The incidence rate of malaria and the ensuing mortality prompts the development of novel antimalarial drugs. In this work, the activity of twenty-eight Amaryllidaceae alkaloids (1-28) belonging to seven different structural types was assessed, as well as twenty semisynthetic derivatives of the β-crinane alkaloid ambelline (28a-28t) and eleven derivatives of the α-crinane alkaloid haemanthamine (29a-29k) against the hepatic stage of Plasmodium infection. Six of these derivatives (28h, 28m, 28n and 28r-28t) were newly synthesized and structurally identified. The most active compounds, 11-O-(3,5-dimethoxybenzoyl)ambelline (28m) and 11-O-(3,4,5-trimethoxybenzoyl)ambelline (28n), displayed IC50 values in the nanomolar range of 48 and 47 nM, respectively. Strikingly, the derivatives of haemanthamine (29) with analogous substituents did not display any significant activity, even though their structures are quite similar. Interestingly, all active derivatives were strictly selective against the hepatic stage of infection, as they did not demonstrate any activity against the blood stage of Plasmodium infection. As the hepatic stage is a bottleneck of the plasmodial infection, liver-selective compounds can be considered crucial for further development of the malaria prophylactics.

• Keywords
• Amaryllidaceae, Plasmodium, alkaloids, ambelline, cytotoxicity, haemanthamine, hepatic stage, malaria,
• Publication type
• Journal Article MeSH

Clivia miniata (Amaryllidaceae) is an herbaceous evergreen flowering plant that is endemic to South Africa and Swaziland and belongs to one of the top-10 traded medicinal plants in informal medicine markets in South Africa. The species has been reported as the most important component of a traditional healer's pallet of healing plants. Eighteen known Amaryllidaceae alkaloids (AAs) of various structural types, and one undescribed alkaloid of homolycorine-type, named clivimine B (3), were isolated from Clivia miniata. The chemical structures of the isolated alkaloids were elucidated by a combination of MS, HRMS, 1D and 2D NMR techniques and by comparison with literature data. Compounds isolated in a sufficient quantity, and not tested previously, were evaluated for their in vitro acetylcholinesterase (AChE; E.C. 3.1.1.7) and butyrylcholinesterase (BuChE; E.C. 3.1.1.8) inhibition activities.

• Keywords
• Amaryllidaceae, Clivia miniata, acetylcholinesterase, butyrylcholinesterase, clivimine B,
• Publication type
• Journal Article MeSH

Alzheimer's disease (AD) is a progressive age-related neurodegenerative disease recognized as the most common form of dementia among elderly people. Due to the fact that the exact pathogenesis of AD still remains to be fully elucidated, the treatment is only symptomatic and available drugs are not able to modify AD progression. Considering the increase in life expectancy worldwide, AD rates are predicted to increase enormously, and thus the search for new AD drugs is urgently needed. Due to their complex nitrogen-containing structures, alkaloids are considered to be promising candidates for use in the treatment of AD. Since the introduction of galanthamine as an antidementia drug in 2001, Amaryllidaceae alkaloids (AAs) and further isoquinoline alkaloids (IAs) have been one of the most studied groups of alkaloids. In the last few years, several compounds of new structure types have been isolated and evaluated for their biological activity connected with AD. The present review aims to comprehensively summarize recent progress on AAs and IAs since 2010 up to June 2021 as potential drugs for the treatment of AD.

• Keywords
• Alzheimer’s disease, acetylcholinesterase, butyrylcholinesterase, docking study, isoquinoline alkaloids, monoaminooxidase, neuroprotective activity, prolyl oligopeptidase,
• MeSH
• Amaryllidaceae Alkaloids metabolism   MeSH
• Alzheimer Disease metabolism   MeSH
• Amaryllidaceae chemistry   MeSH
• Neurodegenerative Diseases metabolism   MeSH
• Prolyl Oligopeptidases metabolism   MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Names of Substances
• Amaryllidaceae Alkaloids MeSH
• Prolyl Oligopeptidases MeSH

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.

