PL218844B1 - New 5-hydroksy-6,7-dipropionoxy flavone and method of its manufacturing - Google Patents
New 5-hydroksy-6,7-dipropionoxy flavone and method of its manufacturingInfo
- Publication number
- PL218844B1 PL218844B1 PL397633A PL39763311A PL218844B1 PL 218844 B1 PL218844 B1 PL 218844B1 PL 397633 A PL397633 A PL 397633A PL 39763311 A PL39763311 A PL 39763311A PL 218844 B1 PL218844 B1 PL 218844B1
- Authority
- PL
- Poland
- Prior art keywords
- dipropionoxyflavone
- hydroxy
- flavone
- new
- hydroksy
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 11
- 229930003944 flavone Natural products 0.000 title description 4
- 235000011949 flavones Nutrition 0.000 title description 4
- GAMYVSCDDLXAQW-AOIWZFSPSA-N Thermopsosid Natural products O(C)c1c(O)ccc(C=2Oc3c(c(O)cc(O[C@H]4[C@H](O)[C@@H](O)[C@H](O)[C@H](CO)O4)c3)C(=O)C=2)c1 GAMYVSCDDLXAQW-AOIWZFSPSA-N 0.000 title 1
- 150000002212 flavone derivatives Chemical class 0.000 title 1
- 238000004519 manufacturing process Methods 0.000 title 1
- VHBFFQKBGNRLFZ-UHFFFAOYSA-N vitamin p Natural products O1C2=CC=CC=C2C(=O)C=C1C1=CC=CC=C1 VHBFFQKBGNRLFZ-UHFFFAOYSA-N 0.000 title 1
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 12
- MGPRUDWXKWMKBN-UHFFFAOYSA-N (5-hydroxy-4-oxo-2-phenyl-6-propanoyloxychromen-7-yl) propanoate Chemical compound C=1C(=O)C=2C(O)=C(OC(=O)CC)C(OC(=O)CC)=CC=2OC=1C1=CC=CC=C1 MGPRUDWXKWMKBN-UHFFFAOYSA-N 0.000 claims description 11
- FXNFHKRTJBSTCS-UHFFFAOYSA-N baicalein Chemical compound C=1C(=O)C=2C(O)=C(O)C(O)=CC=2OC=1C1=CC=CC=C1 FXNFHKRTJBSTCS-UHFFFAOYSA-N 0.000 claims description 10
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 8
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 6
- 238000002360 preparation method Methods 0.000 claims description 5
- RZWZRACFZGVKFM-UHFFFAOYSA-N propanoyl chloride Chemical compound CCC(Cl)=O RZWZRACFZGVKFM-UHFFFAOYSA-N 0.000 claims description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 4
- 238000005886 esterification reaction Methods 0.000 claims description 3
- 239000000376 reactant Substances 0.000 claims description 2
- 230000032050 esterification Effects 0.000 claims 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
- 101100369992 Homo sapiens TNFSF10 gene Proteins 0.000 description 3
- 102000046283 TNF-Related Apoptosis-Inducing Ligand Human genes 0.000 description 3
- 108700012411 TNFSF10 Proteins 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 230000003013 cytotoxicity Effects 0.000 description 3
- 231100000135 cytotoxicity Toxicity 0.000 description 3
- 150000002213 flavones Chemical class 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- 230000001093 anti-cancer Effects 0.000 description 2
- 230000003110 anti-inflammatory effect Effects 0.000 description 2
- 230000006907 apoptotic process Effects 0.000 description 2
- UDFLTIRFTXWNJO-UHFFFAOYSA-N baicalein Chemical compound O1C2=CC(=O)C(O)=C(O)C2=C(O)C=C1C1=CC=CC=C1 UDFLTIRFTXWNJO-UHFFFAOYSA-N 0.000 description 2
- 229940015301 baicalein Drugs 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 230000002113 chemopreventative effect Effects 0.000 description 2
- 231100000433 cytotoxic Toxicity 0.000 description 2
- 230000001472 cytotoxic effect Effects 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- UUFQTNFCRMXOAE-UHFFFAOYSA-N 1-methylmethylene Chemical compound C[CH] UUFQTNFCRMXOAE-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 101710088194 Dehydrogenase Proteins 0.000 description 1
- 102000014150 Interferons Human genes 0.000 description 1
- 108010050904 Interferons Proteins 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- 244000269722 Thea sinensis Species 0.000 description 1
