The Lycopodium alkaloids

Abstract

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.

A review of the use of pteridophytes for treating human ailments

“…Huperzine A obtained from Huperzia species and other members of the Lycopodiaceae, has been shown to improve memory in animals. Huperzia quadrifariata and Huperzia reflexa were also found to cure Alzheimer's disease (Ma and Gang, 2004;Ma et al, 2007;Singh and Singh, 2010;Konrath et al, 2012;Yang et al, 2012). Amentoflavone and ginkgetin, flavonoids found in Selaginella, display neurodefensive activity against cytotoxic stress, which suggests their promising usage to cure neurodegenerative diseases such as stroke and Alzheimer's (Kang et al, 2004).…”

New Lycopodium alkaloids from Lycopodium obscurum

“…1,2 Since the impressively diverse skeletons and interesting biological activities, these alkaloids continue to be of interest from a biogenetic and biological point of view and some of them have been challenging targets for total synthesis. [3][4][5] Lycopodium obscurum L., one of the club moss, has been used in China as a traditional folk medicine for the treatment of contusion, dysmenorrhea, quadriplegia, and arthritic pain.…”

O-iodoxybenzoic acid in water: optimized green alternative for multicomponent one-pot synthesis of 2-amino-3,5-dicarbonitrile-6-thiopyridines

“…These potential therapeutic applications made it as a privileged scaffold. [1][2][3] 2-Amino-3,5-dicarbonitrile-6-thiopyridine derivatives are not only used as anti-prion, 4,5 anti-hepatitis B virus, 6 anti-bacterial 7 and anti-cancer 8 agents but also are used as potassium channel openers for the treatment of urinary incontinence. 9 Recently, it is being used in treatment of Parkinson's disease, hypoxia, asthma, kidney disease, epilepsy, cancer 10 and creutzfeldt-jacob disease.…”