Organotin-oxygen cluster containing ferrocene pyrazole and application of cluster

A technology of ferrocene pyrazolyl and organotin, which is applied in the fields of tin organic compounds, organic chemistry, metallocene, etc., can solve the problems of damaging the immune system of animals, and the low molecular weight organotin compounds are not suitable for anticancer agents, etc. Low, low toxicity, and the effect of improving biological activity

Inactive Publication Date: 2011-06-15
ANHUI UNIVERSITY
1 Cites 11 Cited by

AI-Extracted Technical Summary

Problems solved by technology

Because low-molecular-weight organotin compounds can seriously damage the immune system o...
the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Abstract

The invention provides an organotin-oxygen cluster containing ferrocene pyrazole. The cluster is characterized in that the complexes with the following chemical formulas are prepared from a ligand 3-trifluoromethyl-5-ferrocene pyrazole acetic acid (LCOOH) and monobutyltin oxide, dibutyltin oxide and triphenyltin hydroxide respectively: [BuSnO(OOCL)]6, [Ph4Sn2O(OCH3)(OOCL)]2 and [Bu4Sn2O(OOCL)2]2.The cluster has inhibiting effects on human lung cancer cells (A549), hepatoma cells (HepG2) and mouse melanoma (B16-F10) and the inhibiting effects are obviously superior to the inhibiting effects of the control drugs 5-fluorouracil and cisplatin, so the cluster can be applied to preparing the anti-tumor drugs.

Application Domain

Tin organic compoundsAntineoplastic agents +1

Technology Topic

Image

  • Organotin-oxygen cluster containing ferrocene pyrazole and application of cluster
  • Organotin-oxygen cluster containing ferrocene pyrazole and application of cluster
  • Organotin-oxygen cluster containing ferrocene pyrazole and application of cluster

Examples

  • Experimental program(1)

