CN110092765A - A kind of trivalent Arsenic-bearing gold ore and its preparation method and application - Google Patents
A kind of trivalent Arsenic-bearing gold ore and its preparation method and application Download PDFInfo
- Publication number
- CN110092765A CN110092765A CN201910410328.3A CN201910410328A CN110092765A CN 110092765 A CN110092765 A CN 110092765A CN 201910410328 A CN201910410328 A CN 201910410328A CN 110092765 A CN110092765 A CN 110092765A
- Authority
- CN
- China
- Prior art keywords
- arsenic
- preparation
- gold ore
- bearing gold
- tumor
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- RQNWIZPPADIBDY-UHFFFAOYSA-N arsenic atom Chemical group [As] RQNWIZPPADIBDY-UHFFFAOYSA-N 0.000 title claims abstract description 32
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 title claims abstract description 32
- 239000010931 gold Substances 0.000 title claims abstract description 32
- 229910052737 gold Inorganic materials 0.000 title claims abstract description 32
- 229910052785 arsenic Inorganic materials 0.000 title claims abstract description 31
- 238000002360 preparation method Methods 0.000 title claims abstract description 23
- GOLCXWYRSKYTSP-UHFFFAOYSA-N arsenic trioxide Inorganic materials O1[As]2O[As]1O2 GOLCXWYRSKYTSP-UHFFFAOYSA-N 0.000 claims abstract description 33
- HJTAZXHBEBIQQX-UHFFFAOYSA-N 1,5-bis(chloromethyl)naphthalene Chemical compound C1=CC=C2C(CCl)=CC=CC2=C1CCl HJTAZXHBEBIQQX-UHFFFAOYSA-N 0.000 claims abstract description 29
- VSWDORGPIHIGNW-UHFFFAOYSA-N Pyrrolidine dithiocarbamic acid Chemical compound SC(=S)N1CCCC1 VSWDORGPIHIGNW-UHFFFAOYSA-N 0.000 claims abstract description 19
- 239000007864 aqueous solution Substances 0.000 claims abstract description 10
- 238000006243 chemical reaction Methods 0.000 claims abstract description 4
- 206010028980 Neoplasm Diseases 0.000 claims description 24
- 238000000034 method Methods 0.000 claims description 12
- 150000003235 pyrrolidines Chemical class 0.000 claims description 8
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims 1
- 239000005864 Sulphur Substances 0.000 claims 1
- YOWAEZWWQFSEJD-UHFFFAOYSA-N quinoxalin-2-amine Chemical compound C1=CC=CC2=NC(N)=CN=C21 YOWAEZWWQFSEJD-UHFFFAOYSA-N 0.000 claims 1
- 230000000259 anti-tumor effect Effects 0.000 abstract description 8
- 239000002246 antineoplastic agent Substances 0.000 abstract description 3
- 229940041181 antineoplastic drug Drugs 0.000 abstract description 3
- 239000003814 drug Substances 0.000 description 10
- -1 pyrrolidines aminodithioformic acids Chemical class 0.000 description 10
- 239000000243 solution Substances 0.000 description 9
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 8
- 201000011510 cancer Diseases 0.000 description 8
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 8
- 208000008443 pancreatic carcinoma Diseases 0.000 description 8
- 241001465754 Metazoa Species 0.000 description 7
- 210000004027 cell Anatomy 0.000 description 7
- 238000002474 experimental method Methods 0.000 description 7
- 229940079593 drug Drugs 0.000 description 6
- 238000011580 nude mouse model Methods 0.000 description 6
- 231100000419 toxicity Toxicity 0.000 description 6
- 230000001988 toxicity Effects 0.000 description 6
- 241000699660 Mus musculus Species 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 230000002401 inhibitory effect Effects 0.000 description 5
- 230000012010 growth Effects 0.000 description 4
- 239000013110 organic ligand Substances 0.000 description 4
- 201000002528 pancreatic cancer Diseases 0.000 description 4
- 210000004881 tumor cell Anatomy 0.000 description 4
- 238000000692 Student's t-test Methods 0.000 description 3
- 230000001154 acute effect Effects 0.000 description 3
- HAYXDMNJJFVXCI-UHFFFAOYSA-N arsenic(5+) Chemical compound [As+5] HAYXDMNJJFVXCI-UHFFFAOYSA-N 0.000 description 3
- 230000003833 cell viability Effects 0.000 description 3
- 150000002500 ions Chemical class 0.000 description 3
- 208000032839 leukemia Diseases 0.000 description 3
- 239000003446 ligand Substances 0.000 description 3
- 210000003887 myelocyte Anatomy 0.000 description 3
