CN106905371A - Biflavone manganese complex and its preparation method and application - Google Patents
Biflavone manganese complex and its preparation method and application Download PDFInfo
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- CN106905371A CN106905371A CN201710097622.4A CN201710097622A CN106905371A CN 106905371 A CN106905371 A CN 106905371A CN 201710097622 A CN201710097622 A CN 201710097622A CN 106905371 A CN106905371 A CN 106905371A
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- C07F13/00—Compounds containing elements of Groups 7 or 17 of the Periodic System
- C07F13/005—Compounds without a metal-carbon linkage
Abstract
The invention discloses a kind of bisflavones manganese complex and its preparation method and application., with amentoflavone as part, ion centered on manganese ion is reacted to obtain amentoflavone manganese complex, and the structure of complex is characterized with infrared spectrum, ultraviolet-visible absorption spectroscopy and high resolution mass spectrum for the present invention.Meanwhile, the present invention have studied the antitumor and antioxidation activity of amentoflavone manganese complex.Mtt assay shows that amentoflavone manganese complex has preferable antitumor activity, and antitumor activity is better than amentoflavone；Assay NBT photoreduction, ABTS methods show that the antioxidation activity of amentoflavone manganese complex is better than amentoflavone in itself.The formation of bisflavones manganese complex, improves that amentoflavone is antitumor, antioxidation activity, is expected to be used for the exploitation of medicine.
Description
Technical field
The invention belongs to organic synthesis, pharmaceutical technology field, and in particular to a kind of biflavone-manganese complex and its preparation side
Method and application.
Background technology
Bis-flavonoid is the distinctive chemical composition of gymnosperm, such as ginkgo, Selaginella tamariscina etc., with anti-oxidant, anti-
The bioactivity such as scorching, antiviral, antitumor.Wherein, amentoflavone (Amentoflavone, Ame) is bisflavones chemical combination
Relatively conventional one kind in thing, its structural formula is as follows：
The research such as Sun finds that amentoflavone improves the expression of antioncogene by activating hPPAR γ, so as to reach
Suppress effect [Lee E., Shin S., the Lee J.etal.Cytotoxic of breast cancer cell and cervical cancer cell
activities of amentoflavone against human breast and cervical cancers are
mediated by increasing of pten expression levels due to peroxisome
proliferator-activated receptorγactivation[J].Bulletin of the Korean
Chemical Society,2012,33(7):2219-2223.].Chen etc. research find amentoflavone by suppress because
The activity of sub- NF-kappaB, the generation of line artery and the metabolism of cancer cell, reach the purpose for suppressing growth of tumour cell
[Chen J.H.,Chen W.L.,Liu Y.C.Amentoflavone induces anti-angiogenic and anti-
metastatic effects through suppression of NF-kappa B activation in MCF-7
cells[J].Anticancer Research,2015,35(12):6685-6693.].The research such as Lee finds that amentotaxus is double yellow
Ketone can suppress the expression of the metalloproteinases caused by ultraviolet radioactive, so as to play a part of anti-oxidant, radiation proof [Lee
C.W.,Na Y.,Park N.,etal.Amentoflavone inhibits UVB-induced matrix
metalloproteinase-1expression through the modulation of AP-1 Mnmponents in
normal human fibroblasts[J].Applied Biochemistry and Biotechnology,2012,166:
1137-1147.].The research such as Zhang finds that amentoflavone and ginkgetin have certain antioxidation activity, removes
The ability of DPPH free radicals relatively strong [Zhang Y.P., Shi S.Y., Wang Y.X., etal.Target-guided
isolation and purification of antioxidants from Selaginella sinensis by
offline Mnupling of DPPH-HPLC and HSCCC experiments[J].Journal of
Chromatography B,2011,879:191-196.].The research such as Li shows that amentoflavone has antioxidation activity,
OH can effectively be removed-, O2 -, DPPH, ABTS+Deng free radical, it is possible to protect DNA from OH-The oxidation for causing is damaged
Wound [Li X.C., Wang L., Han W.J., etal.Amentoflavone protects against hydroxyl
radical-induced DNA damage via antioxidant mechanism[J].Turkish Journal of
