Narciindole A, the first representative of Amaryllidaceae alkaloids with an indol-3-ylmethanone framework, was isolated from bulbs of Narcissus pseudonarcissus (L.) cv. Carlton, together with carltonine D and carltonine E, which share the same unusual structural motif as dimeric carltonine C (reported in 2020), exhibiting atropisomerism. Unambiguous structure elucidations have been achieved by NMR spectroscopy, HRMS, and comparison with literature data of related alkaloids. Furthermore, the chirality of known alkaloids with a galanthindole biaryl core was revised using optical rotation. Last, but not least, a biosynthetic pathway for dimeric carltonine-type alkaloids was proposed. Unfortunately, in terms of biological activity, the isolated alkaloids showed only moderate inhibition of human acetylcholinesterase and/or butyrylcholinesterase.
- Klíčová slova
- Alkaloids, Alzheimer's disease, Amaryllidaceae, Atropisomerism, Carltonines, Narcissus pseudonarcissus (L.) cv. Carlton, Specific rotation revised, Structure elucidation,
- Publikační typ
- časopisecké články 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.
- Klíčová slova
- Amaryllidaceae, Clivia miniata, acetylcholinesterase, butyrylcholinesterase, clivimine B,
- Publikační typ
- časopisecké články MeSH
Tuberculosis (TB) is a widespread infectious disease caused by Mycobacterium tuberculosis. The increasing incidence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains has created a need for new antiTB agents with new chemical scaffolds to combat the disease. Thus, the key question is: how to search for new antiTB and where to look for them? One of the possibilities is to search among natural products (NPs). In order to search for new antiTB drugs, the detailed phytochemical study of the whole Dicranostigma franchetianum plant was performed isolating wide spectrum of isoquinoline alkaloids (IAs). The chemical structures of the isolated alkaloids were determined by a combination of MS, HRMS, 1D, and 2D NMR techniques, and by comparison with literature data. Alkaloids were screened against Mycobacterium tuberculosis H37Ra and four other mycobacterial strains (M. aurum, M. avium, M. kansasii, and M. smegmatis). Alkaloids 3 and 5 showed moderate antimycobacterial activity against all tested strains (MICs 15.625-31.25 µg/mL). Furthermore, ten semisynthetic berberine (16a-16k) derivatives were developed and tested for antimycobacterial activity. In general, the derivatization of berberine was connected with a significant increase in antimycobacterial activity against all tested strains (MICs 0.39-7.81 μg/mL). Two derivatives (16e, 16k) were identified as compounds with micromolar MICs against M. tuberculosis H37Ra (MIC 2.96 and 2.78 µM). All compounds were also evaluated for their in vitro hepatotoxicity on a hepatocellular carcinoma cell line (HepG2), exerting lower cytotoxicity profile than their MIC values, thereby potentially reaching an effective concentration without revealing toxic side effects.
- Klíčová slova
- Dicranostigma franchetianum, Papaveraceae, antimycobacterial activity, berberine, cytotoxicity, isoquinoline alkaloids,
- MeSH
- antibakteriální látky farmakologie MeSH
- berberin * farmakologie MeSH
- lidé MeSH
- mikrobiální testy citlivosti MeSH
- Mycobacterium tuberculosis * MeSH
- Papaveraceae * MeSH
- tuberkulóza * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- antibakteriální látky MeSH
- berberin * MeSH
One undescribed indole alkaloid together with twenty-two known compounds have been isolated from aerial parts of Vinca minor L. (Apocynaceae). The chemical structures of the isolated alkaloids were determined by a combination of MS, HRMS, 1D, and 2D NMR techniques, and by comparison with literature data. The NMR data of several alkaloids have been revised, corrected, and missing data have been supplemented. Alkaloids isolated in sufficient quantity were screened for their in vitro acetylcholinesterase (AChE; E.C. 3.1.1.7) and butyrylcholinesterase (BuChE; E.C. 3.1.1.8) inhibitory activity. Selected compounds were also evaluated for prolyl oligopeptidase (POP; E.C. 3.4.21.26), and glycogen synthase 3β-kinase (GSK-3β; E.C. 2.7.11.26) inhibition potential. Significant hBuChE inhibition activity has been shown by (-)-2-ethyl-3[2-(3-ethylpiperidinyl)-ethyl]-1H-indole with an IC50 value of 0.65 ± 0.16 μM. This compound was further studied by enzyme kinetics, along with in silico techniques, to reveal the mode of inhibition. This compound is also predicted to cross the blood-brain barrier (BBB) through passive diffusion.
- Klíčová slova
- (−)-2-ethyl-3[2-(3-ethylpiperidinyl)-ethyl]-1H-indole, Alkaloids, Alzheimer's disease, Apocynaceae, Butyrylcholinesterase, Docking studies, Vinca minor, Vincaminorudeine,
- MeSH
- acetylcholinesterasa MeSH
- Alzheimerova nemoc * farmakoterapie MeSH
- butyrylcholinesterasa MeSH
- fytonutrienty farmakologie MeSH
- GSK3B MeSH
- indolové alkaloidy farmakologie MeSH
- monoterpeny farmakologie MeSH
- nadzemní části rostlin chemie MeSH
- Vinca * chemie MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- acetylcholinesterasa MeSH
- butyrylcholinesterasa MeSH
- fytonutrienty MeSH
- GSK3B MeSH
- indolové alkaloidy MeSH
- monoterpeny MeSH
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.