- 230000035755 proliferation Effects 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 238000012353 t test Methods 0.000 description 3
- 240000002853 Nelumbo nucifera Species 0.000 description 2
- 235000006508 Nelumbo nucifera Nutrition 0.000 description 2
- 235000006510 Nelumbo pentapetala Nutrition 0.000 description 2
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
- 108010087230 Sincalide Proteins 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 229910021529 ammonia Inorganic materials 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- 239000003560 cancer drug Substances 0.000 description 2
- 238000010609 cell counting kit-8 assay Methods 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 238000010668 complexation reaction Methods 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 230000001461 cytolytic effect Effects 0.000 description 2
- 239000012990 dithiocarbamate Substances 0.000 description 2
- 238000009169 immunotherapy Methods 0.000 description 2
- 239000007928 intraperitoneal injection Substances 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- IZTQOLKUZKXIRV-YRVFCXMDSA-N sincalide Chemical compound C([C@@H](C(=O)N[C@@H](CCSC)C(=O)NCC(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(N)=O)NC(=O)[C@@H](N)CC(O)=O)C1=CC=C(OS(O)(=O)=O)C=C1 IZTQOLKUZKXIRV-YRVFCXMDSA-N 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 206010067484 Adverse reaction Diseases 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 102100021590 Bcl-2-like protein 10 Human genes 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 206010011224 Cough Diseases 0.000 description 1
- 101100381384 Homo sapiens BCL2L10 gene Proteins 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 239000006146 Roswell Park Memorial Institute medium Substances 0.000 description 1
- WVKJRLOUCMTOOL-UHFFFAOYSA-N [As].C(=O)O Chemical compound [As].C(=O)O WVKJRLOUCMTOOL-UHFFFAOYSA-N 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 230000001464 adherent effect Effects 0.000 description 1
- 230000006838 adverse reaction Effects 0.000 description 1
- VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 1
- LULLIKNODDLMDQ-UHFFFAOYSA-N arsenic(3+) Chemical compound [As+3] LULLIKNODDLMDQ-UHFFFAOYSA-N 0.000 description 1
- DCYNAHFAQKMWDW-UHFFFAOYSA-N azane;carbamodithioic acid Chemical compound N.NC(S)=S DCYNAHFAQKMWDW-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 230000000536 complexating effect Effects 0.000 description 1
- 150000004696 coordination complex Chemical class 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- 208000021045 exocrine pancreatic carcinoma Diseases 0.000 description 1
- 239000012894 fetal calf serum Substances 0.000 description 1
- 150000004675 formic acid derivatives Chemical class 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 230000009036 growth inhibition Effects 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 201000005296 lung carcinoma Diseases 0.000 description 1
- 239000002075 main ingredient Substances 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 229910021645 metal ion Inorganic materials 0.000 description 1
- 230000000116 mitigating effect Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000005057 refrigeration Methods 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 210000001541 thymus gland Anatomy 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000004565 tumor cell growth Effects 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
- C07D295/20—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carbonic acid, or sulfur or nitrogen analogues thereof
- C07D295/21—Radicals derived from sulfur analogues of carbonic acid
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention relates to a kind of trivalent Arsenic-bearing gold ores and its preparation method and application.The complex structure formula is such as shown in (I).Preparation method includes: to mix Tetramethylenedithiocarbamic acid aqueous solution with arsenic trioxide aqueous solution, complex reaction.The complex is water-soluble state, and bio-toxicity is controllable, and anti-tumor effect is strong, can be used for preparing anti-tumor drug.
