Autor(es):
Pereira, Nelson A. M. ; 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.
Data: 2021
Identificador Persistente: https://hdl.handle.net/10316/107505
Origem: Estudo Geral - Universidade de Coimbra
Projeto/bolsa:
info:eu-repo/grantAgreement/other/CENTRO-01-0145-FEDER-000014//other;
info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UID/PT;
Assunto(s): Photodynamic Therapy; Ring-Fused Chlorins; PEGylated Photosensitizers; Fluorinated Photosensitizer; Skin Malignant Melanoma; Esophageal Adenocarcinoma
Descrição
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.
The authors thank Coimbra Chemistry Centre (CQC), supported by the Portuguese Agency for Scientific Research, “Fundação para a Ciência e a Tecnologia” (FCT) through project UIDB/00313/2020 and UIDP/QUI/00313/2020, co-funded by COMPETE2020-UE. Center for Innovative Biomedicine and Biotechnology (CIBB) is funded by FCT (UID/NEU/04539/2013) and COMPETE-FEDER (POCI-01-0145-FEDER-007440), through the Strategic Project UIDB/04539/2020 and UIDP/04539/2020. Thanks are also due to CIMAGO (Project 06/2019) and FCT, co-funded by the European Regional Development Fund (FEDER) through Portugal 2020/CENTRO 2020 (CENTRO-01-0145-FEDER-000014/MATIS).
