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Studied On The Interaction Of DNA With Small Molecules And Structural Analogues Using Spectrometric Methods And Molecular Modeling

Posted on:2015-07-04Degree:MasterType:Thesis
Country:ChinaCandidate:L J WangFull Text:PDF
GTID:2284330431492757Subject:Analytical Chemistry
Abstract/Summary:PDF Full Text Request
DNA is not only the carrier of biological genetic information, but also a majortarget for small molecules such as anticancer and antiviral drug. So the study ofDNA in the field of life science is extremely important. The effect of drugs and itsstructural analogues on the physical and chemical properties of DNA can change thegene replication and transcription. So researching on the interaction of smallmolecules with DNA can not only find out the binding mode of carcinogenic orcancer drugs with DNA, but also explore the toxicity and pharmacological ofcarcinogenic and anticancer. Hence, it is of great significance for design andsynthesis new drug.This article mainly uses the ultraviolet visible spectrum, fluorescence spectrumand molecular docking methods to study the interactions between structuralanalogues and fsDNA. This paper mainly includes the following four parts:(1)reviews research the status quo of the interaction of biological macromolecules DNAwith small molecular;(2) studies on the interaction of isomeric derivatives and DNAwith spectrometric methods;(3) researches the interaction of norfloxacin andanti-cancer drugs as FNC and the application of detecting FNC;(4) the summaryThis research topic mainly studies the interactions between Cannabinol,Fluorazone series,3-methoxy-1,2-naphthoquinone analogues with fsDNA,respectively. According to fluorescence spectra, the results indicated that they wereable to make the fluorescence quenching of AO-DNA, and the quenchingmechanism is a static quenching type. Then the binding constant, binding sitesnumber, the thermodynamic parameters and other data at different temperatures weremeasured according to the double-logarithm regression equation and Van’t Hoffequation. The results showed that the main interaction forces between cannabinoland DNA were hydrophobic interaction; for fluorazone series, the main interactionforces of SL-a with DNA were hydrophobic interaction and electrostatic force, andfor SL-b, SL-c, SL-d are mainly hydrogen bonding and van der waals force; the main interaction forces of3-methoxy-1,2-naphthoquinone analogues such as a, b, c,d, e, f with DNA were hydrophobic interaction forces. Meanwhile electrostaticforces were existed also for b, c, e and f. These studies also show their binding modewith DNA may be intercalative binding, also with molecular docking methods toexplain the main binding sites. Upon binding to fsDNA, the chromophore ofCannabinol, Fluorazone series,3-methoxy-1,2-naphthoquinone analogues can slideinto the A–T rich region of fsDNA. The interaction of norfloxacin and FNC:analytical application for determination of FNC was also studied. The linear range ofdetection is1.29~36.20μg·mL-1.
Keywords/Search Tags:Structural analogues, DNA, Fluorescence spectroscopy, Moleculardocking methods
PDF Full Text Request
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