This phytochemical study presents the isolation of eight alkaloids from Zephyranthes citrina Baker. The structures of the new alkaloids, zephycitrine (1) and 6-oxonarcissidine (2), were established by analysis of spectroscopic and spectrometric data. Processing the EtOH extract under acid-base conditions yielded the unreported isolation artifacts 3 and 4. This work also provides analytical data for alkaloids not properly described in the literature (5 and 6). The hippeastidine/zephyranine scaffolds in derivatives 3, 4, and 8-10 are also thoroughly discussed. Furthermore, a cytotoxicity screening of 25 Amaryllidaceae alkaloids isolated from Z. citrina was performed. Only the known alkaloids haemanthamine (12), haemanthidine (13), and lycorine (27) showed significant cell growth inhibition.

• MeSH
• alkaloidy amarylkovitých * farmakologie   chemie   izolace a purifikace   MeSH
• Amaryllidaceae * chemie   MeSH
• fenantridiny farmakologie   chemie   MeSH
• fytogenní protinádorové látky farmakologie   chemie   izolace a purifikace   MeSH
• lidé MeSH
• molekulární struktura MeSH
• screeningové testy protinádorových léčiv MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• alkaloidy amarylkovitých * MeSH
• fenantridiny MeSH
• fytogenní protinádorové látky MeSH
• hemanthamine MeSH Prohlížeč
• lycorine MeSH Prohlížeč

Ambelline, an alkaloid from the Amaryllidaceae family with a crinane-type skeleton, has not yet demonstrated any outstanding biological activity. However, its analogues prepared by derivatization of the C-11 hydroxyl group show different interesting effects. Continuing our earlier work, twelve novel aromatic esters were developed (10, 14, 16, 17, 22-25, 30-33) and studied, together with previously synthesized derivatives (2-9, 11-13, 15, 18-21, 26-29) in terms of their cytotoxic activity. The cytotoxic potential was determined on a panel of nine human cancer cell lines and one noncancerous cell line to characterize their biological activity spectrum. To describe and foresee the structure-activity relationship for further research, substances synthesized and described in our previous work were also included in this cytotoxicity study. The most significant activity was associated with analogues having methyl (10), methoxy (14-17), or ethoxy (18) substitution on the phenyl condensed to ambelline. However, the 4-chloro-3-nitrobenzoyl derivative (32) showed the most promising IC50 values, ranging from 0.6 ± 0.1 µM to 9.9 ± 0.2 µM. In vitro cytotoxicity studies indicated the most potent antiproliferative activity of 32 in a dose-dependent and time-dependent manner. Besides, 32 was found to be effective in decreasing viability and triggering apoptosis of MOLT-4 T-lymphoblastic leukemia cells.

• Klíčová slova
• 11-O-(4-Chloro-3-nitrobenzoyl)ambelline, Amaryllidaceae alkaloids, Ambelline, Antiproliferative activity, Cytotoxicity, In vitro,
• Publikační typ
• časopisecké články MeSH

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.

• Klíčová slova
• Amaryllidaceae alkaloids, antiproliferative activity, apoptosis, cell cycle arrest, cytotoxicity, pancracine,
• MeSH
• adenokarcinom plic patologie   MeSH
• alkaloidy izolace a purifikace   farmakologie   MeSH
• Amaryllidaceae chemie   MeSH
• apoptóza účinky léků   MeSH
• buňky A549 MeSH
• buňky Hep G2 MeSH
• fytogenní protinádorové látky izolace a purifikace   farmakologie   MeSH
• heterocyklické sloučeniny tetra- a více cyklické izolace a purifikace   farmakologie   MeSH
• leukemie patologie   MeSH
• lidé MeSH
• MFC-7 buňky MeSH
• nádorové buněčné linie MeSH
• nádory plic patologie   MeSH
• proliferace buněk účinky léků   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• alkaloidy MeSH
• fytogenní protinádorové látky MeSH
• heterocyklické sloučeniny tetra- a více cyklické MeSH
• pancracine MeSH Prohlížeč

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.

• Klíčová slova
• Alzheimer’s disease, Amaryllidaceae, Narcissus pseudonarcissus cv. Carlton, alkaloids, butyrylcholinesterase, carltonine A–C, docking studies,
• MeSH
• alkaloidy chemie   farmakologie   MeSH
• butyrylcholinesterasa chemie   metabolismus   MeSH
• cholinesterasové inhibitory chemie   farmakologie   MeSH
• lidé MeSH
• Narcissus chemie   MeSH
• simulace molekulového dockingu MeSH
• vazba proteinů MeSH
• vazebná místa MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• alkaloidy MeSH
• butyrylcholinesterasa MeSH
• cholinesterasové inhibitory 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.

