In Vitro Photodynamic Activity of N‐Methylated and N‐Oxidised Tripyridyl Porphyrins with Long Alkyl Chains and Their Inhibitory Activity in Sphingolipid Metabolism

Abstract

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 IC values for phototoxicity of two N-oxides, named TOPyP3-C H O and TOPyP3-C H , were still in the nanomolar concentration range for most of the tested cell lines. However, TOPyP3-C H did not show phototoxicity on human foreskin fibroblast cells. Two methylated amphiphilic porphyrins, named TMPyP3-C H and TMPyP4-C H 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-C H and TOPyP3-C H reduced the activity of acid ceramidase, whereas TOPyP3-C H 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.

Cationic Porphyrins as Effective Agents in Photodynamic Inactivation of Opportunistic Plumbing Pathogen Legionella pneumophila

“…We proceeded in this way also to be able to calculate the light doses corresponding to the time of irradiation. In this spectrum, TBO and MB have a very small light absorption, as their respective λ max values are 631 nm and 665 nm [24], while all tested porphyrins have strong absorption with their Soret band around 420 nm [20]. The obtained MEC values (Table 3) indicate a somewhat dark toxicity for all tested dyes after incubation with L. pneumophila for 30 min, the highest being observed for the compound with a long alkyl chain, TMPyP3-C 17 H 35 (>1.56 µM), while the other two porphyrins that are hydrophilic show two-fold dark toxicity (>12.5 µM) in comparison to hydrophilic phenothiazine dyes TBO and MB (>25.6 µM).…”

“…Porphyrins, 5,10,15,20-tetra(3-pyridinyl)porphyrin (TPyP3), 5-(4-acetamidophenyl)-10,15,20-tetra(3-pyridinyl)porphyrin (TPyP3-CH 3 ) and 5-(4-octadecaaminophenyl)-10,15,20-tetra(3-pyridinyl)porphyrin (TPyP3-C 17 H 35 ) were synthetized as previously described [ 19 , 20 ]. However, to prepare N -methylated derivatives of these porphyrins, we used a modified procedure for methylation according to Ezzedine et al [ 21 ] as follows.…”

“…The synthesis of a series of N-methylated tri-and tetrapyrid-3-ylporphyrins was previously described by our group [19,20]. However, to improve ion exchange and purification after the methylation reaction using methyl iodide, we applied a modified methylation method using ammonium hexafluorophosphate (NH 4 PF 6 )/tetrabuthylammonium chloride (TBAC) precipitations, according to procedures described in the literature [21].…”

Photodynamic Inactivation of Legionella pneumophila Biofilm Formation by Cationic Tetra- and Tripyridylporphyrins in Waters of Different Hardness

“…In contrast, 1,3-diphenylisobenzofurane (DPBF), which is often used as a fluorescent probe in the measurements of the singlet oxygen production, reacts with the various ROS [26,27]. Here, we used the method modified from our previous work, where we used non-watersoluble 9,10-dimethylantracene (DMA) [28]. ABMDMA was used in a concentration of 6 µM, mixed with a 1 µM concentration of the PSs, and then irradiated for 10 min (411 nm, fluence rate 7 mW/cm 2 , light dose 4.2 J/cm 2 ).…”

Chemical approaches for the enhancement of porphyrin skeleton-based photodynamic therapy

“…against the A549 cancer cell line, showing 5-fold better inhibitory activity than the reference compound 15 (H 2 TMPyP, IC 50 ¼ 0.30 mM) 34 . Jelovica et al 35 designed and synthesised an amphiphilic porphyrin derivative with a long lipophilic alkyl side chain. The solubility of the compound was markedly improved after the introduction of three 3-pyridyl groups.…”