct.1100series LC/MSD Trap SL type high performance liquid chromatography-GC-MS, comprise quaternary pump (G1311A), online vacuum degassing machine (G1379A), diode-array detector (DAD) (G1315B), column oven (G1316A), automatic sampler (G1313A) and Agilent chromatographic working station (U.S. Agilent company); 670FT-IR type intelligence Fuli's leaf infrared spectrometer (U.S. Nicolet company), Bruke AVANCE-300 nuclear magnetic resonance analyser,
1The observing frequency of H NMR is 300.13MHz,
13The observing frequency of C NMR is 75.47MHz,
1The H90 pulse width is 11.0 μ s,
13The C pulse width is 7.8 μ s.Oxychlorination selenium is available from Shanghai Budweiser spirit reagent company, and rutin is available from Shanghai traditional Chinese medicines group, and all the other reagent are analytical pure.
2. the preparation of compound
Embodiment 1: the preparation of rutin-selenium complexes
1g (0.001641mol) rutin is joined in the exsiccant 20ml pyridine, stir, splash into oxychlorination selenium 0.5ml, down dry, normal-temperature reaction 48h adds diethyl ether and separates out throw out, washes repeatedly with ether, chloroform, get throw out, vacuum lyophilization, the final brown rutin-selenium complexes that gets.The 1.332g that weighs, productive rate 51.5%.New synthetic compound has all carried out the structure evaluation through various physical methods, comprises
1HNMR, MS and ultimate analysis.Its structure following (seeing Figure of description 2):
Fig. 2 rutin-selenium complexes
Mp:185.0-189.0 ℃ of .IR (KBr) 3219cm
-1(O-H), 1654cm
-1(C=O), 1610,1537cm
-1(C=C), 1198cm
-1(C-O-C), 750cm
-2(C-H), 680cm
-2(Se-O).
1H NMR (CDCl
3, 300MHz), δ (ppm): 11.68 (s, 1H, 5-OH), 10.56 (s, 1H, 7-OH), 7.53 (d, 1H, 2 '-H), 7.38 (d, 1H, 5 '-H), 6.70 (d, 1H, 6 '-H), 6.13 (d, 1H, 8-H), 5.96 (d, 1H, 6-H), (rhamnose and gluose's
1H NMR omits).
13CNMR (CDCl
3, 300MHz) δ (ppm) 144.79 (C
2), 138.55 (C
3), 177.08 (C
4), 154.55 (C
5), 98.89 (C
6), 161.56 (C
7), 93.68 (C
8), 103.61 (C
9), 164.01 (C
10), 121.56 (C
1'), 115.21 (C
2'), 144.79 (C
3'), 148.56 (C
4'), 116.16 (C
5'), 121.06 (C
6'), gluose93.68 (C
1"), 76.46 (C
2"), 75.88 (C
3"), 70.55 (C
4"), 74.09 (C
5"), 68.22 (C
6"), rhamnose 98.89 (C
1"), 68.22 (C
2' "), 69.98 (C
3' "), 70.35 (C
4' "), 71.85 (C
5' "), 17.71 (C
6' ") .MS (m/z): 686 (M
-+ Se). molecular formula: C
27H
28O
16Se, ultimate analysis: Calcd for (%) C 47.16, H 4.07, Se11.50; Found (%) C 47.45, H 4.08, Se11.23.
Embodiment 2: the preparation of Quercetin-selenium complexes
2g (0.006623mol) Quercetin is joined in the exsiccant 30ml pyridine, stir, splash into oxychlorination selenium 2.0ml, down dry, normal-temperature reaction 48h adds diethyl ether and separates out throw out, washes repeatedly with ether, chloroform, get throw out, vacuum lyophilization, the final brown Quercetin-selenium complexes that gets.The 2.437g that weighs, productive rate 47.8%.Its structure following (seeing Figure of description 3):
Fig. 3 Quercetin-selenium complexes
Mp:315.0-318.0 ℃ of .IR (KBr) 1651cm
-1(C=O), 1606,1530cm
-1(C=C), 1206cm
-1(C-O-C), 755cm
-1(C-H), 680cm
-1(Se-O).
