Bioorg Med Chem. 2007 Mar 15;15(6):2421-33. Epub 2007 Jan 17.

Synthesis, pharmacological evaluation and electrochemical studies of novel 6-nitro-3,4-methylenedioxyphenyl-N-acylhydrazone derivatives: Discovery of LASSBio-881, a new ligand of cannabinoid receptors.

Duarte CD, Tributino JL, Lacerda DI, Martins MV, Alexandre-Moreira MS, Dutra F, Bechara EJ, De-Paula FS, Goulart MO, Ferreira J, Calixto JB, Nunes MP, Bertho AL, Miranda AL, Barreiro EJ, Fraga CA.

Source

LASSBio--Laboratório de Avaliação e Síntese de Substâncias Bioativas, Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, PO Box 68006, 21944-971, Rio de Janeiro, RJ, Brazil.

Abstract

We describe herein the discovery of LASSBio-881 (3c) as a novel in vivo antinociceptive, anti-inflammatory, and in vitro antiproliferative and antioxidant compound, with a cannabinoid ligand profile. We observed that LASSBio-881 (3c) was able to bind to CB1 receptors (71% at 100microM) and also to inhibit T-cell proliferation (66% at 10microM) probably by binding to CB2 receptors, in a non-proapoptotic manner, different from anandamide (1). It was also demonstrated that LASSBio-881 (3c) had an important antioxidant profile toward free radicals (DPPH and hydroxyl), probably due to its particular redox behavior, which reflects the presence of both nitro and 3,5-di-tert-butyl-4-hydroxyphenyl sub-units, as demonstrated by cyclic voltammetry studies. In addition, we showed that these structural sub-units are essential for the observed pharmacological activity.