Biochemistry-Turk Biyokimya Dergisi,2014,39(1):30-36.]。
Coordination chemistry of traditional Chinese medicine shows that the complex of trace element and organic compound reaction generation has complex equilibrium,
So the bioactivity of original composition can be showed；Again due between trace element, between organic principle, between complex and they
Mutual collaboration and antagonism can weaken or strengthen the bioactivity of original each composition, it is also possible to produce new biology living
Property [chemical species form and biology in the material base and Study on mechanism new approaches ()-Chinese medicine of Cao Zhiquan herbal medicine efficacies
Research [J] the Shanghai Univ. of Traditional Chinese Medicine journal of activity relationship, 2000,14 (1):36-39.].For example, the research such as Zhou finds Mongolian oak
Skin element rare earth compounding removes O2 -Ability be better than Quercetin, Quercetin rare earth compounding can suppress kinds of tumors, and
Antitumor activity is better than Quercetin, and wherein complex has stronger inhibitory action to bladder cancer cells, and Quercetin without
This effect [Zhou J., Wang L.F., Wang J.Y., etal.Synthesis, characterization,
antioxidative and antitumor activities of solid quercetin rare earth(III)
Mnmplexes[J].Journal of Inorganic Biochemistry,2001,83:41-48.]。
Up to the present, synthesis and its research of bioactivity about biflavone complex has no report.
The content of the invention
Goal of the invention：For the deficiencies in the prior art, it is an object of the invention to provide a kind of amentoflavone-
Manganese complex, meets antitumor and anti-oxidation medicine use demand.It is above-mentioned double yellow it is a further object of the present invention to provide one kind
The preparation method of ketone-manganese complex.Further object of the present invention is to provide the application of biflavone-manganese complex.
Technical scheme：For achieving the above object, the technical scheme is that：
Biflavone-manganese complex, structural formula is as follows：
X is NO3 -Or Cl-。
A kind of method for preparing the biflavone-manganese complex：The alcohol that biflavone is added to after manganese salt alcohol is dissolved is molten
In liquid, pH being controlled for 5-7, heating stirring reacts 2-5h, having precipitation to produce, precipitation is filtered, diformazan is used after being washed with alcohol and water
Sulfoxide is dried as solvent recrystallization, obtains biflavone-manganese complex.
Application of the described biflavone-manganese complex in antineoplastic and/or anti-oxidation medicine is prepared.
Biflavone used is amentoflavone, but is not limited to amentoflavone, is referred to 5-OH and 4-C=O
Or 5 "-OH and 4 "-C=O bis-flavonoid.
The alcohol-soluble manganese salts such as manganese salt manganese nitrate used, manganese chloride.
Solvent for use is methyl alcohol, ethanol water of ethanol, methyl alcohol and various concentrations etc..
PH value is adjusted with alkali alcosol, alkali used is including NaOH, potassium hydroxide, ammoniacal liquor, caustic alcohol, sodium methoxide etc.
Conventional bases.
During reaction, heating-up temperature is 30-50 DEG C, and the reaction time is 2-5h.
Biflavone and the mol ratio of manganese ion are 2-2.5 in solution：1.
Recrystallization solvent for use is dimethyl sulfoxide, and drying means is freeze-drying, low-temperature vacuum drying etc..
Beneficial effect：Compared with prior art, synthesis has obtained amentoflavone-manganese complex to the present invention first, adopts
The antitumor activity of Ame-Mn complexs is have studied with mtt assay, is as a result shown, Ame-Mn complexs suppress HCC
And the ability of cervical cancer cell (HeLa) is better than Ame in itself, uv-visible absorption spectra, fluorescence spectrum and viscosimetry (HepG2)
The mechanism for showing Ame-Mn complex antitumor activities is probably complex and embedded insertion DNA, causes Apoptosis.Adjacent benzene
Triphenol Autoxidation Method and ABTS Faxians show that Ame-Mn complex Scavenging abilities are better than Ame in itself, illustrate the anti-of complex
Oxidation activity is better than Ame, is conducive to further developing bis-flavonoid, for new drug research provides foundation, is conducive to the mankind
The development of healthy cause.