- 235000006468 Thea sinensis Nutrition 0.000 description 1
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 230000005809 anti-tumor immunity Effects 0.000 description 1
- 238000003782 apoptosis assay Methods 0.000 description 1
- 235000020279 black tea Nutrition 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000000824 cytostatic agent Substances 0.000 description 1
- 230000001085 cytostatic effect Effects 0.000 description 1
- -1 cytostatics Chemical class 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 229930003935 flavonoid Natural products 0.000 description 1
- 150000002215 flavonoids Chemical class 0.000 description 1
- 235000017173 flavonoids Nutrition 0.000 description 1
- 230000002519 immonomodulatory effect Effects 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 229940047124 interferons Drugs 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000002438 mitochondrial effect Effects 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- WYURNTSHIVDZCO-SVYQBANQSA-N oxolane-d8 Chemical compound [2H]C1([2H])OC([2H])([2H])C([2H])([2H])C1([2H])[2H] WYURNTSHIVDZCO-SVYQBANQSA-N 0.000 description 1
- 230000005522 programmed cell death Effects 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 230000019254 respiratory burst Effects 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 102000003390 tumor necrosis factor Human genes 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 235000014101 wine Nutrition 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
Opis wynalazkuDescription of the invention
Przedmiotem wynalazku jest nowy 5-hydroksy-6,7-dipropionoksyflawon, o wzorze 2, przedstawionym na rysunku, i sposób jego wytwarzania.The present invention relates to a novel 5-hydroxy-6,7-dipropionoxyflavone of the formula II shown in the drawing and a method of its preparation.
Wynalazek może znaleźć zastosowanie w przemyśle farmaceutycznym.The invention may find application in the pharmaceutical industry.
Flawony są obecne w owocach, warzywach, czarnej herbacie, winie.Flavones are present in fruits, vegetables, black tea and wine.
Na podstawie wielu badań epidemiologicznych stwierdzono, że flawony mogą zmniejszać ryzyko zachorowania na niektóre typy nowotworów.Many epidemiological studies have shown that flavones may reduce the risk of developing certain types of cancer.
Flawony, podobnie jak cytostatyki, promieniowanie gamma a także interferony, mogą znamiennie nasilać cytotoksyczne działanie ligandu - czynnika martwicy nowotworu indukującego apoptozę (TRAIL), który jest endogennym, naturalnym czynnikiem przeciwnowotworowym.Flavones, like cytostatics, gamma radiation and interferons, can significantly increase the cytotoxic effect of the ligand - tumor necrosis factor inducing apoptosis (TRAIL), which is an endogenous natural anti-cancer factor.
Flawonoidy i ich pochodne wykazują aktywność przeciwnowotworową, chemoprewencyjną i immunomodulującą.Flavonoids and their derivatives exhibit antitumor, chemopreventive and immunomodulating activity.
Brak jest doniesień literaturowych na temat otrzymania 5-hydroksy-6,7-dipropionoksyflawonu.There are no reports in the literature on the preparation of 5-hydroxy-6,7-dipropionoxyflavone.
Istotą wynalazku jest nowy 5-hydroksy-6,7-dipropionoksyflawon, o wzorze 2, przedstawionym na rysunku.The essence of the invention is the novel 5-hydroxy-6,7-dipropionoxyflavone of formula 2 shown in the drawing.
Istotą wynalazku jest także sposób wytwarzania nowego 5-hydroksy-6,7-dipropionoksyflawonu.The essence of the invention is also the method of producing the new 5-hydroxy-6,7-dipropionoxyflavone.
