CN108101892A - A kind of Chrysin non-natural amino acid derivative and its preparation method and application - Google Patents
A kind of Chrysin non-natural amino acid derivative and its preparation method and application Download PDFInfo
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- CN108101892A CN108101892A CN201711280138.1A CN201711280138A CN108101892A CN 108101892 A CN108101892 A CN 108101892A CN 201711280138 A CN201711280138 A CN 201711280138A CN 108101892 A CN108101892 A CN 108101892A
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- amino acid
- chrysin
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- acid derivative
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- RTIXKCRFFJGDFG-UHFFFAOYSA-N chrysin Chemical compound C=1C(O)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=CC=C1 RTIXKCRFFJGDFG-UHFFFAOYSA-N 0.000 title claims abstract description 45
- 235000015838 chrysin Nutrition 0.000 title claims abstract description 23
- NYCXYKOXLNBYID-UHFFFAOYSA-N 5,7-Dihydroxychromone Natural products O1C=CC(=O)C=2C1=CC(O)=CC=2O NYCXYKOXLNBYID-UHFFFAOYSA-N 0.000 title claims abstract description 22
- 229940043370 chrysin Drugs 0.000 title claims abstract description 22
- 150000003862 amino acid derivatives Chemical class 0.000 title claims abstract description 17
- 238000002360 preparation method Methods 0.000 title claims abstract description 12
- 150000001875 compounds Chemical class 0.000 claims description 15
- 150000001413 amino acids Chemical class 0.000 claims description 8
- DSSYKIVIOFKYAU-XCBNKYQSSA-N (R)-camphor Chemical compound C1C[C@@]2(C)C(=O)C[C@@H]1C2(C)C DSSYKIVIOFKYAU-XCBNKYQSSA-N 0.000 claims description 5
- 229960000846 camphor Drugs 0.000 claims description 5
- 230000000259 anti-tumor effect Effects 0.000 claims description 3
- -1 amino acid methyl esters Chemical class 0.000 abstract description 6
- 238000006243 chemical reaction Methods 0.000 abstract description 5
- 230000000694 effects Effects 0.000 abstract description 5
- YORCIIVHUBAYBQ-UHFFFAOYSA-N propargyl bromide Chemical compound BrCC#C YORCIIVHUBAYBQ-UHFFFAOYSA-N 0.000 abstract description 2
- 235000001014 amino acid Nutrition 0.000 abstract 4
- 239000002585 base Substances 0.000 abstract 3
- 229930003944 flavone Natural products 0.000 abstract 2
- 150000002213 flavones Chemical class 0.000 abstract 2
- 235000011949 flavones Nutrition 0.000 abstract 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 abstract 2
- TURAMGVWNUTQKH-UHFFFAOYSA-N propa-1,2-dien-1-one Chemical group C=C=C=O TURAMGVWNUTQKH-UHFFFAOYSA-N 0.000 abstract 2
- 239000003513 alkali Substances 0.000 abstract 1
- 239000002246 antineoplastic agent Substances 0.000 abstract 1
- 229940041181 antineoplastic drug Drugs 0.000 abstract 1
- 230000007062 hydrolysis Effects 0.000 abstract 1
- 238000006460 hydrolysis reaction Methods 0.000 abstract 1
- 235000013930 proline Nutrition 0.000 abstract 1
- 150000003839 salts Chemical class 0.000 abstract 1
- 229910052708 sodium Inorganic materials 0.000 abstract 1
- 239000011734 sodium Substances 0.000 abstract 1
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N sodium azide Substances [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 abstract 1
- 235000019187 sodium-L-ascorbate Nutrition 0.000 abstract 1
- 210000004027 cell Anatomy 0.000 description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical class CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 210000004881 tumor cell Anatomy 0.000 description 3
- MEKOFIRRDATTAG-UHFFFAOYSA-N 2,2,5,8-tetramethyl-3,4-dihydrochromen-6-ol Chemical compound C1CC(C)(C)OC2=C1C(C)=C(O)C=C2C MEKOFIRRDATTAG-UHFFFAOYSA-N 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 230000001093 anti-cancer Effects 0.000 description 2
- 230000003110 anti-inflammatory effect Effects 0.000 description 2
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 2
- 229960004316 cisplatin Drugs 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 229910052697 platinum Inorganic materials 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Substances [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- CKPXLKWANYQNBL-WCCKRBBISA-N (2s)-pyrrolidine-2-carboxylic acid;sodium Chemical compound [Na].OC(=O)[C@@H]1CCCN1 CKPXLKWANYQNBL-WCCKRBBISA-N 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- QWENRTYMTSOGBR-UHFFFAOYSA-N 1H-1,2,3-Triazole Chemical compound C=1C=NNN=1 QWENRTYMTSOGBR-UHFFFAOYSA-N 0.000 description 1
