Synthesis, Characterization And DNA-binding Studies Of Complexes With Xanthone Derivatives

In this paper,we have reported the synthesis,characterization of ten xanthonederivatives and their metal complexes.Some of them were evaluated for DNAbinding properties and anticancer activities.A series of significant conclusions havebeen achieved from the results.The dissertation includes following four chapters:In chapter one,the research progress in the interactions of DNA with smallmolecules,as well as the interaction mode,influence factors,research methods arereviewed.The important theoretical and practical significance of the research work inthe drug screening and biochemistry are also discussed herein.Moreover,the aim andsignificance of this thesis have been outlined.In chapter two,six isoeuxanthone derivatives (HL¹-HL⁶) and metal complexeshave been synthesized and characterized by elementary analyses,molar conductivity,infrared spectra (IR),¹H NMR and mass spectra (MS).The interactions of the copper(â…¡) complexes with DNA were investigated by spectrophotometric methods andviscosity measurement,which suggested that the complexes bind with DNA inintercalation mode and the different substituting groups lead in different DNA bindingaffinity of the ligands.In addition,the anticancer activity of the complexes wereevaluated toward uterine cervix carcinoma cell (HeLa),human hepatocellular livercarcinoma cell (HepG2) and human liver cell (L02) by acid phosphoatase assay(APA).The result suggested that they showed inhibitory effect against the three celllines.In chapter three,two isomeric multiple hydroxyl xanthones (HL⁷ and HL⁸) andtheir metal complexes were synthesized and characterized.And interactions of thecopper (â…¡) complexes with DNA were studied by spectrophotometric methods.Theresults suggested that they both intercalate into DNA as well as that the different positions of substituent groups don't effect on the binding mode but effect on thebinding affinity.In addition,the pharmacology assay (APA) showed that the twocomplexes had high inhibitory effect toward HeLa,HepG2 and L02 in vitro within therange of safe dosage.In chapter four,two isomeric benzoxanthones (HL⁹ and HL¹⁰) and their metalcomplexes have been synthesized and characterized.And the interactions of the twoligands and the copper (â…¡) complexes with DNA were studied by spectrophotometricmethods and viscosity measurements.The results suggested that they both bind toDNA in intercalation mode and the DNA-binding affinity of the complexes werehigher than that of the ligands,while that the ligand bearing linearly aromatic ringshowed more strong affinity than the ligand bearing angularly aromatic ringFurthermore,the two ligands were tested for cytotoxic activity toward HeLa,HepG2and L02.The result revealed that they showed strong cytotoxic activity toward HeLaand HepG2 but weak cytotoxic activity against L02.