Phthalocyanine Derivatives Possessing 2‑(Morpholin-4-yl)ethoxy Groups As Potential Agents for Photodynamic Therapy

Three 2-(morpholin-4-yl)­ethoxy
substituted phthalocyanines were
synthesized and characterized. Phthalocyanine derivatives revealed
moderate to high quantum yields of singlet oxygen production depending
on the solvent applied (e.g., in DMF ranging from 0.25 to 0.53). Their
photosensitizing potential for photodynamic therapy was investigated
in an in vitro model using cancer cell lines. Biological test results
were found particularly encouraging for the zinc­(II) phthalocyanine
derivative possessing two 2-(morpholin-4-yl)­ethoxy substituents in
nonperipheral positions. Cells irradiated for 20 min at 2 mW/cm2 revealed the lowest IC50 value at 0.25 μM
for prostate cell line (PC3), whereas 1.47 μM was observed for
human malignant melanoma (A375) cells. The cytotoxic activity in nonirradiated
cells of novel phthalocyanine was found to be very low. Moreover,
the cellular uptake, localization, cell cycle, apoptosis through an
ELISA assay, and immunochemistry method were investigated in LNCaP
cells. Our results showed that the tested photosensitizer possesses
very interesting biological activity, depending on experimental conditions.

本研究合成并表征了三种带有2-(4-吗啉基)乙氧基取代基的酞菁（phthalocyanine）。这类酞菁衍生物的单线态氧生成量子产率处于中等至较高水平，具体数值取决于所用溶剂：例如在N,N-二甲基甲酰胺（DMF）中，产率范围为0.25至0.53。本研究通过癌细胞系构建体外模型，对其用于光动力疗法的光敏潜力展开了评估。生物学测试结果显示，带有两个2-(4-吗啉基)乙氧基取代基且位于非周边位的锌(II)酞菁衍生物，其效果尤为喜人。在功率密度2 mW/cm²下照射20分钟后，该衍生物对前列腺癌细胞系（PC3）的半抑制浓度（IC50）最低，仅为0.25 μM；而对人类恶性黑色素瘤细胞系（A375）的半抑制浓度则为1.47 μM。未受照射的细胞中，该新型酞菁的细胞毒活性极低。此外，本研究在LNCaP细胞系中，通过酶联免疫吸附测定（ELISA）与免疫化学法，对该衍生物的细胞摄取、亚细胞定位、细胞周期以及细胞凋亡情况展开了探究。本研究结果表明，所测试的光敏剂具备极具研究价值的生物学活性，其活性水平取决于具体实验条件。