Brief description of the drawings
Fig. 1 is the infrared spectrum spectrogram of Ame and Ame-Mn complexs；
Fig. 2 is the uv-visible absorption spectra spectrogram of Ame and Ame-Mn complexs；
Fig. 3 is Ame mass spectrograms；
Fig. 4 is the mass spectrogram of Ame-Mn complexs；
Fig. 5 is inhibitory action result figure of the Ame and Ame-Mn complexs to HepG2 cells；
Fig. 6 is inhibitory action result figure of the Ame and Ame-Mn complexs to HeLa cells；
Fig. 7 is influence result figures of the fDNA to Ame uv-visible absorption spectras；
Fig. 8 is influence result figures of the fDNA to Ame-Mn complex uv-visible absorption spectras；
Fig. 9 is influence result figure of the Ame-Mn complexs to fDNA-EB system fluorescence emission spectrums；
Figure 10 is influence result figure of the Ame-Mn complexs to fDNA-EB system fluorescence emission spectrums；
Figure 11 is influence result figure of the Ame and Ame-Mn complexs to fDNA solution viscosities；
Figure 12 is influence result figures of the Ame to mouse thymus cells speed；
Figure 13 is influence result figure of the Ame-Mn complexs to mouse thymus cells speed；
Figure 14 is Ame to ABTS+Free Scavenging activity result figure；
Figure 15 is Ame-Mn complexs to ABTS+Free Scavenging activity result figure.
Specific embodiment
With reference to specific embodiment, the present invention is described further.
Embodiment 1
It is accurate to weigh 53.8mg Ame in round-bottomed flask, dissolved with 5mL ethanol, the manganese nitrate solution of accurate weighing 50%
17.9mg (contains manganese nitrate 0.05mmol), is added in 5mL ethanol, and manganese nitrate solution is added drop-wise in Ame solution, molten to reacting
Ethanol-ammoniacal liquor (V/V, 3 are added dropwise in liquid:1) solution, regulation pH is 6,30 DEG C of reaction 4-5h of holding, generation precipitation, filtering, successively
With ethanol, water washing, DMSO recrystallizations, freeze-drying obtains Ame-Mn complexs.
Embodiment 2
It is accurate to weigh 53.8mg Ame in round-bottomed flask, dissolved with the ethanol of 5mL90%, the manganese nitrate of accurate weighing 50%
Solution 17.9mg (contains manganese nitrate 0.05mmol), is added in the ethanol of 5mL90%, and manganese nitrate solution is added drop-wise into Ame solution
In, to ethanol-alcohol sodium solution is added dropwise in reaction solution, regulation pH is 5, keeps 30 DEG C of reaction 4-5h, produces precipitation, is filtered,
Ethanol, water washing are used successively, and DMSO recrystallizations, freeze-drying obtains Ame-Mn complexs.
Embodiment 3
It is accurate to weigh 53.8mg Ame in round-bottomed flask, dissolved with 5mL methyl alcohol, the manganese nitrate solution of accurate weighing 50%
17.9mg (contains manganese nitrate 0.05mmol), is added to in 5mL methyl alcohol, manganese nitrate solution is added drop-wise in Ame solution, to reaction
Methyl alcohol-sodium methoxide solution is added dropwise in solution, regulation pH is 7, keeps 40 DEG C of reaction 3-4h, produce precipitation, first is used in filtering successively
Alcohol, water washing, DMSO recrystallizations, freeze-drying obtain Ame-Mn complexs.
