Park Seyeon
Department of Applied Chemistry, Dongduk Women's University, Seoul 136-714, Korea.
Nutrients. 2015 Oct 30;7(11):8987-9004. doi: 10.3390/nu7115445.
A target-based approach has been used to develop novel drugs in many therapeutic fields. In the final stage of intracellular signaling, transcription factor-DNA interactions are central to most biological processes and therefore represent a large and important class of targets for human therapeutics. Thus, we focused on the idea that the disruption of protein dimers and cognate DNA complexes could impair the transcriptional activation and cell transformation regulated by these proteins. Historically, natural products have been regarded as providing the primary leading compounds capable of modulating protein-protein or protein-DNA interactions. Although their mechanism of action is not fully defined, polyphenols including flavonoids were found to act mostly as site-directed small molecule inhibitors on signaling. There are many reports in the literature of screening initiatives suggesting improved drugs that can modulate the transcription factor interactions responsible for disease. In this review, we focus on polyphenol compound inhibitors against dimeric forms of transcription factor components of intracellular signaling pathways (for instance, c-jun/c-fos (Activator Protein-1; AP-1), c-myc/max, Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and β-catenin/T cell factor (Tcf)).
基于靶点的方法已被用于许多治疗领域开发新型药物。在细胞内信号传导的最后阶段,转录因子与DNA的相互作用是大多数生物过程的核心,因此是一大类重要的人类治疗靶点。因此,我们关注这样一种观点,即蛋白质二聚体和同源DNA复合物的破坏可能会损害这些蛋白质调节的转录激活和细胞转化。从历史上看,天然产物一直被视为能够调节蛋白质-蛋白质或蛋白质-DNA相互作用的主要先导化合物。尽管其作用机制尚未完全明确,但包括黄酮类化合物在内的多酚类物质大多被发现是信号传导方面的位点定向小分子抑制剂。文献中有许多关于筛选计划的报道,表明有改进的药物可以调节导致疾病的转录因子相互作用。在本综述中,我们重点关注针对细胞内信号通路转录因子成分二聚体形式的多酚化合物抑制剂(例如,c-jun/c-fos(激活蛋白-1;AP-1)、c-myc/max、活化B细胞的核因子κB轻链增强子(NF-κB)和β-连环蛋白/T细胞因子(Tcf))。