Synthesis and comparative photodynamic properties of two isosteric alkyl substituted zinc(II) phthalocyanines

• Published in: European journal of medicinal chemistry 2011-11, Vol.46 (11), p.5532-5539
• Main Authors: Gauna, Gabriela A., Marino, Julieta, García Vior, María C., Roguin, Leonor P., Awruch, Josefina
• Format: Article
• Language: English
• Subjects: Alkanes - chemistry; Biological and medical sciences; Biological Transport; Chemistry Techniques, Synthetic; Humans; Indoles - chemical synthesis; Indoles - chemistry; Indoles - metabolism; Indoles - pharmacology; Intracellular Space - drug effects; Intracellular Space - metabolism; KB Cells; Lysosomes; Medical sciences; Organometallic Compounds - chemical synthesis; Organometallic Compounds - chemistry; Organometallic Compounds - metabolism; Organometallic Compounds - pharmacology; Photochemotherapy; Photodynamic therapy; Photoradiation therapy and photosensitizing agent; Photosensitizing Agents - chemical synthesis; Photosensitizing Agents - chemistry; Photosensitizing Agents - metabolism; Photosensitizing Agents - pharmacology; Phthalocyanines; Reactive oxygen species; Reactive Oxygen Species - metabolism; Singlet oxygen; Treatment with physical agents; Treatment. General aspects; Tumors
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2011.09.014

The synthesis and photophysical parameters of two novel isosteric cationic zinc(II) phthalocyanines: 2,9(10),16(17),23(24)-tetrakis[(N-butyl-N-methylammoniumethylsulfanyl]phthalocyaninatozinc(II) tetraiodide (6) and 2,9(10),16(17),23(24)-tetrakis[(N-dibutyl-N-methylammonium)ethoxy]phthalocyaninatozinc(II) tetraiodide (7) were investigated. Maximum absorption values were 686.5 nm and 678 nm for 6 and 7, respectively, whereas singlet molecular oxygen generation was 0.42 and 0.67, respectively. The photodynamic effect and the cellular uptake of both phthalocyanines were evaluated on human nasopharynx KB carcinoma cells. After light exposure, phthalocyanine 6 showed a higher cytotoxic activity than 7. In addition, a higher intracellular uptake of 6 and a preferential localization within lysosomes were demonstrated. The production of a greater amount of reactive oxygen species after phthalocyanine 6 irradiation would be responsible for its potent phototoxic action on KB cells. [Display omitted] ▸ Two novel isosteric cationic zinc(II) phthalocyanines were synthesized for PDT. ▸ The sulfur-linked dye showed the best cytotoxic activity againts KB cells. ▸ A higher intracellular uptake was demonstrated for the sulfur-linked dye. ▸ A preferential localization in lysosomes was established for the sulfur-linked dye.