• Klíčová slova
• Amaryllidaceae, alkaloids, biological activity, derivatives, montanine, montanine-type, pancracine,
• MeSH
• alkaloidy amarylkovitých chemie   izolace a purifikace   farmakologie   MeSH
• Amaryllidaceae chemie   metabolismus   MeSH
• antiprotozoální látky chemie   izolace a purifikace   farmakologie   MeSH
• cholinesterasové inhibitory chemie   izolace a purifikace   farmakologie   MeSH
• fenantridiny chemie   izolace a purifikace   farmakologie   MeSH
• fytogenní protinádorové látky chemie   izolace a purifikace   farmakologie   MeSH
• galantamin chemie   izolace a purifikace   farmakologie   MeSH
• heterocyklické sloučeniny tetra- a více cyklické chemie   izolace a purifikace   farmakologie   MeSH
• inhibiční koncentrace 50 MeSH
• isochinoliny chemie   izolace a purifikace   farmakologie   MeSH
• lidé MeSH
• nádorové buněčné linie MeSH
• nootropní látky chemie   izolace a purifikace   farmakologie   MeSH
• rostlinné extrakty chemie   MeSH
• sekundární metabolismus MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• alkaloidy amarylkovitých MeSH
• antiprotozoální látky MeSH
• cholinesterasové inhibitory MeSH
• fenantridiny MeSH
• fytogenní protinádorové látky MeSH
• galantamin MeSH
• hemanthamine MeSH Prohlížeč
• heterocyklické sloučeniny tetra- a více cyklické MeSH
• isochinoliny MeSH
• montanine MeSH Prohlížeč
• nootropní látky MeSH
• pancracine MeSH Prohlížeč
• rostlinné extrakty 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.

• Klíčová slova
• 7-oxonorpluviine, Amaryllidaceae, Narcissus cv. Professor Einstein, cytotoxicity, pancracine,
• Publikační typ
• časopisecké články 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.

• Klíčová slova
• Alzheimer’s disease, Amaryllidaceae, Nerine, Nerine bowdenii, antitumor activity, folk medicine,
• MeSH
• alkaloidy amarylkovitých farmakologie   MeSH
• Amaryllidaceae chemie   MeSH
• cholinesterasové inhibitory farmakologie   MeSH
• etnobotanika * MeSH
• lidé MeSH
• rostlinné extrakty farmakologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• alkaloidy amarylkovitých MeSH
• cholinesterasové inhibitory MeSH
• rostlinné extrakty MeSH

Twelve derivatives 1a-1m of the β-crinane-type alkaloid haemanthamine were developed. All the semisynthetic derivatives were studied for their inhibitory potential against both acetylcholinesterase and butyrylcholinesterase. In addition, glycogen synthase kinase 3β (GSK-3β) inhibition potency was evaluated in the active derivatives. In order to reveal the availability of the drugs to the CNS, we elucidated the potential of selected derivatives to penetrate through the blood-brain barrier (BBB). Two compounds, namely 11-O-(2-methylbenzoyl)-haemanthamine (1j) and 11-O-(4-nitrobenzoyl)-haemanthamine (1m), revealed the most intriguing profile, both being acetylcholinesterase (hAChE) inhibitors on a micromolar scale, with GSK-3β inhibition properties, and predicted permeation through the BBB. In vitro data were further corroborated by detailed inspection of the compounds' plausible binding modes in the active sites of hAChE and hBuChE, which led us to provide the structural determinants responsible for the activity towards these enzymes.

• Klíčová slova
• Alzheimer’s disease, Amaryllidaceae, acetylcholinesterase, butyrylcholinesterase, docking studies, glycogen synthase kinase-3β inhibition, haemanthamine,
• MeSH
• alkaloidy amarylkovitých chemie   metabolismus   MeSH
• Alzheimerova nemoc metabolismus   MeSH
• Amaryllidaceae chemie   metabolismus   MeSH
• fenantridiny chemie   metabolismus   MeSH
• hematoencefalická bariéra metabolismus   MeSH
• kinasa glykogensynthasy 3beta metabolismus   MeSH
• lidé MeSH
• ligandy MeSH
• molekulární konformace MeSH
• molekulární modely MeSH
• molekulární struktura MeSH
• permeabilita MeSH
• simulace molekulového dockingu MeSH
• vztahy mezi strukturou a aktivitou MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• alkaloidy amarylkovitých MeSH
• fenantridiny MeSH
• hemanthamine MeSH Prohlížeč
• kinasa glykogensynthasy 3beta MeSH
• ligandy MeSH