Nam Nguyen-Hai
University of Pharmacy, 13-15 Le Thanh Tong, Hanoi, Vietnam.
Mini Rev Med Chem. 2006 Aug;6(8):945-51. doi: 10.2174/138955706777934937.
NF-kappaB is a ubiquitous and well-characterised protein responsible for the regulation of complex phenomena, with a pivotal role in controlling cell signalling in the body under certain physiological and pathological conditions. Among other functions, NF-kappaB controls the expression of genes encoding the pro-inflammatory cytokines (e. g., IL-1, IL-2, IL-6, TNF-alpha, etc.), chemokines (e. g., IL-8, MIP-1alpha, MCP1, RANTES, eotaxin, etc.), adhesion molecules (e. g., ICAM, VCAM, E-selectin), inducible enzymes (COX-2 and iNOS), growth factors, some of the acute phase proteins, and immune receptors, all of which play critical roles in controlling most inflammatory processes. Since NF-kappaB represents an important and very attractive therapeutic target for drugs to treat many inflammatory diseases, including arthritis, asthma, and the auto-immune diseases, most attention has been paid in the last decade to the identification of compounds that selectively interfere with this pathway. Recently, a great number of plant-derived substances have been evaluated as possible inhibitors of the NF-kappaB pathway. These include a wide range of compound classess, such as lignans (manassantins, (+)-saucernetin, (-)-saucerneol methyl ether), sesquiterpenes (costunolide, parthenolide, celastrol, celaphanol A), diterpenes (excisanin, kamebakaurin), triterpenes (avicin, oleandrin), polyphenols (resveratrol, epigallocatechin gallate, quercetin), etc. In this mini-review we will discuss the medicinal chemistry of these compounds with regards to the NF-kappaB inhibition.
核因子-κB是一种普遍存在且特征明确的蛋白质,负责调节复杂的生理现象,在某些生理和病理条件下对控制体内细胞信号传导起着关键作用。在其他功能中,核因子-κB控制着编码促炎细胞因子(如白细胞介素-1、白细胞介素-2、白细胞介素-6、肿瘤坏死因子-α等)、趋化因子(如白细胞介素-8、巨噬细胞炎性蛋白-1α、单核细胞趋化蛋白-1、调节激活正常T细胞表达和分泌因子、嗜酸性粒细胞趋化因子等)、黏附分子(如细胞间黏附分子、血管细胞黏附分子、E-选择素)、诱导性酶(环氧化酶-2和诱导型一氧化氮合酶)、生长因子、一些急性期蛋白以及免疫受体的基因的表达,所有这些在控制大多数炎症过程中都起着关键作用。由于核因子-κB是治疗包括关节炎、哮喘和自身免疫性疾病在内的许多炎症性疾病的药物的重要且极具吸引力的治疗靶点,在过去十年中,人们将大部分注意力集中在鉴定选择性干扰该信号通路的化合物上。最近,大量植物来源的物质被评估为核因子-κB信号通路的可能抑制剂。这些物质包括多种化合物类别,如木脂素(马纳桑亭、(+)-异鼠李素、(-)-异鼠李素甲基醚)、倍半萜(木香烃内酯、小白菊内酯、雷公藤红素、塞拉酚A)、二萜(紫衫宁、香榧二萜)、三萜(阿维菌素、夹竹桃苷)、多酚(白藜芦醇、表没食子儿茶素没食子酸酯、槲皮素)等。在本综述中,我们将讨论这些化合物在抑制核因子-κB方面的药物化学。