TETRAAMIDO-SUBSTITUTED 2,3-NAPHTHALOCYANINE ZINC(II) COMPLEXES AS PHOTOTHERAPEUTIC AGENTS - SYNTHESIS, COMPARATIVE PHOTOCHEMICAL AND PHOTOBIOLOGICAL STUDIES

The aim of this study is to report the synthesis and photochemical and phototherapeutic activities of tetraamido-substituted 2,3-naphthalocy anine zinc(II) complexes (ZnNcs 5-8). Four naphthalocyanine complexes, tetrabenzamido- (ZnNc 5), tetramethoxybenzamido- (ZnNc 6), tetrahexyl amido- (ZnNc 7) and tetradodecylamido- (ZnNc 8) naphthalocyanine zinc complexes absorbing at around 770 nm were synthesized. The dye-sensiti zed photo-oxidation of 1,3-diphenylisobenzofuran via O-1(2) was studie d in more detail in order to compare the quantum yields of these diffe rent sensitizers. Pharmacokinetic and photodynamic therapy studies of Lewis lung carcinoma in mice were carried out after administration of liposome incorporated ZnNcs 5-8. The phototherapeutic efficiency was e valuated by changes in the mean tumour diameter with time, regrowth de lay (days), average survival time (days) and electron microscopy obser vations. According to all assessment criteria used, the most promising photosensitizer seems to be tetrabenzamido-substituted ZnNc 5. We sug gest that mainly structural properties are the reason for the better r esults observed. The morphological analysis confirms the mechanism of photonecrosis, which was observed in our previous work with unsubstitu ted and substituted ZnNcs 1-4. Direct photodamage to the membrane, mit ochondria and rough endoplasmic reticulum in the neoplastic cells and delayed photodestruction of the endothelial cells surrounding the tumo ur tissue were detected. Also, changes in lysosomes were observed. The data presented through different parameters are compared with such ob tained for other photodynamic therapy sensitizers.