CN104844635A - Manganese and zinc metal complexes taking alocasia amazonica alkali as ligand as well as synthesis method and application of manganese and zinc metal complexes - Google Patents
Manganese and zinc metal complexes taking alocasia amazonica alkali as ligand as well as synthesis method and application of manganese and zinc metal complexes Download PDFInfo
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- CN104844635A CN104844635A CN201510303864.5A CN201510303864A CN104844635A CN 104844635 A CN104844635 A CN 104844635A CN 201510303864 A CN201510303864 A CN 201510303864A CN 104844635 A CN104844635 A CN 104844635A
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- manganese
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- alkali
- lysicamine
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- 229910052751 metal Inorganic materials 0.000 title claims abstract description 34
- 239000002184 metal Substances 0.000 title claims abstract description 33
- 229910052725 zinc Inorganic materials 0.000 title claims abstract description 32
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 title claims abstract description 30
- 239000003513 alkali Substances 0.000 title claims abstract description 29
- 239000011572 manganese Substances 0.000 title claims abstract description 29
- PWHULOQIROXLJO-UHFFFAOYSA-N Manganese Chemical compound [Mn] PWHULOQIROXLJO-UHFFFAOYSA-N 0.000 title claims abstract description 26
- 229910052748 manganese Inorganic materials 0.000 title claims abstract description 20
- 239000003446 ligand Substances 0.000 title claims abstract description 16
- 244000235115 Alocasia x amazonica Species 0.000 title abstract 4
- 238000001308 synthesis method Methods 0.000 title abstract 2
- 239000002798 polar solvent Substances 0.000 claims abstract description 23
- QVRFMRZEAVHYMX-UHFFFAOYSA-L manganese(2+);diperchlorate Chemical compound [Mn+2].[O-]Cl(=O)(=O)=O.[O-]Cl(=O)(=O)=O QVRFMRZEAVHYMX-UHFFFAOYSA-L 0.000 claims abstract description 13
- RXBXBWBHKPGHIB-UHFFFAOYSA-L zinc;diperchlorate Chemical compound [Zn+2].[O-]Cl(=O)(=O)=O.[O-]Cl(=O)(=O)=O RXBXBWBHKPGHIB-UHFFFAOYSA-L 0.000 claims abstract description 13
- DPBMWJXWUINLQT-UHFFFAOYSA-N Lysicamine Chemical compound O=C1C2=CC=CC=C2C2=C(OC)C(OC)=CC3=CC=NC1=C32 DPBMWJXWUINLQT-UHFFFAOYSA-N 0.000 claims description 39
- WKURQIYEQPIIIA-UHFFFAOYSA-N lysicamine Natural products COc1cc2CCN=C3C(=O)c4ccccc4c(c1OC)c23 WKURQIYEQPIIIA-UHFFFAOYSA-N 0.000 claims description 39
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- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 18
- 238000002156 mixing Methods 0.000 claims description 16
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- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 8
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- WPBNNNQJVZRUHP-UHFFFAOYSA-L manganese(2+);methyl n-[[2-(methoxycarbonylcarbamothioylamino)phenyl]carbamothioyl]carbamate;n-[2-(sulfidocarbothioylamino)ethyl]carbamodithioate Chemical compound [Mn+2].[S-]C(=S)NCCNC([S-])=S.COC(=O)NC(=S)NC1=CC=CC=C1NC(=S)NC(=O)OC WPBNNNQJVZRUHP-UHFFFAOYSA-L 0.000 claims description 4
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Classifications
-
- 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
- C07F3/06—Zinc compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/473—Quinolines; Isoquinolines ortho- or peri-condensed with carbocyclic ring systems, e.g. acridines, phenanthridines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/555—Heterocyclic compounds containing heavy metals, e.g. hemin, hematin, melarsoprol
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
- C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
- C07D221/04—Ortho- or peri-condensed ring systems
- C07D221/18—Ring systems of four or more rings
-
- 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
- C07F13/00—Compounds containing elements of Groups 7 or 17 of the Periodic Table
- C07F13/005—Compounds without a metal-carbon linkage
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (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 invention discloses two new manganese and zinc metal complexes taking alocasia amazonica alkali as a ligand as well as a synthesis method and an application of the manganese and zinc metal complex. The manganese and zinc metal complexes are obtained by dissolving manganese perchlorate or zinc perchlorate and alocasia amazonica alkali in a polar solvent, and carrying out a complexing reaction; the manganese and zinc metal complexes specifically can be synthesised through a solution method or a solvothermal method. The applicant finds that the two new manganese and zinc metal complexes show up superior in-vitro anti-tumour activities compared with the alocasia amazonica alkali ligand by inspecting the proliferation inhibition activities of the two new manganese and zinc metal complexes on human tumour cell strains of NCl-H460, HepG-2, DLD-1, MGC80-3 and the like, and the toxicities of the two new manganese and zinc metal complexes on human normal hepatic cells HL-7702, wherein the zinc metal complex has a low toxicity on normal cells and a good potential medicinal value, and is expected to be used for preparing various anti-tumour medicines. The structural formulas of the complex are shown in formula (I) and formula (II) specified in the description.