- 208000022306 Cerebral injury Diseases 0.000 description 1
- 206010021143 Hypoxia Diseases 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 230000000146 antalgic effect Effects 0.000 description 1
- 230000000049 anti-anxiety effect Effects 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000002082 anti-convulsion Effects 0.000 description 1
- 230000003178 anti-diabetic effect Effects 0.000 description 1
- 230000001857 anti-mycotic effect Effects 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 239000003472 antidiabetic agent Substances 0.000 description 1
- 239000002543 antimycotic Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 239000002249 anxiolytic agent Substances 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 229910052927 chalcanthite Inorganic materials 0.000 description 1
- 230000001149 cognitive effect Effects 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 229940000406 drug candidate Drugs 0.000 description 1
- MVEAAGBEUOMFRX-UHFFFAOYSA-N ethyl acetate;hydrochloride Chemical compound Cl.CCOC(C)=O MVEAAGBEUOMFRX-UHFFFAOYSA-N 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 239000012065 filter cake Substances 0.000 description 1
- 206010017758 gastric cancer Diseases 0.000 description 1
- 208000010749 gastric carcinoma Diseases 0.000 description 1
- 230000007954 hypoxia Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 230000031891 intestinal absorption Effects 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 230000001665 lethal effect Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 201000007270 liver cancer Diseases 0.000 description 1
- 208000014018 liver neoplasm Diseases 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- DKORBWOBRMJQKR-LLVKDONJSA-N methyl (2R)-2-(3-chlorophenyl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]acetate Chemical group COC(=O)[C@H](NC(=O)OC(C)(C)C)c1cccc(Cl)c1 DKORBWOBRMJQKR-LLVKDONJSA-N 0.000 description 1
- HCZXBVJRVCEWCG-LLVKDONJSA-N methyl (2r)-2-(4-chlorophenyl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]acetate Chemical group CC(C)(C)OC(=O)N[C@@H](C(=O)OC)C1=CC=C(Cl)C=C1 HCZXBVJRVCEWCG-LLVKDONJSA-N 0.000 description 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N methylene chloride Substances ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 235000010603 pastilles Nutrition 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- PPASLZSBLFJQEF-RKJRWTFHSA-M sodium ascorbate Substances [Na+].OC[C@@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RKJRWTFHSA-M 0.000 description 1
- 235000010378 sodium ascorbate Nutrition 0.000 description 1
- 229960005055 sodium ascorbate Drugs 0.000 description 1
- PPASLZSBLFJQEF-RXSVEWSESA-M sodium-L-ascorbate Chemical compound [Na+].OC[C@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RXSVEWSESA-M 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 201000000498 stomach carcinoma Diseases 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000007675 toxicity by organ Effects 0.000 description 1
- 231100000155 toxicity by organ Toxicity 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 150000003852 triazoles Chemical class 0.000 description 1
- 201000008827 tuberculosis Diseases 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
The invention discloses Chrysin non-natural amino acid derivative or its pharmaceutically acceptable hydrate and salt, including its stereoisomer or tautomer.Its preparation process includes：5 hydroxyl, 7 propynyloxy base flavones is made under alkali effect with propargyl bromide in Chrysin；（L/D）Halogenated Boc amino acid methyl esters and NaN3It is made under the effect of CuI/L Sodium prolines（L/D）‑N3Boc amino acid methyl esters；5 hydroxyl, 7 propynyloxy base flavones and（L/D）‑N3Boc amino acid methyl esters are again in CuSO4.5H2The lower reaction of O/ sodium ascorbates effect, through de- Boc bases, hydrolysis prepares Chrysin amino acid derivativges.The Chrysin non-natural amino acid derivative of the present invention has antitumaous effect, available for the purposes in treatment anticancer drug.
