Photodynamic therapy of cutaneous T-cell lymphoma cell lines mediated by 5-aminolevulinic acid and derivatives

The delta-amino acid 5-aminolevulinic (ALA), is the precursor of endogenous photosensitiser Protoporphyrin IX (PpIX), and currently approved for Photodynamic Therapy (PDT) certain superficial cancers. However, ALA-PDT not very effective in diseases which T-cells play a significant role. Cutaneous T-cell lymphomas (CTCL) group non-Hodgkin malignant diseases, includes mycosis fungoides (MF) Sézary syndrome (SS). In previous work, we have designed new ALA esters synthesised by three-component Passerini reactions, some them showed higher performance as compared to ALA. This work aimed determine efficacy pro-photosensitisers five 2-hydroxy-N-arylacetamides (1f, 1 g, h, 1i k) lipophilicity than Myla cells MF HuT-78 SS. We also tested its effectiveness against already marketed methyl ester (Me-ALA) hexyl (He-ALA). Both cell SS were effectively equally photoinactivated ALA-PDT. Besides, concentration required induce half maximal porphyrin synthesis was 209 μM 169 cells. As criterion efficacy, calculated derivatives necessary plateau values obtained from These achieved at concentrations 4 12 times lower ALA, according derivative used. For He-ALA, 24 25 inducing comparable both CTCL light doses 50% death (LD50) 1f, h around 18 J/cm2 respectively, after exposure 0.05 mM compounds. On other hand, LD50s compound k 40 57 HuT-78, respectively. contrast, Me-ALA did provoke photokilling since employed far below saturation point these Our results suggest potential use topical application PDT treatment extracorporeal depletion activated