CN107325118A - A kind of bisbenzimidazole Zn complex synthetic method of halogen substitution V types pyridine 2,6 and antitumor activity detection - Google Patents
A kind of bisbenzimidazole Zn complex synthetic method of halogen substitution V types pyridine 2,6 and antitumor activity detection Download PDFInfo
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- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 title claims abstract description 30
- 238000010189 synthetic method Methods 0.000 title claims abstract description 29
- 230000000259 anti-tumor effect Effects 0.000 title claims abstract description 23
- 229910052736 halogen Inorganic materials 0.000 title claims abstract description 15
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 title claims abstract description 15
- 238000006467 substitution reaction Methods 0.000 title claims abstract description 14
- 238000001514 detection method Methods 0.000 title claims abstract description 6
- 125000005843 halogen group Chemical group 0.000 title abstract 2
- INAAIJLSXJJHOZ-UHFFFAOYSA-N pibenzimol Chemical compound C1CN(C)CCN1C1=CC=C(N=C(N2)C=3C=C4NC(=NC4=CC=3)C=3C=CC(O)=CC=3)C2=C1 INAAIJLSXJJHOZ-UHFFFAOYSA-N 0.000 title abstract 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 14
- 230000015572 biosynthetic process Effects 0.000 claims abstract description 13
- 238000003786 synthesis reaction Methods 0.000 claims abstract description 13
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims abstract description 12
- WJJMNDUMQPNECX-UHFFFAOYSA-N Dipicolinic acid Natural products OC(=O)C1=CC=CC(C(O)=O)=N1 WJJMNDUMQPNECX-UHFFFAOYSA-N 0.000 claims abstract description 7
- 238000004176 ammonification Methods 0.000 claims abstract description 7
- 238000006243 chemical reaction Methods 0.000 claims abstract description 7
- 239000012043 crude product Substances 0.000 claims abstract description 7
- 238000001035 drying Methods 0.000 claims abstract description 7
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 7
- 229920000137 polyphosphoric acid Polymers 0.000 claims abstract description 7
- 238000003756 stirring Methods 0.000 claims abstract description 7
- 238000000967 suction filtration Methods 0.000 claims abstract description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 35
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 27
- 210000004027 cell Anatomy 0.000 claims description 27
- 235000019441 ethanol Nutrition 0.000 claims description 14
- 150000002367 halogens Chemical class 0.000 claims description 13
- 238000002329 infrared spectrum Methods 0.000 claims description 12
- 235000015097 nutrients Nutrition 0.000 claims description 12
- 239000008188 pellet Substances 0.000 claims description 12
- 230000002401 inhibitory effect Effects 0.000 claims description 11
- 238000004113 cell culture Methods 0.000 claims description 8
- 239000013078 crystal Substances 0.000 claims description 8
- 238000002474 experimental method Methods 0.000 claims description 8
- 238000003556 assay Methods 0.000 claims description 7
- 238000000034 method Methods 0.000 claims description 7
- 238000010998 test method Methods 0.000 claims description 6
- 210000004881 tumor cell Anatomy 0.000 claims description 5
- 239000002904 solvent Substances 0.000 claims description 4
- GEYOCULIXLDCMW-UHFFFAOYSA-N 1,2-phenylenediamine Chemical compound NC1=CC=CC=C1N GEYOCULIXLDCMW-UHFFFAOYSA-N 0.000 claims description 3
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 claims description 3
- 238000007605 air drying Methods 0.000 claims description 3
- 239000003814 drug Substances 0.000 claims description 3
- 238000001704 evaporation Methods 0.000 claims description 3
- 239000011521 glass Substances 0.000 claims description 3
- 239000007788 liquid Substances 0.000 claims description 3
- 239000002184 metal Substances 0.000 claims description 3
- 238000002156 mixing Methods 0.000 claims description 3
- 239000013110 organic ligand Substances 0.000 claims description 3
- 238000001953 recrystallisation Methods 0.000 claims description 3
- 150000003839 salts Chemical class 0.000 claims description 3