- Klíčová slova
- Alkaloids, Alzheimer's disease, Amaryllidaceae, Docking studies, Narcieliine, Zephyranthes citrina,
- MeSH
- acetylcholinesterasa chemie metabolismus MeSH
- alkaloidy chemie izolace a purifikace farmakologie terapeutické užití MeSH
- Alzheimerova nemoc farmakoterapie patologie MeSH
- Amaryllidaceae chemie metabolismus MeSH
- butyrylcholinesterasa chemie metabolismus MeSH
- cholinesterasové inhibitory chemie metabolismus farmakologie terapeutické užití MeSH
- hematoencefalická bariéra účinky léků metabolismus MeSH
- katalytická doména MeSH
- kinetika MeSH
- lidé MeSH
- magnetická rezonanční spektroskopie MeSH
- molekulární konformace MeSH
- simulace molekulového dockingu MeSH
- vazebná místa MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- acetylcholinesterasa MeSH
- alkaloidy MeSH
- butyrylcholinesterasa MeSH
- cholinesterasové inhibitory MeSH
Cardiac glycosides (CGs) represent a group of sundry compounds of natural origin. Most CGs are potent inhibitors of Na+/K+-ATPase, and some are routinely utilized in the treatment of various cardiac conditions. Biological activities of other lesser known CGs have not been fully explored yet. Interestingly, the anticancer potential of some CGs was revealed and thereby, some of these compounds are now being evaluated for drug repositioning. However, high systemic toxicity and low cancer cell selectivity of the clinically used CGs have severely limited their utilization in cancer treatment so far. Therefore, in this study, we have focused on two poorly described CGs: hyrcanoside and deglucohyrcanoside. We elaborated on their isolation, structural identification, and cytotoxicity evaluation in a panel of cancerous and noncancerous cell lines, and on their potential to induce cell cycle arrest in the G2/M phase. The activity of hyrcanoside and deglucohyrcanoside was compared to three other CGs: ouabain, digitoxin, and cymarin. Furthermore, by in silico modeling, interaction of these CGs with Na+/K+-ATPase was also studied. Hopefully, these compounds could serve not only as a research tool for Na+/K+-ATPase inhibition, but also as novel cancer therapeutics.
- Klíčová slova
- Na+/K+-ATPase inhibitors, anticancer activity, cardiac glycosides, cymarin, deglucohyrcanoside, digitoxin, hyrcanoside, natural product isolation, ouabain, secondary plant metabolites,
- Publikační typ
- časopisecké články 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.
- Klíčová slova
- Amaryllidaceae, Lycoris, Lycoris radiata, alkaloids, biological activity, folk medicine,
- MeSH
- alkaloidy amarylkovitých chemie terapeutické užití MeSH
- Amaryllidaceae chemie MeSH
- antimalarika chemie terapeutické užití MeSH
- fytonutrienty terapeutické užití MeSH
- kořeny rostlin chemie MeSH
- lidé MeSH
- Lycoris chemie MeSH
- rostlinné extrakty chemie terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Geografické názvy
- Čína MeSH
- Názvy látek
- alkaloidy amarylkovitých MeSH
- antimalarika MeSH
- fytonutrienty MeSH
- rostlinné extrakty 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
- antitumorózní látky fytogenní chemie izolace a purifikace farmakologie MeSH
- cholinesterasové inhibitory chemie izolace a purifikace farmakologie MeSH
- fenantridiny 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
- antitumorózní látky fytogenní MeSH
- cholinesterasové inhibitory MeSH
- fenantridiny 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
Bersavine is the new bisbenzylisoquinoline alkaloid isolated from the Berberis vulgaris L.(Berberidaceae) plant. The results of cytotoxicity screening 48 h post-treatment showed thatbersavine considerably inhibits the proliferation and viability of leukemic (Jurkat, MOLT-4), colon(HT-29), cervix (HeLa) and breast (MCF-7) cancer cells with IC50 values ranging from 8.1 to 11 μM.The viability and proliferation of leukemic Jurkat and MOLT-4 cells were decreased after bersavinetreatment in a time- and dose-dependent manner. Bersavine manifested concentration-dependentantiproliferative activity in human lung, breast, ovarian and hepatocellular carcinoma cell linesusing a xCELLigence assay. Significantly higher percentages of MOLT-4 cells exposed to bersavineat 20 μM for 24 h were arrested in the G1 phase of the cell cycle using the flow cytometry method.The higher percentage of apoptotic cells was measured after 24 h of bersavine treatment. Theupregulation of p53 phosphorylated on Ser392 was detected during the progression of MOLT-4 cellapoptosis. Mechanistically, bersavine-induced apoptosis is an effect of increased activity ofcaspases, while reduced proliferation seems dependent on increased Chk1 Ser345 phosphorylationand decreased Rb Ser807/811 phosphorylation in human leukemic cells.
- Klíčová slova
- antiproliferative activity, apoptosis, bersavine, cell cycle, cytotoxicity,
- MeSH
- alkaloidy * chemie izolace a purifikace farmakologie MeSH
- antitumorózní látky fytogenní * chemie izolace a purifikace farmakologie MeSH
- apoptóza účinky léků MeSH
- Berberis chemie MeSH
- buňky Hep G2 MeSH
- buňky HT-29 MeSH
- cytotoxiny * chemie izolace a purifikace farmakologie MeSH
- G1 fáze účinky léků MeSH
- HeLa buňky MeSH
- Jurkat buňky MeSH
- léky antitumorózní - screeningové testy MeSH
- leukemie farmakoterapie metabolismus patologie MeSH
- lidé MeSH
- MFC-7 buňky MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- alkaloidy * MeSH
- antitumorózní látky fytogenní * MeSH
- cytotoxiny * 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