Istota wynalazku polega na tym, że 5,6,7-trihydroksyflawon (bajkaleina), o wzorze 1, rozpuszczony w tetrahydrofuranie (THF), poddaje się estryfikacji, w pozycje 6-OH i 7-OH, za pomocą chlorku propionylu, w obecności pirydyny.The essence of the invention consists in the fact that 5,6,7-trihydroxyflavone (baicalein), of formula 1, dissolved in tetrahydrofuran (THF), is esterified into 6-OH and 7-OH positions with propionyl chloride in the presence of pyridine.
Korzystne jest, gdy reakcję estryfikacji prowadzi się przy ciągłym mieszaniu reagentów, w temperaturze 291-295K.It is advantageous if the esterification reaction is carried out under continuous stirring of the reactants, at a temperature of 291-295K.
Postępując zgodnie z wynalazkiem, w wyniku działania chlorku propionylu w obecności pirydyny, następuje reakcja estryfikacji w pozycje 6-OH i 7-OH 5,6,7-trihydroksyflawonu. Uzyskany w ten sposób produkt wydziela się z mieszaniny poreakcyjnej, znanym sposobem, przez ekstrakcję octanem etylu.In accordance with the invention, the 5,6,7-trihydroxy flavone is esterified into the 6-OH and 7-OH positions by the action of propionyl chloride in the presence of pyridine. The product thus obtained is separated from the reaction mixture by extraction with ethyl acetate in a known manner.
Związek ten nasila cytotoksyczność indukowaną TRAIL w komórkach raka gruczołu krokowego, przez co może wzmacniać odporność przeciwnowotworową.This compound potentiates TRAIL-induced cytotoxicity in prostate cancer cells, which may enhance anti-tumor immunity.
Cytotoksyczność 5-hydroksy-6,7-dipropionoksyflawonu oceniano testem MTT, poprzez pomiar aktywności dehydrogenazy mitochondrialnej. Na podstawie uzyskanych wyników obliczano procent cytotoksyczności, który w przypadku 5-hydroksy-6,7-dipropionoksyflawonu wynosił 72%. W badaniach z wykorzystaniem komórek makrofagowych RAW 264.7, związek, będący przedmiotem wynalazku, silnie hamował wybuch oddechowy, co może wskazywać na potencjalną jego rolę przeciwzapalną.The cytotoxicity of 5-hydroxy-6,7-dipropionoxyflavone was assessed by the MTT test by measuring the activity of mitochondrial dehydrogenase. On the basis of the obtained results, the percentage of cytotoxicity was calculated, which in the case of 5-hydroxy-6,7-dipropionoxyflavone was 72%. In studies using RAW 264.7 macrophage cells, the compound of the invention strongly inhibited respiratory burst, which may indicate its potential anti-inflammatory role.
Będący przedmiotem wynalazku 5-hydroksy-6,7-dipropionoksyflawon nasilał cytotoksyczne działanie TRAIL, zwiększając tym samym podatność na zaprogramowaną śmierć komórki (apoptozę).The inventive 5-hydroxy-6,7-dipropionoxyflavone potentiated the cytotoxic effect of TRAIL, thereby increasing the susceptibility to programmed cell death (apoptosis).
Uzyskany związek może zostać wykorzystany jako preparat lub jeden ze składników farmaceutycznych wspomagających działanie chemoprewencyjne, które ma na celu wspomaganie naturalnych mechanizmów odporności przeciwnowotworowej i przeciwzapalnej.The obtained compound can be used as a preparation or one of the pharmaceutical ingredients supporting the chemopreventive effect aimed at supporting the natural mechanisms of anti-cancer and anti-inflammatory immunity.
Zaletą sposobu, według wynalazku, jest otrzymanie, w temperaturze pokojowej, 5-hydroksy-6,7-dipropionoksyflawonu, jako jedynego produktu reakcji, z wydajnością 92,50%.The advantage of the process according to the invention is the preparation, at room temperature, of 5-hydroxy-6,7-dipropionoxyflavone as the sole reaction product with a yield of 92.50%.
Wynalazek jest bliżej objaśniony w przykładzie wykonania.The invention is explained in more detail in an exemplary embodiment.