- 210000002966 serum Anatomy 0.000 claims description 3
- 238000012360 testing method Methods 0.000 claims description 3
- 239000011592 zinc chloride Substances 0.000 claims description 3
- UWSONZCNXUSTKW-UHFFFAOYSA-N 4,5-Dimethylthiazole Chemical compound CC=1N=CSC=1C UWSONZCNXUSTKW-UHFFFAOYSA-N 0.000 claims description 2
- 230000004663 cell proliferation Effects 0.000 claims description 2
- 230000009977 dual effect Effects 0.000 claims description 2
- 230000005764 inhibitory process Effects 0.000 claims description 2
- 229940079593 drug Drugs 0.000 claims 1
- 238000011534 incubation Methods 0.000 claims 1
- 239000002246 antineoplastic agent Substances 0.000 abstract description 3
- 229940041181 antineoplastic drug Drugs 0.000 abstract description 3
- 239000000460 chlorine Substances 0.000 abstract description 2
- CABMTIJINOIHOD-UHFFFAOYSA-N 2-[4-methyl-5-oxo-4-(propan-2-yl)-4,5-dihydro-1H-imidazol-2-yl]quinoline-3-carboxylic acid Chemical compound N1C(=O)C(C(C)C)(C)N=C1C1=NC2=CC=CC=C2C=C1C(O)=O CABMTIJINOIHOD-UHFFFAOYSA-N 0.000 abstract 1
- BCBNHMSEQFGOFQ-UHFFFAOYSA-N NC1=C(C=CC=C1)N.[Cl] Chemical class NC1=C(C=CC=C1)N.[Cl] BCBNHMSEQFGOFQ-UHFFFAOYSA-N 0.000 abstract 1
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 206010028980 Neoplasm Diseases 0.000 description 3
- 208000005718 Stomach Neoplasms Diseases 0.000 description 3
- 230000000118 anti-neoplastic effect Effects 0.000 description 3
- 206010017758 gastric cancer Diseases 0.000 description 3
- 238000012545 processing Methods 0.000 description 3
- 201000011549 stomach cancer Diseases 0.000 description 3
- 206010009944 Colon cancer Diseases 0.000 description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 1
- -1 4,5- dimethyl thiophenes Azoles Chemical class 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 208000029742 colonic neoplasm Diseases 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F3/00—Compounds containing elements of Groups 2 or 12 of the Periodic Table
- C07F3/003—Compounds containing elements of Groups 2 or 12 of the Periodic Table without C-Metal linkages
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
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- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
- G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
- G01N33/5011—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics for testing antineoplastic activity
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Abstract
The invention belongs to technical field of chemistry and a kind of bisbenzimidazole Zn complex synthetic method of halogen substitution V types pyridine 2,6 and antitumor activity detection are disclosed, including part synthetic method and complex synthetic method, the part synthetic method is：(1) synthesis of Cl bbp parts：Polyphosphoric acids (10g) is weighed in three-necked bottle, then weighs 2,6 pyridinedicarboxylic acid (3mmol; 0.5g), poured into after 4 chlorine o-phenylenediamines (6mmol, 0.8555g) are well mixed in three-necked bottle; 180 DEG C under nitrogen protection, react 5h；Reaction pours into strong stirring in 1L frozen water while hot after terminating, and is completely dissolved rear ammonification water and adjusts pH to be suction filtration after 9 11, filter residue is washed till into neutrality, crude product is obtained after drying, with recrystallizing methanol, yield：73%.The present invention has good antitumor activity, can be prepared into anti-tumor drug.
Description
Technical field
Replace v-shaped pyridine -2,6- bisbenzimidazole Zn complex synthetic method and anti-present invention relates particularly to a kind of halogen
Tumor promotion is detected, belongs to technical field of chemistry.
Background technology
Tumour is the principal disease for threatening human health and life security, captures the life of many people, antineoplastic every year
The research and development of thing are always the focus of chemist and medicine scholar concern, find more efficient, more high selectivity and malicious secondary work
It is the Main way that antineoplastic is researched and developed with small antineoplastic.