• Keywords
• 9-O-demethyllycorenine, Alzheimer’s disease, Amaryllidaceae, narciabduliine,
• MeSH
• Amaryllidaceae Alkaloids chemistry   pharmacology   MeSH
• Alkaloids chemistry   pharmacology   MeSH
• Alzheimer Disease MeSH
• Butyrylcholinesterase chemistry   ultrastructure   MeSH
• Cholinesterase Inhibitors chemistry   pharmacology   MeSH
• Cholinesterases chemistry   ultrastructure   MeSH
• Circular Dichroism MeSH
• Catalytic Domain drug effects   MeSH
• Humans MeSH
• Molecular Structure MeSH
• Molecular Docking Simulation MeSH
• Structure-Activity Relationship MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Amaryllidaceae Alkaloids MeSH
• Alkaloids MeSH
• Butyrylcholinesterase MeSH
• Cholinesterase Inhibitors MeSH
• Cholinesterases MeSH

Lycoris Herbert, family Amaryllidaceae, is a small genus of about 20 species that are native to the warm temperate woodlands of eastern Asia, as in China, Korea, Japan, Taiwan, and the Himalayas. For many years, species of Lycoris have been subjected to extensive phytochemical and pharmacological investigations, resulting in either the isolation or identification of more than 110 Amaryllidaceae alkaloids belonging to different structural types. Amaryllidaceae alkaloids are frequently studied for their interesting biological properties, including antiviral, antibacterial, antitumor, antifungal, antimalarial, analgesic, cytotoxic, and cholinesterase inhibition activities. The present review aims to summarize comprehensively the research that has been reported on the phytochemistry and pharmacology of the genus Lycoris.

• Keywords
• Amaryllidaceae, Lycoris, Lycoris radiata, alkaloids, biological activity, folk medicine,
• MeSH
• Amaryllidaceae Alkaloids chemistry   therapeutic use   MeSH
• Amaryllidaceae chemistry   MeSH
• Antimalarials chemistry   therapeutic use   MeSH
• Phytochemicals therapeutic use   MeSH
• Plant Roots chemistry   MeSH
• Humans MeSH
• Lycoris chemistry   MeSH
• Plant Extracts chemistry   therapeutic use   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Geographicals
• China MeSH
• Names of Substances
• Amaryllidaceae Alkaloids MeSH
• Antimalarials MeSH
• Phytochemicals MeSH
• Plant Extracts MeSH

Thirteen known (1-12 and 16) and three previously undescribed Amaryllidaceae alkaloids of belladine structural type, named carltonine A-C (13-15), were isolated from bulbs of Narcissus pseudonarcissus cv. Carlton (Amaryllidaceae) by standard chromatographic methods. Compounds isolated in sufficient amounts, and not tested previously, 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 BuChE (hBUChE) inhibitory activity was demonstrated by newly described alkaloids carltonine A (13) and carltonine B (14) with IC50 values of 913 ± 20 nM and 31 ± 1 nM, respectively. Both compounds displayed a selective inhibition pattern for hBuChE with an outstanding selectivity profile over AChE inhibition, higher than 100. The in vitro data were further supported by in silico studies of the active alkaloids 13 and 14 in the active site of hBuChE.

• Keywords
• Alzheimer’s disease, Amaryllidaceae, Narcissus pseudonarcissus cv. Carlton, alkaloids, butyrylcholinesterase, carltonine A–C, docking studies,
• MeSH
• Alkaloids chemistry   pharmacology   MeSH
• Butyrylcholinesterase chemistry   metabolism   MeSH
• Cholinesterase Inhibitors chemistry   pharmacology   MeSH
• Humans MeSH
• Narcissus chemistry   MeSH
• Molecular Docking Simulation MeSH
• Protein Binding MeSH
• Binding Sites MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Alkaloids MeSH
• Butyrylcholinesterase MeSH
• Cholinesterase Inhibitors MeSH

Plants of the Amaryllidaceae family are promising therapeutic tools for human diseases and have been used as alternative medicines. The specific secondary metabolites of this plant family, called Amaryllidaceae alkaloids (AA), have attracted considerable attention due to their interesting pharmacological activities. One of them, galantamine, is already used in the therapy of Alzheimer's disease as a long acting, selective, reversible inhibitor of acetylcholinesterase. One group of AA is the montanine-type, such as montanine, pancracine and others, which share a 5,11-methanomorphanthridine core. So far, only 14 montanine-type alkaloids have been isolated. Compared with other structural-types of AA, montanine-type alkaloids are predominantly present in plants in low concentrations, but some of them display promising biological properties, especially in vitro cytotoxic activity against different cancerous cell lines. The present review aims to summarize comprehensively the research that has been published on the Amaryllidaceae alkaloids of montanine-type.

