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Synthetize of AR-DA-Fe(Ⅲ) and Research on Oxidation Damage of Biological Molecules by Catalyzed Hydrogen Peroxide

Author: FanZuoZuo
Tutor: WangJun
School: Liaoning University
Course: Medicinal Chemistry
Keywords: Anthraquinone Compounds Bovine Serum Albumin Deoxyribose Nucleic Acid Oxidation Damage
CLC: R914
Type: Master's thesis
Year: 2011
Downloads: 10
Quote: 0
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The interaction of metal or metal complexes with biomolecule, such as protein DNA and amino acid, can yield abnormal influence on nervous system and damage on DNA and protein directly or indirectly, also provides a starting point for the diagnosis and therapy of human disease. Anthraquinones and natural quinones are the more important class of active molecules, widespread in nature. The literatures have reported to be made in many anthraquinones anti-cancer drugs, anti-malarial drugs, and some antineoplastic agents and some of them have been used in clinical treatment.There are some anthraquinone derivatives can be the role of DNA and can be cracked in a particular position or single-stranded double-stranded DNA. This conclusion had been confirmed by the ultraviolet spectrum (UV), circular dichroism (CD) and fluorescence spectra.In this paper, the interaction of IDA-Fe, NTA-Fe and AR-DA-Fe(3-alizarin methyl amine N, N-two acetic iron) with BSA and DNA, and catalyze H2O2 BSA and DNA to oxidative damage are studied respectively. Meanwhile we identify the damage process of hydroxyl radicals ros produced. There are also studied anthraquinone compounds AR, AR-DA(Alizarin, 3-alizarin methyl amine N, N-two acetic acid) on the interaction and the H2O2 oxidative damage of BSA and DNA. This paper mainly includes the work listed as follows.1.Iron complexes catalyzed H2O2 oxidative damage of BSA and anthraquinone derivatives had an effect on H2O2 of oxidative damage.In this study, the iron complexes were synthesized and characterized. The quenching constant, forming constant, binding constant and the binding site number at room temperature were measured by fluorescence quenching equation. The damage of BSA happened under H2O2 in the presence of anthraquinone compounds and iron complexes (such as standing time of H2O2, drug concentration and H2O2 concentration) were estimated by means of UV-vis and fluorescence spectra.2.Iron complexes catalyzed H2O2 oxidative damage of DNA and anthraquinone derivatives had an effect on H2O2 of oxidative damage. First investigated the interaction between DNA and the mechanism of the compound, obtained by calculating the DNA of the compounds on the quenching mechanism, binding constant and binding sites, and through the synchronous fluorescence spectra of the compounds on DNA conformation. Followed by UV-vis spectroscopy and fluorescence spectroscopy, was investigated under the action of the compounds in the H2O2 effect on DNA damage and examine the influence of other factors (such as H2O2 standing time, drug concentration and H2O2 concentration) on the DNA molecular damage impact.3.The study also used oxidation extraction spectrophotometry IDA-Fe, NTA-Fe and AR-DA-Fe oxide generated during operation situation of reactive oxygen species hydroxyl radical was identified. Mainly the use of active oxygen scavenger diphenylcarbazide after oxidation by reactive oxygen species are in the 565nm UV-vis absorption diphenylcarbazone by ultraviolet-visible spectrophotometry to detect the solubility of total generation Diphenylcarbazone circumstances, this process can prove the existence of reactive oxygen species.This study selected 3-alizarin methyl amine-N, N-diacetic acid was synthesized from 3-alizarin methyl amine-N, N-diacetic acid iron. Through the modification of its structure, will make it better antitumor activity. In the future on the basis of the further research, anthraquinones will be used as a new type of a novel anti-tumor drug in the clinical treatment of cancer.

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