CN102924488B - The pyrazine west not structure of alkali title complex, preparation and the purposes of one class argentiferous - Google Patents

The pyrazine west not structure of alkali title complex, preparation and the purposes of one class argentiferous Download PDF

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CN102924488B
CN102924488B CN201210313238.0A CN201210313238A CN102924488B CN 102924488 B CN102924488 B CN 102924488B CN 201210313238 A CN201210313238 A CN 201210313238A CN 102924488 B CN102924488 B CN 102924488B
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pyrazine
ethylidene
title complex
diaminoethane
base
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CN102924488A (en
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谭学杰
邢殿香
郭宁
赵云雪
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Qilu University of Technology
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Qilu University of Technology
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Abstract

The present invention relates to structure, the Preparation method and use of a class new compound.Molecular formula C<b> 14</b>H<bGreatT.Gr eaT.GT 16</b>N<bGreatT.Gr eaT.GT 6</b>Ag +x -(X -can be NO 3 -, Cl -, Br -, F -, I -deng other pharmaceutically acceptable negatively charged ion), wherein the chemistry of complex cation is called: (N 1e,N 2e)-N 1, N 2-two (1-(1-pyrazine-2-base) ethylidene)-1，2-diaminoethane closes silver-colored coordination ion, part (N 1e,N 2e)-N 1, N 2the structure of-two (1-(1-pyrazine-2-base) ethylidene)-1，2-diaminoethane is as follows:

Description

The pyrazine west not structure of alkali title complex, preparation and the purposes of one class argentiferous
technical field:
The present invention relates to Pharmaceutical Inorganic Chemistry field, be specifically related to the structure of the western not alkali title complex of pyrazine of a class argentiferous, preparation and purposes.
background technology:
Pharmaceutical Inorganic Chemistry becomes the thing that a subject is nearest 30 years.Hallmark events is cis-platinum (cisplatin) [Pt (NH 3) 2cl 2] be found to have antitumour activity.As a new branch of science, Pharmaceutical Inorganic Chemistry lays particular emphasis on the explaination of the design and synthesis of novel inorganic drug molecule, the relation of structure and energy and pharmacologically active.Since cis-platinum is as the widespread use clinically of a kind of important broad-spectrum anti-cancer drug, metal complexes is in the forward position of drug research as antitumor drug always.Although cis-platinum has extraordinary effect in treatment kinds cancer, but various toxic side effect still limits its use, in recent years, the carboplatin (carboplatin) that cis-platinum basis develops and Australia Sa Li platinum (oxaliplatin) compensate for the some drawbacks of cis-platinum, but still have much unsatisfactory place.Most of metal complexes has similar problem in fact, and their have on the one hand the important pharmaceutical use such as antibacterial, antitumor, have multiple toxic side effect on the other hand, and also these defects clinically constantly encourage medicine scholars to carry out various research just.It should be noted that the potential drug that the title complex of silver is widely studied in recent years as a class, demonstrate tempting application prospect, while mainly strong toxicity being shown to some cancer cells because of them, to the very little [W.J.Youngs of Normocellular toxicity, A.R.Knapp, P.O.Wagers, C.A.Tessier ,daltonTrans.41 (2012) 327 – 336.].This seminar successfully synthesized multiple west newly not alkaloid compound, and the basis of these compounds has been carried out their coordination ability and Research on Application Value, obtained a series of stem-winding result.Namely the present invention is a part wherein.
Summary of the invention
Content of the present invention has synthesized a series of novel complexes, the molecular formula C of novel complexes 14 h 16 n 6 ag +x -(X -can be NO 3 -, Cl -, Br -, F -, I -deng other pharmaceutically acceptable negatively charged ion), wherein the chemistry of complex cation is called: (N 1e,N 2e)-N 1, N 2-two (1-(1-pyrazine-2-base) ethylidene)-1，2-diaminoethane closes silver-colored coordination ion, part (N 1e,N 2e)-N 1, N 2the structure of-two (1-(1-pyrazine-2-base) ethylidene)-1，2-diaminoethane is as follows:
1, Structural Identification:
The positively charged ion of this serial title complex is identical, different just negatively charged ion.Scientific analysis shows, complex cation is only the active centre of title complex, and the replacing of negatively charged ion is a normal experiment being very easy to accomplish, therefore the following discussion to structure, synthetic method and activity is all with C 14 h 16 n 6 ag +nO 3 -for example.
Title complex C 14 h 16 n 6 ag +nO 3 -outward appearance be light yellow crystalline powder, fusing point 152 – 153 DEG C.Ultimate analysis shows, the percentage composition of its C, H, N, O, S is respectively (being calculated value in bracket): C, 38.23 (38.37%); H, 3.51 (3.68%); N, 22.45 (22.38%); O, 11.09 (10.95%); 1each peaking positional value (the solvent DMSO-d of HNMR 6): 9.28 (s, 2H), 9.06 (s, 2H), 8.87 (s, 2H), 3.78 (s, 4H), 2.08 (s, 6H) ppm(is shown in accompanying drawing 1). 13the each peaking positional value of CNMR (DMSO- d 6): 166.239 (C=N), 149.345 (pyrazineC), 145.828 (pyrazineCH), 145.127 (pyrazineCH), 144.516 (pyrazineCH), 53.391 (CH 2), 16.334 (CH 3) ppm(is shown in accompanying drawing 2); Quadrupole moment-flight time mass spectrum (Q-TOF-MS) analysis shows to there is C in its structure 14 h 16 n 6 ag +, corresponding m/za peak in=375.0480(accompanying drawing 3), have also discovered the protonated peak [M+H] of part in addition +, m/zb peak in=271.0107(accompanying drawing 3), and the rear quasi-molecular ions [C formed of imine linkage fracture in part 8h 13n 4] +, m/zc peak in=165.1136(accompanying drawing 3).The MasshunterB04 software that these mass spectra peaks and corresponding isotopic peak are carried by instrument can analyze the molecular formula of mating most, analytical results shows, the integrate score of target molecule is all the highest [Score (MFG, MS) of the isotopic peak of A, B, C peak and correspondence thereof is respectively 98.68,96.83 and 87.45].More than analyze the existence demonstrating on the one hand the complex cation that Ag ion is formed with part, it should be N instead of C that another aspect also demonstrates ligating atom, because coordination ion and part 13in CNMR spectrum, the chemical shift change of all types of carbon is all very little.
2, synthetic method:
Title complex C 14 h 16 n 6 ag +nO 3 -feature in synthetic method is: with part (N 1e,N 2e)-N 1, N 2-two (1-(1-pyrazine-2-base) ethylidene)-1，2-diaminoethane and AgNO 3for raw material, mixing, reflux in suitable organic solvent.
Step is as follows:
1) by part (N 1e,N 2e)-N 1, N 2-two (1-(1 ,-pyrazine-2-base) ethylidene)-1，2-diaminoethane and AgNO 3add in organic solvent, be made into the solution of suitable concn, then mix by a certain percentage, lucifuge reflux 3-5h;
2) filtered while hot, can obtain target product;
Preferably, part (N 1e,N 2e)-N 1, N 2-two (1-(1 – pyrazine-2-base) ethylidene)-1，2-diaminoethane and AgNO 3mol ratio be: 2: 1 ~ 1: 2;
Preferably, described organic solvent is selected from: methyl alcohol, ethanol, acetonitrile.
3, anti tumor activity in vitro:
By being in the A549 lung carcinoma cell of logarithmic phase growth, using 0.25% trypsin digestion cell, becoming unicellular, making concentration with the F12K nutrient solution containing 10% foetal calf serum is 1.25 × 10 7the single cell suspension of individual/L, is inoculated in 96 well culture plates by cell, every every hole 2.5 × 10 of hole 200 μ L( 3individual cell).96 porocyte culture plates are placed in CO 2in incubator, at 37 DEG C, 5%CO 2under condition, cultivate 48h.
When hole, inner cell covers with (90% is full), empirically grouping adds the complex solution (200 μ L/ hole) of various dose, make the final concentration of testing compound be respectively 5 μMs, 10 μMs, 30 μMs, 50 μMs, 100 μMs, often group establishes 3 multiple holes, cultivates 96h.
Adding 20 μ L concentration in each hole is respectively the MTT of 0.5g/L, continues to cultivate 4h, makes MTT be reduced to first a ceremonial jade-ladle, used in libation (Formazan).After the whole supernatant liquor of sucking-off, every hole adds the DMSO of 200 μ L, jolts 15min, after first a ceremonial jade-ladle, used in libation is fully dissolved, uses enzyme-linked immunosorbent assay instrument to measure the absorbancy (OD value) at 490nm place.Then calculate according to the following formula:
Cell inhibitory rate %=(control group OD value-experimental group OD value)/control group OD value × 100%
Test result shows, complex molecule is to the half-inhibition concentration of the IC50(medicine of lung cell A549) be 9.73 μMs.This shows that complex molecule has good inhibition to lung carcinoma cell, with the inhibition (IC of cis-platinum to A549 lung carcinoma cell 50=7.0 μMs) quite.
Embodiment
Content for a better understanding of the present invention, further illustrates technical scheme of the present invention below by several specific embodiment.Following examples do not limit the present invention.
Embodiment 1
Get 0.805g part (N 1e,N 2e)-N 1, N 2-two (1-(1-pyrazine-2-base) ethylidene)-1,2-quadrol is in flask, add 60mL dehydrated alcohol, heating for dissolving, then add Silver Nitrate 0.510g, with the molar ratio reaction of 1:1, be mixed in flask, shading is reacted, and return stirring is after 3 hours, heat filtering solution, obtains yellow title complex powder.Embathed by product dehydrated alcohol, after removing the reactant that may exist, dry sealing is preserved, and is target product C 14 h 16 n 6 ag +nO 3 -.
Accompanying drawing explanation
Fig. 1 is (N 1e,N 2e)-N 1, N 2-two (1-(1-pyrazine-2-base) ethylidene)-1，2-diaminoethane closes silver-colored nitrate 1hNMR spectrogram.
Fig. 2 is (N 1e,N 2e)-N 1, N 2-two (1-(1-pyrazine-2-base) ethylidene)-1，2-diaminoethane closes silver-colored nitrate 13cNMR spectrogram.
Fig. 3 is (N 1e,N 2e)-N 1, N 2-two (1-(1-pyrazine-2-base) ethylidene)-1，2-diaminoethane closes the Q-TOF-MS spectrogram of silver-colored nitrate.Three important peaks (A, B, C) are enlarged into independent spectrogram respectively.

