Department of Chemistry, Purdue University, 560 Oval Drive, West Lafayette, IN 47907-2084, USA.
Future Med Chem. 2009 Apr;1(1):179-200. doi: 10.4155/fmc.09.15.
The nuclear transcription factor NF-κB has gained considerable importance due to its major involvement in inflammation and constitutive activity in malignant cells. It is induced by a variety of stimuli and controls the expression of several proteins involved in biological processes. Numerous natural products and synthesized organic molecules have been reported to inhibit NF-κB and have played an integral role in identifying implicated pathways. Prominent among them are the sesquiterpene lactones, polyphenolic enones and other α,β-unsaturated carbonyl-containing molecules, particularly α-methylene-γ-butyrolactones.
This mini-review provides an introductory overview of some of the associated pathways involving NF-κB in cancer and discusses the structures and mode of action of natural α,β-unsaturated carbonyl-containing inhibitors and their synthetic counterparts. A review of the recent methods for the synthesis of α-alkylidene-γ-butyrolactones is also provided, with the aim of arousing the interest of synthetic chemists for the design and development of novel NF-κB inhibitors.
Modulating damaging effects without harming the inflammatory and immune responses are crucial parameters for developing NF-κB inhibitors. Examination of novel α,β-unsaturated carbonyls and the further discovery of simple methods to prepare such molecules should lead to the identification of site-specific inhibitors.
核转录因子 NF-κB 由于其在炎症和恶性细胞中的组成性活性中的重要作用而备受关注。它由多种刺激诱导，并控制参与生物过程的几种蛋白质的表达。据报道，许多天然产物和合成有机分子能够抑制 NF-κB，并在确定相关途径方面发挥了重要作用。其中突出的是倍半萜内酯、多酚烯酮和其他α，β-不饱和羰基化合物，特别是α-亚甲基-γ-丁内酯。
这篇迷你评论提供了一些与癌症中 NF-κB 相关的途径的介绍性概述，并讨论了天然α，β-不饱和羰基抑制剂及其合成对应物的结构和作用模式。还提供了对α-亚烷基-γ-丁内酯合成方法的最新综述，旨在引起合成化学家对设计和开发新型 NF-κB 抑制剂的兴趣。
在不损害炎症和免疫反应的情况下调节破坏性影响是开发 NF-κB 抑制剂的关键参数。对新型α，β-不饱和羰基化合物的研究以及发现制备此类分子的简单方法，应能鉴定出具有特定作用部位的抑制剂。
