The Amaryllidaceae alkaloids: an untapped source of acetylcholinesterase inhibitors

Abstract

The AChE inhibitory activity of alkaloid extracts and compounds has been in the focus of research on the plants of Amaryllidoideae subfamily since the approval of galanthamine in 2001 by FDA for treatment of mild to moderate Alzheimer's disease. A small fraction of the huge biodiversity of the plants producing Amaryllidaceae alkaloids has been studied as a source of AChE inhibitors. Less than 20% of the known Amaryllidaceae alkaloids have been tested in vitro for their ability to inhibit AChE. Galanthamine, lycorine and haemanthamine are scaffolds for semi-synthesis of potent AChE inhibitors. In the last years, galanthamine has been studied in silico for drug optimization and synthesis of potent dual-binding AChE inhibitors. In silico studies of other Amaryllidaceae alkaloids have also provoked the interest of researchers in the last years. The aim of this article is to provide a comprehensive review on studies of the AChE inhibitory activity of extracts and compounds from the plants of Amaryllidoideae subfamily covering the literature from the last two decades.

Exploiting Natural Niches with Neuroprotective Properties: A Comprehensive Review

“…In fact, over 100 cultivars from the Amaryllidoideae subfamily have been studied for their AChE inhibitory activity [92]. Compounds derived from diverse skeleton types have demonstrated potent AChE inhibitory properties, thereby presenting avenues for structure optimization and the semi-synthesis of potent AChE inhibitors [93]. Among these, Galanthamine, which was approved in 2001 by the FDA for AD treatment, showed a strong AChE inhibitory activity (IC 50 of 0.3-0.5 µM) [20], exerted by inhibiting substrate accommodation and hydrolysis in the active site of the enzyme [94].…”

A Comparative Study between Lycorine and Galantamine Abilities to Interact with AMYLOID β and Reduce In Vitro Neurotoxicity

“…In addition to GAL, other Amaryllidaceae alkaloids have strong AChE inhibitory activity. Among these haemanthamine, narciclasine, crinine and lycorine have recently been considered [32,[45][46][47]. All of these alkaloids, strictly related to the leading compound galantamine, have interesting features and deserve to be further investigated for promoting new natural molecules for AD treatment.…”

Evaluation of Mollugo oppositifolia Linn. as cholinesterase and β-secretase enzymes inhibitor

“…Physostigmine from Physostigma venenosum Balf. is another AChE inhibitor that provided a scaffold for the development of more effective cholinesterase inhibitors like rivastigmine ( Berkov et al, 2021 ). Besides, there are several other drug candidates under different phases of the clinical trial for example Huperzine A from Huperzia serrata (Thunb.)…”