Portal de Periódicos da CAPES

Artigo Produção Nacional Revisado por pares

BIBTEX RIS

Synthesis, characterization and biological evaluation of carboranylmethylbenzo[b]acridones as novel agents for boron neutron capture therapy

2014; Royal Society of Chemistry; Volume: 12; Issue: 28 Linguagem: Inglês

10.1039/c4ob00644e

1477-0539

A. Filipa F. da Silva, Raquel S. G. R. Seixas, Artur M. S. Silva, Joana Coimbra, A.C. Fernandes, Joana P. Santos, António Matos, José Rino, Isabel Santos, Fernanda Marques,

Nuclear Physics and Applications

Herein we present the synthesis and characterization of benzo[b]acridin-12(7H)-ones bearing carboranyl moieties and test their biological effectiveness as boron neutron capture therapy (BNCT) agents in cancer treatment. The cellular uptake of these novel compounds into the U87 human glioblastoma cells was evaluated by boron analysis (ICP-MS) and by fluorescence imaging (confocal microscopy). The compounds enter the U87 cells exhibiting a similar profile, i.e., preferential accumulation in the cytoskeleton and membranes and a low cytotoxic activity (IC50 values higher than 200 μM). The cytotoxic activity and cellular morphological alterations after neutron irradiation in the Portuguese Research Reactor (6.6 × 10(7) neutrons cm(-2) s(-1), 1 MW) were evaluated by the MTT assay and by electron microscopy (TEM). Post-neutron irradiation revealed that BNCT has a higher cytotoxic effect on the cells. Accumulation of membranous whorls in the cytoplasm of cells treated with one of the compounds correlates well with the cytotoxic effect induced by radiation. Results provide a strong rationale for considering one of these compounds as a lead candidate for a new generation of BNCT agents.