The DNA Interaction And Anti-cancer Activity Of Tin And Gallium Corroles

Cancer therapy has always been a difficult problem for modern medicine.Developing new and effective anticancer drugs is the goal of many scientists.At present,a number of literatures have been reported that porphyrin is a potential anticancer drug.Corrole is one of the porphyrin analogues.Studies on corrole have never stopped,especially on its metal complexes.Many cororle complexes exhibit good antitumor effects,so the study of corrole and its complexes on inorganic chemistry is a promising field.DNA is an important target of anticancer drugs.Researches on the interaction of DNA and corrole may be an effective method to solve cancer problem.This thesis focuses on studying methyl benzoate tin and gallium corrole complexes.The interactions between two corrole complexes and DNA were investigated.Furthermore,their photonuclease activities and anti-tumor activities were studied too.The main points as follows:Firstly,5,10,15-tris(4-methoxycarbonylphenyl)corrole(1)and its tin(IV)complex(1-Sn),gallium(III)complex(1-Ga)were synthesized and characterized by UV-Vis,HR-MS,NMR and elemental analysis.Secondly,the interaction between two complexes and calf thymus DNA were studied by UV-Vis absorption titration experiments,circular dichroism titration experiments and viscosity experiments.Results showed that two complexes could bind with DNA via outside binding mode.DNA doking indicated all corroles are located in the major groove of DNA,and the binding ability is as follows: 1-Sn >1-Ga >1.Thirdly,the photonuclease activities of two complexes were studied by agarose gel electrophoresis experiments.Control group corrole 1 showed no cleavage activity towards DNA while 1-Sn and 1-Ga exhibited remarkable photocleavage activities and were both good DNA cleavage agents.Inhibitor testing revealed that superoxide anion is the main active species in the DNA photocleavage of 1-Sn and 1-Ga.EPR spectra also confirmed the conclusion.Fourthly,the cytotoxicity of 1-Sn against A549 was detected by MTT assay.Control group corrole 1 displayed no cytotoxicity towards A549 cells whenever in dark or light conditions.However,1-Sn exhibited significant dark cytotoxicity towards tested tumor cell lines.There was nearly no toxicity at low concentration(?10 ?M)and about 30% and 40% cells were killed at a dose of 20 ?M and 40 ?M respectively.After irradiation,no obvious enhancement in cytotoxicity could be observed.Fifthly,in the cellular uptake apoptotic pathway experiments,Hoechst-33342 was used as a fluorescent probe.Because the fluorescence of 1-Sn would decrease greatly when the complex dissolved in PBS buffer solution,the cell uptake of 1-Sn could not be detected by fluorescence.But apoptosis assay suggested that the A549 tumor cell death induced by 1-Sn may not via an apoptosis pathwayLastly,JC-1 is a fluorescent probe to elucidate the role of 1-Sn in altering the mitochondrial membrane potential.High concentration of 1-Sn may cause mitochondrial membrane potential destruction which will trigger the tumor cell death.