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.

本实验成功合成了三种2-(吗啉-4-基)乙氧基取代的酞菁化合物，并对其进行了表征。酞菁衍生物在不同溶剂（例如，在DMF中其量子产率从0.25增至0.53）下展现出中等到高的单线态氧产生效率。通过体外模型，利用癌细胞系研究了其在光动力治疗中的光敏化潜力。生物测试结果显示，具有两个非周边位置的2-(吗啉-4-基)乙氧基取代基的锌(II)酞菁衍生物尤为令人鼓舞。在2 mW/cm2的辐照强度下，照射20分钟后，对于前列腺癌细胞系（PC3），其最低IC50值达到0.25 μM，而对于人恶性黑色素瘤细胞（A375），该值为1.47 μM。新型酞菁在非辐照细胞中的细胞毒性极低。此外，通过ELISA检测和免疫化学方法，还研究了其在LNCaP细胞中的细胞摄取、定位、细胞周期以及通过凋亡途径的影响。实验结果表明，所测试的光敏剂在实验条件下表现出极为有趣的生物活性。