Description
Technical field
Application the present invention relates to Chrysin non-natural amino acid derivative and its in pharmacy belongs to medical science neck
Domain.
Background technology
Chrysin (5,7-dihydroxyflavone) is a kind of chromocor compound being widely present in nature, have antibacterial,
The extensive pharmacological activity such as anti-oxidant, antitumor, anti-inflammatory, anti-diabetic, antianxiety.Recent studies have shown that it can also prevent
Organ toxicity caused by cis-platinum and cognitive defect and cerebral injury caused by improvement interval hypoxia.However, due to its it is water-soluble compared with
Difference, intestinal absorption is few, in vivo easy metabolic inactivation.In order to improve its pharmacological activity, structural modification and transformation are carried out to it, it is right
It is of great significance in the novel drug candidate for obtaining high-efficiency low-toxicity.
Amino acid is the elementary cell for forming protein, as bioactive molecule important in human body, participates in a variety of life and lives
Dynamic process.Amino acid has good dissolubility and compatibility, and tumour cell is higher than normal cell to amino acid requirement amount.By its
It is introduced into drug molecule and is conducive to drug arrival and plays a role into the cell, and then selection of the raising drug molecule to tumour cell
Property.
1,2,3- triazole is pharmaceutical synthesis important link unit, many compounds containing triazole have it is antimycotic,
A variety of bioactivity such as antibacterium, treating tuberculosis, anticancer, antiviral, anti-inflammatory and antalgic, anticonvulsion.The present invention passes through 1,2,3- tri-
Nitrogen azoles ring is combined alpha-non-natural amino acid with Chrysin molecule, it is desirable to be improved the dissolubility of Chrysin, be reduced to normal cell
Lethal effect improves active anticancer.
The content of the invention
It is an object of the invention to provide a kind of Chrysin non-natural amino acid derivative, with antitumaous effect.
Another object of the present invention is to provide the preparation method of above-mentioned Chrysin non-natural amino acid derivative.
It is still another object of the present invention to provide the purposes of above-mentioned Chrysin non-natural amino acid derivative.
The present invention will be described in detail below.
Chrysin non-natural non-natural amino acid derivative provided by the invention or its pharmaceutically acceptable hydrate, including
Its stereoisomer or tautomer, structure are as follows：
In formula,
；
Alpha-non-natural amino acid is configured as L-type, D- types.
The Chrysin non-natural amino acid derivative concrete structure example is as follows：
The present invention also provides the preparation methods of above-claimed cpd：
In formula,
;
Alpha-non-natural amino acid is configured as L-type, D- types；Z1Each stand alone as Cl, when Br, I, Z2For H；Z1For H, during OH, Z2Each
Stand alone as Cl, Br, I；Z3For N3When, Z4For H；Z3For H, during OH, Z4For N3；N is 0,1.
The Chrysin non-natural amino acid derivative of the present invention or its pharmaceutically acceptable hydrate, including its alloisomerism
Body or tautomer have antitumor action.
The present invention is further illustrated by following embodiment, but should be noted that the scope of the present invention and implement from these
Any restrictions of example.
