Amaryllidaceae Alkaloids Research Articles

Neuroprotective Activities of Crossyne flava Bulbs and Amaryllidaceae Alkaloids: Implications for Parkinson's Disease.

Parkinson’s disease (PD) is one of the most common neurodegenerative diseases and affects approximately 6.3 million people worldwide. To date, the treatment of PD remains a challenge, as available treatment options are known to be associated with serious side effects; hence, the search for new treatment strategies is critical. Extracts from the Amaryllidaceae plant family as well as their alkaloids have been reported to have neuroprotective potentials. This study, therefore, investigated the biological activities of Crossyne flava and its isolated alkaloids in an in vitro MPP+ (1-methyl-4-phenylpyridinium) PD model using SH-SY5Y cells. The effects of the total extract as well as the four compounds isolated from Crossyne flava (i.e., pancratinine B (1), bufanidrine (2), buphanisine (3), and epibuphanisine (4)) were evaluated for cell viability, neuroprotection, levels of reactive oxygen species (ROS), adenosine triphosphate activity (ATP), and caspase 3/7 activity in SH-SY5Y cells. The results obtained showed that pre-treatment with both the extract and the isolated compounds was effective in protecting the SH-SY5Y cells from MPP+-induced neurotoxicity and inhibited ROS generation, ATP depletion as well as apoptosis induction in the SH-SY5Y cells. The results of this study show that the Amaryllidaceae plant family may be a source of novel compounds for the treatment of neurodegenerative diseases, which validates the reported traditional uses.

BIOCHEMICA INVESTIGATION OF THE PHARMACEUTICAL AND COSMETIC USE OF NARCISSUS (Narcissus tazetta L. subsp. tazetta L.) GROWING NATURALLY AROUND IN MUĞLA, TURKEY

Amaryllidaceae is a monocot plant family represented in the world with approximately 85 genera and 1100 species, which has a great economic value as an ornamental plant, as well as plants that are widely used in treatment [1,2]. Narcissus L. species, a member of the Amaryllidaceae family, are perennial, herbaceous plants with bulbs that bear fragrant flowers and up to 30 different species grow naturally in Western Europe, the Mediterranean Region, China and Japan [3,4]. 
 Amaryllidaceous plants have biological activities of medical uses, and their alkaloids have wide applications worldwide [5, 6, 7]. These alkaloids are a group of secondary metabolites on which many studies have been carried out due to their biogenesis, pharmacological and physiological activities. Until today, more than 500 Amaryllidaceae alkaloids have been isolated from different plants of the family, and modern phytochemical studies have shown that these alkaloids are responsible for many pharmacological activities [5, 8, 9, 10]. Due to their similarity to morphine and codeine skeletons, they have high analgesic effects. Among the pharmacological activities, including anti-cholinesterasic, antifungal, anti-inflammatory, cytotoxic, anticancer, antiplatelet, antifeedantan, antiparasitic and antiviral [5, 11]. In the Narcissus genus, the alkaloids found are divided into eight groups according to their skeleton type. These groups, according to the name of the representing alkaloid; It is expressed as norbelladin, lycorine, homolicoline, hemantamine, narciclasin, tazettin, pancracin and galantamine [5]. Among these alkaloids, especially galantamine, analgesic [12], antiviral, cytotoxic [13], antimicrobial and antioxidant [14]. activities have been reported, and it is known to be used in the treatment of Alzheimer's due to its acetylcholinesterase inhibition effect [15]. Apart from these known therapeutic effects of the plant, it is a valuable main product in the cosmetic industry. In ancient times, in the Aegean region, it was grown and essence was obtained from its flowers [4].
 The aim of this work was to perform collect the Narcissus flower, which grows naturally in Muğla and its surroundings in February-April and draws attention with its scent, to determine some of its bioactivities and to conduct research on the purification of the protease enzyme for pharmaceuticals effects, as well as to research the use of the plant in this field by making a perfume design for the cosmetic industry.

Pancracine, a Montanine-Type Amaryllidaceae Alkaloid, Inhibits Proliferation of A549 Lung Adenocarcinoma Cells and Induces Apoptotic Cell Death in MOLT-4 Leukemic Cells.