The content of the invention
The technical problem to be solved in the present invention overcomes existing defect, and there is provided a kind of halogen substitution v-shaped pyridine -2,6- is double
Benzimidazole Zn complex synthetic method and antitumor activity detection, with good anti tumor activity in vitro, can be prepared into
Anti-tumor drug, the problem of effectively can solving in background technology.
In order to solve the above-mentioned technical problem, the invention provides following technical scheme：
The present invention provides a kind of halogen substitution v-shaped pyridine -2,6- bisbenzimidazole Zn complex synthetic method and antitumor
Activity determination, including part synthetic method and complex synthetic method, the part synthetic method is：(1) Cl-bbp parts
Synthesis：Polyphosphoric acids (10g) is weighed in three-necked bottle, then weighs 2,6- pyridinedicarboxylic acids (3mmol, 0.5g), 4- chlorine neighbour's benzene two
Poured into after amine (6mmol, 0.8555g) is well mixed in three-necked bottle, 180 DEG C under nitrogen protection, react 5h；Reaction is taken advantage of after terminating
Heat pours into strong stirring in 1L frozen water, is completely dissolved rear ammonification water and adjusts pH to be suction filtration after 9-11, filter residue is washed till into neutrality, after drying
Crude product is obtained, with recrystallizing methanol, yield：73%；(2) synthesis of Br-bbp parts：Polyphosphoric acids is weighed in three-necked bottle
(10g), then 2,6- pyridinedicarboxylic acids (3mmol, 0.5g) are weighed, after 4- bromines o-phenylenediamine (6mmol, 1.1222g) is well mixed
Pour into three-necked bottle, 180 DEG C under nitrogen protection, react 5h；Reaction pours into strong stirring in 1L frozen water while hot after terminating, completely
Ammonification water adjusts pH to be suction filtration after 9-11 after dissolving, and filter residue is washed till into neutrality, crude product is obtained after drying, with ethyl alcohol recrystallization, yield：
78%.
It is preferred that, the complex synthetic method is：(1) complex Zn (Cl-bbp) Cl2(1) synthesis：Weigh ZnCl2
Metal salt (0.0054g, 0.04mmol) is dissolved in 4mL ethanol, adds organic ligand Cl-bbp (0.0038g, 0.01mmol) second
It is put into glass sample bottle, stands at ambient temperature after alcoholic solution, mixing, solvent is slowly volatilized, solution evaporation method one week
The yellow crystals of complex 1 are obtained afterwards, are washed with ethanol, air drying；Yield：62% (in terms of Zn), infrared spectrum：
(KBr/pellet, cm-1)：3401m, 3069m, 1606m, 1579s, 1447s, 1419s, 1311s, 1237s, 1058m, 1016w,
930m, 861m, 815s, 667m；(2) complex Zn (Br-bbp) Cl2(2) synthesis：With Br-bbp (0.0042g,
Cl-bbp parts 0.01mmol) are substituted, are stored at room temperature after 4 days, filters, obtains yellow crystals, after being washed with ethanol, are dried；Production
Rate：56% (in terms of Zn), infrared spectrum (KBr/pellet, cm-1)：3435m, 1627s, 1605s, 1578s, 1478s, 1447s,
1385m, 1312s, 1237w, 1157w, 922m, 866w；
It is preferred that, the infrared spectrum the step of part synthetic method in (1) is：(KBr/pellet, cm-1)：
3193s, 1625m, 1601m, 1574m, 1460s, 1434s, 1383m, 1312m, 1155w, 1060s, 928s, 736s, 692m.
It is preferred that, the infrared spectrum the step of part synthetic method in (2) is：(KBr/pellet, cm-1)：
3190s, 1619m, 1599s, 1578s, 1458s, 1307s, 1228m, 1158w, 916s, 805s, 682s, 654m, 590m.
