Cholinesterase-inhibitory effect and in silico analysis of alkaloids from bulbs of Hieronymiella species

ORTIZ, JAVIER E.; GARRO, ADRIANA; PIGNI, NATALIA B.; AGÜERO, MARÍA BELÉN; ROITMAN, GERMAN; SLANIS, ALBERTO; ENRIZ, RICARDO D.; FERESIN, GABRIELA E.; BASTIDA, JAUME; TAPIA, ALEJANDRO

PHYTOMEDICINE

ELSEVIER GMBH

Año: 2018 vol. 39 p. 66 - 74

0944-7113

Background: In Argentina, the Amaryllidaceae family (59 species) comprises a wide variety of genera, only a fewspecies have been investigated as a potential source of cholinesterases inhibitors to treat Alzheimer disease (AD).Purpose: To study the acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities of thebasic dichloromethane extracts (E) from Hieronymiella aurea, H. caletensis, H. clidanthoides, H. marginata, and H.speciosa species, as well as the isolated compounds from these plant extracts.Study design and methods: AChE and BChE inhibitory activities were evaluated with the Ellman´s spectro-photometric method. The alkaloids composition from the E was obtained by gas chromatography-mass spec-trometry (GC-MS). The E were successively chromatographed on a silica gel column and permeated on SephadexLH-20 column to afford the main alkaloids identified by means of spectroscopic data. Additionally, an in silicostudy was carried out.Results: Nine known alkaloids were isolated from the E of five Hieronymiella species. Galanthamine was iden-tified in all the species by GC-MS standing out H. caletensis with a relative abundance of 9.79% of the total ioncurrent. Strong AChE (IC 50 = 1.84 - 15.40 μg/ml) and moderate BChE (IC50 = 23.74 - 136.40 μg/ml) inhibitoryactivities were displayed by the extracts. Among the isolated alkaloids, only sanguinine and chlidanthine (ga-lanthamine-type alkaloids) demonstrated inhibitory activity toward both enzymes. The QTAIM study suggeststhat sanguinine has the strongest affinity towards AChE, attributed to an additional interaction with Ser200 aswell as stronger molecular interactions Glu199 and His440.These results allowed us to differentiate the mole-cular behavior in the active site among alkaloids possessing different in vitro inhibitory activities.Conclusion: Hieronymiella species growing in Argentina represent a rich and widespread source of galanthamineand others AChE and BChE inhibitors alkaloids. Additionally, the new trend towards the use of natural extractsas pharmaceuticals rather than pure drugs opens a pathway for the development of a phytomedicine derivedfrom extracts of Hieronymiella spp.