Pancracine, a montanine-type Amaryllidaceae alkaloid (AA), is one of the most potent compounds among natural isoquinolines. In previous studies, pancracine exhibited cytotoxic activity against diverse human cancer cell lines in vitro. However, further insight into the molecular mechanisms that underlie the cytotoxic effect of pancracine have not been reported and remain unknown. To fill this void, the cell proliferation and viability of cancer cells was explored using the Trypan Blue assay or by using the xCELLigence system. The impact on the cell cycle was determined by flow cytometry. Apoptosis was evaluated by Annexin V/PI and by quantifying the activity of caspases (-3/7, -8, and -9). Proteins triggering growth arrest or apoptosis were detected by Western blotting. Pancracine has strong antiproliferative activity on A549 cells, lasting up to 96 h, and antiproliferative and cytotoxic effects on MOLT-4 cells. The apoptosis-inducing activity of pancracine in MOLT-4 cells was evidenced by the significantly higher activity of caspases. This was transmitted through the upregulation of p53 phosphorylated on Ser392, p38 MAPK phosphorylated on Thr180/Tyr182, and upregulation of p27. The pancracine treatment negatively altered the proliferation of A549 cells as a consequence of an increase in G1-phase accumulation, associated with the downregulation of Rb phosphorylated on Ser807/811 and with the concomitant upregulation of p27 and downregulation of Akt phosphorylated on Thr308. This was the first study to glean a deeper mechanistic understanding of pancracine activity in vitro. Perturbation of the cell cycle and induction of apoptotic cell death were considered key mechanisms of pancracine action.

Martin McAinsh.

Martin McAinsh.

GC-MS analysis of Amaryllidaceae and Sceletium-type alkaloids in bioactive fractions from Narcissus cv. Hawera.

Narcissus cv. Hawera has been found to biosynthesize some Sceletium-type alkaloids with antidepressant and anxiolytic activities. This ornamental plant has been poorly studied as a source of bioactive alkaloids including some contraversive reports on in vitro and intact plants. In this study, a detailed GC-MS characterization of its alkaloid fractions is presented. GC-MS was used for the identification of compounds in the alkaloid fractions. Both underivatized and silylated samples were analyzed simultaneously. Elevated plus maze and tail suspension tests were used to assay the anxiolytic and antidepressant activities. Ellman's and MTT-dye reduction assays were used to evaluate the acetylcholinesterase (AChE) inhibitory and cytotoxicity activities, respectively. Of the 29 alkaloids, 13 of Sceletium-type were detected. Two new alkaloids were identified as 2-oxo-mesembrine and 2-oxo-epi-mesembrenol. Lycorine was found as a major compound (43.5%) in the crude silylated methanol extract. After the elimination of lycorine by pre-crystallization, the major alkaloids were 40.8% 6-epi-mesembranol, 16.2% 6-epi-mesembrenol, and 13.8% sanguinine. This fraction showed anxiolytic and antidepressant-like activities as well as potent AChE inhibitory and antineoplastic activities. Silylation of the alkaloid fractions from Narcissus cv. Hawera provides better separation, structural information, and improved sensitivity for compounds with two and more hydroxyl groups. The lycorine-free alkaloid fraction shows a great potential for further pharmacological studies.

Activity of Some Plant and Fungal Metabolites towards Aedes albopictus (Diptera, Culicidae).

Aedes albopictus (Skuse) is a widespread mosquito, a vector of important human arboviruses, including Chikungunya, Dengue and Zika. It is an extremely difficult species to control even for the onset of resistances to chemicals insecticides, therefore ecofriendly products are urgently needed. In this study, the activity of Amaryllidaceae alkaloids and some of their semisynthetic derivatives, of 2-methoxy-1,4-naphthoquinone and two analogues, of cyclopaldic acid and epi-epoformin on the survival and development of Ae. albopictus larvae was evaluated. First-instar larval exposure for 24 and 48 h to cyclopaldic acid, resulted in mortality mean per-centage of 82.4 and 96.9 respectively; 1,2-O,O-diacetyllycorine 48h post-treatment caused 84.7% mortality. Larval and pupal duration were proved to decrease significantly when larvae were exposed to cyclopaldic acid, 1,2-O,O-diacetyllycorine and N-methyllycorine iodide. The mean number of third-instar larvae surviving to 2-methyl-1,4-naphthoquinone, 2-hydroxy-1,4-naphthoquinone and 2-methoxy-1,4-naphthoquinone was significantly lower than the number of correspondent control larvae over the time. This study indicated that 1,2-O,O’-diacetyllycorine, N-methyllycorine iodide, cyclopaldic acid and 1,4-naphthoquinone structural derivatives have good potential for developing bioinsecticides for mosquito control programs. The obtained results are of general interest due to the global importance of the seri-ous human diseases such a vector is able to spread.

