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

• Autor(a) principal: Pereira, Nelson A. M.
• Data de Publicação: 2021
• Outros Autores: Laranjo, Mafalda, Nascimento, Bruno F. O., Simões, João C. S., Pina, João, Costa, Bruna D. P., Brites, Gonçalo Sousa, Braz, João, Melo, J. Sérgio Seixas de, Piñeiro Gomez, Marta, Botelho, Maria Filomena, Pinho e Melo, Teresa M. V. D.
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10316/107505; https://doi.org/10.1039/d0md00433b
• topic: Photodynamic Therapy; Ring-Fused Chlorins; PEGylated Photosensitizers; Fluorinated Photosensitizer; Skin Malignant Melanoma; Esophageal Adenocarcinoma

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.