Ring-Fused meso-Tetraarylchlorins as Auspicious PDT Sensitizers: Synthesis, Structural Characterization, Photophysics, and Biological Evaluation

• Tipo: Artigo em Revista Científica Internacional
• Data: 2022

Autores

Laranjo, M (Autor) Outra; Pereira, NAM (Autor) Outra; Oliveira, ASR (Autor) Outra; Aguiar, MC (Autor) Outra; Brites, G (Autor) Outra; Nascimento, BFO (Autor) Outra; Serambeque, B (Autor) Outra; Costa, BDP (Autor) Outra; Pina, J (Autor) Outra; de Melo, JSS (Autor) Outra; Pineiro, M (Autor) Outra; Botelho, MF (Autor) Outra; Melo, TMVDPE (Autor) Outra

Revista

Título: Frontiers in Chemistry

Vol. 10

ISSN: 2296-2646

Editora: FRONTIERS MEDIA SA

Indexação

ISI Web of Knowledge - 2 Citações

Scopus - 2 Citações

Outras Informações

ID Authenticus: P-00W-NDG

DOI: 10.3389/fchem.2022.873245

Abstract (EN): 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.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 14