Chemical Profiling and Cholinesterase Inhibitory Activity of Five Phaedranassa Herb. (Amaryllidaceae) Species from Ecuador

Abstract

It is estimated that 50 million people in the world live with dementia, 60–70% of whom suffer from Alzheimer’s disease (AD). Different factors are involved in the development of AD, including a reduction in the cholinergic neurotransmission level. The Amaryllidaceae plant family contains an exclusive, large, and still understudied alkaloid group characterized by a singular skeleton arrangement and a broad spectrum of biological activities. The chemistry and biodiversity of Ecuadorian representatives of the Phaedranassa genus (Amaryllidaceae) have not been widely studied. In this work, five Ecuadorian Phaedranassa species were examined in vitro for their activity towards the enzymes acetyl- (AChE) and butyrylcholinesterase (BuChE), and the alkaloid profile of bulb extracts was analyzed by GC-MS. The species Phaedranassa cuencana and Phaedranassa dubia showed the most AChE and BuChE inhibitory activity, respectively. To obtain insight into the potential role of the identified alkaloids in these inhibitory effects, docking experiments were carried out, and cantabricine showed in silico inhibitory activity against both cholinesterase structures. Our results show that Amaryllidaceae species from Ecuador are a potential source of new drugs for the palliative treatment of AD.

Alkaloids of Phaedranassa dubia (Kunth) J.F. Macbr. and Phaedranassa brevifolia Meerow (Amaryllidaceae) from Ecuador and its cholinesterase-inhibitory activity

“…In a previous study, a similar alkaloid profile was reported for another P. dubia sample collected in Ecuador at the Pichincha (Pululahua) locality ( Moreno et al., 2020 ). The authors described the presence of anhydrolycorine, 11,12-dehydroanhydrolycorine, lycorine, galanthamine, N -demethylgalanthamine and one unidentified compound, m/z 268 [M + =329] in this species ( Moreno et al., 2020 ).…”

“…In a previous study, a similar alkaloid profile was reported for another P. dubia sample collected in Ecuador at the Pichincha (Pululahua) locality ( Moreno et al., 2020 ). The authors described the presence of anhydrolycorine, 11,12-dehydroanhydrolycorine, lycorine, galanthamine, N -demethylgalanthamine and one unidentified compound, m/z 268 [M + =329] in this species ( Moreno et al., 2020 ). In another work, a different alkaloidal composition was reported for P. dubia collected in Colombia, which presented seven alkaloids: phaedranamine, haemanthamine, pseudolycorine, ungeremine, zefbetaine, sanguinine, galanthamine and epinorgalanthamine ( Osorio et al., 2010 ).…”

“…The AChE and BuChE results obtained for P. dubia sample contrast with Moreno et al. (2020) , which obtained IC 50 values of 2.20 ± 0.08 and 14.26 ± 2.71 μg.mL −1 , respectively, for the same species.…”

“…All optimized alkaloids were confirmed as a minimum on the potential energy surface. Docking simulations for the set of optimized ligands were performed using the AutoDock v.4.2 program (Molecular Graphics Laboratory, La Jolla, USA) ( Moris et al., 2009 ) as described at Moreno et al. (2020) .…”

Chemistry and Biological Activity of Alkaloids from the Genus Lycoris (Amaryllidaceae)

“…Three AChE inhibitors, namely donepezil, galanthamine ( 13 ) and rivastigmine, are currently used as the main therapeutic option for AD treatment [ 72 ]. Since the Amaryllidaceae alkaloid galanthamine ( 13 ) has been introduced into clinical practice, other Amaryllidaceae alkaloids have received attention as potential AChE inhibitors [ 5 , 73 , 74 , 75 , 76 ]. Surprisingly, only a few AAs isolated from Lycoris plants have been studied in terms of their AChE inhibition potential.…”