Costa Débora S S, Martino Thiago, Magalhães Fernanda C, Justo Graça, Coelho Marsen G P, Barcellos Julio C F, Moura Victor B, Costa Paulo R R, Sabino Kátia C C, Dias Ayres G
Laboratório de Química Bioorgânica, IPPN, CCS, s H1027, Cidade Universitária, Universidade Federal do Rio de Janeiro, Brazil.
Laboratório Imunologia Aplicada e Bioquímica de Proteínas e Produtos Naturais, IBRAG, Universidade do Estado do Rio de Janeiro, Brazil.
Bioorg Med Chem. 2015 May 1;23(9):2053-61. doi: 10.1016/j.bmc.2015.03.014. Epub 2015 Mar 10.
New O-isoprenylated-N-methylarylnitrones derived from isomeric o, m and p-hydroxybenzaldehydes have been prepared and the antineoplastic effects on human cancer cell lines were evaluated. The O-geranylated nitrone LQB-278 (1b) and its isomers 2b and 3b inhibited the NO production, but the anti-leukemic activity was drastically dependent on nitrone isomer, with the 1b being the most effective one (IC₅₀ of 6.7 μM) on Jurkat leukemia cell, by MTT assay. In addition, 1b up-regulated p21CIP1/WAF1/Sdi1 protein expression (flow cytometry), a cell cycle inhibitor, reduced cell growth, and induced DNA fragmentation (increased sub-G1 phase cells) and phosphatidylserine externalization in plasmatic membrane (increased annexin V positive cells). Finally, the 1b up-regulation of p21 expression and apoptosis induction seem to be the mechanisms by which it promotes its anti-leukemic effects, making this new molecular architecture a promising prototype for leukemia intervention.
