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Synthesis and Pharmacology Activeness Study of Chromone Derivatives and Their Complexes Based on Magnetic Nanoparticles as Carrier

Author: WangBaoDui
Tutor: YangZhengYin
School: Lanzhou University
Course: Inorganic Chemistry
Keywords: Metal complexes Graduate thesis Lanzhou University Iron oxide Lanthanide complexes Insert effect Ligand Drug Carriers Diethylenetriamine pentaacetic acid Chromone
CLC: O641.4
Type: PhD thesis
Year: 2008
Downloads: 280
Quote: 0
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Abstract


Malignant tumor is a common disease that threatens the human heath. At present, the mortality rate induced by malignant tumor is at the second places in all disease, followed the cardiovascular disease. The chemistry therapy is still the mostly means in all methods that cure tumour. However, many drugs used in clinic suffer from several drawbacks: high toxicity, low solubility, poor target character and short blood circulation. In order to solve these problems, on the one hand, people are struggling to synthesize the new drugs that have high cure effect to tumour cells and low toxicity to normal cells; on the other hand, drug delivery system are used to decrease the toxicity and enhance the targeted ability of the drugs. In this work, the chromone derivatives that have high anticancer activity and low toxicity to normal cells are used as ligand to synthesize the metal complexes. At the same time, we use the magnetic nanoparticles as drug carrier to delivery the anticancer drug.This paper is divided into four parts:1. It was given a brief review of the research progress about anticancer drug. At the same time, the preparation and application of magnetic nanoparticles used as drug carrier were summarized.2. Using iron oxide and gold-iron oxide nanoparticles, we synthesized two drug carriers. These two drug carriers can control release the chromone and Cisplatin, respectively.3. Iron oxide nanoparticles were successfully introduced into the framework of Gd（DTPA）2-. The advantages of this work exhibit two aspects: （1） enhanced the targeted ability of Gd （DTPA）2-, （2） increased the spin-lattice relaxation time of Gd （DTPA）2-. Due to iron oxide nanoparticles can realize the T2 imagine, the MRI agent synthesized in this work is a multifunction agent. Another work is synthesis two novel MRI agents that use chromone to modify the Gd （DTPA）2-. Because compounds containing chromone framework have good anticancer activity. Using these compounds to modify the Gd （DTPA）2-, we can obtain bifunctional MRI agents that bear the survey and cure function. 4. In order to seek the new drugs that have high cure effect to tumour cells and low toxicity to normal cells, eleven chromones Schiff-base ligands and forty corresponding metal complexes have been synthesized and characterized on the basis of elemental analyses, molar conductivities, IR spectra, 1H NMR spectra and crystal structure. We investigate the interaction mode of these compounds with CT-DNA. The experiment results suggest that these compounds can bind DNA by intercalation mode, but binding affinities of these compounds to DNA are much higher than ligand. Cytotoxic activities experiments in vivo suggest that these compounds exhibit good activities to tumour cells in our measure range.

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CLC: > Mathematical sciences and chemical > Chemistry > Physical Chemistry ( theoretical chemistry ),chemical physics > Structural Chemistry > Complex chemistry ( coordination chemistry )
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