Ma Xiaoqiang, Gang David R
Department of Plant Sciences and Bio5 Institute, University of Arizona, 303 Forbes Building, Tucson, AZ 85721-0036, USA.
Nat Prod Rep. 2004 Dec;21(6):752-72. doi: 10.1039/b409720n. Epub 2004 Oct 21.
Lycopodium alkaloids are quinolizine, or pyridine and alpha-pyridone type alkaloids. Some Lycopodium alkaloids are potent inhibitors of acetylcholinesterase (AChE). Huperzine A (HupA) is reported to increase efficiency for learning and memory in animals, and it shows promise in the treatment of Alzheimer's disease (AD). 201 Lycopodium alkaloids from 54 species of Lycopodium (sensu lato) have been reported so far. This review is intended to to cover the chemical, pharmacological and clinical research on Lycopodium alkaloids reported in the literature from the spring of 1993 to August 2004. Structures of 81 new Lycopodium alkaloids are presented, classified and analyzed. The structural characters and biogenetic relationships of the four major Lycopodium alkaloid groups (lycopodine, lycodine, fawcettimine and miscellaneous) are discussed. Bioactivities of Lycopodium alkaloids, especially HupA, are summarized. In particular, the effect of HupA and other cholinesterase inhibitors (anti-AD drugs) on acetylcholine esterase (AChE) activity in the rat cortex and butylcholine esterase activity are compared. Structure-activity relationships and structure modifications of HupA and its analogs are described. Information on clinical trials with HupA and its derivative ZT-1 is presented. The state of HupA availability and recent advances in in vitro propagation of HupA producing plants are outlined. Finally, hypotheses about Lycopodium alkaloid biosynthetic pathways are discussed.
石松生物碱是喹嗪类、吡啶类和α-吡啶酮类生物碱。一些石松生物碱是乙酰胆碱酯酶（AChE）的有效抑制剂。据报道，石杉碱甲（HupA）可提高动物的学习和记忆效率，在治疗阿尔茨海默病（AD）方面显示出前景。迄今为止，已报道了来自54种广义石松属植物的201种石松生物碱。本综述旨在涵盖1993年春季至2004年8月文献中报道的石松生物碱的化学、药理学和临床研究。介绍、分类并分析了81种新石松生物碱的结构。讨论了四大类石松生物碱（石松定碱、石松碱、法西替明及其他类）的结构特征和生源关系。总结了石松生物碱的生物活性，尤其是石杉碱甲的生物活性。特别比较了石杉碱甲和其他胆碱酯酶抑制剂（抗AD药物）对大鼠皮层乙酰胆碱酯酶（AChE）活性和丁酰胆碱酯酶活性的影响。描述了石杉碱甲及其类似物的构效关系和结构修饰。介绍了石杉碱甲及其衍生物ZT-1的临床试验信息。概述了石杉碱甲的可得状态以及产石杉碱甲植物体外繁殖的最新进展。最后，讨论了关于石松生物碱生物合成途径的假说。