It is preferred that, a kind of described halogen substitution v-shaped pyridine -2,6- bisbenzimidazole Zn complex antitumor activity is examined
Survey, including tumor cell culture method and mtt assay survey cell anti-tumor activity test method, (1) described tumor cell culture side
Method is：By HCT116, it (is 10% serum and 1% pair containing volume ratio that BGC823 cells, which are inoculated in fill DMEM nutrient solutions respectively,
It is anti-) culture dish in, be positioned over 37 DEG C of cell culture incubators and (contain 5%CO2With 95% air) in be incubated, experiment every time takes and is in
The cell of logarithmic phase；(2) the mtt assay survey cell anti-tumor activity test method is：Use MTT (3- (4,5- dimethyl thiophenes
Azoles -2) -2,5- diphenyltetrazolium bromide bromides) method tested the antitumor activity of complex 1 and 2 respectively, before experiment,
Complex 1-2 uses DMSO hydrotropies respectively, is then diluted with nutrient solution, and the DMSO contents in whole solution are no more than 3 ‰；By cell
HCT116, BGC823 are inoculated on 96 orifice plates respectively, per the μ L of hole 200, and cell number is controlled (5 × 103-6.5×103Individual/
Hole)；Grow after 24h, remove old nutrient solution and be added separately to the nutrient solution containing various concentrations complex 1 or 2 accordingly
96 orifice plates in, the concentration gradient of complex is 5-50 μM, and each concentration sets 5 multiple holes.It is incubated after the corresponding period, often
MTT solution (5mg/mL) 20 μ L are added in hole, and continuation is incubated 4 hours in incubator；Take out 96 orifice plates and gently suck hole
Interior liquid, is then separately added into 150 μ L DMSO solutions per hole, shakes 5-10min on shaking table at room temperature, thing to be crystallized is complete
After fully dissolved, the OD values in each hole are detected at 492nm with ELIASA；Calculate inhibiting rate：Inhibiting rate (%)=(AControl-AExperiment)/
AControl× 100, antitumor activity result IC50Value expression, IC50It is worth medicine when 50% inhibition is reached for cell proliferation
Concentration, calculates according to inhibiting rate and obtains.
The beneficial effect that is reached of the present invention is：With good antitumor activity, anti-tumor drug can be prepared into.
Brief description of the drawings
Accompanying drawing is used for providing a further understanding of the present invention, and constitutes a part for specification, the reality with the present invention
Applying example is used to explain the present invention together, is not construed as limiting the invention.
In the accompanying drawings：
Fig. 1 is that a kind of halogen substitution v-shaped pyridine -2,6- bisbenzimidazole Zn complex described in the embodiment of the present invention is closed
Into the crystal structure of method complex 1, hydrogen atom elliptical structure figure；
Fig. 2 is that a kind of halogen substitution v-shaped pyridine -2,6- bisbenzimidazole Zn complex described in the embodiment of the present invention is closed
Into the crystal structure of method complex 2, hydrogen atom and free solvent molecule elliptical structure figure is not coordinated；
Embodiment
The preferred embodiments of the present invention are illustrated below in conjunction with accompanying drawing, it will be appreciated that preferred reality described herein
Apply example to be merely to illustrate and explain the present invention, be not intended to limit the present invention.
