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
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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DOI：
10.1016/j.bmc.2007.01.013
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发表时间：
2007-03-15
影响因子：
3.5
通讯作者：
Fraga, Carlos A. M.
中科院分区：
文献类型：
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作者：
Duarte, Carolina D.;Tributino, Jorge L. M.;Fraga, Carlos A. M.
我们在本文中描述了发现LASSBio-881（3c）作为具有大麻素配体特征的新型体内抗伤害感受、抗炎和体外抗增殖和抗氧化化合物。我们观察到LASSBio-881（3c）能够与CBI受体结合（100 μ M时为71%），并且还能够抑制T细胞增殖（10 μ M时为66%），这可能是通过与CB 2受体结合，以非促凋亡的方式，不同于大麻素（1）。还证明了LASSBio-881（3c）对自由基（DPPH和羟基）具有重要的抗氧化剂特性，这可能是由于其特定的氧化还原行为，其反映了硝基和3，5-二叔丁基-4-羟基苯基亚单元的存在，如通过循环伏安法研究所证明的。此外，我们发现，这些结构亚单位是必不可少的观察到的药理活性。(c)2007爱思唯尔有限公司保留所有权利。
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 CBI receptors (71% at 100 mu M) and also to inhibit T-cell proliferation (66% at 10 mu M) 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. (c) 2007 Elsevier Ltd. All rights reserved.