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Application of aluminum ammonium sulfate dodecahydrate in preparation of antitumor matrix metal protease inhibitors

A technology of protease inhibitors and matrix metals, applied in the direction of antineoplastic drugs, aluminum/calcium/magnesium active ingredients, drug combinations, etc., can solve the problem of reducing the selective inhibitory ability of MMPs, and achieve strong MMPs inhibitory activity, convenient acquisition, The effect of simple structure

Inactive Publication Date: 2012-12-12
NORTHWEST UNIV(CN)
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The zinc ion chelation inhibitor structure itself reduces its selective inhibitory ability to MMPs

Method used

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  • Application of aluminum ammonium sulfate dodecahydrate in preparation of antitumor matrix metal protease inhibitors
  • Application of aluminum ammonium sulfate dodecahydrate in preparation of antitumor matrix metal protease inhibitors
  • Application of aluminum ammonium sulfate dodecahydrate in preparation of antitumor matrix metal protease inhibitors

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0037] Inhibitory effect of ammonium aluminum sulfate on MMP-16: the reaction was carried out in 50mmol / L HEPES buffer system (pH6.8), which contained 200mmol / L NaCl, 10mmol / L CaCl 2 , 20μmol / L ZnCl 2 , 10mmol / L MgCl 2 and 0.01% Brij-35. At a certain enzyme concentration, ammonium aluminum sulfate was added to the reaction mixture at different concentrations, and left at 37 °C for 30 minutes. The reaction was initiated by adding 1 μL, 200 μg / ml DQ-gelatin substrate. Inhibition efficiency was determined by comparing enzyme activity with or without inhibitors. Fluorescence was detected by FLX800 fluorescent microplate reader (Bio-Tek). The excitation wavelength is at 495nm and the emission wavelength is at 515nm. All experiments were performed in 96-well plates, and each measurement was corrected for background fluorescence absorbance. The measured aluminum ammonium sulfate has a good inhibitory effect on MMP-16, and its IC 50 It is 3.14 μmol / L.

Embodiment 2

[0039] Inhibitory effect of aluminum potassium sulfate on MMP-16: the reaction was carried out in a 50mmol / L HEPES buffer system (pH 6.8), which contained 200mmol / L NaCl, 10mmol / L CaCl 2 , 20μmol / L ZnCl 2 , 10mmol / L MgCl 2 and 0.01% Brij-35. At a certain concentration of enzyme concentration, potassium aluminum sulfate was added to the reaction mixture at different concentrations, and left at 37 °C for 30 minutes. The reaction was initiated by adding 1 μL, 200 μg / ml DQ-gelatin substrate. The inhibition efficiency was determined by comparing the enzyme activity with or without inhibitors, and the fluorescence was detected by FLX800 fluorescent microplate reader (Bio-Tek). The excitation wavelength is at 495nm and the emission wavelength is at 515nm. All experiments were performed in 96-well plates, and each measurement was corrected for background fluorescence absorbance. The measured aluminum potassium sulfate has a good inhibitory effect on MMP-16, and its IC 50 It is 2...

Embodiment 3

[0041] Inhibitory effect of aluminum sulfate on MMP-16: the reaction was carried out in 50mmol / L HEPES buffer system (pH6.8), which contained 200mmol / L NaCl, 10mmol / L CaCl 2 , 20μmol / L ZnCl 2 , 10mmol / L MgCl 2 and 0.01% Brij-35. At a certain concentration of enzyme concentration, aluminum sulfate was added to the reaction mixture at different concentrations, and left at 37°C for 30 minutes. The reaction was initiated by adding 1 μL, 200 μg / ml DQ-gelatin substrate. The inhibition efficiency was determined by comparing the enzyme activity in the presence or absence of inhibitors, and the fluorescence was detected by FLX800 fluorescence microplate reader (Bio-Tek) with excitation wavelength at 495nm , the emission wavelength is at 515nm. All experiments were performed in 96-well plates, and each measurement was corrected for background fluorescence absorbance. It was measured that aluminum sulfate has a good inhibitory effect on MMP-16, and its IC 50 It is 1.56 μmol / L.

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Abstract

The invention discloses an application of AlNH4(SO4)2.12H2O in the preparation of antitumor matrix metal protease inhibitors. Compared with previous MMPs inhibitors, the AlNH4(SO4)2.12H2O disclosed in the invention has the advantages of strong inhibition activity to the MMPs, simple structure, low price and convenient obtaining.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, in particular to a class of anti-tumor matrix metalloproteinase inhibitors. Background technique [0002] In recent years, the research on anti-tumor matrix metalloproteinases (MMPs) has progressed rapidly, and all 23 human MMPs have been cloned. In the process of tumor cell invasion and metastasis, cancer cells first need to degrade extracellular matrix (extracellular matrix, ECM) and basement membrane (BM), and the degradation of ECM components is a necessary step for cancer cell invasion and metastasis. This degradation function is mainly performed by proteolytic enzymes, and MMPs are an important class of proteolytic enzymes, and they are the most important proteases that degrade ECM. MMPs can enhance tumor angiogenesis and promote cancer cell invasion and metastasis by degrading basement membrane and vascular matrix. Because MMPs play an important role in tumor invasion and metastasis,...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K33/06A61P35/00
Inventor 申烨华李聪房学迅杨诚周红刚田渭花蒋坤
Owner NORTHWEST UNIV(CN)
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