norbelladine OR C000629946 Dotaz Zobrazit nápovědu
Alzheimer's disease (AD) is a multifactorial neurodegenerative condition of the central nervous system (CNS) that is currently treated by cholinesterase inhibitors and the N-methyl-d-aspartate receptor antagonist, memantine. Emerging evidence strongly supports the relevance of targeting butyrylcholinesterase (BuChE) in the more advanced stages of AD. Within this study, we have generated a pilot series of compounds (1-20) structurally inspired from belladine-type Amaryllidaceae alkaloids, namely carltonine A and B, and evaluated their acetylcholinesterase (AChE) and BuChE inhibition properties. Some of the compounds exhibited intriguing inhibition activity for human BuChE (hBuChE), with a preference for BuChE over AChE. Seven compounds were found to possess a hBuChE inhibition profile, with IC50 values below 1 μM. The most potent one, compound 6, showed nanomolar range activity with an IC50 value of 72 nM and an excellent selectivity pattern over AChE, reaching a selectivity index of almost 1400. Compound 6 was further studied by enzyme kinetics, along with in-silico techniques, to reveal the mode of inhibition. The prediction of CNS availability estimates that all the compounds in this survey can pass through the blood-brain barrier (BBB), as disclosed by the BBB score.
- MeSH
- acetylcholinesterasa chemie MeSH
- alkaloidy amarylkovitých chemie MeSH
- butyrylcholinesterasa chemie MeSH
- cholinesterasové inhibitory chemie farmakologie MeSH
- lidé MeSH
- nádorové buňky kultivované MeSH
- neuroblastom farmakoterapie patologie MeSH
- počítačová simulace MeSH
- proliferace buněk MeSH
- simulace molekulového dockingu * MeSH
- tyramin analogy a deriváty chemie MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- hodnotící studie MeSH
Glycosides of benzodioxole-indole alkaloid 6-hydroxy-galanthindole (7-(6'-(hydroxymethyl)benzo[d][1',3']dioxol-5'-yl)-1-methyl-1H-indol-6-ol) having axial chirality were isolated from Narcissus cultivar 'Dutch Master'. The structure, including absolute configuration, was determined by means of extensive spectroscopic data such as UV, IR, CD, MS, 1D and 2D NMR spectra, and computational chiroptical methods. The aglycone has a structure containing two aromatic moieties with substituents hindering rotation about the biaryl axis and is connected to a saccharide moiety linked at C-6 and made up of one, two, or three sugars (glucose, alpha-L-rhamnopyranosyl-(1-->6)-beta-D-glucopyranose, and trisaccharide ([beta-D-xylopyranosyl(1-->2)]-[alpha-L-rhamnopyranosyl-(1-->6)]-beta-D-glucopyranose).
- MeSH
- alkaloidy amarylkovitých chemie MeSH
- benzodioxoly chemie izolace a purifikace MeSH
- glykosidy chemie izolace a purifikace MeSH
- indolové alkaloidy chemie izolace a purifikace MeSH
- molekulární struktura MeSH
- Narcissus chemie MeSH
- rostlinné extrakty chemie MeSH
- sacharidy MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Eleven Amaryllidaceae alkaloids (1-11) were isolated from fresh bulbs of Chlidanthus fragrans Herb. The chemical structures were elucidated by MS, and 1D and 2D NMR spectroscopic experiments. Complete NMR assignments were achieved for deoxypretazzetine (1). All compounds were evaluated for their erythrocytic acetylcholinesterase and serum butyrylcholinesterase inhibition activity using Ellman's method. In the prolyl oligopeptidase assay, Z-Gly-Pro-p-nitroanilide was used as substrate. In biological assays, only the crinine type Amaryllidaceae alkaloid undulatine showed promising acetylcholinesterase and prolyl oligopeptidase inhibition activity with IC50 values of 23.0 +/- 1.0 microM and 1.96 +/- 0.12 mM, respectively. Other isolated compounds were considered inactive.
- MeSH
- acetylcholinesterasa metabolismus MeSH
- alkaloidy amarylkovitých chemie izolace a purifikace metabolismus MeSH
- butyrylcholinesterasa metabolismus MeSH
- liliovité chemie enzymologie MeSH
- magnetická rezonanční spektroskopie MeSH
- serinové endopeptidasy metabolismus MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem 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.
Glycogen synthase kinase-3β (GSK-3β) is a multifunctional serine/threonine protein kinase that was originally identified as an enzyme involved in the control of glycogen metabolism. It plays a key role in diverse physiological processes including metabolism, the cell cycle, and gene expression by regulating a wide variety of well-known substances like glycogen synthase, tau-protein, and β-catenin. Recent studies have identified GSK-3β as a potential therapeutic target in Alzheimer´s disease, bipolar disorder, stroke, more than 15 types of cancer, and diabetes. GSK-3β is one of the most attractive targets for medicinal chemists in the discovery, design, and synthesis of new selective potent inhibitors. In the current study, twenty-eight Amaryllidaceae alkaloids of various structural types were studied for their potency to inhibit GSK-3β. Promising results have been demonstrated by alkaloids of the homolycorine-{9-O-demethylhomolycorine (IC50 = 30.00 ± 0.71 µM), masonine (IC50 = 27.81 ± 0.01 μM)}, and lycorine-types {caranine (IC50 = 30.75 ± 0.04 μM)}.
