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Synthesis and Biological Activities of Genistein Chemically Modified Compounds

Author: LiuRong
Tutor: DengZeYuan;CaoShuWen
School: Nanchang University
Course: Of Food Science
Keywords: Genistein Chemically modified Antioxidant activity BSA ctDNA Anti-cancer activity
CLC: R96
Type: PhD thesis
Year: 2009
Downloads: 325
Quote: 0
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Abstract


Genistein (5,7,4 '- genistein) is widespread in nature phytoestrogen isoflavones, a variety of physiological activity for the prevention of breast cancer, prostate cancer, cardiovascular disease, and menopausal syndrome. However, genistein lipophilic and hydrophilic weak, there is a strong first-pass effect, result in its bioavailability is low, it is difficult to achieve the purpose of treating disease clinical application. Therefore, this thesis genistein lead compound, its the hydroxyl chemical structure modified, new chemical modification of genistein Antioxidant activity, as well as with bovine serum albumin (BSA) and calf thymus the interaction between DNA (ctDNA) and anti-cancer activity screening. To improve the solubility of genistein to improve their targeting, blocking its first pass effect of the departure, the paper is targeted to select lactose and ferulic acid genistein glycosylation and esterification modification. The use of phase transfer catalysis initial selective synthesis of three genistein galactosidase modifications - genistein 4'-O-beta-topiramate breast-feeding glucoside, dye lignin 7-O-beta-topiramate breast-feeding glycoside and dyes the lignin 7,4 '- di-O-beta-pyrazol glycoside of lactation; using Schotten-Bamann reaction synthesis obtained the two genistein esterification modification was - genistein - acetyl ferulates and dye lignin 7 , 4'-di - acetyl ferulic acid esters, and the optimization of the synthesis reaction conditions. All new compounds were characterized by IR, MS, , 1 H NMR and 13 C NMR structures were confirmed. The genistein and Chemical Modification of scavenging DPPH · and hydroxyl free radicals and inhibiting superoxide radicals and protect DNA from hydroxyl radical damage, a comparative study. Genistein modified by glycosylation and esterification, Clear DPPH · and hydroxyl free radicals have improved, and the esterification modifications scavenging and stronger than glycosylation modifications. Genistein increased ability to inhibit superoxide radicals by esterification modified glycosylation modification; due to self-oxidation effects, genistein galactosidase modifications of superoxide radical inhibition rate were lower than its parent aglycone, even negative suppression. Genistein and its chemical modifications with a strong protect DNA from hydroxyl radical damage ability, its mechanism of action is not only related to the ability of compounds clear the hydroxyl radical, may be affected by other factors. The simulation animal body under physiological conditions, the use of UV - visible spectroscopy and fluorescence spectroscopy genistein and its chemical modifications with BSA. The results showed that genistein galactosidase and esterification modifications are intrinsic fluorescence quenching of BSA can. Genistein galactosidase; genistein esterified modifications quenching of fluorescence of BSA BSA fluorescence quenching mechanism for the joint action of the static quenching compounds inner filter effect, it is a static and dynamic sudden off coexist only in low concentrations static quenching. Compound with BSA binding occurs spontaneously. Genistein after modification by esterification with BSA binding capacity enhancement, and glycosylation modification is not conducive to the binding of the compound with BSA. Inferred based on the thermodynamic parameters, genistein and its mono-substituted galactosidase modification and BSA binding force between the hydrophobic interaction based; genistein 7 - acetyl ferulic acid mainly to the electrostatic force; and two disubstituted modifications are mainly the result of the role of hydrogen bonds and van der Waals forces. F (o | ¨) rster energy transfer theory to calculate the distance genistein and Chemical Modification and BSA binding role, the results show that the non-radiative energy transfer between the BSA and the compound. While taking advantage of the synchronous fluorescence spectrometry, genistein and its chemical modification on the conformation of BSA. Other chemical modifications with BSA binding between genistein and genistein 7-O-beta-pyran-galactosidase so that the conformation of BSA change the conformation of BSA are not generated. In order to study of genistein its chemical modification and interaction of calf thymus DNA (ctDNA), for the first time established genistein prime 7-O-beta-pyran-galactosidase ctDNA complex structural model, and molecular dynamics simulations of the dynamic effects of the interaction between them; ultraviolet spectroscopy, fluorescence spectroscopy and viscosity method to explore the possible role of genistein and Chemical Modification and ctDNA between and calculate the binding constant . The results showed that genistein galactosidase modifications were mainly groove binding to DNA, genistein 7 - acetyl ferulic acid and ctDNA has a strong role in the binding constants for the 2.81 × 10 < sup> 6 L mol -1 binding mode for insert into effect; genistein 7,4 '- 2 - acetyl ferulic acid ctDNA weak , the binding constant of 1.19 × 10 4 L · mol -1 , the main groove combination. Ethidium bromide (EB) as a fluorescent probe tracers interaction with DNA, fluorescence screening of the anti-cancer activity of genistein galactosidase modifications; MTT assay and further investigated two The genistein substituted lactosides on human hepatoma SMMC-7721 cells and human breast cancer MCF-7 cell growth inhibition. The results show that the the MTT staining fluorescence screening method results in vitro screening results are consistent; genistein 4'-and 7 - positions after lactose glycosylation modification anti-human hepatoma SMMC-7721 cells and anti-human breast cancer cells MCF-7 activity were significantly improved.

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