title: Synthesis, characterization and biological evaluation of carboranylmethylbenzo[b]acridones as novel agents for boron neutron capture therapy.
abstract: 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.
authors.affiliation: Departamento de Química-QOPNA, Universidade de Aveiro, 3810-193 Aveiro, Portugal.
authors.forename: A Filipa F
authors.initials: AF
authors.lastname: da Silva
authors.forename: Raquel S G R
authors.initials: RS
authors.lastname: Seixas
authors.forename: Artur M S
authors.initials: AM
authors.lastname: Silva
authors.forename: Joana
authors.initials: J
authors.lastname: Coimbra
authors.forename: Ana C
authors.initials: AC
authors.lastname: Fernandes
authors.forename: Joana P
authors.initials: JP
authors.lastname: Santos
authors.forename: António
authors.initials: A
authors.lastname: Matos
authors.forename: José
authors.initials: J
authors.lastname: Rino
authors.forename: Isabel
authors.initials: I
authors.lastname: Santos
authors.forename: Fernanda
authors.initials: F
authors.lastname: Marques
mesh_terms: D054831:Acridones / Q000138:chemical synthesis* / Q000494:pharmacology; D008841:Actin Cytoskeleton / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects / Q000648:ultrastructure; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001692:Biological Transport; D001896:Boron Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D016754:Boron Neutron Capture Therapy / Q000379:methods; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects / Q000648:ultrastructure; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D018613:Microscopy, Confocal; D009457:Neuroglia / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects / Q000648:ultrastructure; D009502:Neutrons
chemical_list: D054831:Acridones; D000970:Antineoplastic Agents; D001896:Boron Compounds