Novel fluorinated ring-fused chlorins as promising PDT agents against melanoma and esophagus cancer.

Investigation of novel 4,5,6,7-tetrahydropyrazolo[1,5-a]pyridine-fused chlorins, derived from 5,10,15,20-tetrakis(pentafluorophenyl)porphyrin, as PDT agents against melanoma and esophagus cancer is disclosed. Diol and diester fluorinated ring-fused chlorins, including derivatives with 2-(2-hydroxyethoxy)ethanamino groups at the phenyl rings, were obtained via a two-step methodology, combining SNAr and [8π + 2π] cycloaddition reactions. The short-chain PEG groups at the para-position of the phenyl rings together with the diol moiety at the fused pyrazole ring promote a red-shift of the Soret band, a decrease of the fluorescence quantum yield and an increase of the singlet oxygen formation quantum yield, improving the photophysical characteristics required to act as a photosensitizer. Introduction of these hydrophilic groups also improves the incorporation of the sensitizers by the cells reaching cellular uptake values of nearly 50% of the initial dose. The rational design led to a photosensitizer with impressive IC50 values, 13 and 27 nM against human melanoma and esophageal carcinoma cell lines, respectively. This journal is © The Royal Society of Chemistry.

Citation

Nelson A M Pereira, Mafalda Laranjo, Bruno F O Nascimento, João C S Simões, João Pina, Bruna D P Costa, Gonçalo Brites, João Braz, J Sérgio Seixas de Melo, Marta Pineiro, Maria Filomena Botelho, Teresa M V D Pinho E Melo. Novel fluorinated ring-fused chlorins as promising PDT agents against melanoma and esophagus cancer. RSC medicinal chemistry. 2021 Apr 28;12(4):615-627

PMID: 34046633

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