Embodiment 4
It is accurate to weigh 53.8mg Ame in round-bottomed flask, dissolved with the methyl alcohol of 5mL85%, the manganese nitrate of accurate weighing 50%
Solution 17.9mg (contains manganese nitrate 0.05mmol), is added in the methyl alcohol of 5mL85%, and manganese nitrate solution is added drop-wise into Ame solution
In, to methyl alcohol-sodium methoxide solution is added dropwise in reaction solution, regulation pH is 7, keeps 50 DEG C of reaction 2-3h, produces precipitation, is filtered,
Methyl alcohol, water washing are used successively, and DMSO recrystallizations, freeze-drying obtains Ame-Mn complexs.
Embodiment 5
It is accurate to weigh 53.8mg Ame in round-bottomed flask, dissolved with 5mL ethanol, the chloride hydrate manganese of accurate weighing four
9.9mg, is dissolved with 5mL ethanol, and manganese chloride solution is added drop-wise in Ame solution, to dropwise addition ethanol-ammoniacal liquor (V/ in reaction solution
V,3:1) solution, regulation pH is 6,30 DEG C of reaction 4-5h of holding, generation precipitation, filtering, and successively with ethanol, water washing, DMSO is heavy
Crystallization, freeze-drying obtains Ame-Mn complexs.
Embodiment 6
It is accurate to weigh 53.8mg Ame in round-bottomed flask, dissolved with the ethanol of 5mL90%, the chloride hydrate of accurate weighing four
Manganese 9.9mg, is dissolved with the ethanol of 5mL90%, and manganese chloride solution is added drop-wise in Ame solution, to be added dropwise in reaction solution ethanol-
Alcohol sodium solution, regulation pH is 5,30 DEG C of reaction 4-5h of holding, generation precipitation, filtering, and successively with ethanol, water washing, DMSO is heavy
Crystallization, freeze-drying obtains Ame-Mn complexs.
Embodiment 7
It is accurate to weigh 53.8mg Ame in round-bottomed flask, dissolved with 5mL methyl alcohol, the chloride hydrate manganese of accurate weighing four
9.9mg, is dissolved with 5mL methyl alcohol, and manganese chloride solution is added drop-wise in Ame solution, to dropwise addition methyl alcohol-sodium methoxide in reaction solution
Solution, regulation pH is 7,40 DEG C of reaction 3-4h of holding, generation precipitation, filtering, and successively with methyl alcohol, water washing, DMSO is recrystallized, cold
Lyophilized dry Ame-Mn complexs.
Embodiment 8
It is accurate to weigh 53.8mg Ame in round-bottomed flask, dissolved with the methyl alcohol of 5mL85%, the chloride hydrate of accurate weighing four
Manganese 9.9mg, is dissolved with the methyl alcohol of 5mL85%, and manganese chloride solution is added drop-wise in Ame solution, to be added dropwise in reaction solution methyl alcohol-
Sodium methoxide solution, regulation pH is 7,50 DEG C of reaction 2-3h of holding, generation precipitation, filtering, and successively with methyl alcohol, water washing, DMSO is heavy
Crystallization, freeze-drying obtains Ame-Mn complexs.
Embodiment 9
Product prepared by embodiment 1-8 is characterized, the infrared spectrogram of Ame and Ame-Mn complexs is as shown in Figure 1.
As seen from the figure, Ame is in 2800-3500cm-1Have absorption wide, this be form with hydroxyl stretching vibration peak because in Ame molecules
Between 5-OH and 4-C=O, 5 " intramolecular hydrogen bond is formd between-OH and 4 "-C=O.And the suction in Ame-Mn complexs herein
Receipts narrow, and in 3405cm-1The peak shape of left and right becomes sharp, and after illustrating to form complex, intramolecular hydrogen bond is destroyed；
1657cm in Ame-1The strong peak at place causes for the stretching vibration of carbonyl, is the characteristic absorption peak of carbonyl, after forming complex, this
Place's absworption peak is moved to lower wave number, is moved to 1625cm-1, illustrate that carbonyl take part in coordination；Complex is in 631cm-1Between produce
One absworption peak, this is that Mn-O stretching vibrations cause, and is the strong proof that oxygen atom participates in coordination.Therefore, it can speculate, Ame
In carbonyl, hydroxyl take part in coordination, and most probable coordination site is 5-OH, 4-C=O, 5 "-OH and 4 "-C=O.
