Cholinesterase Inhibition Activity, Alkaloid Profiling and Molecular Docking of Chilean Rhodophiala (Amaryllidaceae)

Abstract

Amaryllidaceae plants are the commercial source of galanthamine, an alkaloid approved for the clinical treatment of Alzheimer’s disease. The chemistry and bioactivity of Chilean representatives of Rhodophiala genus from the family of Amaryllidaceae have not been widely studied so far. Ten collections of five different Chilean Rhodophiala were analyzed in vitro for activity against enzymes such as acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) as well as for their alkaloid composition by GC-MS. To obtain an insight into the potential AChE and BuChE inhibitory activity of the alkaloids identified in the most active samples, docking experiments were carried out. Although galanthamine was found neither in aerial parts nor in bulbs of R. splendens, these plant materials were the most active inhibitors of AChE (IC50: 5.78 and 3.62 μg/mL, respectively) and BuChE (IC50: 16.26 and 14.37 μg/mL, respectively). Some 37 known alkaloids and 40 still unidentified compounds were detected in the samples, suggesting high potential in the Chilean Amaryllidaceae plants as sources of both novel bioactive agents and new alkaloids.

In vitro micropropagation and alkaloids analysis by GC–MS of Chilean Amaryllidaceae plants: Rhodophiala pratensis

“…Previous studies in species of the Rhodophiala genus have reported the presence of 37 alkaloids characteristic of the family Amaryllidaceae and 40 compounds corresponding to alkaloids, which according to their fragmentation patterns would present a skeleton of the lycorine type, haemanthamine, tazettine, homolycorine, galanthamine, montanine and narciclasine . Our study contributes to the knowledge of the alkaloids present in the species R. pratensis , which had not been included in the previously reported studies.…”

“…However, other alkaloids such as haemanthamine, that appears in the samples studied in this work, present serious problems of thermal‐decomposition in GC, so its quantification is not reliable. Therefore, our work followed the conditions described previously, which used the areas of different alkaloids and standardised with the area of codeine (internal standard).…”

“…However, other alkaloids such as haemanthamine, that appears in the samples studied in this work, present serious problems of thermal-decomposition in GC, so its quantification is not reliable. Therefore, our work followed the conditions described previously, 9,13 Table 2. Internal standard (IS): codeine; IAA, indole acetic acid; BAP, 6-benzylaminopurine; 2,4-D, 2,4-dichlorophenoxyacetic SCHEME 1 Biosynthetic relationships between the different alkaloid types identified in Rhodophiala pratensis 18 For instance, 2,4-D induces callus formation when it is used in combination with auxins because it promotes DNA synthesis and mitosis.…”

“…which used the areas of different alkaloids and standardised with the area of codeine (internal standard).Previous studies in species of the Rhodophiala genus have reported the presence of 37 alkaloids characteristic of the family Amaryllidaceae and 40 compounds corresponding to alkaloids, which according to their fragmentation patterns would present a skeleton of the lycorine type, haemanthamine, tazettine, homolycorine, galanthamine, montanine and narciclasine 9,14,15. Our study contributes to the knowledge of the alkaloids present in the species R. pratensis, which had not been included in the previously reported studies.When comparing the amount and type of alkaloids obtained from both wild bulbs and those obtained by in vitro culture, it can be observed that wild plants have 34 alkaloids whereas in vitro bulbs show only 12.…”

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.…”