Description
Technical field
The invention belongs to Arsenic-bearing gold ore and its preparation method and application field, in particular to a kind of trivalent Arsenic-bearing gold ore and its
Preparation method and application.
Background technique
The drug therapy of tumour is one of the three big basic skills of current treatment malignant tumour.Arsenic trioxide (chemistry point
Minor: As2O3) be Chinese medicine arsenic or arsenolite main ingredient, to acute myelocyte leukaemia (APL) though treatment in state
It inside still all has received widespread attention in the world, becomes the model of Chinese medicine treatment tumor research.In China, arsenic trioxide
It is not approved only for treating acute myelocyte leukaemia, is also used to the treatment of later period of hepatocarcinoma, in addition to this, also there is researcher's spy
Arsenic trioxide is used for the treatment of other malignant tumours such as cancer of pancreas by rope.But current laboratory and clinical research shows to remove
Except acute myelocyte leukaemia, whens arsenic trioxide in treatment other malignant tumours, cannot reach satisfactory clinic
Effect is found worldwide in widespread attention for treating the arsenic preparation of tumour on the basis of arsenic trioxide.
Arsenic is traditional toxic herb, and the human body of main component arsenic trioxide on normal has significant toxicity.
And complexation reaction can occur with certain organic ligands for the trivalent arsenic ion that arsenic trioxide releases, and form low toxicity or nontoxic
Complex.Modern study shows that the complex that certain organic ligands and metal ion are formed has than independent organic ligand or gold
Belong to the stronger anti-tumor effect of ion, it is found that antitumor metal ligand complex is important tumour medicine R&D direction.
Summary of the invention
Technical problem to be solved by the invention is to provide a kind of trivalent Arsenic-bearing gold ore and its preparation method and application, with gram
Arsenic trioxide has toxicity and the bad defect of therapeutic effect of malignant tumour to clothes in the prior art.
The present invention provides a kind of trivalent Arsenic-bearing gold ore, the complex structure formula are as follows:
The complex molecule formula are as follows: C10H16AsN2S4, chemical name are as follows: two (pyrrolidines aminodithioformic acids) close arsenic
(III)。
The present invention also provides a kind of preparation methods of trivalent Arsenic-bearing gold ore, comprising:
Tetramethylenedithiocarbamic acid aqueous solution is mixed with arsenic trioxide aqueous solution, complex reaction obtains three
Valence Arsenic-bearing gold ore, wherein the molar ratio of arsenic trioxide and Tetramethylenedithiocarbamic acid is 1:4~8.
The Tetramethylenedithiocarbamic acid is ammonium pyrrolidine dithiocarbamate.
The present invention also provides a kind of trivalent Arsenic-bearing gold ores prepared by the above method.
The present invention also provides a kind of trivalent Arsenic-bearing gold ores prepared by the above method in preparation tumor
Application.Including being used to prepare treatment pancreatic cancer drug.
The present invention also provides a kind of application of above-mentioned complex in preparation tumor.Including being used to prepare treatment
Pancreatic cancer drug.
The present invention prepares above-mentioned trivalent Arsenic-bearing gold ore by following methods: ligand ammonium pyrrolidine dithiocarbamate is molten
Yu Shui (such as concentration is 100mg/ml, and 4 DEG C stored refrigerated), arsenic trioxide is dissolved in water, and (such as concentration is 1mg/ml, and 4 DEG C of refrigerations are protected
Deposit), (mass ratio, arsenic trioxide: ammonium pyrrolidine dithiocarbamate=1:5 is about 1:6 by this molar ratio, is protected in proportion
It is excessive to hold ligand molal quantity) ammonium pyrrolidine dithiocarbamate aqueous solution is added in arsenic trioxide aqueous solution, it is sufficiently mixed
It closes, complex reaction occurs in aqueous solution and generates pyrrolidines aminodithioformic acid-Arsenic-bearing gold ore.
