CN106432185A - Complex [Co(L1)2(H2O)] and application thereof in preparation of anticancer drugs - Google Patents

Complex [Co(L1)2(H2O)] and application thereof in preparation of anticancer drugs Download PDF

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Publication number
CN106432185A
CN106432185A CN201610818040.6A CN201610818040A CN106432185A CN 106432185 A CN106432185 A CN 106432185A CN 201610818040 A CN201610818040 A CN 201610818040A CN 106432185 A CN106432185 A CN 106432185A
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complex
room temperature
pyridine
pure
hydroxyl
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肖瑜
张菁玲
张淑华
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Guilin University of Technology
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Guilin University of Technology
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/13—Crystalline forms, e.g. polymorphs

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  • Organic Chemistry (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The invention discloses complex [Co(L1)2(H2O)] and application thereof in the preparation of anticancer drugs. A molecular formula of [Co(L1)2(H2O)] is C20H18CoN6O7, with a molecular weight of 513.33 and good bioactivity. The complex is synthesized by: (1) dissolving 0.05-0.15 g of analytically pure methyl 1-(2-pyridine)-5-hydroxyl-1H-pyrazole-3-carboxylate and 0.05-0.15 g of analytically pure cobalt acetate dihydrate in 15-20 ml of a mixed solution of anhydrous acetonitrile and analytically pure ethanol having a volume ratio of 8:2; (2) transferring to a polytetrafluoroethylene reactor, reacting at 80-90 DEG C for 60-80 h, cooling to room temperature, filtering, and naturally volatilizing and crystallizing at room temperature. [Co(L1)2(H2O)] is equivalent to cis-platinum in IC50 value for HepG2 cancer cell line and MGC80-3 cancer cell line, but far lower than cis-platinum in toxicity for HL-7702 normal hepatic cell line cells. The defects of solvent method are overcome, the process is simple and low in cost, chemical components are easy to control, repeatability is good, and the yield is high.

Description

Complex [Co (L1)2(H2O)] and prepare cancer therapy drug application
Technical field
The present invention relates to a kind of complex [Co (L1)2(H2O)] and prepare cancer therapy drug application.
Background technology
In pyrazole compound, e derivatives are most important classes in pyrazole derivatives, and its attention rate is also relatively High.E derivatives all contain a pyrazole ring, belong to five-ring heterocycles, have certain armaticity, have certain alkalescence simultaneously, Hydrogen on 4, its derivative very vivaciously it is easy to being acylated and forming beta-diketon structure, brings colourful to its derivative Physics and chemical property.Research shows, the pyrazolone compound that synthesis has chiral centre has potential pharmaceutical applications valency Value.Based on its pharmaceutical applications great potential, research how to construct the higher structure of medical value be its research focus it One.
Metal complex with 1- (2- pyridine) -5- hydroxyl -1H- pyrazoles -3- carboxylate methyl ester as Material synthesis has uniqueness Biologically active, can serve as designing synthesis there is the effective antibacterial of low toxicity of application prospect, medicine, the functional material such as antitumor Presoma, there is important potential use.
Content of the invention
The purpose of the present invention is exactly for designing pyridine synthesis-pyrazole derivatives metal complex, using solvent heat side Method synthetic technology synthetic compound [Co (L1)2(H2O)](L1=1- (2- pyridine) -5- hydroxyl -1H- pyrazoles -3- carboxylate methyl ester) and Prepare cancer therapy drug application.
Complex [Co (L according to the present invention1)2(H2O molecular formula)] is：C20H18CoN6O7, molecular weight is：513.33, There is good biologically active, its crystallographic parameter is shown in Table one, and part bond distance, bond angle are shown in Table two, the IC50 to part cancer cell Value is shown in Table three.
Table one：Complex [Co (L1)2(H2O crystallographic parameter)]
aR1=Σ | | Fo|–|Fc||/Σ|Fo|.bwR2=[Σ w (| Fo 2|–|Fc 2|)2/Σw(|Fo 2|)2]1/2
Table two：Complex [Co (L1)2(H2O part bond distance)], bond angle
Table three：Complex [Co (L1)2(H2O the)] IC to different cell lines50Value
In table：MGC30-8 is gastric carcinoma cells, and HepG2 is human liver cancer cell, and NCI-H460 is human lung carcinoma cell, BEL- 7404 is human liver cancer cell, and HL-7702 is human normal hepatic cell strain.
[Co(L1)2(H2O synthetic method)] concretely comprises the following steps：
(1) by 0.05-0.15 gram of analysis pure 1- (2- pyridine) -5- hydroxyl -1H- pyrazoles -3- carboxylate methyl ester and 0.05-0.15 Gram analyze pure two water cobalt acetates be dissolved in 15-20 milliliter volume ratio be 8：In the mixed solution of 2 anhydrous acetonitrile and the pure methyl alcohol of analysis.
(2) solution obtained by step (1) is proceeded in the reactor of polytetrafluoroethylene (PTFE), react 60-80 at 80-90 DEG C Hour, it is cooled to room temperature, filters, filtrate puts at room temperature volatilization crystallization naturally, obtains monocrystalline level complex [Co (L after 16 days1)2 (H2O)].
Instant invention overcomes the shortcoming of solvent method, there is process is simple, with low cost, chemical constituent is easily controllable, repetition Property well and yield high the advantages of.
Brief description
Fig. 1-2 is complex of the present invention [Co (L1)2(H2O structure chart)].
In figure：C- carbon atom, N- nitrogen-atoms, O- oxygen atom, Co- cobalt atom, numeral and lowercase letter atomic order Sequence number.
Fig. 3 is complex of the present invention [Co (L1)2(H2O three-dimensional structure accumulation graph)].
Specific embodiment
Embodiment 1：
The present invention relates to complex [Co (L1)2(H2O molecular formula)] is：C20H18CoN6O7, molecular weight is：513.33, tool There is good biologically active.
[Co(L1)2(H2O synthetic method)] concretely comprises the following steps：
(1) will be pure to 0.109 gram of analysis pure 1- (2- pyridine) -5- hydroxyl -1H- pyrazoles -3- carboxylate methyl ester and 0.125 gram of analysis It is 8 that two water cobalt acetates are dissolved in 15 milliliters of volume ratios：In the mixed solution of 2 anhydrous acetonitrile and the pure methyl alcohol of analysis.
(2) solution obtained by step (1) is proceeded in the reactor of polytetrafluoroethylene (PTFE), reacts 72 hours at 80 DEG C, It is cooled to room temperature, filters, filtrate puts at room temperature volatilization crystallization naturally, obtains monocrystalline level [Co (L after 16 days1)2(H2O)] coordinate Thing.
Embodiment 2：
The present invention relates to complex [Co (L1)2(H2O molecular formula)] is：C20H18CoN6O7, molecular weight is：513.33, tool There is good biologically active.
[Co(L1)2(H2O synthetic method)] concretely comprises the following steps：
(1) will be pure to 0.055 gram of analysis pure 1- (2- pyridine) -5- hydroxyl -1H- pyrazoles -3- carboxylate methyl ester and 0.065 gram of analysis It is 8 that two water cobalt acetates are dissolved in 18 milliliters of volume ratios：In the mixed solution of 2 anhydrous acetonitrile and analysis ethanol.
(2) solution obtained by step (1) is proceeded in the reactor of polytetrafluoroethylene (PTFE), reacts 60 hours at 90 DEG C, It is cooled to room temperature, filters, filtrate puts at room temperature volatilization crystallization naturally, obtains monocrystalline level [Co (L after 16 days1)2(H2O)] coordinate Thing.

