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

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

Corboba, Argentina

Congreso; ELAFOT (XI Encuentro Latinoamericano de Fotoquímica y Fotobiología); 2012

UNRC, FCQ (UNC), UTN, CONICET, ANPCyT

Phthalocyanines (Pcs) are important dyes used in medicinal field as promising candidates for photodynamic therapy (PDT) in cancer treatment. It has been reported that peripheral substituents, the nature of the central metal ion as well as the axial ligand coordinated to the metal center of phthalocyanines, change their physical, chemical, and biological properties. Zinc(II) phthalocyaninates showing improved photophysical properties have been developed during the last years. In addition, attempts have been made both to increase the uptake of the dye by the targeted cells and to improve subcellular localization within the cells.. The lipophilicity of two novel isosteric zinc(II) phthalocyanines as compared with their analogs: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]ph-thalocyaninatozinc(II) tetraioidide Pc13 [1] was increased in order to obtain a better photodynamic 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[(N-dibutyl-N-methylammonium)ethoxy]phthalocyaninatozinc(II) tetraiodide (P7) were synthesized and their photophysical parameters and photobiological potentials were evaluated on human nasopharynx KB carcinoma cells The photobiological studies showed a better phototoxic effect for the sulfur-linked cationic phthalocyanine Pc6 (IC50= 1.45 ± 1 mM) with respect to the oxygen-linked phthalocyanine Pc7 (IC50= 10.5 ± 2 mM). This result could be explained by the higher cellular uptake obtained for 6, which was mainly localized within lysosomes. After irradiation, the production of a greater amount of ROS by phthalocyanine Pc6 led to a more effective cell death. Besides, Pc6 was more photoactive in vitro than Pc13 [2], since the IC50 values obtained under similar experimental conditions were two-fold higher for Pc6 than for Pc13 (IC50 = 2.7 ± 0.6 mM). Conclusions It is possible to consider a structure-activity relationship of alkylthio peripheral substituted zinc(II) phthalocyanines for photobiological purposes. Therefore, further photobiological studies, as well as search for improved phthalocyanine structures, are already in progress. Acknowledgements: Agencia de Promoción Científica y Tecnológica, Argentina. Consejo nacional de Investigaciones Científicas y Técnicas, Argentina. Universidad de Buenos Aires, Argentina. References [1] J. Marino, M.C. Garcia Vior, L.E. Dicelio, L. P. Roguin, J. Awruch. Photodynamic effects of isosteric water-soluble phthalocyanines on human nasopharynx KB carcinoma cells. Eu. J. Med. Chem., 2010, 45, 4129-4139. [2] . G. A. Gauna, J. Marino, M. C. García Vior, L. P. Roguin, J. Awruch. Synthesis and comparative photodynamic properties of two isosteric alkyl substituted zinc(II) phthalocyanines. Eu. J. Med. Chem., 2011, 46, 5532-5539.