A comparative study of the photodynamic properties of two isosteric alkyl substituted phthalocyanines.

GAUNA G. A., MARINO J., GARCIA VIOR M. C., ROGUIN L.P., AWRUCH J

Congreso; XI Encuentro Latinoamericano de Fotoquímica y Fotobiología; 2012

Phthalocyanines (Pcs) are important dyes used in medicinal field as promising candidates forphotodynamic therapy (PDT) in cancer treatment. It has been reported that peripheralsubstituents, the nature of the central metal ion as well as the axial ligand coordinated to themetal center of phthalocyanines, change their physical, chemical, and biological properties.Zinc(II) phthalocyaninates showing improved photophysical properties have been developedduring the last years. In addition, attempts have been made both to increase the uptake of thedye by the targeted cells and to improve subcellular localization within the cells..The lipophilicity of two novel isosteric zinc(II) phthalocyanines as compared with theiranalogs:2,9(10),16(17),23(24)-tetrakis[(2-trimethylammonium)ethoxy]phthalocyaninatozinc(II)tetraiodide (Pc11) and 2,9(10),16(17),23(24)-tetrakis[(2-trimethylammonium)ethylsulfanyl]phthalocyaninatozinc(II) tetraioidide Pc13 [1] was increased in order to obtain a betterphotodynamic behavior.Thus, 2,9(10),16(17),23(24)-tetrakis[(N-butyl-N-methylammonium)-ethylsulfanyl]phthalocyaninatozinc(II) tetraiodide (P6) and 2,9(10),16(17),23(24)-tetrakis[(Ndibutyl-N-methylammonium)ethoxy]phthalocyaninatozinc(II) tetraiodide (P7) were synthesizedand their photophysical parameters and photobiological potentials were evaluated on humannasopharynx KB carcinoma cellsThe photobiological studies showed a better phototoxic effect for the sulfur-linked cationicphthalocyanine Pc6 (IC50= 1.45 􀁲 1 􀁐M) with respect to the oxygen-linked phthalocyanine Pc7(IC50= 10.5 􀁲 2 􀁐M). This result could be explained by the higher cellular uptake obtained for6, which was mainly localized within lysosomes. After irradiation, the production of a greateramount of ROS by phthalocyanine Pc6 led to a more effective cell death. Besides, Pc6 wasmore photoactive in vitro than Pc13 [2], since the IC50 values obtained under similarexperimental conditions were two-fold higher for Pc6 than for Pc13 (IC50 = 2.7 􀁲 0.6 􀁐M).ConclusionsIt is possible to consider a structure-activity relationship of alkylthio peripheral substitutedzinc(II) phthalocyanines for photobiological purposes. Therefore, further photobiologicalstudies, as well as search for improved phthalocyanine structures, are already in progress.