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.