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
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.
Bioorg Med Chem. 2007 Mar 15;15(6):2421-33. doi: 10.1016/j.bmc.2007.01.013. Epub 2007 Jan 17.
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.
我们在此描述了LASSBio - 881（3c）作为一种新型的体内具有抗伤害感受、抗炎作用，体外具有抗增殖和抗氧化作用的化合物的发现，其具有大麻素配体特征。我们观察到LASSBio - 881（3c）能够与CB1受体结合（在100微摩尔时结合率为71%），并且可能通过与CB2受体结合，以非促凋亡的方式抑制T细胞增殖（在10微摩尔时抑制率为66%），这与花生四烯乙醇胺（1）不同。还证明了LASSBio - 881（3c）对自由基（DPPH和羟基自由基）具有重要的抗氧化特性，这可能归因于其特殊的氧化还原行为，循环伏安法研究表明这反映了硝基和3,5 - 二叔丁基 - 4 - 羟基苯基亚基的存在。此外，我们表明这些结构亚基对于观察到的药理活性至关重要。
Zotero 插件