The object of the present invention is to provide the trivalent Arsenic-bearing gold ores that can be realized effectively treatment malignant tumour.By the method for the present invention
The trivalent Arsenic-bearing gold ore of preparation has efficient characteristic of biological activity, can further apply and prepare anti-tumor drug.
More specifically, the present invention provides a kind of trivalent Arsenic-bearing gold ore that can be used for antineoplaston, precursor compounds
It is the organic ligand with arsenic ion complexing power, trivalent arsenic ion can be complexed in Tetramethylenedithiocarbamic acid, formed
Pyrrolidines aminodithioformic acid-Arsenic-bearing gold ore, the Arsenic-bearing gold ore toxicity formed after the two generation complexation reaction is controllable, has aobvious
The anti-tumor effect of work.
The present invention according to Coordinative Chemistry principle, select to have the Tetramethylenedithiocarbamic acid of metal complex effect with
Arsenic trioxide aqueous solution is mixed with complex, and it is significant anti-to show that this complex has by animal active Immunotherapy of Cancer Induced
Tumor effect.Cell experiment inhibits as a result, it was confirmed that according to pyrrolidines aminodithioformic acid-Arsenic-bearing gold ore that the present invention synthesizes
Tumor cell proliferation effect significantly increases compared with individual pyrrolidines aminodithioformic acid (ammonium) or arsenic trioxide, experiment
The tumor cell line being related to include human pancreas cancer system (SW1990, BXPC3, Mia-PACA2), Bel7402 (HepG2) and
Human lung carcinoma cell (A549)；Results of animal confirms, within the scope of experiment detectable concentration, by the pyrrolidines two of the invention synthesized
Thiocarbamic acid-Arsenic-bearing gold ore animal toxicity is controllable, can effectively inhibit animal lotus human pancreas cancer thin in safe-dosaging limits
The growth of born of the same parents' transplantable tumor.
It can be in the thio ammonia of pyrrolidines two according to pyrrolidines aminodithioformic acid-Arsenic-bearing gold ore prepared by the method for the present invention
The clinical medicine of preparation treatment malignant tumour on the basis of base formates and arsenic trioxide clinical application.
The present invention identifies the structure of trivalent Arsenic-bearing gold ore using mass-spectrometric technique.Cooperate through animal active Immunotherapy of Cancer Induced
Influence of the water-soluble preparation of object to tumor proliferation.Results of animal confirms that the trivalent Arsenic-bearing gold ore is in safe-dosaging limits
The interior growth that can effectively inhibit animal-transplanted tumor illustrates that the trivalent Arsenic-bearing gold ore toxicity synthesized by the method for the present invention is controllable, has
Significant anti-tumor activity.
Beneficial effect
Trivalent arsenic metal complex is water-soluble state in the present invention, and bio-toxicity is controllable, and anti-tumor effect is strong, can be used for making
In standby anti-tumor drug.
Detailed description of the invention
Fig. 1 be in the embodiment of the present invention 1 each group drug to the inhibiting effect comparison diagram of cell viability.
Fig. 2 is the mass spectrogram of complex of the present invention.
Fig. 3 is zoopery tumor entity figure in the embodiment of the present invention 3.
Specific embodiment
Present invention will be further explained below with reference to specific examples.It should be understood that these embodiments are merely to illustrate the present invention
Rather than it limits the scope of the invention.In addition, it should also be understood that, after reading the content taught by the present invention, those skilled in the art
Member can make various changes or modifications the present invention, and such equivalent forms equally fall within the application the appended claims and limited
Range.
