DNA cleavage by synthetic agents

iiDNA CLEAVEGE BY SYNTHETIC AGENTSBircan ÇEKENABSTRACTThe ultimate aim of this thesis was to investigate the effect of different arylsubstituted analogues of benzenediazonium tetrafluoroborate on radical reactivity andDNA cleavage ability. The results indicated that cleavage of a DNA duplex frompBluescript M13+ DNA was observed by the different substituted aryl diazonium salts,in the presence of inorganic one-electron donor. Moreover, DNA cleavage was partlyaffected by different substitute group and DNA strand-scission was also observedwithout one electron donor in the presence of some tested diazonium salts. Itsmechanism involves the generation of the aryl radical that cleaving DNA by hydrogenatom abstraction from deoxyribose sugar.The protective effect of Hypericum retusum Aucher, Hypericum scabrum L.,Hypericum lysimachioides Boiss&Nöe var .lysimachioides, Achillea aleppica D.C.subsp. aleppica, Achillea aleppica D.C. subsp. zederbaueri (Hayek) Hub. -Mor. veAchillea biebersteinii Afan. plants extracts on DNA cleavage mediated by aryl radicalwas also investigated using pBluescript M13+ plasmid DNA, as judged by agarose gelelectrophoresis. It was found that aryl radical induced DNA strand scission was notprevented by ethanol extracts of Hypericum and Achillea. On the contrary, DNAcleavage was increased in the presence of plant extracts. Therefore, we decided toinvestigate the DNA cleavage ability of plant extracts alone and also in the presence ofcopper (II) chloride. It was found that the naturally occuring plant extracts caused strandscission of DNA in the presence of copper ion. The mechanism of the DNA strandscission by plant extracts (in the presence of Cu II ion) indicated an involvement ofoxygenation of aromatic nucleus, affording catecholic moieties that were proposed tocoordinate Cu2+ and subsequently effect the reduction of dioxygen to reactive species,followed by the oxidation of catecholic moiety via the coordinated Cu II ion.Keywords: DNA Cleavage, Free Radical, Radical Scavenger, Copper, Hypericum,Achillea