1H NMP (CDCl
3, 300MHz), δ (ppm) 11.88 (s, 1H, 5-OH), 10.50 (s, 1H, 7-OH), 10.26 (s, 1H, 3-OH), 7.60 (d, 1H, 2 '-H), 7.29 (d, 1H, 5 '-H), 6.71 (d, 1H, 6 '-H), 6.18 (d, 1H, 8-H), 5.98 (d, 1H, 6-H), MS (m/z): 378.1 (M
-+ Se). molecular formula: C
15H
8O
7Se, ultimate analysis: Calcd for (%) C 47.49, H 2.11, and Se 20.84; Found (%) C 48.22, H 2.29, Se 20.67.
3. pharmacological testing
Pharmacology is implemented: the anti tumor activity in vitro of rutin-selenium complexes
CNE2 (nasopharyngeal carcinoma), HEP2 (laryngocarcinoma), BEL-7404 (liver cancer), KB (oral epithelium cancer) and HELA (cervical cancer) cell are cultivated in the culturing bottle that fills DMEM liquid (including 10% (V/V) calf serum) respectively, and culture condition is 37 ℃, 5%CO
2, eugonic cancer cells after the digestion of 0.25% trypsin solution, is made into 50000 suspension with DMEM (containing 10% calf serum), add 96 orifice plates, every hole 100 μ L put cultivation 24h in the incubator.Adopt the improvement mtt assay, every hole adds the hungry DMEM nutrient solution (containing 0.4% calf serum) of 100 μ L, puts in the incubator and abandons supernatant behind the hungry 24h of cultivation.Every hole adds the different medicine of 100 μ L concentration.In incubator, cultivate 48h.Every hole adds the MTT of 20 μ L5mg/mL, puts and cultivates 4h in the incubator, sops up supernatant, and every hole adds the pre-temperature nutrient solution of 0.2mL to be cleaned one time, adds the DMSO mixing of 0.15mL again, surveys the OD value with the 490nm wavelength after 30 minutes on enzyme connection detector.
The OD value of the value/negative control hole in cell inhibitory rate=100%-dosing hole.Utilize the SPSS11.5 of statistical software, rutin and rutin-selenium complexes pair cell half-inhibition concentration (IC
50) draw IC by dose effect curve
50, under the similarity condition, make positive control with cis-platinum, record IC
50, the results are shown in following table:
Table 1 rutin-selenium complexes is to the IC of tumour cell
50
| Cell | CNE2 | HEP2 | BEL-7404 (IC 50/μg·ml -1) | KB | HELA |
| Rutin-selenium rutin cis-platinum | 26.78 - 4.5 | 0.42 - 0.16 | 8.37 - 0.99 | 1.89 29.6 0.23 | 0.35 15.3 0.04 |
Conclusion (of pressure testing): this test shows that rutin-selenium complexes has the activity of stronger inhibition tumour cell to CNE2, HEP2, BEL-7404, KB and HELA cell, might develop into the new medicine with these five kinds of cancers of treatment and related neoplasms effect.
Claims (7)
1. o-dihydroxyflavone-selenium complexes or its pharmacy acceptable salt represented of following formula, its structural formula is as follows,
R wherein
1, R
3Can be hydroxyl, hydrogen or methoxyl group, R
2Can be hydroxyl, monose, polysaccharide, rutinose
2. o-dihydroxyflavone-selenium complexes or the application of its pharmacy acceptable salt in the medicine of tumor diseases such as preparation treatment leukemia, nasopharyngeal carcinoma, liver cancer, the rectum cancer, cancer of the stomach, mammary cancer, malignant lymphoma represented of the compound of claim 1;
The o-dihydroxyflavone-selenium complexes represented of the compound of claim 1 or its pharmacy acceptable salt in preparation treatment or prevention by the application in the medicine of inflammation caused by bacterial infection;
The o-dihydroxyflavone-selenium complexes represented of the compound of claim 1 or its pharmacy acceptable salt in preparation agricultural chemicals, sterilant application and the application in the fodder additives;
5. o-dihydroxyflavone-selenium complexes or the application of its pharmacy acceptable salt in preparation healthcare products, plant-growth regulator represented of the compound of claim 1;
6. pharmaceutical composition wherein contains compound or its pharmacy acceptable salt of the claim 1 for the treatment of significant quantity, and contains conventional pharmaceutical carrier, and pharmaceutical excipient.