The uv-visible absorption spectra of Ame and Ame-Mn complexs is as shown in Fig. 2 Ame is in 337nm (band I) and 270nm
There are two characteristic absorption peaks at (band II) place, and this is the characteristic absorption of flavone compound, and band I and band II correspond to cinnamyl respectively
The UV absorption of system and benzoyl system, is what the transition of π-π * caused.Ame-Mn complexs are produced between 375-450nm
It is raw to absorb platform, it is caused by band I red shifts, to illustrate that cinnamyl system take part in coordination, although band II positions do not have significant change,
It is absorption intensity relative reduction, and new absworption peak is also created at 298nm, these phenomenons shows to belong to cinnamyl system altogether
Coordination is take part in the carbonyl of benzoyl system, after coordination, conjugated system increase, energy reduction, π-π * required for electron transition
Generation is more easy to, therefore there is red shift in band I.And 4-C=O is more easy to n- π * transition, therefore a new peak is produced at 298nm.Can push away
It is disconnected, Mn2+The site for forming complex with Ame is 5-OH, 4-C=O, 5 "-OH, 4 "-C=O.
In the positive-ion mode, mass spectral analysis has been made to Ame and Ame-Mn complexs respectively, and has been obtained according to mass spectrum simulation
The corresponding ionic structure formula of molecular ion peak on spectrogram, and conclude therefrom that the structure of Ame-Mn.
Fig. 3 is mass spectrograms of the Ame in positive ion mode, and quasi-molecular ion peak m/z 539.0920 is attributed to [Ame+H]+。
Fig. 4 a are the mass spectrogram of Ame-Mn complexs, and Ame-Mn complexs have two main quasi-molecular ion peaks, and with one just
Electric charge, respectively m/z 748.0492 and m/z 826.0636.Fig. 4 b, are the isotope of quasi-molecular ion peak m/z 748.0492
Mass spectrogram, it can be seen that the isotopic peak of quasi-molecular ion peak m/z748.0492 be m/z 749.0521, m/z 750.0523,
M/z 751.0464, the molecular weight of adjacent quasi-molecular ion peak differs 1.0029,1.0002 and 0.9941 respectively, so as to confirm this
Quasi-molecular ions one positive charge of band.From infrared and ultraviolet spectra, Ame and Mn2+The coordination site for forming complex is 5-OH, 4-C
=O, 5 "-OH, 4 "-C=O.Because the solvent for recrystallizing and dissolving complex is DMSO, DMSO contains oxygen atom and sulphur atom,
With strong coordination ability, and more difficult ionization, therefore DMSO may be contained in complex, thus speculate quasi-molecular ion peak m/z
748.0492 are attributed to [Mn (Ame-H) (DMSO)2]+, element composition C34H29O12MnS3, with quasi-molecular ion peak m/z
748.0492 possible element compositions are consistent (Fig. 4 c).Meanwhile, using Software SMS to [Mn (Ame-H) (DMSO)2]+Enter
Row simulation, obtains simulating mass spectrogram, as shown in figure 4d.[Mn (Ame-H) (DMSO) as seen from the figure2]+Isotope ion peak
There are four, respectively m/z 748.0475, m/z 749.0509, m/z 750.0433, m/z 751.0467, with quasi-molecular ion
The isotope mass spectrometry peak match degree of peak m/z 748.0492 is very high, therefore, it can confirm that the corresponding ions of m/z 748.0492 are
[Mn(Ame-H)(DMSO)2]+.Similarly, the corresponding ions of quasi-molecular ion peak m/z 826.0636 (Fig. 4 e) are [Mn (Ame-H)
(DMSO)3]+.In sum, Ame and Mn2+Form 1:1 complex；Infrared spectrum and ultraviolet-visible spectrum prove Ame with
Mn2+The coordination site for forming complex is 5-OH, 4-C=O, 5 "-OH and 4 "-C=O；Nuclear magnetic data shows, the 5 of Ame " change of-OH
