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 |
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| Authors: | Duarte Carolina D Tributino Jorge L M Lacerda Daniel I Martins Marina V Alexandre-Moreira Magna S Dutra Fernando Bechara Etelvino J H De-Paula Francine S Goulart Marilia O F Ferreira Juliano Calixto João B Nunes Marise P Bertho Alvaro L Miranda Ana Luisa P Barreiro Eliezer J Fraga Carlos A M |
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| Affiliation: | 1. 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;2. Programa de Pós-Graduação em Química Orgânica, Instituto de Química, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil;3. Departamento de Farmacologia Básica e Clínica, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil;4. LaFI—Laboratório de Farmacologia e Imunidade, Departamento de Fisiologia, Centro de Ciências Biológicas, Universidade Federal de Alagoas, Maceió, AL, Brazil;5. Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, SP, Brazil;6. Instituto de Química e Biotecnologia, Universidade Federal de Alagoas, Maceió, AL, Brazil;7. Departamento de Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil;8. Departamento de Imunologia, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil |
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| 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. |
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