Specific embodiment
Embodiment 1
Compound（1）Preparation
By 2.5g (10 mmol) Chrysins and 3.36g (20 mmol) K2CO3Add in the reactor for filling 100mL anhydrous propanones
In, it is vigorously stirred down and is slowly added to 2 mL propargyl bromides, back flow reaction 3h.Reaction finishes, and adds in 50 mL water, acetone is removed under reduced pressure,
Filtering, filter cake is dry successively with water, 1M HCl solution and water washing, obtains yellow solid, is compound（I）, yield 95%.mp:
153.7-154.5℃; 1HNMR(CDCl3,400MHz)δ:12.72(s,1H), 7.89(d,J=4Hz,2H),7.53(m,3H),
6.68(s,1H),6.59(d,J=1.6Hz,1H),6.45(d,J = 2.0 Hz,1H),4.77(d,J = 2.0 Hz,2H),
2.61(s, 1H)；ESI-MS( m/z): 293[M+H]+。
By (the L) -4-Br-Boc-PheOMe of 3.58g (10mmol) and the NaN of 0.78g (12 mmol)3It adds in
In 15mLDMSO, the L-PROLINE sodium of the CuI and 0.41g (3 mmol) of 0.19g (1 mmol) are added, is heated to 90 DEG C, instead
5h is answered, adds in 50mLH2O, filtering, adds 50mLCH2Cl2, layering, organic layer saturated common salt water washing 3 times, concentration, column
Chromatographic purifying obtains (L) -4-N3- Boc-PheOMe, yield 86%.
By 3.84g (12 mmol) (L) -4-N3- Boc-PheOMe and 2.92g (10 mmol) compound（I）Add in 100
ML volume ratios are 1：1 tert-butyl alcohol and the mixed solvent of water sequentially add 39.6mg (0.2 mmol) sodium ascorbate under stirring
With 25mg (0.1 mmol) CuSO4·5H2O, 50 DEG C are vigorously stirred lower reaction 5h.Reaction system is down to room temperature, adds in 100mL
CH2Cl2With the HCl liquid separations of 20mL2mol/L, organic phase is washed with water 2 times, dry, filters, be concentrated under reduced pressure to obtain crude product.Column layer
Analysis purifying, obtains intermediate（III).Yield 85%.
In 5.98g (10 mmol) intermediate（III the HCl ethyl acetate solutions of 20mL saturations are added in), are stirred at room temperature
5h, evaporated under reduced pressure, residue add in 20mL methanol and the NaOH solution of 20mL2mol/L, 2h are stirred at room temperature, dilute hydrochloric acid tune pH3 subtracts
Pressure concentration, column chromatography purifying, obtains compound（1）, yield 86%.ESI-MS(m/z):499[M+1]+。Anal. Calcd. for
C27H22N4O6: C, 65.05; H, 4.45; N, 11.24; found C, 65.08; H, 4.42; N, 11.26.
Embodiment 2
Compound（2）Preparation
(L) -4-Br-Boc-PheOMe is replaced with (D) -4-Br-Boc-PheOMe, compound is made with embodiment 1 in other operations
（2）, yield 86%.
Embodiment 3
Compound（3）Preparation
(L) -4-Br-Boc-PheOMe is replaced with (L) -3-I-Boc-PheOMe, compound is made with embodiment 1 in other operations
（3）, yield 88%.
Embodiment 4
Compound（4）Preparation
(L) -4-Br-Boc-PheOMe is replaced with (D) -3-Cl-Boc- Phenylglycine methyl esters, other operations are made with embodiment 1
Compound（4）, yield 77%.ESI-MS(m/z):485[M+1]+。Anal. Calcd. For C26H20N4O6: C, 64.46;
H, 4.16; N, 11.56; found C, 64.43; H, 4.15; N, 11.56.
