Grycová Lenka, Dostál Jirí, Marek Radek
National Center for Biomolecular Research, Faculty of Science, Masaryk University, Kamenice 5/A4, CZ-625 00 Brno, Czech Republic.
Phytochemistry. 2007 Jan;68(2):150-75. doi: 10.1016/j.phytochem.2006.10.004. Epub 2006 Nov 15.
This contribution reviews some general aspects of the quaternary iminium protoberberine alkaloids. The alkaloids represent a very extensive group of secondary metabolites with diverse structures, distribution in nature, and biological effects. The quaternary protoberberine alkaloids (QPA), derived from the 5,6-dihydrodibenzo[a,g]quinolizinium system, belong to a large class of isoquinoline alkaloids. Following a general introduction, the plant sources of QPA, their biosynthesis, and procedures for their isolation are discussed. Analytical methods and spectral data are summarized with emphasis on NMR spectroscopy. The reactivity of QPA is characterized by the sensitivity of the iminium bond CN(+) to nucleophilic attack. The addition of various nucleophiles to the protoberberine skeleton is discussed. An extended discussion of the principal chemical reactivity is included since this governs interactions with biological targets. Quaternary protoberberine alkaloids and some related compounds exhibit considerable biological activities. Recently reported structural studies indicate that the QPA interact with nucleic acids predominantly as intercalators or minor groove binders. Currently, investigations in many laboratories worldwide are focused on the antibacterial and antimalarial activity, cytotoxicity, and potential genotoxicity of QPA.
本文综述了季铵型亚胺原小檗碱生物碱的一些一般方面。这些生物碱代表了一类非常广泛的次生代谢产物，具有多样的结构、在自然界中的分布以及生物效应。季铵型原小檗碱生物碱（QPA）源自5,6-二氢二苯并[a,g]喹嗪鎓系统，属于一大类异喹啉生物碱。在进行一般介绍之后，讨论了QPA的植物来源、生物合成及其分离方法。总结了分析方法和光谱数据，重点是核磁共振光谱。QPA的反应活性以亚胺键CN(+)对亲核攻击的敏感性为特征。讨论了各种亲核试剂与原小檗碱骨架的加成反应。由于这决定了与生物靶点的相互作用，因此对主要化学反应活性进行了扩展讨论。季铵型原小檗碱生物碱和一些相关化合物表现出相当大的生物活性。最近报道的结构研究表明，QPA主要作为嵌入剂或小沟结合剂与核酸相互作用。目前，全球许多实验室的研究都集中在QPA的抗菌和抗疟活性、细胞毒性以及潜在的遗传毒性上。
