Please use this identifier to cite or link to this item: https://hdl.handle.net/10316/107428
Title: Ring-Fused meso-Tetraarylchlorins as Auspicious PDT Sensitizers: Synthesis, Structural Characterization, Photophysics, and Biological Evaluation
Authors: Laranjo, Mafalda 
Pereira, Nelson A. M. 
Oliveira, Andreia S. R. 
Aguiar, Márcia Campos 
Brites, Gonçalo Sousa 
Nascimento, Bruno F. O. 
Serambeque, Beatriz 
Costa, Bruna D. P. 
Pina, João 
Seixas de Melo, J. Sérgio 
Pineiro, Marta 
Botelho, M. Filomena 
Pinho e Melo, Teresa M. V. D. 
Keywords: chlorins; photodynamic therapy; photosensitizer; subcellular accumulation; cancer
Issue Date: 2022
Publisher: Frontiers
Project: Project PTDC/QUI-QOR/0103/2021 was financed by Fundação para a Ciência e a Tecnologia (FCT), I.P./MCTES, by national funds (PIDDAC). Coimbra Chemistry Centre (CQC) was supported by FCT under projects UIDB/00313/2020 and UIDP/00313/2020. CIBB was funded by FCT Strategic Projects UID/NEU/04539/2019, UIDB/04539/2020, and UIDP/04539/ 2020 and the support of Teresa Ribeiro-Rodrigues from the iLAB, where image acquisition was performed. iLAB is the Microscopy and Bioimaging Lab, a facility of Faculty of Medicine of University of Coimbra and a node of the Portuguese Platform of BioImaging (PPBI), supported by POCI-01-0145-FEDER-022122. 
Serial title, monograph or event: Frontiers in Chemistry
Volume: 10
Abstract: Novel 4,5,6,7-tetrahydropyrazolo[1,5-a]pyridine-fused meso-tetraarylchlorins, with different degrees of hydrophilicity (with methyl ester, hydroxymethyl, and carboxylic acid moieties), have been synthesized and their photophysical characterization as well as in vitro photocytotoxicity assessment against human melanoma and esophageal and bladder carcinomas was carried out. An integrated analysis of the photosensitizers' performance, considering the singlet oxygen generation data, cell internalization, and intracellular localization, allowed to establish relevant structure-photoactivity relationships and the rationalization of the observed photocytotoxicity. In the diacid and monoalcohol series, chlorins derived from meso-tetraphenylporphyrin proved to be the most efficient photodynamic therapy agents, showing IC50 values of 68 and 344 nM against A375 cells, respectively. These compounds were less active against OE19 and HT1376 cells, the diacid chlorin with IC50 values still in the nano-molar range, whereas the monohydroxymethyl-chlorin showed significantly higher IC50 values. The lead di(hydroxymethyl)-substituted meso-tetraphenylchlorin confirmed its remarkable photoactivity with IC50 values below 75 nM against the studied cancer cell lines. Subcellular accumulation of this chlorin in the mitochondria, endoplasmic reticulum, and plasma membrane was demonstrated.
URI: https://hdl.handle.net/10316/107428
ISSN: 2296-2646
DOI: 10.3389/fchem.2022.873245
Rights: openAccess
Appears in Collections:FMUC Medicina - Artigos em Revistas Internacionais
I&D CIBB - Artigos em Revistas Internacionais
I&D ICBR - Artigos em Revistas Internacionais
I&D CQC - Artigos em Revistas Internacionais

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