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.

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 100 μM) and also to inhibit T-cell proliferation (66% at 10 μM) 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.