Cytotoxic Agents in the Minor Alkaloid Groups of the Amaryllidaceae.

Over 600 alkaloids have to date been identified in the plant family Amaryllidaceae. These have been arranged into as many as 15 different groups based on their characteristic structural features. The vast majority of studies on the biological properties of Amaryllidaceae alkaloids have probed their anticancer potential. While most efforts have focused on the major alkaloid groups, the volume and diversity afforded by the minor alkaloid groups have promoted their usefulness as targets for cancer cell line screening purposes. This survey is an in-depth review of such activities described for around 90representatives from 10 minor alkaloid groups of the Amaryllidaceae. These have been evaluated against over 60cell lines categorized into 18 different types of cancer. The montanine and cripowellin groups were identified as the most potent, with some in the latter demonstrating low nanomolar level antiproliferative activities. Despite their challenging molecular architectures, the minor alkaloid groups have allowed for facile adjustments to be made to their structures, thereby altering the size, geometry, and electronics of the targets available for structure-activity relationship studies. Nevertheless, it was seen with a regular frequency that the parent alkaloids were better cytotoxic agents than the corresponding semisynthetic derivatives. There has also been significant interest in how the minor alkaloid groups manifest their effects in cancer cells. Among the various targets and pathways in which they were seen to mediate, their ability to induce apoptosis in cancer cells is most appealing.

Structure Elucidation and Cholinesterase Inhibition Activity of Two New Minor Amaryllidaceae Alkaloids.

Two new minor Amaryllidaceae alkaloids were isolated from Hippeastrum × hybridum cv. Ferrari and Narcissus pseudonarcissus cv. Carlton. The chemical structures were identified by various spectroscopic (one- and two-dimensional (1D and 2D) NMR, circular dichroism (CD), high-resolution mass spectrometry (HRMS) and by comparison with literature data of similar compounds. Both isolated alkaloids were screened for their human acetylcholinesterase (hAChE) and butyrylcholinesterase (hBuChE) inhibition activity. One of the new compounds, a heterodimer alkaloid of narcikachnine-type, named narciabduliine (2), showed balanced inhibition potency for both studied enzymes, with IC50 values of 3.29 ± 0.73 µM for hAChE and 3.44 ± 0.02 µM for hBuChE. The accommodation of 2 into the active sites of respective enzymes was predicted using molecular modeling simulation.

Plants of the 'Libellus de Medicinalibus Indorum Herbis' from Mexico, 1552. Zephyranthes fosteri (Amaryllidaceae) Alkaloids.

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 in vitro. 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.

Molecular Identification of Endophytic Bacteria in Leucojum aestivum In Vitro Culture, NMR-Based Metabolomics Study and LC-MS Analysis Leading to Potential Amaryllidaceae Alkaloid Production.

In this study, endophytic bacteria belonging to the Bacillus genus were isolated from in vitro bulblets of Leucojum aestivum and their ability to produce Amaryllidaceae alkaloids was studied. Proton Nuclear Magnetic Resonance (1H NMR)-based metabolomics combined with multivariate data analysis was chosen to compare the metabolism of this plant (in vivo bulbs, in vitro bulblets) with those of the endophytic bacteria community. Primary metabolites were quantified by quantitative 1H NMR (qNMR) method. The results showed that tyrosine, one precursor of the Amaryllidaceae alkaloid biosynthesis pathway, was higher in endophytic extract compared to plant extract. In total, 22 compounds were identified including five molecules common to plant and endophyte extracts (tyrosine, isoleucine, valine, fatty acids and tyramine). In addition, endophytic extracts were analyzed using Liquid Chromatography-Mass Spectrometry (LC-MS) and Gas Chromatography-Mass Spectrometry (GC-MS) for the identification of compounds in very low concentrations. Five Amaryllidaceae alkaloids were detected in the extracts of endophytic bacteria. Lycorine, previously detected by 1H NMR, was confirmed with LC-MS analysis. Tazettine, pseudolycorine, acetylpseudolycorine, 1,2-dihydro-chlidanthine were also identified by LC-MS using the positive ionization mode or by GC-MS. In addition, 11 primary metabolites were identified in the endophytic extracts such as tyramine, which was obtained by decarboxylation of tyrosine. Thus, Bacillus sp. isolated from L. aestivum bulblets synthesized some primary and specialized metabolites in common with the L. aestivum plant. These endophytic bacteria are an interesting new approach for producing the Amaryllidaceae alkaloid such as lycorine.