Example Embodiment

[0037] The present invention is further explained in detail through the following examples, but it should be noted that the scope of the present invention is not limited by these examples.
[0038] 1. The synthesis of ligand [3-trifluoromethyl-5-ferrocenepyrazole acetic acid (LCOOH)]:
[0039] Weigh 5-ferrocenyl-3-trifluoromethylpyrazole S (6.40g, 0.02mol) and dissolve it in acetonitrile, then weigh t-BuOK (3.36g, 0.03mol) and add it to the above solution, 60 After heating at ℃ for 2h, BrCH 2 COOC 2 H 5 (6.68g, 0.04mol) was dropped into the flask drop by drop, the reaction was carried out for 4 to 5 hours after the dropping, and TLC detection showed that the reaction was basically over. Acetonitrile was distilled off under reduced pressure, and water was added to heat and reflux to hydrolyze the product. After 1.5 hours, the reaction was completed. The mixture was taken out. Under ice bath, diluted HCl (1M) was added dropwise to the above mixture to adjust the pH of the solution to weak acidity (pH=5~6) . Repeatedly extract with ethyl acetate, save the ethyl acetate layer, use anhydrous MgSO 4 Dry overnight and filter. The ethyl acetate was evaporated to obtain a yellow oil, which was separated by column chromatography. Obtained pure product 3.40g, yield 45%, MS: (EI, 70eV): MS: (EI): M/z=378.02[M + ].Anal.Calc for C 15 H 13 O 2 N 2 F 3 Fe: C 47.70, H3.39, N 7.38%; Found: C 47.62, H 3.44, N 7.41%. 1 H NMR(400MHz, CDCl 3 ): δ=4.293 (s, 5H), 4.490 (s, 4H), 5.086 (s, 2H), 6.512 (s, 1H)
[0040]
[0041] 2. Synthesis of organotin oxygen clusters
[0042] 1. [Ph 4 Sn 2 O(OCH 3 )(OOCL)] 2 Synthesis
[0043] Weigh Ph 3 SnOH (0.1472, 0.4mmol) and LCOOH (0.1512g, 0.4mmol) were placed in a 50mL round bottom flask, 25mL of benzene was added, and a small amount of water generated in the reaction was removed with an oil-water separator. After refluxing for 12 hours, the benzene was distilled off under reduced pressure to obtain a yellow solid , Dissolved in dichloromethane:methanol=2:1 (v/v), filtered, transferred to a 50mL small Erlenmeyer flask and allowed to stand still. After one week, yellow crystals were precipitated. Anal.Calcd.for C 82 H 70 N 4 O 8 F 6 Fe 2 Sn 4 : C 50.77, H 3.64, N 2.89; Found: C 50.57, H 3.655, N 2.902 (%). 119 Sn NMR(CDCl 3 ): δ=-88.243ppm.
[0044] 2. [BuSnO(OOCL)] 6 Synthesis
[0045] Weigh n-BuSnO(OH) (0.0836g, 0.4mmol) and LCOOH (0.1512, 0.4mmol) into a 50mL round bottom flask, add 25mL of benzene, use an oil-water separator to remove a small amount of water generated in the reaction, and reflux for 12h. The benzene was removed by pressure distillation to obtain a yellow oil, which was dissolved and filtered with acetonitrile, transferred to a 50 mL small Erlenmeyer flask, and allowed to stand still. After three days, yellow massive crystals were precipitated. Anal.Calcd forC 120 H 124 N 12 O 18 F 18 Fe 6 Sn 6 : C 42.25, H 3.66, N 4.93; Found: C 42.18, H 3.723, N 4.648 (%). 119 Sn NMR(CDCl3): δ=-478.1ppm.
[0046] 3. [Bu 4 Sn 2 O(OOCL) 2 ] 2 Synthesis
[0047] Weigh n-Bu 2 SnO (0.0996g, 0.4mmol) and LCOOH (0.1512, 0.4mmol) were put into a 50mL round bottom flask, 25mL of benzene was added, and a small amount of water generated in the reaction was removed with an oil-water separator. After refluxing for 12 hours, the benzene was distilled under reduced pressure to obtain a yellow oil The substance was dissolved in methanol and filtered, transferred to a 50mL small Erlenmeyer flask and allowed to stand still. After one week, yellow lumpy crystals were precipitated. Anal.Calcd.forC 96 H 120 N 8 O 10 F 12 Fe 4 Sn 4 : C 46.64; H 4.89; N 4.53; Found: C 46.48, H 4.810; N 4.312 (%). 119 Sn NMR(CDCl 3 ): δ=-200.568, -204.243ppm.
[0048] 3. In vitro anti-tumor activity of ferrocene pyrazolyl organotin oxygen clusters
[0049] MTT [3-(4,5)-bismethyl-2-thiazole-(2,5)-phenyltetrazolium bromide blue] method was used to determine the effects of derivatives on human lung cancer cells (A549) and human liver cancer The minimal inhibitory concentration (MIC) of cells (HepG2) and mouse melanoma (B16-F10).
[0050] (1) Preparation of culture medium (per liter): ①Suspension cells: one bag of RPMI-1640 culture powder (10.4g), 100 mL of newborn calf serum, 0.5 mL of penicillin solution (200,000 U/mL), streptomycin solution ( 200,000 U/mL) 0.5mL, add three distilled water to dissolve, use 5.6% NaHCO 3 Adjust the pH of the solution to 7.2-7.4, and finally dilute to 1000 mL. Filter sterilize. ②Adherent cells: Same as above, then add NaHCO 3 2.00g, HEPES 2.38g.
[0051] (2) Preparation of D-Hanks buffer (per liter): NaCl 8.00g, KCl 0.40g, Na 2 HPO 4 ·12H 2 O 0.06g, KH 2 PO 4 0.06g, NaHCO 3 0.35g. Autoclave.
[0052] (3) Preparation of trypsin solution: use D-Hanks buffer to prepare a 0.5% trypsin solution. Filter sterilization.
[0053] (4) Preparation of experimental drug solution: Dissolve the test sample with a small amount of three-distilled water to prepare a stock solution, which is generally 10 times the highest concentration of the experiment. Depending on the solubility of the compound, it can be directly dissolved in three-distilled water, or a small amount of DMSO can be used to aid the solution, and then three-distilled water can be added to dissolve. The concentration of DMSO in the culture medium should not be too large, and the final concentration of DMSO in the cell suspension per well after the addition of the drug is generally not more than 0.05%-0.1%. Store the stock solution in a refrigerator at -20°C for later use.
[0054] (5) Cultivation of human lung cancer cells (A549): adherent growth cells, routinely cultured in RPMI-1640 medium (containing 10% calf serum, 100U/mL streptomycin), placed at 37°C, 5% CO 2 Cultivate in an incubator, passaging once every 3-4 days. When passaging, first discard the original culture medium, then wash with D-Hanks buffer; then digest with 0.5% trypsin for about 30 seconds, add a small amount of fresh culture medium to stop the digestion; pipette to make the adherent cells fall off the culture bottle wall ; Pipette an appropriate amount to a fresh culture flask, and then replenish fresh culture fluid to the original volume (the volume of the culture fluid is about 1/10 of the volume of the culture flask).
[0055] (6) Cultivation of human liver cancer cells (HepG2): cells grown in suspension, routinely cultured in RPMI-1640 medium (containing 10% calf serum, 100U/mL streptomycin), placed at 37°C, 5% CO 2 Cultivate in an incubator, passaging once every 3-4 days. During subculture, transfer the culture medium in the original bottle to a centrifuge tube, centrifuge at 1000 rpm for 5 minutes, discard the original culture medium, add an equal amount of fresh culture medium, pipette evenly, transfer an appropriate amount to a fresh culture flask, and then add fresh culture medium to the original Volume (the volume of the culture medium is about 1/10 of the volume of the culture flask).
[0056] (7) Cultivation of mouse melanoma (B16-F10): the same method as that of human liver cancer cell (HepG2).
[0057] (8) Cell incubation: Take 3 types of tumor cells in the logarithmic growth phase and adjust the cell suspension concentration to 1-1.5×10 5 ML -1. Add 100μL of cell suspension to each well of 96-well culture plate, place at 37℃, 5% CO 2 Cultivate for 24h in an incubator. After culturing for 24 hours, add the drug solution according to the design.
[0058] (9) Dosing: Add the test liquid to each hole according to the concentration gradient of the final concentration, and set 6 parallel holes for each concentration. The experiment is divided into a drug test group (adding different concentrations of test drugs), a control group (only culture medium and cells, no test drug), and a blank group (only culture fluid, no cells and test drugs). Place the 96-well plate after dosing at 37°C, 5% CO 2 Cultivate for 48h in an incubator. The activity of the positive control drugs (pentafluorouracil, cisplatin) was determined according to the method of the test sample.
[0059] (10) Determination of viable cells: In a 96-well plate after 48 hours of culture, add 40 μL of MTT (4 mg/mL with D-Hanks buffer) to each well. After standing at 37°C for 4 hours, the supernatant was removed. Add 150μL DMSO to each well and shake for 5min to dissolve the formazan crystals. Finally, an automatic microplate reader was used to detect the optical density (OD value) of each well at a wavelength of 570nm.
[0060] Calculation of inhibition rate: The inhibition rate of cell growth is calculated according to the following formula:
[0061] Growth inhibition rate=(1-survival rate)×100%=[1-(OD experiment -O blank )/(OD Control -OD blank )]×100%(OD experiment Indicates the average optical density of the test drug group, OD Control Indicates the average optical density of the control group, OD blank Represents the average optical density of the control group).
[0062] Half inhibitory concentration (IC 50 ) Is defined as the drug concentration when 50% of tumor cells survive. According to the measured optical density (OD value), a standard curve of the cell growth inhibition rate was made, and the corresponding drug concentration was calculated on the standard curve. Measured IC 50 See Table 1
[0063] Table 1 The inhibitory IC of some organotin carboxylates containing ferrocene pyrazolyl on tumor cells listed in the present invention 50 Value (μg/mL)
[0064]
[0065] It can be seen that the inhibitory effects of the three complexes on A549, HepG2 and B16-F10 are significantly better than the control drugs pentafluorouracil and cisplatin, and are expected to be used in the preparation of anti-tumor drugs.
the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