Embodiment：Refer to Fig. 1-2, a kind of halogen substitution v-shaped pyridine -2,6- bisbenzimidazole Zn complex of the invention
Synthetic method, including part synthetic method and complex synthetic method, the part synthetic method is：
(1) synthesis of Cl-bbp parts：Polyphosphoric acids (10g) is weighed in three-necked bottle, then weighs 2,6- pyridinedicarboxylic acids
(3mmol, 0.5g), is poured into three-necked bottle, under nitrogen protection after 4- chlorine o-phenylenediamine (6mmol, 0.8555g) is well mixed
180 DEG C, react 5h；Reaction pours into strong stirring in 1L frozen water while hot after terminating, and is completely dissolved rear ammonification water and adjusts pH for after 9-11
Suction filtration, neutrality is washed till by filter residue, crude product is obtained after drying, with recrystallizing methanol, yield：73%, infrared spectrum is：(KBr/
Pellet, cm-1)：3193s, 1625m, 1601m, 1574m, 1460s, 1434s, 1383m, 1312m, 1155w, 1060s, 928s,
736s, 692m；
(2) synthesis of Br-bbp parts：Polyphosphoric acids (10g) is weighed in three-necked bottle, then weighs 2,6- pyridinedicarboxylic acids
(3mmol, 0.5g), is poured into three-necked bottle, under nitrogen protection after 4- bromines o-phenylenediamine (6mmol, 1.1222g) is well mixed
180 DEG C, react 5h；Reaction pours into strong stirring in 1L frozen water while hot after terminating, and is completely dissolved rear ammonification water and adjusts pH for after 9-11
Suction filtration, neutrality is washed till by filter residue, crude product is obtained after drying, with ethyl alcohol recrystallization, yield：78%, infrared spectrum is：(KBr/
Pellet, cm-1)：3190s, 1619m, 1599s, 1578s, 1458s, 1307s, 1228m, 1158w, 916s, 805s, 682s,
654m, 590m；
The complex synthetic method is：
(1) complex Zn (Cl-bbp) Cl2(1) synthesis：Weigh ZnCl2Metal salt (0.0054g, 0.04mmol) is dissolved in
4mL ethanol, adds organic ligand Cl-bbp (0.0038g, 0.01mmol) ethanol solution, glass sample bottle is put into after mixing
In, stand at ambient temperature, solvent is slowly volatilized, solution evaporation method obtains the yellow crystals of complex 1 after one week, use second
Alcohol is washed, air drying；Yield：62% (in terms of Zn), infrared spectrum：(KBr/pellet, cm-1)：3401m, 3069m,
1606m, 1579s, 1447s, 1419s, 1311s, 1237s, 1058m, 1016w, 930m, 861m, 815s, 667m；
(2) complex Zn (Br-bbp) Cl2(2) synthesis：Cl-bbp is substituted with Br-bbp (0.0042g, 0.01mmol)
Part, was stored at room temperature after 4 days, filtering, obtained yellow crystals, after being washed with ethanol, dried；Yield：56% (in terms of Zn) is infrared
Spectrum (KBr/pellet, cm-1)：3435m, 1627s, 1605s, 1578s, 1478s, 1447s, 1385m, 1312s, 1237w,
1157w, 922m, 866w；
A kind of halogen substitution v-shaped pyridine -2,6- bisbenzimidazole Zn complex antitumor activity detection, including tumour are thin
Born of the same parents' cultural method and mtt assay survey cell anti-tumor activity test method,
(1) the tumor cell culture method is：By HCT116, BGC823 cells are inoculated in respectively fills DMEM nutrient solutions
In the culture dish of (being that 10% serum and 1% are dual anti-containing volume ratio), it is positioned over 37 DEG C of cell culture incubators and (contains 5%CO2With 95%
Air) in be incubated, every time experiment take the cell in logarithmic phase；
(2) the mtt assay survey cell anti-tumor activity test method is：Using MTT (3- (4,5- dimethylthiazole -2) -
2,5- diphenyltetrazolium bromide bromides) method tested the antitumor activity of complex 1 and 2 respectively, before experiment, complex
1-2 uses DMSO hydrotropies respectively, is then diluted with nutrient solution, and the DMSO contents in whole solution are no more than 3 ‰；By cell HCT116,
BGC823 is inoculated on 96 orifice plates respectively, per the μ L of hole 200, and cell number is controlled (5 × 103-6.5×103Individual/hole)；Growth
After 24h, remove old nutrient solution and the nutrient solution containing various concentrations complex 1 or 2 is added separately to corresponding 96 orifice plate
In, the concentration gradient of complex is 5-50 μM, and each concentration sets 5 multiple holes.It is incubated after the corresponding period, is added in every hole
The μ L of MTT solution (5mg/mL) 20, and continuation is incubated 4 hours in incubator；Take out 96 orifice plates and gently suck the liquid in hole,
Then 150 μ L DMSO solutions are separately added into per hole, shake 5-10min on shaking table at room temperature, after thing to be crystallized is completely dissolved,
The OD values in each hole are detected at 492nm with ELIASA；Calculate inhibiting rate：Inhibiting rate (%)=(AControl-AExperiment)/AControl× 100,
Antitumor activity result IC50Value is represented.