GC-MS of some lycorine-type Amaryllidaceae alkaloids.

The search for novel bioactive compounds and the identification of known ones in the plant kingdom are a challenge for the scientists working in different fields of plant science. In the recent years, mass spectrometry is the most frequently applied method for analysis of complex mixtures of plant metabolites. Twenty-two alkaloids of different lycorine skeleton subtypes (with a Δ3,4 double bond, with a Δ4,11 double bond, with saturated rings C and D, and with aromatic ring C) were subjected to separation with gas chromatography and studied with electron impact mass spectrometry including single quadropole (GC-EIMS), tandem mass (GC-EIMS/MS) and high resolution mass (EI-HRMS) detectors in order to determine their fragmentation pattern. The compounds showed excellent separation and specific MS fragmentation allowing structural determination. The GC-MS can be successfully applied for searching new and identification of known bioactive molecules, chemotaxonomical and chemoecological studies, among others, within the Amaryllidoideae subfamily.

LED Light Quality Affect Growth, Alkaloids Contents, and Expressions of Amaryllidaceae Alkaloids Biosynthetic Pathway Genes in Lycoris longituba

Lycoris longituba is an important ornamental and medicinal plant and contains various Amaryllidaceae alkaloids such as galanthamine (GAL), lycorine (LYC), and lycoramine (LYCM), which have been reported to exhibit medicinal values. However, the effects of light quality on L. longituba are unknown. The present study aimed to explore the effects of different light emitting diode (LED) light quality on growth, physiological characteristics, and alkaloid accumulations in the seedlings. Lycoris longituba seedlings were cultured under different ratios of blue and red LEDs. The results showed that compared to CK, RB (1:2) treatment improved growth, biomass accumulation, and the synthesis of photosynthetic pigments and reduced membrane lipid peroxidation. Blue light increased GAL, LYC, and LYCM contents which were 2.45-, 1.74-, and 1.92-fold higher than CK, respectively. Most of Amaryllidaceae alkaloids biosynthetic pathway genes including PAL, C4H, NBS, TYDC, OMT, and CYP96T1 were upregulated under B treatment. In general, RB (1:2) was the optimal light quality condition for the growth of L. longituba seedlings. B treatment could promote the accumulation of alkaloids and related gene expressions. This study has established the theoretical foundation and technical support for the use of LED light quality control technology in the production of high-quality L. longituba seedlings.

Total syntheses of (+)- and (−)-Crinane via Pd(0)-Catalyzed deacylative allylation

Abstract An efficient Pd(0)-catalyzed deacylative allylation (DaA) of enolcarbonates (pro-nucleophile) prepared from 2-arylcyclohexanones sharing acyl functionality at C2-position with readily available allylic alcohols (pro-electrophiles) by employing Pd(0)-catalysis under mild reaction conditions. The methodology can be extended for deacylative benzylations (DaB) of enolcarbonates of 2-arylcyclohexanones. As an application of our methodology, we have shown asymmetric total synthesis of Amaryllidaceae alkaloids, (+)- and (−)-crinane.

Relative expression of putative genes involved in galanthamine and other Amaryllidaceae alkaloids biosynthesis in Narcissus field and in vitro tissues.