7. according to claim 6, it is characterized in that: the dosage form of described medicine comprises injection, tablet, capsule, suppository, film, pill, externally applied liniment, ointment, controlled release or sustained release dosage or nanometer formulation.
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101845033A (en) * | 2010-05-19 | 2010-09-29 | 江苏科技大学 | Paramagnetic iron and selenium quercetin complex and preparation method as well as application thereof |
| MD4014C2 (en) * | 2009-04-23 | 2010-09-30 | Татьяна ГУЦУЛ | Polyoxometalate complexes with antitumor activity |
| CN104119260A (en) * | 2013-04-25 | 2014-10-29 | 上海爱启生态科技有限公司 | Polyphenol selenium compound using alkali metal ion selenium complex as functional group |
| CN104892478A (en) * | 2014-03-06 | 2015-09-09 | 上海爱启生态科技有限公司 | Selenized resveratrol preparation for treating cancers |
| CN109942532A (en) * | 2019-03-19 | 2019-06-28 | 上海大学 | A kind of multicore flavonoids complex and its preparation method and application |
| CN111393408A (en) * | 2020-04-30 | 2020-07-10 | 上海爱启医药技术有限公司 | Method for preparing natural flavone selenium |
-
2007
- 2007-01-26 CN CNA200710066974XA patent/CN101148445A/en active Pending
Cited By (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| MD4014C2 (en) * | 2009-04-23 | 2010-09-30 | Татьяна ГУЦУЛ | Polyoxometalate complexes with antitumor activity |
| CN101845033A (en) * | 2010-05-19 | 2010-09-29 | 江苏科技大学 | Paramagnetic iron and selenium quercetin complex and preparation method as well as application thereof |
| CN104119260A (en) * | 2013-04-25 | 2014-10-29 | 上海爱启生态科技有限公司 | Polyphenol selenium compound using alkali metal ion selenium complex as functional group |
| WO2014173014A1 (en) * | 2013-04-25 | 2014-10-30 | 上海爱启生态科技有限公司 | Polyphenol selenium compound having alkali metal ion complexes as functional groups |
| CN104892478A (en) * | 2014-03-06 | 2015-09-09 | 上海爱启生态科技有限公司 | Selenized resveratrol preparation for treating cancers |
| WO2015131423A1 (en) * | 2014-03-06 | 2015-09-11 | 上海爱启生态科技有限公司 | Selenized resveratrol preparation for treating cancers |
| US20160068481A1 (en) * | 2014-03-06 | 2016-03-10 | Shanghai Ai Qi Ecological Technology Co., Ltd. | Resveratrol selenide preparation for treating cancer |
| US9637448B2 (en) * | 2014-03-06 | 2017-05-02 | Shanghai Ai Qi Ecological Technology Co., Ltd. | Resveratrol selenide preparation for treating cancer |
| CN109942532A (en) * | 2019-03-19 | 2019-06-28 | 上海大学 | A kind of multicore flavonoids complex and its preparation method and application |
| CN109942532B (en) * | 2019-03-19 | 2022-09-02 | 上海大学 | Polynuclear flavonoid complex and preparation method and application thereof |
| CN111393408A (en) * | 2020-04-30 | 2020-07-10 | 上海爱启医药技术有限公司 | Method for preparing natural flavone selenium |
| WO2021217824A1 (en) * | 2020-04-30 | 2021-11-04 | 上海爱启医药技术有限公司 | Method for preparing natural flavone selenium |
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Open date: 20080326 |