The present invention tests the reagent and raw material used:
1 640 culture medium of RPMI (RPMI 1640+10% fetal calf serum)；CCK-8 (is purchased from colleague chemical company product).
Embodiment 1
Prepare pyrrolidines aminodithioformic acid-water-soluble preparation of Arsenic-bearing gold ore:
The commercially available ammonium pyrrolidine dithiocarbamate of 1g is taken, deionized water is added, is dissolved to 10ml volume, obtains 100mg/L
Concentration ammonium pyrrolidine dithiocarbamate solution, closed, 4 DEG C save backup.
The commercially available arsenic trioxide sodium chloride solution of 10mg is taken, 1mg/ml arsenic trioxide solution is obtained, closed, 4 DEG C of preservations are standby
With.
15ml volume sterile centrifugation tube is taken, 10ml arsenic trioxide solution, then arsenic trioxide in molar ratio: pyrrole is first added
It coughs up alkane ammonium dithiocarbamate=1:6 and ammonium pyrrolidine dithiocarbamate solution is added, mix well, preparing becomes pyrroles
Alkane aminodithioformic acid-water-soluble the preparation of Arsenic-bearing gold ore.
(electric spray ion source, positive/negative ion mode, sweeps level four bars flight time mass spectrum combined instrument ultra performance liquid chromatography-
Retouch range m/z 50-1000) detection solution proton quasi-molecular ions be 366.94, with molecular formula C10H16AsN2S4Molecular weight data phase
Symbol illustrates that the chemical solution major solute ingredient being made by experimental method is the trivalent Arsenic-bearing gold ore of structure formula (I).
Embodiment 2
Antitumor cytolytic activity cell experiment:
Human pancreas cancer Mia-Paca2 cell culture is in 1640+10%FBS culture solution, 5%CO2, 37 DEG C of routine cultures.96
Well culture plate, every hole are implanted into 5000 cells, after 12 hour cell adherent growth of preculture, using containing 1 μM of three oxidation respectively
+ 6 μM of two arsenic (ATO), 6 μM of ammonium pyrrolidine dithiocarbamate (APDC), 1 μM of arsenic trioxide pyrrolidines dithiocarbamates first
The 1640+10%FBS culture solution routine culture of the water-soluble preparation of sour ammonium (APDC-ATO) (indicating concentration by arsenic trioxide equivalent)
After 48 hours, using CCK-8 reagent, the every hole absorbance value (OD) of microplate reader 450nm wavelength detecting is calculated using the following equation swollen
Tumor cell growth inhibiting rate and cell viability, depression effect of the assessment drug to tumour cell.
Growth of tumour cell inhibiting rate=(ODBlank-ODExperiment)/ODBlank× 100%,
Cell viability=ODExperiment/ODBlank× 100%.
(as shown in Figure 1) as the result is shown, in the case where examining concentration conditions, independent arsenic trioxide or pyrrolidines dithiocarbamates
Ammonium formate has certain inhibitory effects on proliferation to two kinds of pancreatic carcinomas, and pyrrolidines aminodithioformic acid-arsenic is water-soluble
Preparation is noticeably greater than individual arsenic trioxide to the inhibitory effects on proliferation of both human pancreatic cancer cells or pyrrolidines two is thio
Aminoquinoxaline, APDC-ATO group have statistical difference (t-test) compared with other three groups.