Description
Technical field
The present invention relates to medical art, manganese, zinc metal complexes and preparation method and use thereof that to be specifically related to lysicamine alkali be part.
Background technology
Lysicamine alkali (Lysicamine) belongs to isoquinoline alkaloid, extracts lysicamine alkali composition in Menispermaceae Radix Stephaniae Cepharanthae, annonaceae and nymphaeaceae plant lotus lotus leaf.Modern pharmacological research proves, lysicamine alkali has antisepsis and anti-inflammation and antineoplastic action.From the current research conditions to lysicamine alkali, mainly comprise two aspects: in the plant on the one hand for never equal genus (as Aristolochia contorta root, Spina Date Seed, Radix Stephaniae Cepharanthae cauline leaf and Magnolia bilola etc.), dose and composition analysis are carried out to it, on the other hand, then the research to its pharmacologically active particularly anti-tumor activity, investigator has conducted extensive research the pharmacological action of lysicamine alkali and has obtained greater advance, experiment proves that lysicamine alkali has antitumor significantly, antiviral, bacteriostatic activity, antimycotic and antibacterium breeding effect, recent research is then directed to its antitumous effect and AntiHIV1 RT activity effect more, find that the growth of lysicamine alkali to human hepatocarcinoma cells HepG-2 and lung carcinoma cell NCI-H460 has significant restraining effect, the apoptosis of cancer cells can be brought out, and the comparatively discussion of system has been carried out to its mechanism of action.
Inorganic drug research based on medical active part is becoming hot research field along with the flourish of bio-inorganic chemistry in recent years.In order to there be the innovation and breakthrough of essence, based on one of the transition metal metal complexes main focus becoming research of active skull cap components.These metallic elements generally refer to and are positioned at the periodic table of elements period 4 and are manganese-Mn (II), the iron-Fe (II), cobalt-Co (II), nickel-Ni (II), copper-Cu (II), zinc-Zn (II) etc. of micro elements needed by human.The trace existence in the human body or organism of health of this dvielement but extensively distributes, and they are by being combined with protein or some organic group coordination, form the biomolecules such as enzyme, hormone or VITAMIN, play crucial or important physiological action in vivo.As Mn (II) can promote plastosome substance metabolism and energy transformation, its existence can activate multiple enzymic activity; Zn (II) is the required composition of tens kinds of enzymes such as archaeal dna polymerase, and its effect has been considered to support structure but not katalysis etc.At present, still belong to blank based on the chemosynthesis of the transition metal complex of lysicamine alkali and bioactivity research.
Summary of the invention
Manganese, zinc metal complexes that it is part that the technical problem to be solved in the present invention is to provide with lysicamine alkali, and their preparation method and use.
The molecular formula of lysicamine alkali (Lysicamine) is C
18h
13nO
3, molecular weight is 291.31g/mol, and its chemical structural formula is shown below (LY of the following stated is that lysicamine aar ligand is called for short):
In this molecular structure, heterocycle atom N and carbonyl O atom have stronger coordination ability, can form following coordination mode in coordination reaction: N, O bidentate chelating mode; Coordination chelating is carried out with the quinoline N of lysicamine alkali and carbonyl O two atoms and Mn (II), Zn (II), obtain manganese metal complexes and zinc metal complexes, their structural formula is respectively as shown in following formula (I), formula (II):
The synthetic method of above-mentioned title complex is: stoichiometrically take Manganese perchlorate or zinc perchlorate and lysicamine aar ligand, be dissolved in polar solvent, and then coordination reaction is carried out in mixing, namely obtains corresponding manganese metal complexes or zinc metal complexes.Synthetic route is as follows:
In synthetic method of the present invention, the described lysicamine aar ligand as raw material can be undertaken synthesizing or extracting from corresponding medicinal plant by prior art, concrete can with reference to existing document (Bioorganic & Medicinal Chemistry, 2004,12 (2), 439-446.) be prepared; The ratio of the amount of substance of described lysicamine aar ligand and Manganese perchlorate is generally 1 ~ 3:1, and the ratio of the amount of substance of lysicamine aar ligand and zinc perchlorate is generally 1 ~ 3:1.