Chemical shift of the displacement study than 5-OH is big, illustrate 5 " cloud density of-OH is relatively low, and hydrogen atom is more easy to leave away, and acidity is stronger, because
This, Ame and Mn2+The coordination site for forming complex is 5 "-OH and 4 "-C=O possibility it is maximum.Therefore [Mn (Ame-H) (DMSO)2]+
[Mn (Ame-H) (DMSO)3]+Most possible structure is as follows：
It can be found that ion [Mn (Ame-H) (DMSO)2]+[Mn (Ame-H) (DMSO)3]+Structure is similar, and difference is only
DMSO molecules containing varying number, its reason is ion [Mn (Ame-H) (DMSO)3]+One is lost under equipment voltage effect
DMSO, therefore, the structure of complex ion is [Mn (Ame-H) (DMSO)3]+.Further, since slaine is nitrate in experiment
Or hydrochloride, therefore contain nitrate anion or chlorion in complex, therefore, the structural formula of Ame-Mn complexs is as follows：
X is NO3 -Or Cl-。
Embodiment 10
The antitumor activity of Ame and Ame-Mn complexs is have studied using mtt assay, process is as follows：
(1) by HepG2, HeLa cell line inoculation of suspension liquid in 96 well culture plates, 100 μ L, (1 × 10 are added per hole5Individual/
ML), 37 DEG C, in 5%CO224h is cultivated in incubator；
(2) after culture 24h, supernatant is abandoned, the sample for adding 100 μ L beforehand dilutions good, each concentration sets 10 multiple holes, in
5%CO224h is cultivated in incubator；Simultaneously set control wells (DMSO, cell liquid, MTT), zeroing hole (culture medium, DMSO,
MTT)；
(3) after culture 36h, supernatant is abandoned, adds DMEM culture mediums of the 100 μ L containing MTT (5mg/mL), continue to cultivate 4h；
(4) careful removal supernatant after 4h, 200 μ L DMSO are added per hole, and 15min, enzyme mark are fully vibrated in constant temperature oscillator
Mensuration absorbance value at instrument 595nm, inhibiting rate of the sample to HepG2, HeLa cell is calculated by OD values, with improvement Karber
Formula calculates half-inhibition concentration IC50Value.
lgIC50=Xm-I (P- (3-Pm-Pn)/4) (formula 2)
In formula, IR is inhibiting rate, OD0It is the absorbance of control group, OD1It is the absorbance of sample sets, Xm is lg (maximum agent
Amount), I is lg (maximum dose/adjacent doses), and P is positive reaction rate sum, and Pm is maximum positive reaction rate, and Pn is minimum sun
Property reactivity.
Result is as seen in figs. 5-6.Experiment finds that Ame-Mn complexs can effectively suppress hepatocellular carcinoma H22 and cervical carcinoma is thin
The growth of born of the same parents HeLa, IC50Value is respectively 5.286 and 5.503 μm of olL-1, the IC than Ame50Small (the IC of Ame of value50Value is respectively
13.633 and 8.040 μm of olL-1), illustrate Ame-Mn complexs antitumor activity preferably, and be better than Ame.Using ultraviolet-visible
The interaction of Ame and Ame-Mn complexs and herring sperm dna (fDNA) of spectroscopic methodology, fluorescent spectrometry and POLYURETHANE MICELLE,
Further to disclose the mechanism of antitumor activity, gained collection of illustrative plates as illustrated in figures 7-11, as a result shows, Ame and Ame-Mn complexs
Interaction with fDNA is intercalation pattern, and complex is better than Ame with fDNA ability to functions.Thereby it is assumed that, Ame and
The mechanism of the antitumor activity of its complex is probably that Ame or its complex enter cell interior, and intercalation occurs with DNA makees
With causing Apoptosis.Because the interaction of complex and DNA is better than Ame, therefore its antitumor activity is also better than Ame.
