Wallert Maria, Kluge Stefan, Schubert Martin, Koeberle Andreas, Werz Oliver, Birringer Marc, Lorkowski Stefan
Department of Biochemistry and Physiology of Nutrition, Institute of Nutritional Sciences, Friedrich Schiller University Jena, Jena, Germany.
Department of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, Friedrich Schiller University Jena, Jena, Germany.
Front Pharmacol. 2020 Apr 21;11:362. doi: 10.3389/fphar.2020.00362. eCollection 2020.
Natural chromanols and chromenols comprise a family of molecules with enormous structural diversity and biological activities of pharmacological interest. A recently published systematic review described more than 230 structures that are derived from a chromanol ortpd chromenol core. For many of these compounds structure-activity relationships have been described with mostly anti-inflammatory as well as anti-carcinogenic activities. To extend the knowledge on the biological activity and the therapeutic potential of these promising class of natural compounds, we here present a report on selected chromanols and chromenols based on the availability of data on signaling pathways involved in inflammation, apoptosis, cell proliferation, and carcinogenesis. The chromanol and chromenol derivatives seem to bind or to interfere with several molecular targets and pathways, including 5-lipoxygenase, nuclear receptors, and the nuclear-factor "kappa-light-chain-enhancer" of activated B-cells (NFκB) pathway. Interestingly, available data suggest that the chromanols and chromenols are promiscuitively acting molecules that inhibit enzyme activities, bind to cellular receptors, and modulate mitochondrial function as well as gene expression. It is also noteworthy that the molecular modes of actions by which the chromanols and chromenols exert their effects strongly depend on the concentrations of the compounds. Thereby, low- and high-affinity molecular targets can be classified. This review summarizes the available knowledge on the biological activity of selected chromanols and chromenols which may represent interesting lead structures for the development of therapeutic anti-inflammatory and chemopreventive approaches.
天然色满醇和色烯醇包含一类结构多样性巨大且具有药理学意义生物活性的分子。最近发表的一项系统综述描述了230多种源自色满醇或色烯醇核心的结构。对于其中许多化合物，已经描述了其构效关系，主要具有抗炎和抗癌活性。为了扩展对这类有前景的天然化合物的生物活性和治疗潜力的认识，我们在此基于有关炎症、细胞凋亡、细胞增殖和致癌作用相关信号通路的数据可用性，给出一份关于选定色满醇和色烯醇的报告。色满醇和色烯醇衍生物似乎能结合或干扰多种分子靶点和信号通路，包括5-脂氧合酶、核受体以及活化B细胞的核因子“κ轻链增强子”（NFκB）信号通路。有趣的是，现有数据表明色满醇和色烯醇是具有多种作用的分子，它们能抑制酶活性、结合细胞受体并调节线粒体功能以及基因表达。同样值得注意的是，色满醇和色烯醇发挥作用的分子作用模式很大程度上取决于化合物的浓度。由此，可以区分低亲和力和高亲和力分子靶点。本综述总结了关于选定色满醇和色烯醇生物活性的现有知识，这些化合物可能是开发抗炎治疗和化学预防方法的有趣先导结构。