Specifically when synthesizing, solution method or solvent-thermal method can be adopted to synthesize.
When adopting solution method synthesis, comprise the following steps:
1) stoichiometrically take Manganese perchlorate or zinc perchlorate and lysicamine aar ligand, be dissolved in polar solvent, obtain mixing solutions;
2) react between the boiling point of gained mixing solutions in 20 DEG C to polar solvent;
3) gained reacting liquid filtering, throw out, through washing, drying, namely obtains corresponding manganese metal complexes or zinc metal complexes.
The step 1 of the method) in, polar solvent can be selection conventional in prior art, preferably adopts a kind of or two or more arbitrarily in them combination be selected from water, methyl alcohol, ethanol, acetone, dimethyl sulfoxide (DMSO), chloroform and methylene dichloride.When polar solvent be chosen as mixtures two or more in them time, the proportioning between them can be any proportioning.The consumption of described polar solvent can be determined as required, and under normal circumstances, calculate with the Manganese perchlorate of 1mmol or zinc perchlorate, total consumption of whole raw material polar solvent used is generally 10 ~ 100mL.In concrete dissolving step, Manganese perchlorate or zinc perchlorate and lysicamine aar ligand can be dissolved with polar solvent respectively, remix reacts together; Also can by additive polarity solvent again after Manganese perchlorate or zinc perchlorate and the mixing of lysicamine aar ligand.
The step 2 of the method) in, mixing solutions, whether completely by thin-layer chromatography tracing detection, is preferably carried out back flow reaction by reaction between 60 DEG C of boiling points to polar solvent, and when the time of reacting is 6 ~ 24h, productive rate can reach more than 50%; Also can as required the reaction times be controlled at more than 24h.When reacting, according to the character of reactant, suitable reaction environment can be selected, as photosensitive material and readily oxidizable substance, needing to take lucifuge and inert atmosphere conditions etc. respectively.
The step 3 of the method) in, usually adopt water, methyl alcohol, ethanol, chloroform or methylene dichloride polar solvent washing precipitate.Drying conditions can be vacuum-drying under 30 ~ 80 DEG C of conditions or constant pressure and dry.In present method, product is generally with the Form generation of precipitation, if previous step 1) add-on of Semi-polarity solvent comparatively large (upper limit as close to proportioning) or the polar solvent selected are to the solvability of product better (as dimethyl sulfoxide (DMSO), acetone, chloroform or methylene dichloride or combinations etc. two or more arbitrarily in them), then after reaction, solution may be clear state, now can by solution decompression distillation after reaction with remove portion solvent, product is separated out with crystalline form, after isolating crystal, carries out next step operation again.
When adopting solvent structure, described synthetic method is: stoichiometrically take Manganese perchlorate or zinc perchlorate and lysicamine aar ligand, add polar solvent to dissolve, gained mixing solutions is placed in container, vacuum is evacuated to after liquid nitrogen freezing, sealing by fusing, then reacts under 60 ~ 150 DEG C of conditions, namely obtains corresponding manganese metal complexes or zinc metal complexes.
In above-mentioned solvent-thermal method, polar solvent can be selection conventional in prior art, preferably adopts a kind of or two or more arbitrarily in them combination be selected from water, methyl alcohol, ethanol, acetone, dimethyl sulfoxide (DMSO), chloroform and methylene dichloride.When polar solvent be chosen as mixtures two or more in them time, the proportioning between them can be any proportioning.The consumption of described polar solvent can be determined as required, and under normal circumstances, calculate with the Manganese perchlorate of 1mmol or zinc perchlorate, total consumption of whole raw material polar solvent used is generally 0.5 ~ 30mL.In concrete dissolving step, Manganese perchlorate or zinc perchlorate and lysicamine alkali can be dissolved with polar solvent respectively, remix reacts together; Also can by additive polarity solvent again after Manganese perchlorate or zinc perchlorate and the mixing of lysicamine alkali.In the method, described container is generally heavy-walled glass pipe, and the time that mixing solutions reacts under 60 ~ 150 DEG C of conditions is generally 12 ~ 72h, and productive rate can more than 40%; Also as required the reaction times can be extended to more than 72h.React rear taking-up heavy-walled glass pipe, cooled, left standstill, namely have product to generate.Isolate product, after washing, drying, namely obtain corresponding title complex.
