Use of two (quinazolin-4-yl) diselenide compounds in the preparation of anticancer drugs

A kind of technology of bisquinazoline and compound, applied in the field of anticancer biological activity of antitumor drug diselenide

Inactive Publication Date: 2015-09-23
LUDONG UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] The compound bis(quinazolin-4-yl) diselenide involved in this patent application is a known compound, and its CAS number is 87356-36-3. It uses 4-chloroquinazoline as raw material and sodium selenium hydride in tetrahydrofuran and ethanol Reaction in a mixed solvent for 12 hours, yield 50%, no activity test involved (Harjit S., Nageshwar M. Indian J. Chem. Sect. B. 1983, 22(4): 328-330)

Method used

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  • Use of two (quinazolin-4-yl) diselenide compounds in the preparation of anticancer drugs
  • Use of two (quinazolin-4-yl) diselenide compounds in the preparation of anticancer drugs
  • Use of two (quinazolin-4-yl) diselenide compounds in the preparation of anticancer drugs

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0020] Embodiment 1, the synthesis of two (quinazolin-4-yl) diselenides.

[0021] In a three-necked flask equipped with a reflux condenser and a thermometer, add 0.51g (2.5mmol) Na 2 Se 2 Add 0.83g (5.0mmol) 4-chloroquinazoline in batches in the ethanol solution of the above, add in about 1 hour, continue reflux reaction 17 hours, cooling, adjust system pH value with glacial acetic acid to be 5, reaction solution precipitation, use DMF -H 2 O(V DMF :V H2O =2.5:1) Recrystallized to obtain 0.46 g of orange-red solid, m.p.: 260-262°C, yield 44.2%. IR (KBr) v: 3140.8, 3055.6 (v Ar-H ), 1617.2-1466.4 (quinazoline skeleton vibration), 838.2 (δ Ar-H ) cm -1 . 1 H NMR (DMSO- d 6 , 600 MHz) δ: 8.61 (t, J =7.8Hz, 2H, quinazoline H-7), 8.21 (t, J =7.8Hz, 2H, quinazoline H-6), 7.99 (d, J =8.4Hz, 2H, quinazoline H-5), 7.76 (d, J =8.4Hz, 2H, quinazoline H-8), 7.66 (s, 2H, quinazoline H-2). 13 C NMR (DMSO- d 6 , 150 MHz) δ: 127.6 (quinazoline C-5), 129.5 (quinazoline C-6), 1...

Embodiment 2

[0022] Example 2. Determination of inhibition of bis(quinazolin-4-yl)diselenide on the proliferation of human breast cancer cell line MDA-MB-435.

[0023] Test method: the drug was dissolved in DMSO to prepare various concentrations, and each concentration was repeated three times; MDA-MB-435 cells were digested to make a suspension 4×10 4 cells / mL, take 10 mL and add it to a large petri dish, and after 24 hours adhere to the wall, add the drug treatment; after 24 hours, randomly take 2 dishes to take pictures and record the state of the cells; suck out the original medium and replace it with the drug-containing medium (10 %FBS 1640) for 72 hours; add 1.5 mL of trypsin, digest for 4 minutes, add the original drug-containing medium to stop digestion, mix well, count the number of cells, take the average value, and calculate the inhibition rate.

[0024] Test results: After testing, when the concentration of bis(quinazolin-4-yl)diselenide was 10 μmol / L, the inhibition rate of MD...

Embodiment 3

[0025] Example 3. The morphological effects of bis(quinazolin-4-yl)diselenide on human breast cancer cell MDA-MB-435 for 12, 36 and 72 hours.

[0026] Test method: After the test cells were treated with DMSO (negative control), oxaliplatin (positive control), and the compound of formula (I), they were placed in a 96-well plate. Under L, the drug acts for 12 hours, 36 hours, and 72 hours, and the changes in cell morphology are observed with an inverted microscope at 100 times magnification.

[0027] Test results: It can be seen from the morphological observation that when the concentration of bis(quinazolin-4-yl) diselenide is 10 μmol / L, the effect on MDA-MB-435 cells after 12, 36, and 72 hours, The cell morphology changed significantly, which was more significant than that of the positive control drug oxaliplatin, showing extremely high anticancer activity.

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Abstract

The invention discloses di(quinazoline-4-group)diselenide (which is an antitumor drug) or a pharmaceutically acceptable salt thereof which is a compound shown in a structural formula described in the specification. According to the invention, di(quinazoline-4-group)diselenide is synthesized from 4-chlorinated quinazoline, sodium diselenate or lithium diselenate in the presence of absolute ethyl alcohol serving as a solvent. The compound and the pharmaceutically acceptable salt thereof disclosed by the invention can be used for treating and preventing various benign tumors or malignant tumors, in particular have excellent multiplication inhibitory effect and good anti-cancer activity to the non-small cell lung cancer and breast cancer cells.

Description

technical field [0001] The invention belongs to organic selenium nitrogen-containing heterocyclic quinazoline drugs, in particular to the anticancer biological activity of antitumor drug bis(quinazolin-4-yl)diselenide. Background technique [0002] In recent years, a large number of research data have shown that quinazoline compounds exhibit good biological activities, especially in inhibiting the phosphorylation of EGF receptors and their tyrosine kinases. There are a large number of literature, patents, papers and other reports every year. In terms of medicine, commercialized Iressa (ZD1839), Tarceva (OSI-774), PD153035, PD169414, etc. have inhibitory effects on EGFR, thereby exhibiting anticancer activity, as well as antimalarial, antitumor and antiHIV activities. Quinazoline small molecule compounds can bind to EGFR with high selectivity and are potent tyrosine kinase inhibitors. Clinical studies have shown that these drugs can make cells stay in G 1 Expect. In terms ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K31/517A61P35/00A61P35/02
Inventor 刘刚黄银久孙林刘春萍徐胜广刘希光温全武
Owner LUDONG UNIVERSITY
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