A series of N-methylated and N-oxidised tripyridyl porphyrins were synthesised, characterised, and their PDT activity was studied with six cell lines. All the tested porphyrins with a long alkyl chain, except one, were more efficient for PDT than an N-methylated hydrophilic porphyrin and N-oxidised porphyrin without the long alkyl chain. Generally, N-methylated tripyridyl porphyrins were more active than those N-oxidised, but IC₅₀ values for phototoxicity of two N-oxides, named TOPyP3-C₁₇ H₃₃ O and TOPyP3-C₁₇ H₃₅ , were still in the nanomolar concentration range for most of the tested cell lines. However, TOPyP3-C₁₇ H₃₅ did not show phototoxicity on human foreskin fibroblast cells. Two methylated amphiphilic porphyrins, named TMPyP3-C₁₇ H₃₃ and TMPyP4-C₁₇ H₃₅_, showed significant dark toxicity, whereas none of the oxidopyridyl porphyrins were toxic without light activation. The selected photosensitisers were shown to be apoptosis inducers, and had inhibitory effects on the clonogenic growth of HCT116 and HeLa cells. All three N-methylated amphiphilic porphyrins significantly reduced the migratory potential of HCT116 cells. Porphyrins TMPyP3-C₁₇ H₃₅ and TOPyP3-C₁₇ H₃₅ reduced the activity of acid ceramidase, whereas TOPyP3-C₁₇ H₃₃ O had a significant inhibitory effect on sphingosine kinase 1 activity in HeLa cells. Compounds with this dual activity were shown to be the most promising photosensitisers, with potential to treat invasive cancers.

Mateo Jelovica

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