Claims (2)

1. a kind of complex [Co (L1)2(H2O)] it is characterised in that complex [Co (L1)2(H2O molecular formula)] is： C20H18CoN6O7, molecular weight is：513.33, its crystallographic parameter is shown in Table one, and part bond distance, bond angle are shown in Table two；Wherein L1=1- (2- pyridine) -5- hydroxyl -1H- pyrazoles -3- carboxylate methyl ester；
Table one：Complex [Co (L1)2(H2O crystallographic parameter)]
aR1=Σ | | Fo|–|Fc||/Σ|Fo|.bwR2=[Σ w (| Fo 2|–|Fc 2|)2/Σw(|Fo 2|)2]1/2
Table two：Complex [Co (L1)2(H2O part bond distance)], bond angle
Described [Co (L1)2(H2O synthetic method)] concretely comprises the following steps：
(1) by 0.05-0.15 gram of analysis pure 1- (2- pyridine) -5- hydroxyl -1H- pyrazoles -3- carboxylate methyl ester and 0.05-0.15 gram point Analyse pure two water cobalt acetates to be dissolved in 15-20 milliliter volume ratio is 8：In the mixed solution of 2 anhydrous acetonitrile and the pure methyl alcohol of analysis；
(2) solution obtained by step (1) is proceeded in the reactor of polytetrafluoroethylene (PTFE), at 80-90 DEG C, reaction 60-80 is little When, it is cooled to room temperature, filters, filtrate puts at room temperature volatilization crystallization naturally, obtains monocrystalline level complex [Co (L after 16 days1)2 (H2O)].
2. complex [Co (L according to claim 11)2(H2O application)] is it is characterised in that complex [Co (L1)2 (H2O)] cancer therapy drug application is prepared in conduct.
CN201610818040.6A 2016-09-13 2016-09-13 Complex [Co(L1)2(H2O)] and application thereof in preparation of anticancer drugs Pending CN106432185A (en)

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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101260121A (en) * 2007-03-07 2008-09-10 卡南吉医药科技（上海）有限公司 Complex compound of heteroaromatic thiosemicarbazone and transition metal, and application thereof in preparing antineoplastic medicine
CN101885689A (en) * 2010-07-08 2010-11-17 云南大学 Fat soluble dual-core cobalt (III) anti-tumor coordination compound and preparation method thereof
CN102260293A (en) * 2011-05-04 2011-11-30 广西师范大学 Transition metal coordination compounds with oxoglaucine as ligand, synthesizing method thereof, and application thereof
CN105669723A (en) * 2016-03-23 2016-06-15 桂林理工大学 Synthesizing method of complex [Zn(L)2].(H2O) and application of complex [Zn(L)2] (H2O) to preparation of anticancer medicine

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101260121A (en) * 2007-03-07 2008-09-10 卡南吉医药科技（上海）有限公司 Complex compound of heteroaromatic thiosemicarbazone and transition metal, and application thereof in preparing antineoplastic medicine
CN101885689A (en) * 2010-07-08 2010-11-17 云南大学 Fat soluble dual-core cobalt (III) anti-tumor coordination compound and preparation method thereof
CN102260293A (en) * 2011-05-04 2011-11-30 广西师范大学 Transition metal coordination compounds with oxoglaucine as ligand, synthesizing method thereof, and application thereof
CN105669723A (en) * 2016-03-23 2016-06-15 桂林理工大学 Synthesizing method of complex [Zn(L)2].(H2O) and application of complex [Zn(L)2] (H2O) to preparation of anticancer medicine

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Application publication date: 20170222