Porphyrin Compounds:Synthesis,Characterization And Their Anticancer Activity Evaluation In Vitro

Cancer as a common disease has always threatened human life,is a difficult problem in clinical medicine nowadays.Three high incidence of the cancer are lung cancer,breast cancer and colorectal cancer according to statistics.Furthermore,lung cancer,liver cancer and stomach cancer are the highest fatality in the world.For the reasons as elaborated above,the prevention and treatment of cancer has become a major problem which needs to be solved urgently.Photodynamic therapy(PDT)is an emerging clinical modality for treatment of neoplastic and non-malignant lesions and has found applications in cancer therapy.It is based on the biological effects that result from the photosensitized generation of singlet oxygen in the target material.Which cancer-selective accumulation is an important consideration for photosensitizer overcomes side effects and normal tissue injury in the surgery,chemotherapy,radiotherapy and any other traditional cancer therapy methods.Porphyrins are macromolecule existing in biological organism With 18 ? electrons,which have good photosensitiveness and can target tumor cells.While the Sciff base and hydrazones schiff bases show good bacteriostasis and antitumor activities because of its structure characteristics.They are widely used in medicine,pesticides,and so on.Based on the above research background,this paper focuses on the new porphyrin photosensitizer design and synthesis,and then we further exploited the photodynamic therapeutic efficiency of porphyrins by four kinds of cells including BGC823 cells,HepG2 cells,MCF-7 cells and LO2 cells.The detail research contents are as follows:Firstly,two kinds of free aldehyde porphyrin in chapter 2,they are 5,10,15-triphenyl-20-(4-phenoxy)phenyl porphyrin(H2Pp1)and 5,10,15-tri(p-fluiorphenyl)-20-(4-phenoxy)phenyl porphyrin(H2FPP1)were synthesized and their corresponding metal porphyrin ZnPp1 and ZnFPp1.Then eight Schiff-base porphyrins were successfully synthesized by the condensation of HZPP1 and ZnFPp1 with compounds bearing amino,namely,free porphyrins H2Pp2-H2Pp5 and metalloporphyrins ZnPp2-ZnPp5.Meanwhile,nine hydrazone and acyl hydrazone schiff base porphyrin(H2Pp6-H2Pp9 and H2FPp2-H2FPp6)of H2Pp1 and H2FPp1 had been prepared too in chapter 4.All of them were characterized by fluorescence analysis,MS,FT-IR and UV-Vis,and 1H-NMR.Secondly,Photostability of porphyrin in DMF was observed using the bleaching(13.3J/cm2)when porphyrin was continuously exposed to the excitation light at 417 nm for 30 minutes.The results show that the fluorescence emission intensity was merely declined after repetitive illumination,and porphyrins have good anti-photooxidation.Metalloporphyrin has less fluorescence quantum yield and porphyrin H2Pp6 and H2FPp2 is higher than that of tetraphenyl porphyrin.Other porphyrins show almost the same yield compare with tetraphenyl porphyrin.The abilities of producing singlet oxygen are determined by the degradation measurement of DPBF.The results reveal that porphyrin with Scifffbase group and metalloporphyrins show good ability of singlet oxygen.Finally,the results of fluorescent microscope showed that all porphyrins can enter the cancer cell through the emission of red fluorescence,but porphyrin H2Pp9 falled in the emission of red fluorescence in the BGC823 cells.MTT was used to decide survival rate of tumor cells.The PDT of porphyrin H2Pp1-H2Pp5,ZnPp1-ZnPp5,H2FPp1 and ZnFPp1 found that H2Pp4 and ZnPp4 showed strong photodynamic activity,but has dark toxicity at high concentrations.The rest porphyrin did not show dark cytotoxicity and can kill cancer cells after exposing to the light,especially H2Pp5 and ZnPp5 had a strong effect of PDT to cancer cell.Porphyrin H2Pp4,ZnPp1,ZnPp2,ZnPp4,and ZnFPp1 showed phototoxic at high concentration and H2Pp4 and ZnPp4 show dark cytotoxicity on LO2 cell.The PDT of porphyrin H2Pp6-H2Pp9 and H2FPp2-H2FPp6 on BG823 and MCF-7 found that all porphyrins showed strong PDT activities except porphyrin H2Pp9 on cancer cells after exposing to the light and had no dark cytotoxicity.The porphyrin H2Pp7 and H2FPp3 were the most phototoxic.