• Keywords
• Amaryllidaceae, alkaloids, biological activity, derivatives, montanine, montanine-type, pancracine,
• MeSH
• Amaryllidaceae Alkaloids chemistry   isolation & purification   pharmacology   MeSH
• Amaryllidaceae chemistry   metabolism   MeSH
• Antiprotozoal Agents chemistry   isolation & purification   pharmacology   MeSH
• Cholinesterase Inhibitors chemistry   isolation & purification   pharmacology   MeSH
• Phenanthridines chemistry   isolation & purification   pharmacology   MeSH
• Antineoplastic Agents, Phytogenic chemistry   isolation & purification   pharmacology   MeSH
• Galantamine chemistry   isolation & purification   pharmacology   MeSH
• Heterocyclic Compounds, 4 or More Rings chemistry   isolation & purification   pharmacology   MeSH
• Inhibitory Concentration 50 MeSH
• Isoquinolines chemistry   isolation & purification   pharmacology   MeSH
• Humans MeSH
• Cell Line, Tumor MeSH
• Nootropic Agents chemistry   isolation & purification   pharmacology   MeSH
• Plant Extracts chemistry   MeSH
• Secondary Metabolism MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Names of Substances
• Amaryllidaceae Alkaloids MeSH
• Antiprotozoal Agents MeSH
• Cholinesterase Inhibitors MeSH
• Phenanthridines MeSH
• Antineoplastic Agents, Phytogenic MeSH
• Galantamine MeSH
• hemanthamine MeSH Browser
• Heterocyclic Compounds, 4 or More Rings MeSH
• Isoquinolines MeSH
• montanine MeSH Browser
• Nootropic Agents MeSH
• pancracine MeSH Browser
• Plant Extracts MeSH

In this detailed phytochemical study of Narcissus cv. Professor Einstein, we isolated 23 previously known Amaryllidaceae alkaloids (1-23) of several structural types and one previously undescribed alkaloid, 7-oxonorpluviine. The chemical structures were identified by various spectroscopic methods (GC-MS, LC-MS, 1D, and 2D NMR spectroscopy) and were compared with literature data. Alkaloids which had not previously been isolated and studied for cytotoxicity before and which were obtained in sufficient amounts were assayed for their cytotoxic activity on a panel of human cancer cell lines of different histotype. Above that, MRC-5 human fibroblasts were used as a control noncancerous cell line to determine the general toxicity of the tested compounds. The cytotoxicity of the tested alkaloids was evaluated using the WST-1 metabolic activity assay. The growth of all studied cancer cell lines was inhibited by pancracine (montanine-type alkaloid), with IC50 values which were in the range of 2.20 to 5.15 µM.

• Keywords
• 7-oxonorpluviine, Amaryllidaceae, Narcissus cv. Professor Einstein, cytotoxicity, pancracine,
• Publication type
• Journal Article MeSH

Nerine Herbert, family Amaryllidaceae, is a genus of about 30 species that are native to South Africa, Botswana, Lesotho, Namibia, and Swatini (formerly known as Swaziland). Species of Nerine are autumn-flowering, perennial, bulbous plants, which inhabit areas with summer rainfall and cool, dry winters. Most Nerine species have been cultivated for their elegant flowers, presenting a source of innumerable horticultural hybrids. For many years, species of Nerine have been subjected to extensive phytochemical and pharmacological investigations, which resulted in either the isolation or identification of more than fifty Amaryllidaceae alkaloids belonging to different structural types. Amaryllidaceae alkaloids are frequently studied for their interesting biological properties, including antiviral, antibacterial, antitumor, antifungal, antimalarial, analgesic, cytotoxic, and cholinesterase inhibition activities. The present review aims to summarize comprehensively the research that has been reported on the phytochemistry and pharmacology of the genus Nerine.

• Keywords
• Alzheimer’s disease, Amaryllidaceae, Nerine, Nerine bowdenii, antitumor activity, folk medicine,
• MeSH
• Amaryllidaceae Alkaloids pharmacology   MeSH
• Amaryllidaceae chemistry   MeSH
• Cholinesterase Inhibitors pharmacology   MeSH
• Ethnobotany * MeSH
• Humans MeSH
• Plant Extracts pharmacology   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Names of Substances
• Amaryllidaceae Alkaloids MeSH
• Cholinesterase Inhibitors MeSH
• Plant Extracts MeSH