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Synthesis and Study on Physiological Activity of Acenaphthopyrazine Derivatives

Author: XingJunLing
Tutor: CuiJingNan
School: Dalian University of Technology
Course: Fine Chemicals
Keywords: DNA Antitumor Embedded agents Fluorescence Tyrosine
CLC: O626
Type: Master's thesis
Year: 2010
Downloads: 100
Quote: 0
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Abstract


Study DNA targets small organic molecules, the interaction between DNA and the cell cycle, apoptosis, and research, development of new toxicity, good selective anticancer drugs has important guiding significance. According to the reported DNA targeted molecular design theory, designed a series of DNA-targeting acenaphthene pyrazine compound 1, which is characterized by one end of the flexible side chain amino straight chain or cyclic group for electron withdrawing group and the other end to the two cyano groups as electron-withdrawing group, having a rigid ring plane of the four planes conjugated system. Compound 1 is acenaphthenequinone as raw material, bromide, ring structure, nucleophilic aromatic substitution reaction obtained. Tetrazolium salt (microculture tetrozolium, MTT) reduction method MCF-7 (human breast cancer cells) in vitro anti-tumor activity test. Compound la (3 - (2-Dimethylamino-ethylamino)-acenaphtho [1,2-b] pyrazine-8 ,9-dicarbonitrile) and 1g (3-Morpholin-4-yl-Acenaphtho [1,2-b] pyrazine- 8,9-dicarbonitrile) MCF-7 cells, IC50 values ??were 4.60 and 6.46μM, has excellent anti-tumor activity in vitro. Ultraviolet spectroscopy, fluorescence spectroscopy, circular dichroism and viscosity test methods to study the interactions between the compounds and DNA. These compounds are mainly in combination by embedding interaction with DNA. Binding constants are up more than 105 orders of magnitude, is a moderate-intensity DNA intercalator. UV fluorescence spectroscopy experiments show that such compounds have the longer emission the wavelength (λflo gt; 560 nm), higher quantum efficiency (Φf = 0.59,1 g toluene) and large Stoke displacement (ΔS gt; 130 nm) , indicating that such compounds have potential applications in the field of fluorescent probe design, optoelectronic materials. Naphthalimide fluorophore, as raw materials by a nucleophilic aromatic substitution reaction with o-bromonitrobenzene, a nitro group reduction reaction, Buchwald-Hartwig reaction of the fluorescent probe molecules, S-1 (6 - [2 - (Bis- pyridin-2-ylmethyl-amino)-phenylamino]-2-butyl-benzo [de] isoquinoline-1 ,3-dione), S-2 (6 - [2 - (2-Dimethylamino-ethylamino)-phenylamino] -2 -propyl-benzo [de] isoquinoline-1 ,3-dione). Probe S-1, S-2 H, metal ions, amino acids, etc. spectra, so that the probe detected copper ions it redshift blue shift of the fluorescence wavelength of the S-1 mercury ions, but the two metal ion fluorescence quenching compound S-1. The phenolic hydroxyl group of the probe S-2 have a certain recognition ability. With the addition of tyrosine 517 nm fluorescence intensity gradually increased, and a fluorescence emission peak at 599 nm, and gradually increased, probe the S-2 through o-phenylenediamine nitrogen and tyrosine phenol hydroxy complex to form a stable compound in the form of hydrogen bonds and to achieve recognition of tyrosine.

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CLC: > Mathematical sciences and chemical > Chemistry > Organic Chemistry > Heterocyclic compounds
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