The present invention also comprises and is above-mentionedly preparing the application in antitumor drug with the lysicamine alkali manganese that is part, zinc metal complexes.
The present invention also comprises the above-mentioned antitumor drug prepared for effective constituent with the lysicamine alkali manganese that is part, zinc metal complexes.
The present invention with lysicamine alkali for part, the lysicamine alkali manganese with anti-tumor activity has been synthesized with transition metal manganese and zinc coordination reaction, zinc metal complexes, by investigating them to NCI-H460, HepG-2, DLD-1, the proliferation inhibition activity of the human tumor cell lines such as MGC80-3 and the toxicity of Human normal hepatocyte HL-7702, find that they show the anti tumor activity in vitro more superior than lysicamine aar ligand, wherein zinc metal complexes has lower toxicity to normal cell, there is good potential pharmaceutical use, be expected to the preparation for various antitumor drug.
Accompanying drawing explanation
Fig. 1 is the Mn that the embodiment of the present invention 1 obtains
iI-LY title complex X-ray single crystal diffraction figure;
Fig. 2 is the Zn that the embodiment of the present invention 2 obtains
iI-LY title complex X-ray single crystal diffraction figure.
Embodiment
Below in conjunction with specific embodiment, the present invention is described in further detail, and to understand content of the present invention better, but the present invention is not limited to following examples.
Embodiment 1: with solution method synthesis Mn
iI-LY metal complexes
0.15mmol Mn (ClO
4)
26H
2o is dissolved in 5mL dimethyl sulfoxide (DMSO), and 0.1mmol LY is dissolved in 10mL methyl alcohol, and after two solution mixing, at 65 DEG C, stirring and refluxing reacts 24 hours, after completion of the reaction, is down to 25 DEG C, obtains red solution; Concentrating under reduced pressure removes most of solvent, has a large amount of Precipitation, leaves standstill, and separates out, cooled and filtered, and gained precipitation, through washing, drying, obtains red crystals product (productive rate 83%).
Carry out infrared spectra, ultimate analysis, electrospray ionization mass spectrum, single crystal diffraction analysis to gained red crystals, concrete spectral characteristic is as follows:
(1) infrared spectra
IR(KBr):(Ar-H)2942(m),(C＝O)1609(m),(C＝C)158814801466(s),(C-O)14121269(vs),(C＝N)1096(s)cm
-1。
(2) ultimate analysis
Anal.Calc.(for C
56H
41Cl
8MnN
3O
17)C％:56.63；H％:3.469；N％:3.65Found.C％：7.543；H％:3.490；N％:3.73。
(3) electrospray ionization mass spectrum, ESI-MS m/z:1027.05 [Mn (LY)
2(ClO
4)]
+.
(4) X-ray single crystal diffraction is analyzed, and structure as shown in Figure 1.
Comprehensive four kinds of qualification results can determine that this product is title complex [C
56h
41cl
8mnN
3o
17].
Embodiment 2: with solution method synthesis Zn
iI-LY title complex
0.15mmol Zn (ClO
4)
26H
2o is dissolved in 5mL acetone, and 0.1mmol LY is dissolved in 10mL acetone, and after two solution mixing, at 80 DEG C, stirring and refluxing reacts 18 hours, after completion of the reaction, is down to 25 DEG C, obtains red solution; Filter this solution, filtrate reduced in volume is removed most of solvent, leave standstill, separate out, isolate red crystals, washing, drying, obtain red crystals product (productive rate 90%).
Carry out infrared spectra, ultimate analysis, electrospray ionization mass spectrum, single crystal diffraction analysis to gained red crystals, concrete spectral characteristic is as follows:
(1) infrared spectra
IR(KBr):(Ar-H)2944(m),(C＝O)1608(m),(C＝C)157814821467(s),(C-O)14121275(vs),(C＝N)1045(s)cm
-1
(2) ultimate analysis, Anal.Calc. (for C
36h
26cl
2znN
2o
14) C%:50.65; H%:2.961; N%:3.24Found.C%:51.18; H%:3.104; N%:3.32.
