Design And Synthesis Of Photosentizing New Drugs-Meso-Tetraphenyl Porphin (Chlorin) Derivatives

Photodynamic therapy(PDT) is a non-invaoive or minimally invasive,non-thermogenesis treatment by destroying the target tissues and cells with photochem reaction.It has many advantages such as good treatment efficiency,little side effect,simple conditions for treatment compared with traditional treatment.Choosing a suitable photosensitizer is crucial for PDT,which will directly affect the effect of PDT.Different kinds of photosensitizers have different absorptions in visible light region.And our main synthesis work is to get photosensitizers which have long wavelength absorption. Photosensitizer is transfered into the focus through the blood,so it must be water-solubility.And photosensitizer must penetrate through the cell membranes and has a high selectivity absorption in the cancer cells,it must be fat-solubility.In this dissertation the main work is about the structure modification of chlorophyll derivatives.We have made some modifications on phenyl of porphin and chlorine derivatives.Compared with Porphyrin,clorin,as the second-generation photosensitizer for photodynamic therapy,has many advantages such as chemical purity,strong absorption in the red spectral region et al.New optimu tumor/virus-photosentizing drugs are expected to be screened from them to overcome or minimize the present drawbacks of PDT with Photofrin.The studies of chlorin beacame one of the current hot topics in the field of photodynamic therapy.So we synthesized six meso-tetraphenyl porphin(chlorin) compounds.It is expected these new compounds can reach tumor tissue directly and kill cancer cell,so as to improve the curative effect.In this dissertation,six new compounds were synthesized including four meso-tetraphenyl chlorin and two meso-tetraphenyl porphin.They were all characterized by ~1H-NMR,MS,IR and UV.The reaction conditions such as temperature,sovle,reaction time and concentration were studies,and the best synthesis conditions were found.From UV spectra,it was found there were five absorption peaks between 300～700nm in CH2C12 of the four meso-tetraphenyl chlorin derivatives,and the maximum absorption peaks appeared at about 423nm,the second abosorption peaks at about 652nm.The maximum absorption wavelength of chlorin derivatives is higher than that of porphyin derivatives,which suggests the potential application of chlorin derivatives as photodynamic drug in PDT.The luther in virto studies with tumor cell using these new compounds are now in progress.