The Libellus de Medicinalibus Indorum Herbis (Booklet of Indian Medicinal Plants) is the first book of medicinal plants written in the American continent. It was first published in 1939 as 'An Aztec Herbal'. One of the depicted plants is Huetzcanixochitl (laughing flower) interpreted as Zephyranthes fosteri (Amaryllidaceae). No chemical or pharmacological studies are reported for this species; so, we decide to investigate it. The GC/MS of the bulbs and aerial parts extracts indicated that they contain Amaryllidaceae alkaloids, among them: lycorine, 3-O-acetylpowelline, and norlycoramine. An unknown major alkaloid was isolated and identified by (1) H, (13) C-NMR and MS, as 3'-demethoxy-6-epimesembranol (1). The methanolic extract, the alkaloid fraction, and compound 1 inhibited acetylcholinesterase invitro. Mesembrine alkaloids are found in Sceletium species (Aizoaceae). Several are known as serotonin recapture inhibitors and have been proposed as potential antidepressant drugs. The presence of 1 suggests that Z. fosteri was probably used in pre-Columbian times in Mexico as a 'stimulant and euphoriant', alike Sceletium tortuosum by several ethnic groups in South Africa.
Plants of the Amaryllidaceae family are well-known (not only) for their ornamental value but also for the alkaloids that they produce. In this report, the first phytochemical study of Clinanthus genus was carried out. The chemical composition of alkaloid fractions from Clinanthus microstephium was analyzed by GC/MS and NMR. Seven known compounds belonging to three structural types of Amaryllidaceae alkaloids were identified. An epimeric mixture of a haemanthamine-type compound (6-hydroxymaritidine) was tested as an inhibitor against acetyl- and butyrylcholinesterase enzymes (AChE and BChE, respectively), two enzymes relevant in the treatment of Alzheimer's disease, with good results. Structure-activity relationships through molecular docking studies with this alkaloid and other structurally related compounds were discussed.
BACKGROUND: In Argentina, the Amaryllidaceae family (59 species) comprises a wide variety of genera, only a few species 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 the basic 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 spectrophotometric method. The alkaloids composition from the E was obtained by gas chromatography-mass spectrometry (GC-MS). The E were successively chromatographed on a silica gel column and permeated on Sephadex LH-20 column to afford the main alkaloids identified by means of spectroscopic data. Additionally, an in silico study was carried out. RESULTS: Nine known alkaloids were isolated from the E of five Hieronymiella species. Galanthamine was identified in all the species by GC-MS standing out H. caletensis with a relative abundance of 9.79% of the total ion current. Strong AChE (IC50=1.84 - 15.40microg/ml) and moderate BChE (IC50=23.74 - 136.40microg/ml) inhibitory activities were displayed by the extracts. Among the isolated alkaloids, only sanguinine and chlidanthine (galanthamine-type alkaloids) demonstrated inhibitory activity toward both enzymes. The QTAIM study suggests that sanguinine has the strongest affinity towards AChE, attributed to an additional interaction with Ser200 as well as stronger molecular interactions Glu199 and His440.These results allowed us to differentiate the molecular 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 galanthamine and others AChE and BChE inhibitors alkaloids. Additionally, the new trend towards the use of natural extracts as pharmaceuticals rather than pure drugs opens a pathway for the development of a phytomedicine derived from extracts of Hieronymiella spp.
Two new alkaloids, 4-O-methylnangustine (1) and 7-hydroxyclivonine (2) (montanine and homolycorine types, respectively), and four known alkaloids were isolated from the bulbs of Hippeastrum argentinum, and their cholinesterase-inhibitory activities were evaluated. These compounds were identified using GC-MS, and their structures were defined by physical data analysis. Compound 2 showed weak butyrylcholinesterase (BuChE)-inhibitory activity, with a half-maximal inhibitory concentration (IC50) value of 67.3 +/- 0.09 muM. To better understand the experimental results, a molecular modeling study was also performed. The combination of a docking study, molecular dynamics simulations, and quantum theory of atoms in molecules calculations provides new insight into the molecular interactions of compound 2 with BuChE, which were compared to those of galantamine.
Plants belonging to the Amaryllidaceae contain an exclusive group of alkaloids, known as sources of important biological activities. In the present work, Pancratium illyricum L., a species belonging to this family and endemic of Sardinia (Italy), was investigated for its alkaloid content. Fresh bulbs and leaves were processed separately. Standard extraction and purification procedures were applied to obtain fractions and compounds for GC-MS and NMR analysis. In addition to eight already known alkaloids (1-8), 11alpha-hydroxy-O-methylleucotamine (9) was isolated for the first time and its structure completely determined by one and two-dimensional 1H and 13C NMR spectroscopy. This new galanthamine-type compound exhibited a pronounced in vitro acetylcholinesterase (AChE) inhibitory activity (IC50=3.5+/-1.1muM) in comparison to the reference standard galanthamine hydrobromide (IC50=1.5+/-0.2muM).
The Amaryllidaceae family is well known for its pharmacologically active alkaloids An important approach to treat Alzheimer&'s disease involves the inhibition of the enzyme acetylcholinesterase AChE Galanthamine an Amaryllidaceae alkaloid is an effective selective reversible and competitive AchE inhibitor This work was aimed at studying the alkaloid composition of four wild Argentinian Amarillydaceae species for the first time as well as analyzing their inhibitory activity on acetylcholinesterase Alkaloid content was characterized by means of GC-MS analysis Chloroform basic extracts from Habranthus jamesonii Phycella herbertiana Rhodophiala mendocina and Zephyranthes filifolia collected in the Argentinian Andean region all contained galanthamine and showed a strong AChE inhibitory activity IC(50 between 1.2 and 2 181;g/mL To our knowledge no previous reports on alkaloid profiles and AChEIs activity of wild Argentinian Amarillydaceae species have been publisihed The demand for renewable sources of industrial products like galanthamine and the need to protect plant biodiversity creates an opportunity for Argentinian farmers to produce such crops.
Plants of the Amaryllidaceae family are a well-known source of tetrahydroisoquinoline alkaloids with a wide range of biological activities including antiviral antitumoral antiparasitic psychopharmacological and acetylcholinesterase inhibitory among others Recent advances in the use of GC or LC coupled to MS have allowed a chemically guided isolation of uncommon and bioactive alkaloids In the present work analytical methods were applied to study the alkaloid profile of Narcissus broussonetii a plant endemic to North Africa Using the GC-MS technique and an in-home mass fragmentation database twenty-three alkaloids were identified including the very rare dinitrogenous alkaloids obliquine plicamine and secoplicamine Applying LC-ESI-LTQ-Orbitrap-MS fragmentation profiles were found to be similar for obliquine and plicamine but different for secoplicamine Pretazettine a potent cytotoxic alkaloid was also isolated from N broussonetii although its identification by GC-MS was only possible after a BSTFA-derivatization The silylated crude methanolic extract only showed the presence of pretazettine-TMS confirming that tazettine was formed after the alkaloid extraction The same observation was made in Narcissus cultivars in which tazettine had been detected as the major alkaloid As part of an ongoing project on MS of Amaryllidaceae alkaloids the silylated tazettine and pretazettine were studied by GC-MS/MS and found to differ in their fragmentation routes Finally the EtOAc extract of N broussonetii showed notable in vitro activity against Trypanosoma cruzi with an IC(50 value of 1.77mug/ml.