The Narcissus pseudonarcissus cv. Carlton contains Amaryllidaceae alkaloids namely galanthamine, lycorine, homolycorine, narciclasine, which are noted for their pharmaceutical properties such as for the treatment of early to mid-stage Alzheimer's diseases, cancer, tumor etc. Alkaloid biosynthesis using plant in vitro systems has been considered as a tool for drug discovery and the pathways are starting to be understood but still far from complete. Therefore, the study was emphasized to observe the relative expressions of putative genes involved in the biosynthetic pathway leading to the Amaryllidaceae alkaloids in field grown bulbs and developing cell culture systems in Narcissus. MS media fortified with growth regulators were used for the development of tissue culture from Carlton twin-scale explants. MS medium with high auxin, 20mg/l NAA was the best medium for callus growth and maintenance while media with low auxin, 4mg/l NAA and MS basal media gave the maximum bulblets. Field tissues showed a higher amount of galanthamine content; i.e. basal plate (1050-1310µg Gal/g FW) and bulb (980-1150µg Gal/g FW) than the culture derived samples; callus (1.0-7.0µg Gal/g FW) and bulblets (12-215µg Gal/g FW) on a fresh weight (FW) basis. GC-MS chromatograms of samples under study also showed the presence of other important alkaloids i.e. lycorine, homolycorine, lycorenine, haemanthamine, crinamine, lycoramine and tazettine. RNA extracted from in vitro callus, bulblets and field grown bulb, basal plate were used for PCR to detect the relative expression of putative genes; P450, PAL, TYDC and NpO4OMT normalized to actin. The selected transcripts for P450s and TYDC were expressed in both field and in vitro tissues. Higher expressions of PAL were observed in calli than field samples. The expression of NpN4OMT was notably higher in field samples than in vitro tissues. Therefore, in vitro tissues could be a good source for the reproducible and easy extraction of alkaloids from plants.

Chemical evaluation and anticholinesterase activity of Hippeastrum puniceum (Lam.) Kuntz bulbs (Amaryllidaceae)

Hippeastrum puniceum is a species that belongs to the Amaryllidaceae family. A particular characteristic of this family is the consistent and very specific presence of isoquinoline alkaloids, which have demonstrated a wide range of biological activities such as antioxidant, antiviral, antifungal, antiparasitic, and acetylcholinesterase inhibitory activity, among others. In the present work, fifteen alkaloids were identified from the bulbs of Hippeastrum puniceum (Lam.) Kuntz using a GC-MS approach. The alkaloids 9-O-demethyllycoramine, 9-demethyl-2α-hydroxyhomolycorine, lycorine and tazettine were isolated through chromatographic techniques. The typical Amaryllidaceae alkaloids lycorine and tazettine, along with the crude and ethyl acetate extract from bulbs of the species were evaluated for their inhibitory potential on α-amylase, α-glucosidase, tyrosinase and acetylcholinesterase activity. Although no significant inhibition activity was observed against α-amylase, α-glucosidase and tyrosinase from the tested samples, the crude and ethyl acetate extracts showed remarkable acetylcholinesterase inhibitory activity. The biological activity results that correlated to the alkaloid chemical profile by GC-MS are discussed herein. Therefore, this study contributed to the knowledge of the chemical and biological properties of Hippeastrum puniceum (Lam.) and can subsidize future studies of this species.

The Theoretical Total Synthesis of an Aromatic Esters of the Crinane Amaryllidaceae Alkaloid Ambelline

ABSTRACT. A series of crinane-type alkaloid ambelline derivatives were assessed for their potency to inhibit both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), which has been shown to be effective medicine for the treatment of Alzheimer’s disease. However, no enzyme modification has been reported total synthesis. In this work, two possible theoretical synthesis paths of Crinane-type alkaloid ambelline were discussed in this article. The major difficulty of the proposed synthesis was the synthesis of the quaternary carbon. One of the approaches emphasized on the reactions between cyclic and heterocyclic compounds and substrates on the intermediates to generate the quaternary carbon shown on the desired product. The other approach utilized series of amine reactions and Michael addition to create the precursor for the reactant in the Diels-Alder reaction and, therefore, the quaternary carbon, and finally, the desired natural product was obtained after a weak acid workup. The synthesis of ambelline has the potential to provide new pathways for treatment of Alzheimer’s disease.