(3) electrospray ionization mass spectrum, ESI-MS m/z:745.05 [Zn (LY)
2(ClO
4)]
+.
(4) X-ray single crystal diffraction is analyzed, and structure as shown in Figure 2.
Comprehensive four kinds of qualification results can determine that this product is title complex [C
36h
26cl
2znN
2o
14].
Embodiment 3: solvent structure Mn
iI-LY metal complexes
In the heavy-walled glass pipe of at one end opening, add 0.1mmol Mn (ClO
4)
26H
2o and 0.1mmolLY, add 2mL chloroform again, after liquid nitrogen freezing under vacuumized conditions by opening end sealing by fusing, react 72 hours under 80 DEG C of conditions after mixing, except desolventizing after reaction, the red solid of getting gained is washed with ethanol, to remove unreacted reactant and impurity, 40 DEG C of vacuum-drying 8 hours, obtain red solid, this product is defined as title complex [C through infrared spectra, ultimate analysis test, mass spectrum, Advances in crystal X-ray diffraction
56h
41cl
8mnN
3o
17].
Embodiment 4: solvent structure Zn
iI-LY metal complexes
In the heavy-walled glass pipe of at one end opening, add 0.1mmol Zn (ClO
4)
26H
2o and 0.1mmolLY, add the mixed solvent of 1mL ethanol and 1.5mL methylene dichloride again, after liquid nitrogen freezing under vacuumized conditions by opening end sealing by fusing, react 24 hours under 100 DEG C of conditions after mixing, except desolventizing after reaction, the red solid of getting gained is washed with ethanol, to remove unreacted reactant and impurity, 40 DEG C of vacuum-drying 4 hours, obtain red solid, this product is defined as title complex [C through infrared spectra, ultimate analysis test, mass spectrum, Advances in crystal X-ray diffraction
36h
26cl
2znN
2o
14].
In order to absolutely prove manganese of the present invention, the purposes of zinc metal complexes in pharmacy, manganese metal complexes obtained for the embodiment of the present invention 1 and 2 and zinc metal complexes have been carried out proliferation inhibition activity experiment to various human tumor cell line by applicant.
1, cell strain and cell cultures
4 kinds of human tumor cell lines and the Human normal hepatocyte HL-7702 such as human lung carcinoma cell NCI-H460, human liver cancer cell HepG-2, human colon carcinoma DLD-1, gastric carcinoma cells MGC80-3 are selected in this experiment.All cells strain is all cultivated in the RPMI-1640 nutrient solution containing the little ox blood of 10wt%, 100U/mL penicillin, 100U/mL Streptomycin sulphate, puts 37 DEG C containing volumetric concentration 5%CO
2cultivate in incubator.
2, the preparation of testing compound
Purity >=95% of title complex used, be mixed with the whole solution of 20 μm of ol/L after being diluted by its DMSO liquid storage physiological buffer, wherein final concentration≤1% of solubility promoter DMSO, under testing this concentration, title complex is to the suppression degree of various growth of tumour cell.
3, cell growth inhibition test (mtt assay)
(1) tumour cell of taking the logarithm vegetative period, after tryptic digestion, the cell suspension that number concentration is 5000/mL is mixed with the nutrient solution containing 10% calf serum, be inoculated in 96 well culture plates with every hole 190 μ L, make hole, cell density to 1000 ~ 10000 to be measured (the aseptic PBS of marginal pore fills);
(2) 5%CO
2, hatch 24h for 37 DEG C, be paved with at the bottom of hole to cell monolayer, every hole adds the medicine 10 μ L of finite concentration gradient, and each concentration gradient establishes 4 multiple holes;
(3) 5%CO
2, hatch 48 hours for 37 DEG C, observe under inverted microscope;
(4) every hole adds the MTT solution (5mg/mL PBS, i.e. 0.5%MTT) of 10 μ L, continues to cultivate 4h;
(5) stop cultivating, carefully suck nutrient solution in hole, the DMSO that every hole adds 150 μ L fully dissolves first a ceremonial jade-ladle, used in libation precipitation, and after vibrator mixing, be 570nm at microplate reader wavelength, reference wavelength is the optical density value that 450nm measures each hole;
(6) zeroing hole (substratum, MTT, DMSO) is set simultaneously, control wells (the medicine dissolution medium of cell, same concentrations, nutrient solution, MTT, DMSO).