Claims (4)

1. the pyrazine west of a class argentiferous not alkali title complex, molecular formula C 14 h 16 n 6 ag +x -, wherein X -represent NO 3 -, Cl -, Br -, F -or I -, wherein the chemistry of complex cation is called: (N 1e,N 2e)-N 1, N 2-two (1-(1-pyrazine-2-base) ethylidene)-1，2-diaminoethane closes silver-colored coordination ion, part (N 1e,N 2e)-N 1, N 2the structure of-two (1-(1-pyrazine-2-base) ethylidene)-1，2-diaminoethane is as follows: .
2. title complex as claimed in claim 1, is characterized in that, Ag in complex cation structure +with one or several atom N coordination in part.
3. the synthetic method of title complex described in claim 1, is characterized in that: with part (N 1e,N 2e)-N 1, N 2-two (1-(1-pyrazine-2-base) ethylidene)-1，2-diaminoethane and silver ions are raw material, lucifuge reflux in organic solvent methyl alcohol, ethyl acetate, methylene dichloride, ethanol or acetonitrile, filtered while hot.
4. acceptable salt, preparing the application prevented and/or treated in tumour medicine, is characterized in that: described tumour is lung cancer on title complex or its pharmacology as claimed in claim 1.
CN201210313238.0A 2012-08-30 2012-08-30 The pyrazine west not structure of alkali title complex, preparation and the purposes of one class argentiferous Expired - Fee Related CN102924488B (en)

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