Inhibitory activity of the complex to colon cancer HCT116 cells：Utilize mtt assay, test human colon carcinoma HCT116 cell warps
Complex 1-2 handles the IC after 24,48,72h50Value.HCT116 cells are after the processing of complex 1 24,48,72h, IC50Value difference
For 30.0 ± 2.4,13.0 ± 2.1,7.5 ± 1.2 μM；HCT116 cells are after the processing of complex 2 24,48,72h, IC50Value difference
For 42.9 ± 2.4,18.1 ± 2.9,9.5 ± 1.1 μM, obvious time dependence is embodied, in order to be carried out pair with complex
Than testing part Cl-bbp and Br-bbp in inhibitory activity of the 48h to HCT116 cells.Part Cl-bbp and Br-bbp distinguish
Handle the IC after HCT116 cells 48h50Value is respectively 33.0 ± 2.3,29.2 ± 2.6 μM.
Inhibitory activity of the complex to human gastric cancer BGC823 cells：Human gastric cancer BGC823 cells are tested, are handled through complex 1
After 24,48,72h, IC50Value is respectively 39.1 ± 2.0,28.8 ± 3.1,15.7 ± 1.1 μM.24,48,72h are handled through complex 2
Afterwards, IC50Value is respectively 68.4 ± 5.0,43.9 ± 4.7,22.7 ± 2.5 μM, part Cl-bbp and Br-bbp processing human gastric cancer
IC after BGC823 cells 48h50Value is respectively 48.8 ± 2.8,49.1 ± 2.0 μM.
Finally it should be noted that：The preferred embodiments of the present invention are the foregoing is only, are not intended to limit the invention,
Although the present invention is described in detail with reference to the foregoing embodiments, for those skilled in the art, it still may be used
To be modified to the technical scheme described in foregoing embodiments, or equivalent substitution is carried out to which part technical characteristic.
Within the spirit and principles of the invention, any modification, equivalent substitution and improvements made etc., should be included in the present invention's
Within protection domain.
Claims (4)
1. a kind of halogen replaces v-shaped pyridine -2,6- bisbenzimidazole Zn complex synthetic method, including part synthetic method and
Complex synthetic method, it is characterised in that：The part synthetic method is：
(1) synthesis of Cl-bbp parts：Polyphosphoric acids (10g) is weighed in three-necked bottle, then weighs 2,6- pyridinedicarboxylic acids
(3mmol, 0.5g), is poured into three-necked bottle, under nitrogen protection after 4- chlorine o-phenylenediamine (6mmol, 0.8555g) is well mixed
180 DEG C, react 5h；Reaction pours into strong stirring in 1L frozen water while hot after terminating, and is completely dissolved rear ammonification water and adjusts pH for after 9-11
Suction filtration, neutrality is washed till by filter residue, crude product is obtained after drying, with recrystallizing methanol, yield：73%；
(2) synthesis of Br-bbp parts：Polyphosphoric acids (10g) is weighed in three-necked bottle, then weighs 2,6- pyridinedicarboxylic acids
(3mmol, 0.5g), is poured into three-necked bottle, under nitrogen protection after 4- bromines o-phenylenediamine (6mmol, 1.1222g) is well mixed
180 DEG C, react 5h；Reaction pours into strong stirring in 1L frozen water while hot after terminating, and is completely dissolved rear ammonification water and adjusts pH for after 9-11
Suction filtration, neutrality is washed till by filter residue, crude product is obtained after drying, with ethyl alcohol recrystallization, yield：78%.
