Galanthamine inhibitory activity

Extracts of some amaryllids, as well as alkaloids isolated therefrom, have exhibited various biological activities. These activities cover central nervous system, antitumor, antiviral, antibacterial, anti-inflammatory and antiparasitic conditions 8, 18, 52, 53, 54). However, the more recently demonstrated potent anticancer activity of pancratistatin 14 and the selective, reversible acetylcholinestrase (ACHE) inhibitory activity of galanthamine 5 has fuelled the search for bioactive Amaryllidaceae alkaloids toward the development of antitumor and anti-Alzheimer s drags 55). 

Sanguinine (81) has a more potent acetylcholinesterase inhibitory activity than galanthamine (75) due to an extra hydroxyl group available for potential interaction with acetylcholinesterase (93,555). Sanguinine, in turn, is 10-fold more selective than galanthamine for acetylcholinesterase (AChE) vs. butyrylcholinesterase (BuChE)... 

Compared with AChE in animals such as horse and rat, HA is a weaker inhibitor of human serum BuChE. This selectivity for AChE as opposed to BuChE (similar to that of galanthamine) may suggest a better side-effects profile. However, a stronger inhibition of BuChE could be important in the later stage of AD and could offer more protection over amyloid p-peptide (Ap) plaque deposition. In contrast to isoflurophate, the AChE activity did not decrease with the prolongation of incubation with HA in vitro, and the AChE activity returned to 94% of the control after being washed five times, which indicates a reversible inhibitory action. ... 

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