The Synthesis Of The Photodynamic Anticancer Drugs Possessing Chlorophyll Skeleton

Photodynamic therapy (PDT) is a promising new treatment modality for cancer. The light, O2, and photosensitizer (PS) which can be accumulated selectively in the tumor are combined to produce a selective therapeutic effect for cancer cell in PDT process.In Part I of this dissertation, the photochemistry, photophysics of PS, the mechanism of selective accumulation of the PS in the tumor, the mechanism of cell death in PDT, and the characteristics of the ideal PS are discussed. The research progress in the use of tetrapyrrolic photosensitizers, especially chlorophyll derivatives in PDT, is also reviewed in this part.The concrete research contents of this dissertation is described from Part II to Part IV. Methyl pheophorbide a prepared from silkworm droppings was used as starting material, and a seires of new chlorin compounds were synthesized by 1,3-dipolar cycloaddition reaction with diazomethane, diazoethane and several benzonitrile oxide derivatives at 3-vinyl group; by electrophilic substitution reaction with various electrophilic regents at 20-meso-position; by air oxidation and rearrangement reaction of E-ring in the base condition. The structures of all new compounds were characterized by elemental analysis, 1H NMR, UV-Vis and IR spectra. The reaction mechanism and the spectroscopy characteristics of the new compounds were discussed. The special attention was paid to the relationship between Uv spectra of chlorins and its chemical structure according to important role in PDT for photosenstizers.In order to discuss the effect of the change of the chemical structure of compound or photophysical characteristics on its photosensitizing activity in vitro, the singlet-oxygen yield (ΦΔ), triplet-state lifetime (τt) and its hydrophobic constant (CLogP) of some new compounds were determined, and the effect of these compounds on the survival rate of the mouse sarcoma S-180 cell line was also determined using the colorimetric MTT assay (accomplished by Dr. Judit Jakus, Hungarian Academy of Sciences). To the conclusion, the in vitro photosensitizing activity of these chlorophyll compounds is mainly affected not by the singlet-oxygen yield (ΦΔ) and triplet-state lifetime (τt), but by the hydrophobic constant. In general, the smaller the hydrophobic constant of these compounds, the higher their photosensitizing activity in vitro is.