(7) according to the optical density value (OD value) recorded, judge viable cell quantity, OD value is larger, and cytoactive is stronger.Utilize the inhibiting rate of following formulae discovery drug on tumor Growth of Cells, then calculate the IC of title complex 1 to above-mentioned several tumor cell line respectively with Bliss method
50value.Its result as shown in the following Table 1.
Table 1: ligand L Y, Mn/Zn title complex are to the IC of different tumor cell line and normal cell strain
50value (μM)
From IC
50result, title complex all shows certain proliferation inhibition activity to four kinds of human tumor cell lines, gained title complex has better anticancer growth activity than part LY, although both is different title complex, but identical Anticancer Effect and Mechanism may be had, extremely contribute to the propagation suppressing some tumour cell.On the other hand, title complex Zn
iI-LY is little to Human normal hepatocyte HL-7702 cytotoxicity, its IC
50value is greater than 50 μMs, and this is a result having positive effect, shows title complex Zn
iI-LY, while the broad-spectrum anti-tumor activity that performance is certain, also has lower toxicity, i.e. title complex Zn
iI-LY has certain cytotoxic selectivity.
In sum, be part with lysicamine alkali manganese, zinc metal complexes of the present invention, aggregate performance has gone out obvious anti tumor activity in vitro and toxicity selectivity, has good potential pharmaceutical use, is expected to the preparation for various antitumor drug.
Claims (7)
1., with manganese, zinc metal complexes that lysicamine alkali is part, their structural formula is respectively as shown in following formula (I), formula (II):
2. according to claim 1 with the synthetic method of the lysicamine alkali manganese that is part, zinc metal complexes, comprise the following steps:
1) stoichiometrically take Manganese perchlorate or zinc perchlorate and lysicamine aar ligand, be dissolved in polar solvent, obtain mixing solutions;
2) react between the boiling point of gained mixing solutions in 20 DEG C to polar solvent;
3) gained reacting liquid filtering, throw out, through washing, drying, namely obtains corresponding manganese metal complexes or zinc metal complexes.
3. synthetic method according to claim 2, is characterized in that: described polar solvent is a kind of or two or more arbitrarily in them combination be selected from water, methyl alcohol, ethanol, acetone, dimethyl sulfoxide (DMSO), chloroform and methylene dichloride.
4. according to claim 1 with the synthetic method of the lysicamine alkali manganese that is part, zinc metal complexes, it is characterized in that: stoichiometrically take Manganese perchlorate or zinc perchlorate and lysicamine aar ligand, add polar solvent to dissolve, gained mixing solutions is placed in container, vacuum is evacuated to after liquid nitrogen freezing, sealing by fusing, then reacts under 60 ~ 150 DEG C of conditions, namely obtains corresponding manganese metal complexes or zinc metal complexes.
5. synthetic method according to claim 4, is characterized in that: described polar solvent is a kind of or two or more arbitrarily in them combination be selected from water, methyl alcohol, ethanol, acetone, dimethyl sulfoxide (DMSO), chloroform and methylene dichloride.
6. according to claim 1ly preparing the application in antitumor drug with the lysicamine alkali manganese that is part, zinc metal complexes.
7. with the antitumor drug prepared for effective constituent with the lysicamine alkali manganese that is part, zinc metal complexes according to claim 1.
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| 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 |
| CN104478908A (en) * | 2014-12-12 | 2015-04-01 | 广西师范大学 | Zinc and cobalt metal complex taking nantenine oxide as ligand as well as synthetic method and application thereof |
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| CN104478908A (en) * | 2014-12-12 | 2015-04-01 | 广西师范大学 | Zinc and cobalt metal complex taking nantenine oxide as ligand as well as synthetic method and application thereof |
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| CN114409707A (en) * | 2022-01-21 | 2022-04-29 | 玉林师范学院 | 8-hydroxyquinoline-N-manganese oxide complex and synthesis method and application thereof |
| CN114409707B (en) * | 2022-01-21 | 2023-10-10 | 玉林师范学院 | 8-hydroxyquinoline-N-oxide manganese complex and synthetic method and application thereof |
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