Embodiment 11
Ame and Ame-Mn complex Scavenging abilities, step have studied using assay NBT photoreduction, ABTS methods
It is as follows：
(1) assay NBT photoreduction
Mouse thymus cells speed V0Measure：At 25 DEG C, the Tris-HCl bufferings of 2mL are added in 10mL sample cells
Liquid (pH=8.20), and 100 μ L DMSO are added as control, after adding 0.8mL distilled water, concentration is added for 2mmolL-1
Pyrogallol solution 0.2mL, poured into cuvette after mixing, with pure water as blank, determine 322nm place absorbance, often 10s
A value of record, coreaction 4min.With t as abscissa, A carries out linear regression for ordinate, and its straight slope is V0, determine
Three times, average.
Add mouse thymus cells speed V after sample1Measure：At 25 DEG C, add 2mL's in 10mL sample cells
Tris-HCl buffer solutions (pH=8.2), and the sample DMSO solution of 100 μ L various concentrations is added, after adding 0.8mL distilled water,
Concentration is added for 2mmolL-1Pyrogallol solution 0.2mL, poured into cuvette after mixing, with distilled water as blank, survey
Determine the absorbance at 322nm, an A value, coreaction 4min are recorded per 10s.With t as abscissa, A is linearly returned for ordinate
Return, its straight slope is V1, determine three times, average.Free radical scavenging activity is calculated according to formula 3.
SR (%)=(1-v1/v0) × 100% (formula 3)
(2) ABTS methods
Blank sample removes ABTS+Radical ion ability is determined：At 25 DEG C, add 2.9mL's in 10mL sample cells
ABTS+Radical ion working solution, and 100 μ L DMSO are added, after reaction 5min, ultraviolet-visible spectrum is measured, and record
Absorption intensity A at 730nm0。
Sample removes ABTS+Radical ion ability is determined：At 25 DEG C, add 2.9ml's in 10mL sample cells
ABTS+Radical ion working solution, and the sample DMSO solution of 100 μ L various concentrations is added, after reaction 5min, measurement is purple
Outward-visible spectrum, and record the absorption intensity A at 730nm1.ABTS is calculated according to formula 4+Radical ion clearance rate.
SR (%)=(1-A1/A0) × 100% (formula 4)
As shown in figs. 12-15.Assay NBT photoreduction result shows that Ame and Ame-Mn complexs remove O2 -Free radical
IC50It is 23.273 μm of olL-1With 5.716 μm of olL-1, it can be found that Ame-Mn complexs remove O2 -The ability of free radical
It is significantly stronger than Ame.
Ame and Ame-Mn complexs are to ABTS+The Scavenging activity of free radical has concentration dependent, in certain scope
Interior, clearance rate is linear with concentration.The present invention depicts the curve of clearance rate and concentration (c), obtains corresponding linear side
Journey, and it is calculated maximum 503nhibiting concentration (IC50Value), Ame and Ame-Mn complexs remove ABTS+The IC of free radical50Value
Respectively 20.703 and 10.175 μm olL-1, it can be seen that Ame-Mn complexs remove ABTS+The ability of free radical is obvious
It is better than Ame.
Synthesis has obtained amentoflavone-manganese complex to the present invention first, and its antitumor and antioxidation activity is entered
Row research, it is found that the antitumor of complex, antioxidation activity are better than biflavone in itself, open bisflavones complex
Research work, for new drug development provides important reference value.
Claims (10)
1. biflavone-manganese complex, it is characterised in that structural formula is as follows：
X is NO3 -Or Cl-。
2. a kind of method for preparing biflavone-manganese complex described in claim 1, it is characterised in that：After manganese salt is dissolved with alcohol
It is added in the alcoholic solution of biflavone, controls pH for 5-7, heating stirring reacts 2-5h, have precipitation to produce, precipitation is filtered, uses
Dried as solvent recrystallization with dimethyl sulfoxide after alcohol and water washing, obtain biflavone-manganese complex.
3. the method for preparing biflavone-manganese complex according to claim 2, it is characterised in that：Biflavone used is fringe
Flower China fir biflavone.
4. the method for preparing biflavone-manganese complex according to claim 2, it is characterised in that：Manganese salt used is nitric acid
Manganese, manganese chloride.