Evidence gathered in various studies points to the fact that haemanthamine, an isoquinoline alkaloid, has multiple medicinally interesting characteristics, including antitumor, antileukemic, antioxidant, antiviral, anticonvulsant and antimalarial activity. This work presents, for the first time, a universal LC-MS/MS method for analysis of haemanthamine in plasma, bile and urine which has been verified in a pilot pharmacokinetic experiment on rats. Chromatographic separation was performed on a pentafluorophenyl core-shell column in gradient elution mode with a mobile phase consisting of acetonitrile-methanol-ammonium formate buffer. A sample preparation based on liquid-liquid extraction with methyl tert-butyl ether was employed with ambelline used as an internal standard. Quantification was performed using LC-MS-ESI(+) in Selected Reaction Monitoring mode. The method was validated according to the European Medicines Agency guideline in a concentration range of 0.1-10 μmol/L in plasma, bile and urine. The concentration-time profiles of haemanthamine in plasma, bile and urine after a single i.v. bolus of 10 mg/kg have been described for the first time. The presented study addresses the lack of information on haemanthamine pharmacokinetics and also introduces a new universal method of haemanthamine analysis in complex biological matrices. Copyright © 2015 John Wiley & Sons, Ltd.
- MeSH
- alkaloidy amarylkovitých krev farmakokinetika moč MeSH
- fenantridiny krev farmakokinetika moč MeSH
- krysa rodu rattus MeSH
- limita detekce MeSH
- pilotní projekty MeSH
- reprodukovatelnost výsledků MeSH
- tandemová hmotnostní spektrometrie metody MeSH
- žluč metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- validační studie MeSH
In this study, the South African Amaryllid Boophone haemanthoides was examined for its phytochemical composition and cytotoxicity. In the process eight alkaloid structures, including the new compound distichaminol, were identified in bulb ethanolic extracts. Of the isolates, lycorine and distichamine exhibited strong activities against human acute lymphoblastic leukemia (CEM), breast adenocarcinoma (MCF7) and cervical adenocarcinoma (HeLa) cells with IC50S ranging from 1.8 to 9.2 microM.
- MeSH
- alkaloidy amarylkovitých chemie izolace a purifikace MeSH
- antitumorózní látky fytogenní chemie izolace a purifikace MeSH
- fenantridiny izolace a purifikace MeSH
- HeLa buňky MeSH
- léky antitumorózní - screeningové testy MeSH
- lidé MeSH
- liliovité chemie MeSH
- MFC-7 buňky MeSH
- molekulární struktura MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The underivatized alkaloid mixture extracted from the bulbs of Chlidanthus fragrans Herb. was investigated by capillary GC/MS for the first time. Fifteen known Amaryllidaceae alkaloids of five structure types were identified. The main alkaloids were tazzetine (9, tazettine-type), chlidanthine (2, galanthamine-type), belladine (8, belladine-type) and lycorine (12, lycorine-type). The alkaloid extract from the bulbs showed promising human blood acetylcholinesterase (IC50 = 20.1 +/- 2.9 microg/mL) and human plasma butyrylcholinesterase (IC50 = 136.8 +/- 6.9 microg/mL) inhibitory activity.
- MeSH
- alkaloidy amarylkovitých chemie izolace a purifikace MeSH
- cholinesterasové inhibitory chemie izolace a purifikace MeSH
- lidé MeSH
- liliovité chemie MeSH
- plynová chromatografie s hmotnostně spektrometrickou detekcí MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
From the bulbs of Zephyranthes robusta Baker (Amaryllidaceae), seven known compounds, belonging to four structural types of Amaryllidaceae alkaloids, were identified and quantified by GC-MS. The alkaloid extract from the bulbs showed promising acetylcholinesterase and butyrylcholinesterase inhibitory activities against HuAChE (IC50 = 35.9 +/- 3.5 microg/mL) and HuBuChE (IC50 = 190.9 +/- 8.2 microg/mL).
- MeSH
- alkaloidy amarylkovitých analýza farmakologie MeSH
- butyrylcholinesterasa metabolismus MeSH
- cholinesterasové inhibitory farmakologie MeSH
- lidé MeSH
- liliovité chemie MeSH
- plynová chromatografie s hmotnostně spektrometrickou detekcí metody MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Studying stress pathways on the level of secondary metabolites that are found in very small concentration in the cells is complicated. In the algae, the role of individual metabolites (such as carotenoids, phenolic compounds, organic acids, and vitamins) and miRNAs that participate in plant's defence are very poorly understood during stressful conditions. Therefore, in the present experiment, the model organism Chlamydomonas reinhardtii was exposed to stress conditions (Lyc and UV-C irradiation) to detect these substances, even at very low concentrations. The purpose was to monitored changes at each response level with a future view to identifying their specific roles under different stress factors. In stress-treated cultures, numerous transcriptomic and metabolomic pathways were triggered in C. reinhardtii. Although Lyc significantly decreased the concentration of AA, suggesting that Lyc has a similar function in C. reinhardtii as in plants. The negative effect of UV-C radiation was based on the production of ROS and enhancement of antioxidant responses, resulting in increased levels of polyphenols and simple phenolic compounds. Both treatments did lead to extensive changes in transcript levels and miRNA expression patterns.
- MeSH
- alkaloidy amarylkovitých farmakologie MeSH
- Chlamydomonas reinhardtii účinky léků genetika metabolismus účinky záření MeSH
- fenantridiny farmakologie MeSH
- mikro RNA * MeSH
- polyfenoly metabolismus MeSH
- reaktivní formy kyslíku metabolismus MeSH
- regulace genové exprese u rostlin účinky léků účinky záření MeSH
- RNA rostlin * MeSH
- ultrafialové záření * MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