Embodiment 3
Antitumor cytolytic activity zoopery:
Arsenic trioxide in molar ratio: the ammonium pyrrolidine dithiocarbamate=thio ammonia of 1:6 Extemporaneous pyrrolidines two
Base formic acid-arsenic compound (APDC-ATO) water-soluble preparation indicates compound formulation concentration with arsenic trioxide concentration.5 week old BCLB/
C thymus gland immune deficiency nude mouse, male and female are regardless of the raising of SPF environment.6 nude mices are first taken, right side omoplate is subcutaneously injected into Mia-
Paca2 human pancreatic cancer cell 1 × 107/ only, and after 3 weeks, tumour growth to~500mm3, it is conventional to put to death nude mice, tumor mass is taken, life is chosen
Long two vigorous tumor mass, are cut into the rectangular fragment of 1mm × 1mm × 1mm, and it is subcutaneous to be implanted into other 6 nude mice omoplates.When nude mice lotus knurl
Grow to~150mm3When size (2 weeks), it is randomly divided into control group (n=6) and treatment group (n=6) carries out pharmaceutical intervention: control
Group: intraperitoneal injection and the isometric physiological saline for the treatment of group's medication；Treatment group: by 10mg/Kg: arsenic trioxide equivalent is given
The water-soluble preparation of APDC-ATO, intraperitoneal injection, one time a day, and weekly treatment 5 days, continuous treatment 4 weeks；Gross tumor volume is measured every three days,
Gross tumor volume calculation formula: V=(L × W2) × 0.5, in formula, L is tumor major diameter, and W is tumor minor axis.All routinely at the 28th day
Processing takes out tumor mass, takes pictures, and retains tumor tissues.
According to the 28th day tumor volume measurement as a result, compared with the control group, the results show that drug is to treatment group nude mice
Lotus knurl growth inhibition ratio is 68.1% (P=0.003, t-test).In medication process, animal does not show significant adverse reaction, controls
Weight has mitigation to treatment group compared with the control group, but without significant statistical difference (P=0.196, t-test), shows drug at this
Toxicity animal under concentration conditions is still resistant to.
Claims (6)
1. a kind of trivalent Arsenic-bearing gold ore, which is characterized in that the complex structure formula are as follows:
2. a kind of preparation method of trivalent Arsenic-bearing gold ore, comprising:
Tetramethylenedithiocarbamic acid aqueous solution is mixed with arsenic trioxide aqueous solution, complex reaction obtains trivalent arsenic
Complex, wherein the molar ratio of arsenic trioxide and Tetramethylenedithiocarbamic acid is 1:4~6.
3. method according to claim 2, which is characterized in that the Tetramethylenedithiocarbamic acid is two sulphur of pyrrolidines
For aminoquinoxaline.
4. a kind of trivalent Arsenic-bearing gold ore that method as claimed in claim 2 is prepared.
5. a kind of trivalent Arsenic-bearing gold ore that method as claimed in claim 2 is prepared answering in preparation tumor
With.
6. a kind of application of complex as described in claim 1 in preparation tumor.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910410328.3A CN110092765A (en) | 2019-05-16 | 2019-05-16 | A kind of trivalent Arsenic-bearing gold ore and its preparation method and application |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910410328.3A CN110092765A (en) | 2019-05-16 | 2019-05-16 | A kind of trivalent Arsenic-bearing gold ore and its preparation method and application |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN110092765A true CN110092765A (en) | 2019-08-06 |
Family
ID=67448320
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201910410328.3A Pending CN110092765A (en) | 2019-05-16 | 2019-05-16 | A kind of trivalent Arsenic-bearing gold ore and its preparation method and application |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN110092765A (en) |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1471925A (en) * | 2002-08-02 | 2004-02-04 | 丛繁滋 | Arsenic contained composition for directly hard tumour medoicine feed, preparation, preparing method thereof |