5. the method for preparing biflavone-manganese complex according to claim 2, it is characterised in that：Solvent for use be methyl alcohol,
Ethanol and their aqueous solution.
6. the method for preparing biflavone-manganese complex according to claim 2, it is characterised in that：Adjusted with alkali alcosol
Section pH value, alkali used includes NaOH, potassium hydroxide, ammoniacal liquor, caustic alcohol, sodium methoxide.
7. the method for preparing biflavone-manganese complex according to claim 2, it is characterised in that：Reaction temperature is 30-50
DEG C, the reaction time is 2-5h.
8. the method for preparing biflavone-manganese complex according to claim 2, it is characterised in that：In solution biflavone with
The mol ratio of manganese ion is 2-2.5：1.
9. the method for preparing biflavone-manganese complex according to claim 2, it is characterised in that：Recrystallization solvent for use
It is dimethyl sulfoxide, drying means is freeze-drying, low-temperature vacuum drying.
10. application of the biflavone-manganese complex described in claim 1 in antineoplastic and/or anti-oxidation medicine is prepared.
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| PCT/CN2018/076751 WO2018153333A1 (en) | 2017-02-22 | 2018-02-13 | Biflavonoid-manganese complex and preparation method and application thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2018153328A1 (en) * | 2017-02-22 | 2018-08-30 | 南京林业大学 | Biflavonoid-iron complex, preparation method therefor and use thereof |
| WO2018153333A1 (en) * | 2017-02-22 | 2018-08-30 | 南京林业大学 | Biflavonoid-manganese complex and preparation method and application thereof |
| CN108752383A (en) * | 2018-05-02 | 2018-11-06 | 江苏理工学院 | One kind having active pyrazole carboxylate manganese complexes of SOD and preparation method thereof |
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| CN101857583A (en) * | 2009-04-08 | 2010-10-13 | 温州医学院 | Method for preparing isoflavone metal complexes and anti-tumor medical application |
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| US20060024691A1 (en) * | 2004-03-25 | 2006-02-02 | Buck Institute For Age Research | Novel pathways in the etiology of cancer |
| CN106905371B (en) * | 2017-02-22 | 2019-11-12 | 南京林业大学 | Biflavone-manganese complex and its preparation method and application |
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| CN101857583A (en) * | 2009-04-08 | 2010-10-13 | 温州医学院 | Method for preparing isoflavone metal complexes and anti-tumor medical application |
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| QAMAR UDDIN等: "The biflavonoid, amentoflavone degrades DNA in the presence of Nipper ions", 《TOXICOLOGY IN VITRO》 * |
| 刘衍季等: "黄酮类金属配合物的生物活性研究进展", 《中国中药杂志》 * |
| 唐丽君等: "黄酮类金属配合物的研究进展", 《广东微量元素科学》 * |
| 李海霞等: "黄酮类化合物金属配合物研究进展", 《中国药房》 * |
| 赵兵等: "国内黄酮金属配合物的研究进展", 《化学试剂》 * |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2018153328A1 (en) * | 2017-02-22 | 2018-08-30 | 南京林业大学 | Biflavonoid-iron complex, preparation method therefor and use thereof |
| WO2018153333A1 (en) * | 2017-02-22 | 2018-08-30 | 南京林业大学 | Biflavonoid-manganese complex and preparation method and application thereof |
| US10889606B2 (en) | 2017-02-22 | 2021-01-12 | Nanjing Forestry University | Biflavone-iron complex, preparation method and application thereof |
| CN108752383A (en) * | 2018-05-02 | 2018-11-06 | 江苏理工学院 | One kind having active pyrazole carboxylate manganese complexes of SOD and preparation method thereof |
| CN108752383B (en) * | 2018-05-02 | 2020-10-30 | 江苏理工学院 | Pyrazole carboxylate manganese complex with SOD activity and preparation method thereof |
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| WO2018153333A1 (en) | 2018-08-30 |
| CN106905371B (en) | 2019-11-12 |
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