Details

Autor(en) / Beteiligte

• Pereira, Nelson A. M
• Laranjo, Mafalda
• Nascimento, Bruno F. O
• Simões, João C. S
• Pina, João
• Costa, Bruna D. P
• Brites, Gonçalo
• Braz, João
• Seixas de Melo, J. Sérgio
• Pineiro, Marta
• Botelho, Maria Filomena
• Pinho e Melo, Teresa M. V. D

Titel

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

Ist Teil von

• RSC medicinal chemistry, 2021-04, Vol.12 (4), p.615-627

Ort / Verlag

England: RSC

Erscheinungsjahr

2021

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• 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 S N Ar 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 IC 50 values, 13 and 27 nM against human melanoma and esophageal carcinoma cell lines, respectively. Novel 4,5,6,7-tetrahydropyrazolo[1,5- a ]pyridine-fused chlorins, derived from 5,10,15,20-tetrakis(pentafluorophenyl)porphyrin, as impressive photosensitizers for photodynamic therapy of melanoma and esophagus cancer have been developed.