PrzykładExample
Do 60.00 mg (0.25 mmola) 5,6,7-trihydroksyflawonu (bajkaleiny) rozpuszczonego w 5 ml tetrahydrofuranu (THF) dodaje się 0.05 ml (0.62 mmola) pirydyny oraz 0.05 ml (0.58 mmola) chlorku propionylu. Całość miesza się w temperaturze pokojowej przez 2 godziny. Postęp reakcji kontroluje się przy użyciu TLC, w układzie rozwijającym heksan:octan etylu, 7:3. Po zakończeniu reakcji do mieszaniny reakcyjnej dodaje się 5 ml octanu etylu i przemywa 0.5 M roztworem kwasu solnego, do uzyskania odczynu kwaśnego (pH około 5). Warstwę organiczną oddziela się, a warstwę wodną dodatkowo ekstrahuje się octanem etylu (3x5 ml). Połączone roztwory octanowe przemywa się solanką do uzyskania odczynu obojętnego i suszy bezwodnym MgSO4. Po odparowaniu rozpuszczalnika otrzymuje się 78.57 mg czystego 5-hydroksy-6,7-dipropionoksyflawonu, co stanowi 92.50% wydajności teoretycznej.To 60.00 mg (0.25 mmol) of 5,6,7-trihydroxy flavone (baicalein) dissolved in 5 ml of tetrahydrofuran (THF), 0.05 ml (0.62 mmol) of pyridine and 0.05 ml (0.58 mmol) of propionyl chloride are added. The mixture is stirred at room temperature for 2 hours. The progress of the reaction is monitored by TLC by developing hexane: ethyl acetate, 7: 3. After completion of the reaction, 5 ml of ethyl acetate are added to the reaction mixture and washed with a 0.5 M hydrochloric acid solution until acidic (pH about 5). The organic layer was separated and the aqueous layer was further extracted with ethyl acetate (3 x 5 ml). The combined acetate solutions are washed with brine until neutral and dried with anhydrous MgSO4. After evaporating off the solvent, 78.57 mg of pure 5-hydroxy-6,7-dipropionoxyflavone are obtained, representing 92.50% of theory.
Uzyskany produkt charakteryzuje się następującymi danymi spektralnymi:The obtained product is characterized by the following spectral data:
T.t. = 126-132°C 1H NMR (THF-d8) δ: 1,25 (6H, 2t, CH3CH·-); 2,67 (4H, 2q, CH3CH2-); 6,93 (1H, s, H-8); 7,07 (1H, s, H-3); 7,55 (3H, m, H-3, H-4',H-5'); 8,04 (2H, m, H-2', H-6'), 13,03 (1H, s, 5-OH).Mp = 126-132 ° C 1 H NMR (THF-d8) δ: 1.25 (6H, 2t, CH3CH · -); 2.67 (4H, 2q, CH 3 CH 2 -); 6.93 (1H, s, H-8); 7.07 (1H, s, H-3); 7.55 (3H, m, H-3, H-4 ', H-5'); 8.04 (2H, m, H-2 ', H-6'), 13.03 (1H, s, 5-OH).
Claims (4)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PL397633A PL218844B1 (en) | 2011-12-29 | 2011-12-29 | New 5-hydroksy-6,7-dipropionoxy flavone and method of its manufacturing |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PL397633A PL218844B1 (en) | 2011-12-29 | 2011-12-29 | New 5-hydroksy-6,7-dipropionoxy flavone and method of its manufacturing |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| PL397633A1 PL397633A1 (en) | 2012-08-13 |
| PL218844B1 true PL218844B1 (en) | 2015-02-27 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PL397633A PL218844B1 (en) | 2011-12-29 | 2011-12-29 | New 5-hydroksy-6,7-dipropionoxy flavone and method of its manufacturing |
Country Status (1)
| Country | Link |
|---|---|
| PL (1) | PL218844B1 (en) |
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2011
- 2011-12-29 PL PL397633A patent/PL218844B1/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| PL397633A1 (en) | 2012-08-13 |
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Effective date: 20140731 |