ESR And In Vitro Anticancer Activity Study Of Novel Spin Traps

Free radical is a kind of substance which has high reactivity, it is widespread in nature and the human body.Free radical plays an important role in the biochemical activities of our human body.lt is harmful to the human body because of its highreactivity. Many studies have shown that free radical has some relationship with a variety of disease and injury,such as ischemia-reperfusion injury, inflammation, cancer.cardiovascular disease and so on. On the other hand, the appropriate concentration of free radical in the body is necessary. So the study of free radical in vivo is of great significance. Spin-trapping is a technical which can make active free radical more stable and detect it. Spin trap not only capture and detect free radical, but also has some influence with free radical in vivo. As a kind on nitron spin trap.PBN has been studied earlier. Numerous studies show that PBN has medicine activity and certain anti-tumor activity.This thesis consists of four parts. Part1:Synthesized PBN, a PBN derivative (ChPBN) which has a cholesterol group, and MitoPBN. a Mitochondria-targeting compound, the structures were confirmed by1H NMR.13C NMR. IR, Part2:The spin trapping property of ChPBN) was measured by ESR. Part3:ChPBN liposome was prepared by the film-ultrasonic technique. Part4:Cytotoxicity of PBN.ChPBN.MitoPBN and ChPBN liposome was studied.In pat2, the property of spin trapping was measured by ESR. We did some research on hydroxyl free radical and carbon-centered free radical. All of theses free radicals are generated from Fenton reaction. We found that the ability of ChPBN spin trapping is·OH>· CH(OH)Me>· CH2OH>· CH(OH)Et>· C(OH)Me.and it can trap hydroxyl free radical easily.In part3,ChPBN lipsome was prepared by the film-ultrasonic The formulation was optimized by orthogonal design and encapsulation efficiency is evaluation. RT-HPLC is used to measure the concentration of ChPBN. it’s convenient and accurate.Part4.the growth inhibition of PBN. MitoPBN、ChPBN and ChPBN liposome to cells was analyzed by MTT method.The results suggests that the order of toxicity is MitoPBN>ChPBNliposome>ChPBN>PBN, The results suggests that the toxicity of PBN is related with its spin trapping ability. Free radical in vivo is mainly from mitochondria, MitoPBN is a kind of mitochondria-targeting compound. so it can trap most free radical, and has the highest toxicity. ChPBN has a cholesterol grup. the cholesterol group makes it more easy to be accepted by the cell,and this makes ChPBN have higher toxicity. Liposome enhanced biocompatibility of ChPBN. it becomes more easily for the drug to enter cells, and the toxicity increased...