Fernandes Patricia D, Zardo Renata S, Figueiredo Gabriella S M, Silva Bárbara V, Pinto Angelo C
Universidade Federal do Rio de Janeiro, Instituto de Ciências Biomédicas, Laboratório de Farmacologia da Dor e da Inflamação, Av. Carlos Chagas Filho, 373. Prédio do CCS, bloco J, sala 10, 21941-902 Rio de Janeiro, Brazil.
Universidade Federal do Rio de Janeiro, Instituto de Ciências Biomédicas, Laboratório de Farmacologia da Dor e da Inflamação, Av. Carlos Chagas Filho, 373. Prédio do CCS, bloco J, sala 10, 21941-902 Rio de Janeiro, Brazil.
Life Sci. 2014 Oct 22;116(1):16-24. doi: 10.1016/j.lfs.2014.08.019. Epub 2014 Sep 6.
Convolutamydine A is an oxindole alkaloid that can be isolated from a marine bryozoan. Due to the variety of biological effects, two analogues were synthesized and their anti-inflammatory properties were evaluated.
The anti-inflammatory effects of convolutamydine A and its analogues (ISA003 and ISA147) were investigated in a formalin-induced licking behaviour model, where mice received an intraplantar injection of formalin and their licking behaviour was evaluated for 30min. Additionally, inflammatory parameters were evaluated in a subcutaneous air pouch (SAP) model of carrageenan-induced inflammation. Exudates were collected for leukocyte counts; measurement of protein, prostaglandin E2 (PGE2) and cytokines by ELISA; and analysis of nitric oxide (NO) using a nitrate conversion protocol. Cyclooxygenase-2 (COX2) and inducible nitric oxide synthase (iNOS) from RAW 264.7 cells were quantified by immunoblotting.
Convolutamydine A and its two analogues inhibited the formalin-induced licking response at doses as low as 0.01mg/kg. An inhibitory effect was also observed on leukocyte migration and the production of NO, PGE2 and cytokines (IL-6 and TNF-α). The reduction in inflammatory parameters did not appear to be correlated with a direct reduction in the number of cells in the SAP, because a reduction in NO and PGE2 production by cultured macrophages was observed in addition to the inhibition of iNOS and COX2 enzyme expression.
These results indicate that convolutamydine A and its two analogues have significant anti-inflammatory effects. These substances can be improved to generate lead compounds for the synthesis of new anti-inflammatory drugs.
环褶米定A是一种可从海洋苔藓虫中分离得到的氧化吲哚生物碱。鉴于其具有多种生物学效应，合成了两种类似物并评估了它们的抗炎特性。
在福尔马林诱导的舔舐行为模型中研究环褶米定A及其类似物（ISA003和ISA147）的抗炎作用，给小鼠足底注射福尔马林，然后评估其30分钟内的舔舐行为。此外，在角叉菜胶诱导炎症的皮下气囊（SAP）模型中评估炎症参数。收集渗出液进行白细胞计数；通过酶联免疫吸附测定法测量蛋白质、前列腺素E2（PGE2）和细胞因子；并使用硝酸盐转化方案分析一氧化氮（NO）。通过免疫印迹法定量RAW 264.7细胞中的环氧化酶-2（COX2）和诱导型一氧化氮合酶（iNOS）。
环褶米定A及其两种类似物在低至0.01mg/kg的剂量下即可抑制福尔马林诱导的舔舐反应。还观察到对白细胞迁移以及NO、PGE2和细胞因子（IL-6和TNF-α）产生的抑制作用。炎症参数的降低似乎与SAP中细胞数量的直接减少无关，因为除了抑制iNOS和COX2酶表达外，还观察到培养的巨噬细胞产生的NO和PGE2减少。
这些结果表明环褶米定A及其两种类似物具有显著的抗炎作用。这些物质可以进一步优化以生成用于合成新型抗炎药物的先导化合物。
