Narrow Results

Four recently synthesized cationic zinc(II)-benzonaphthaporphyrazines 1–4 were studied in vitro and in vivo for their photodynamic therapy (PDT) effectivity. The photophysical measurements showed that in solution and in Cremophor micelles all examined compounds exhibit very high absorption intensity in the spectral range between 680 to 750 nm. The fluorescence emission for 3 and 4 was very well expressed in different media, as well as in cell culture. The dark toxicity examinations on invasive human bladder carcinoma cell line EJ did not show any traces of toxicity. The investigations connected with the detection of their phototoxic capacity on the same cell line demonstrated very promising results especially with photosensitizers 3 and 4. The in vivo studies with these two compounds demonstrating high cell-phototoxic effect were carried out against Lewis lung carcinoma in mice after incorporation in Cremophor micelles. The excitation was done at the respective maximum absorption wavelength for each of the sensitizers at a fluence rate of 380 mW cm^-2 and a fluence of 360 J cm^-2. The phototherapeutic effect was evaluated through macroscopic observations (tumour growth delay) and by electron microscopy detection. According to these approaches the best effect (including tumour destroyment) was detected after PDT treatment with the cationic tribenzonaphthoporphyrazinato-zinc(II) 3. Typical features of random, but not of programmed, cell death necrosis were observed.

The MacDonald's [2 + 2] condensation of unsubstituted dipyrromethane and 3- or 4-hydroxyalkoxybenzoaldehydes afforded 5,15-meso-hydroxyalkoxyphenylporphyrins. The hydroxyl groups on the side chains were then transformed to tertiary amines via synthesis of the mesylate and substitution with the appropriate amines or aminoalcohols. Methylation of such products afforded a series of cationic porphyrins which have been tested in vitro as photodynamic agents against microorganisms, showing high antimicrobial activity.

A variety of 1,8(11),15(18),22(25)- and 2,9(10),16(17),23(24)-tetra-substituted and 2,3,9,10,16,17,23,24-octa-susbtituted Zn(II) phthalocyanines, bearing dialkylaminophenoxy and trialkylammoniumphenoxy groups, have been synthetized, characterized and tested as photosensitizers against S. aureus, E. coli and C. albicans. All phthalocyanines exhibited intense absorption bands in the phototherapeutically useful 670-700 nm region, with a molar extinction coefficient of the order of 10⁵ M^-1.cm^-1. All derivatives bearing positive charges showed a good photosensitizing efficiency (causing a greater than 4 log reduction in cell survival), as well as a high quantum yield for generation of singlet oxygen. Variations of the chemical structure appeared to strongly affect both the physicochemical properties and the phototoxic activities against microorganisms.