| CN103408477A (en) * | 2013-08-22 | 2013-11-27 | 陈鹏飞 | Arsenic coordination compound and preparation method thereof |
| CN103588687A (en) * | 2012-11-21 | 2014-02-19 | 复旦大学附属肿瘤医院 | Copper(I) metal complex, preparation method therefor and applications thereof |
| CN103655613A (en) * | 2013-02-08 | 2014-03-26 | 复旦大学附属肿瘤医院 | Application of arsenic trioxide and water-soluble object thereof in preparing medicine for treating pancreatic cancer |
-
2019
- 2019-05-16 CN CN201910410328.3A patent/CN110092765A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1471925A (en) * | 2002-08-02 | 2004-02-04 | 丛繁滋 | Arsenic contained composition for directly hard tumour medoicine feed, preparation, preparing method thereof |
| CN103588687A (en) * | 2012-11-21 | 2014-02-19 | 复旦大学附属肿瘤医院 | Copper(I) metal complex, preparation method therefor and applications thereof |
| CN103655613A (en) * | 2013-02-08 | 2014-03-26 | 复旦大学附属肿瘤医院 | Application of arsenic trioxide and water-soluble object thereof in preparing medicine for treating pancreatic cancer |
| CN103408477A (en) * | 2013-08-22 | 2013-11-27 | 陈鹏飞 | Arsenic coordination compound and preparation method thereof |
Non-Patent Citations (7)
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Balfourier et al. | Unexpected intracellular biodegradation and recrystallization of gold nanoparticles | |
| Collins et al. | Titanium (IV) citrate speciation and structure under environmentally and biologically relevant conditions | |
| Cao et al. | Tablet-like TiO2/C nanocomposites for repeated type I sonodynamic therapy of pancreatic cancer | |
| CN106727432A (en) | A kind of Prussian blue analogue nano particle and preparation method and application | |
| Fourie et al. | Cytotoxicity of ferrocenyl–ethynyl phosphine metal complexes of gold and platinum | |
| CN113041353A (en) | Metal organic framework nano-drug, preparation method thereof and application thereof in antitumor therapy | |
| CN109549954B (en) | Phosphorus-based material preparation and preparation method and application thereof | |
| CN105713047B (en) | One eka-platinium (II) complex and its preparation method and application | |
| Qiu et al. | Auricularia auriculajudae polysaccharide-cisplatin complexes conjugated with folic acid as new tumor targeting agents | |
| Benedetti et al. | Adsorption of the cis-[Pt (NH3) 2 (P2O7)] 2−(phosphaplatin) on hydroxyapatite nanocrystals as a smart way to selectively release activated cis-[Pt (NH3) 2Cl2](cisplatin) in tumor tissues | |
| CN110403916B (en) | Nano therapeutic agent and preparation method and application thereof | |
| CN107353313A (en) | New chemical entities calcium mangafodipir and other hybrid metal complex, preparation method, composition and treatment methods | |
| CN110092765A (en) | A kind of trivalent Arsenic-bearing gold ore and its preparation method and application | |
| CN102631683A (en) | Application of functionalized nano-selenium in tumor angiogenesis inhibiting and antitumor drugs | |
| RU2319491C1 (en) | Antitumor, antibacterial and antiviral pharmaceutical composition (its variants) | |
| JP7503800B2 (en) | Enhanced efficacy of plasma therapy for cancer or tumor treatment | |
| CN116036129A (en) | Novel cGAS-STING agonist and application thereof | |
| CN110101713A (en) | A kind of application of arsenic trioxide composition | |
| CN105055447B (en) | Ferric oxide nanometer particle is used to prepare the application for improving Tarceva drug resistance medicine | |
| Cheng et al. | Folic acid mediated cisplatin magnetic nanodrug targeting in the treatment of oral squamous cell carcinoma | |
| CN103588687B (en) | A kind of monovalence copper metal complex and its production and use | |
| Wheatley et al. | Infiltration of intra-abdominal organs by ascites tumours | |
| CN110384703A (en) | Metal based on 6- thioguanine-drug coordination Nano medication and its preparation method and application | |
| CN102895669A (en) | Cis-platinum complex and preparation method thereof | |
| Yan et al. | Acidic Environment-Responsive Metal Organic Framework-Mediated Dihydroartemisinin Delivery for Triggering Production of Reactive Oxygen Species in Drug-Resistant Lung Cancer |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20190806 |