Lead structures for applications in photodynamic therapy. 5. Synthesis and biological evaluation of water soluble phosphorus(V) 5,10,15,20-tetraalkylporphyrins for PDT

• A practical synthesis of meso tetraalkyl P(V)porphyrins was developed.
• The porphyrins are water soluble.
• HCS showed that the porphyrins are readily taken up by esophageal cancer cells.
• The photocytotoxicity of the P(V)porphyrins is comparable to mTHPC (Temoporfin®).
• P(V)porphyrins offer potential as a new class of PDT drugs.

SummaryImproved photosensitizers for use in photomedicine must possess good water-solubility and optimal photophysical properties. Phosphorus(V) porphyrins fulfill these criteria and are a class of porphyrins with significant potential applications in phototherapy. Five phosphorus(V) porphyrins bearing alkyl substituents have been synthesized. Reasonable to good yields were obtained for all P(V) insertions and all compounds underwent biological evaluation for their PDT activity on two esophageal cancer cell lines, OE33 and SKGT-4. Their cellular uptake was investigated using a high content screening method. Notably, three compounds displayed good uptake and using the MTS cell proliferation assay, two were shown to have photocytotoxicity comparable to mTHPC (Temoporfin®) with IC50 values of 6.5 and 5.5 μM.

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