The complex synthetic method is：
(1) complex Zn (Cl-bbp) Cl2(1) synthesis：Weigh ZnCl2Metal salt (0.0054g, 0.04mmol) is dissolved in 4mL second
Alcohol, adds organic ligand Cl-bbp (0.0038g, 0.01mmol) ethanol solution, is put into after mixing in glass sample bottle, in room
Stood under the conditions of temperature, solvent is slowly volatilized, solution evaporation method obtains the yellow crystals of complex 1 after one week, washed with ethanol,
Air drying；Yield：62% (in terms of Zn), infrared spectrum：(KBr/pellet, cm-1)：3401m, 3069m, 1606m,
1579s, 1447s, 1419s, 1311s, 1237s, 1058m, 1016w, 930m, 861m, 815s, 667m；
(2) complex Zn (Br-bbp) Cl2(2) synthesis：Cl-bbp parts are substituted with Br-bbp (0.0042g, 0.01mmol),
It is stored at room temperature after 4 days, filters, obtain yellow crystals, after being washed with ethanol, dries；Yield：56% (in terms of Zn), infrared spectrum
(KBr/pellet, cm-1)：3435m, 1627s, 1605s, 1578s, 1478s, 1447s, 1385m, 1312s, 1237w, 1157w,
922m, 866w.
2. a kind of halogen substitution v-shaped pyridine -2,6- bisbenzimidazole Zn complex synthetic method according to claim 1,
It is characterized in that：Infrared spectrum in the step of part synthetic method (1) is：(KBr/pellet, cm-1)：3193s,
1625m, 1601m, 1574m, 1460s, 1434s, 1383m, 1312m, 1155w, 1060s, 928s, 736s, 692m.
3. a kind of halogen substitution v-shaped pyridine -2,6- bisbenzimidazole Zn complex synthetic method according to claim 1,
It is characterized in that：Infrared spectrum in the step of part synthetic method (2) is：(KBr/pellet, cm-1)：3190s,
1619m, 1599s, 1578s, 1458s, 1307s, 1228m, 1158w, 916s, 805s, 682s, 654m, 590m.
4. a kind of halogen substitution antitumor work of v-shaped pyridine -2,6- bisbenzimidazole Zn complex according to claim 1
Property detection, including tumor cell culture method and mtt assay survey cell anti-tumor activity test method, it is characterised in that：
(1) the tumor cell culture method is：By HCT116, BGC823 cells are inoculated in respectively to be filled DMEM nutrient solutions and (contains
Volume ratio is 10% serum and 1% dual anti-) culture dish in, be positioned over 37 DEG C of cell culture incubators and (contain 5%CO2With 95%
Air) middle incubation, test take the cell in logarithmic phase every time；
(2) the mtt assay survey cell anti-tumor activity test method is：Use MTT (3- (4,5- dimethylthiazole -2) -2,5-
Diphenyltetrazolium bromide bromide) method tested the antitumor activity of complex 1 and 2 respectively, before experiment, complex 1-2
DMSO hydrotropies are used respectively, are then diluted with nutrient solution, and the DMSO contents in whole solution are no more than 3 ‰；By cell HCT116,
BGC823 is inoculated on 96 orifice plates respectively, per the μ L of hole 200, and cell number is controlled (5 × 103-6.5×103Individual/hole)；Growth
After 24h, remove old nutrient solution and the nutrient solution containing various concentrations complex 1 or 2 is added separately to corresponding 96 orifice plate
In, the concentration gradient of complex is 5-50 μM, and each concentration sets 5 multiple holes.It is incubated after the corresponding period, is added in every hole
The μ L of MTT solution (5mg/mL) 20, and continuation is incubated 4 hours in incubator；Take out 96 orifice plates and gently suck the liquid in hole,
Then 150 μ L DMSO solutions are separately added into per hole, shake 5-10min on shaking table at room temperature, after thing to be crystallized is completely dissolved,
The OD values in each hole are detected at 492nm with ELIASA；Calculate inhibiting rate：Inhibiting rate (%)=(AControl-AExperiment)/AControl× 100,
Antitumor activity result IC50Value expression, IC50It is worth drug concentration when 50% inhibition is reached for cell proliferation, according to
Inhibiting rate is calculated and obtained.
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