no PUM

Description & Claims & Application Information

We can also present the details of the Description, Claims and Application information to help users get a comprehensive understanding of the technical details of the patent, such as background art, summary of invention, brief description of drawings, description of embodiments, and other original content. On the other hand, users can also determine the specific scope of protection of the technology through the list of claims; as well as understand the changes in the life cycle of the technology with the presentation of the patent timeline. Login to view more.
the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Similar technology patents

Simultaneous removal method of manganese and nitrate in underground water

ActiveCN107082489ALow infrastructure and operating costsImprove biological activityWater treatment compoundsWater contaminantsIonChemistry
Owner:XI'AN UNIVERSITY OF ARCHITECTURE AND TECHNOLOGY

Pesticide composition containing imidacloprid

InactiveCN103734171AGood slow releaseImprove biological activityBiocideFungicidesSheath blightHigh activity
Owner:BEIJING YOLOO BIO TECH CORP

Amphiphilic amido inulin and preparation method thereof

Owner:YANTAI INST OF COASTAL ZONE RES CHINESE ACAD OF SCI

Classification and recommendation of technical efficacy words

  • Improve biological activity
  • Raw materials are cheap and easy to get

Sol-gel method for preparing earth silicon/titanic oxide hollow microballoon

InactiveCN101274246AFlexible production processRaw materials are cheap and easy to getPolystyrene microsphereSol-gel
Owner:SHANGHAI INST OF CERAMIC CHEM & TECH CHINESE ACAD OF SCI
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products