Novel unsymmetrical silicon(IV) phthalocyanines as highly potent anticancer photosensitizers. Synthesis, characterization, and in vitro photodynamic activities. (June 2020) - Zheng, Bi-Yuan
Abstract: A series of novel unsymmetrical silicon (IV) phthalocyanines (SiPcs) di-substituted axially with tyramine and different oligomeric ethylene glycol moieties have been synthesized by alkoxy exchange reactions, and their singlet oxygen quantum yields ( Φ Δ ) and in vitro photodynamic activities have also been evaluated. The unsymmetrical SiPcs 2 –5 show slightly higher photosensitizing efficiency ( Φ Δ = 0.08–0.12) than the corresponding symmetrical SiPc 1 ( Φ Δ = 0.05), but are less efficient compared to the symmetrical SiPc 6 ( Φ Δ = 0.33). All the compounds exhibit high photocytotoxicities against BGC-823 cancer cells with IC50 values ranging from 3 nM to 20 nM. Particularly for the unsymmetrical SiPc 5, the IC50 value toward BGC-823 cells is significantly lower than its corresponding symmetrical SiPcs 1 and 6, which could be attributed to its higher cellular uptake. In addition, SiPc 5 can essentially bind to mitochondria and induces cell death of BGC-823 cells mainly through apoptosis. So SiPc 5 is a highly promising photosensitizer for photodynamic therapy. Graphical abstract: Image 1 Highlights: Four novel unsymmetrical SiPcs substituted with tyramine and different oligomeric ethylene glycol moieties are synthesized. The structure-activity relationship of these silicon (IV) phthalocyanines was discussed. The unsymmetrical SiPc 5 showed the highest photodynamic activity against BGC-832 cells as a result of high cellular uptake.