Embodiment 5
Compound（5）Preparation
(L) -4-Br-Boc-PheOMe is replaced with (L) -3-Cl-Boc- methyl-P-tyrosines, other operations are the same as embodiment 1, obtainedization
Close object（5）, yield 74%.ESI-MS(m/z):515[M+1]+。Anal. Calcd. For C27H22N4O7: C, 63.03; H,
4.31; N, 10.89; found C, 63.01; H, 4.34; N, 10.86.
Embodiment 6
Compound（6）Preparation
(L) -4-Br-Boc-PheOMe is replaced with (D) -4-Cl-Boc- Phenylglycine methyl esters, other operations are made with embodiment 1
Compound（6）, yield 79%.
Embodiment 7
Inhibition of the Chrysin non-natural amino acid derivative to HepG2 and MGC-803
Human liver cancer cell HepG2 and gastric carcinoma cells MGC-803 are incubated at the hyclone containing volume fraction 10%, 1x105U/
L penicillin and 1x105In the PRM1-1640 culture mediums of U/L streptomysins, at 37 DEG C, 5%CO2Incubator in cultivate.It takes the logarithm life
Long-term tumor cell inoculation adds in 100 μ L single cell suspensions per hole in 96 well culture plates（5x103A cell）, for 24 hours after,
Supernatant is abandoned, 200 μ L pastille culture mediums are added in per hole, it is 120,60,30,15 Hes to make HepG2 cell lines final compound concentration
7.5 μm of ol/L, MGC-803 cell lines final compound concentration are 20,10,5,2.5 and 1.25 μm of ol/L, while set cis-platinum as sun
Property control, HepG2 cell lines cis-platin concentrations be 100,50,25,12.5 and 6.25 μm of ol/L, MGC-803 cell line cis-platin concentrations
For 20,10,5,2.5,1.25 μm of ol/L, vehicle control group is to add the culture solution of 0.1%Tween-80, zeroing group containing 0.2%DMSO
Only to add the culture solution of equivalent.Each concentration sets 5 multiple holes, and after cultivating 48h, 20 μ LMTT (5g/L) solution are added in per hole, are mixed
It is even, continue to cultivate 4h.Culture solution in hole is abandoned in suction, and 150 μ LDMSO are added in per hole, shakes 10min, makes bluish violet crystallization fully molten
Solution, OD values are measured with microplate reader at 570nm wavelength, are carried out data statistic analysis with SPSS18.0 softwares, are measured IC50 values.
The results show that the Chrysin non-natural amino acid derivative had had HepG2 cells and MGC-803 cells
Inhibitory action（Table 1）.
Claims (4)
1. Chrysin non-natural amino acid derivative or its pharmaceutically acceptable hydrate, including its stereoisomer or mutual variation
Structure body, is shown below：
tu1
In formula,
tu2；
Alpha-non-natural amino acid is configured as L-type, D- types.
2. Chrysin non-natural amino acid derivative or its pharmaceutically acceptable hydrate according to right 1, vertical including it
Body isomers or tautomer, which is characterized in that the specific example of the compound includes：
tu3。
3. Chrysin non-natural amino acid derivative according to claim 1 or its pharmaceutically acceptable hydrate, including
Its stereoisomer or tautomer, its preparation method comprise the following steps：
tu3
In formula,
tu6
tu2;
Alpha-non-natural amino acid is configured as L-type, D- types；Z1Each stand alone as Cl, when Br, I, Z2For H；Z1For H, during OH, Z2Each solely
It stands as Cl, Br, I；Z3For N3When, Z4For H；Z3For H, during OH, Z4For N3；N is 0,1.
4. Chrysin non-natural amino acid derivative according to claim 1 or its pharmaceutically acceptable hydrate, including
Its stereoisomer or tautomer have antitumor action.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN114057736A (en) * | 2021-11-15 | 2022-02-18 | 北京师范大学 | Synthesis method of chrysin bridged indole derivatives and application of chrysin bridged indole derivatives in anti-tumor direction |
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