Synthesis of pyrazole substituted methyl pheophorbide-a derivatives and their preliminary in vitro cell viabilities.

The unique ability of chlorophyll derivatives to accumulate in tumorous tissues and to cause a photodynamic effect under laser radiation has been successively used in photodynamic therapy. In this connection, enormous research on modifications of the peripheral substituents in chlorophyll has shown that the presence and position of the substituents in the chlorin derivatives make a remarkable difference in biological activity. As a result, we directed our attention to synthesize methyl pheophorbide-a derivatives, chlorophyll-a derivatives, possessing heterocyclic aromatic substituents or pyrazole moieties on the peripheral positions and to examine preliminary in vitro effects of these new derivatives on A549 cancer cells for PDT. From our experimental results, it was observed that the biological effect induced by photosensitizers on cancer cells may also depend upon the chemical structure of the photosensitizers.

Synthesis and biological evaluation of new imidazolium and piperazinium salts of pyropheophorbide-a for photodynamic cancer therapy.

We have designed imidazolium and piperazinium salts of pyropheophorbide-a in order to develop effective photosensitizers which have good solubility in polar and non polar media and to reveal the possible influences of the piperazine and imidazole moieties on the biological activities of pyropheophorbide-a. The phototoxicity of those pyropheophorbide-a salts against A549 cells was studied in vitro and compared with that of pyropheophorbide-a. The result showed that complexing piperazine and imidazole into pyropheophorbide-a decreases its dark toxicity without greatly decreasing phototoxicity and, enhances its phototoxicity without greatly increasing dark toxicity, respectively. This work not only describes novel amphiphilic salt complexes of pyropheophobide-a which retain the biological activities of the parent compound pyropheophorbide-a and could be effective candidate for PDT, but also reveals the possibility of developing effective photosensitizers by complexing imidazole and piperazine into other hydrophobic photosensitizers.