Alkaloids of Zephyranthes citrina (Amaryllidaceae) and their implication to Alzheimer's disease: Isolation, structural elucidation and biological activity

Twenty known Amaryllidaceae alkaloids of various structural types, and one undescribed alkaloid of narcikachnine-type, named narcieliine (3), have been isolated from fresh bulbs of Zephyranthes citrina. The chemical structures of the isolated alkaloids were elucidated by a combination of MS, HRMS, 1D and 2D NMR, and CD spectroscopic techniques, and by comparison with literature data. The absolute configuration of narcieliine (3) has also been determined. Compounds isolated in a sufficient quantity were evaluated for their in vitro acetylcholinesterase (AChE; E.C. 3.1.1.7), butyrylcholinesterase (BuChE; E.C. 3.1.1.8), and prolyl oligopeptidase (POP; E.C. 3.4.21.26) inhibition activities. Significant human AChE/BuChE (hAChE/hBuChE) inhibitory activity was demonstrated by the newly described alkaloid narcieliine (3), with IC50 values of 18.7 ± 2.3 µM and 1.34 ± 0.31 µM, respectively. This compound is also predicted to cross the blood–brain barrier (BBB) through passive diffusion. The in vitro data were further supported by in silico studies of 3 in the active site of hAChE/hBuChE.

Lycorine, a non-nucleoside RNA dependent RNA polymerase inhibitor, as potential treatment for emerging coronavirus infections

Background: Highly effective novel treatments need to be developed to suppress emerging coronavirus (CoV) infections such as COVID-19. The RNA dependent RNA polymerase (RdRp) among the viral proteins is known as an effective antiviral target. Lycorine is a phenanthridine Amaryllidaceae alkaloid isolated from the bulbs of Lycoris radiata (L'Hér.) Herb. and has various pharmacological bioactivities including antiviral function.Purpose: We investigated the direct-inhibiting action of lycorine on CoV's RdRp, as potential treatment for emerging CoV infections.Methods: We examined the inhibitory effect of lycorine on MERS-CoV, SARS-CoV, and SARS-CoV-2 infections, and then quantitatively measured the inhibitory effect of lycorine on MERS-CoV RdRp activity using a cell-based reporter assay. Finally, we performed the docking simulation with lycorine and SARS-CoV-2 RdRp.Results: Lycorine efficiently inhibited these CoVs with IC50 values of 2.123 ± 0.053, 1.021 ± 0.025, and 0.878 ± 0.022 μM, respectively, comparable with anti-CoV effects of remdesivir. Lycorine directly inhibited MERS-CoV RdRp activity with an IC50 of 1.406 ± 0.260 μM, compared with remdesivir's IC50 value of 6.335 ± 0.731 μM. In addition, docking simulation showed that lycorine interacts with SARS-CoV-2 RdRp at the Asp623, Asn691, and Ser759 residues through hydrogen bonding, at which the binding affinities of lycorine (−6.2 kcal/mol) were higher than those of remdesivir (−4.7 kcal/mol).Conclusions: Lycorine is a potent non-nucleoside direct-acting antiviral against emerging coronavirus infections and acts by inhibiting viral RdRp activity; therefore, lycorine may be a candidate against the current COVID-19 pandemic.

A novel and unusual tetramethoxylated crinine alkaloid from Ammocharis coranica (Amaryllidaceae)

Ammocharis coranica is a bulbous southern African species reported to be used to treat mental illness. Eight Amaryllidaceae alkaloids of the aromatic, lycorine or crinine type were found in the current study, five of which, hippadine, lycorine, caranine, acetylcaranine, and 1-O-acetyl-9-O-demethylpluviine have previously been isolated from this species. A further three alkaloids, 6α-hydroxybuphanidrine, golceptine and a new compound of the crinine type, charisine, were isolated in this work. Charisine is a tetramethoxylated crinine alkaloid, and the first documented to be methoxylated on the 5,10b-ethano bridge of this subclass.

Advances in the Chemical and Biological Characterization of Amaryllidaceae Alkaloids and Natural Analogues Isolated in the Last Decade.

Amaryllidaceae are bulbous wild and cultivated plants well known for their beautiful flowers and pharmaceutical applications, essentially due to the alkaloids and flavonoids content. Hundreds of alkaloids have been isolated until now and several scientific publications reported their sources, chemical structures, and biological activities. During the last decade, some unstudied Amaryllidaceae plants were the object of in-depth investigations to isolate and chemically and biologically characterize new and already known alkaloids as well as some analogues. This review describes the isolation and chemical and biological characterization of the Amaryllidaceae alkaloids, and their analogues obtained in the last decade, focusing the discussion on the new ones.