montanine-type
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Alzheimeŕs disease (AD) is the most common neurodegenerative disorder, characterized by neuronal loss and cognitive impairment. Currently, very few drugs are available for AD treatment, and a search for new therapeutics is urgently needed. Thus, in the current study, twenty-eight new derivatives of montanine-type Amaryllidaceae alkaloids were synthesized and evaluated for their ability to inhibit human recombinant acetylcholinesterase (hAChE) and butyrylcholinesterase (hBuChE). Three derivatives (1n, 1o, and 1p) with different substitution patterns demonstrated significant selective inhibitory potency for hAChE (IC50 < 5 μM), and one analog, 1v, showed selective hBuChE inhibition activity (IC50 = 1.73 ± 0.05 μM). The prediction of CNS availability, as disclosed by the BBB score, suggests that the active compounds in this survey should be able pass through the blood-brain barrier (BBB). Cytotoxicity screening and docking studies were carried out for the two most pronounced cholinesterase inhibitors, 1n and 1v.
- MeSH
- acetylcholinesterasa metabolismus MeSH
- alkaloidy chemická syntéza chemie farmakologie MeSH
- Alzheimerova nemoc farmakoterapie metabolismus MeSH
- butyrylcholinesterasa metabolismus MeSH
- cholinesterasové inhibitory chemická syntéza chemie farmakologie MeSH
- hematoencefalická bariéra účinky léků metabolismus MeSH
- isochinoliny chemická syntéza chemie farmakologie MeSH
- lidé MeSH
- molekulární struktura MeSH
- simulace molekulového dockingu * MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem 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.
- 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
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.
- 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
The isoquinoline alkaloids found in Amaryllidaceae are attracting attention due to attributes that can be harnessed for the development of new drugs. The possible molecular mechanisms by which montanine exerts its inhibitory effects against cancer cells have not been documented. In the present study, montanine, manthine and a series of 15 semisynthetic montanine analogues originating from the parent alkaloid montanine were screened at a single test dose of 10 μM to explore their cytotoxic activities against a panel of eight cancer cell lines and one non-cancer cell line. Among montanine and its analogues, montanine and its derivatives 12 and 14 showed the highest cytostatic activity in the initial single-dose screening. However, the native montanine exhibited the greatest antiproliferative activity against cancer cells, with a lower mean IC50 value of 1.39 μM, compared to the displayed mean IC50 values of 2.08 μM for 12 and 3.57 μM for 14. Montanine exhibited the most potent antiproliferative activity with IC50 values of 1.04 μM and 1.09 μM against Jurkat and A549 cell lines, respectively. We also evaluated montanine's cytotoxicity and cell death mechanisms. Our results revealed that montanine triggered apoptosis of MOLT-4 cells via caspase activation, mitochondrial depolarisation and Annexin V/PI double staining. The Western blot results of MOLT-4 cells showed that the protein levels of phosphorylated Chk1 Ser345 were upregulated with increased montanine concentrations. Our findings provide new insights into the mechanisms underlying the cytostatic, cytotoxic and pro-apoptotic activities of montanine alkaloids in lung adenocarcinoma A549 and leukemic MOLT-4 cancer cell types.
... společně s lékem Bryonia alba (kvůli zhoršení bolestí při sebemenším pohybu), aby byly léčeny oba typy ... ... Léčba -- • Hypericum perforatum 15 CH: 1 dávku dvakrát týdně, • Arnica montana 9 CH: 1 dávku při zátěži ... ... Arnica montana, jak již bylo řečeno, je lékem potíží, které rozpoutává a zhoršuje námaha či traumatismus ...
2 nečíslované strany ; 30 cm
Leták se věnuje homeopatické léčbě ischiatických bolestí a homeopatické léčbě bolestí kostrče.
- MeSH
- homeopatie MeSH
- ischialgie MeSH
- Publikační typ
- letáky MeSH
- Konspekt
- Fyzioterapie. Psychoterapie. Alternativní lékařství
- NLK Obory
- homeopatie
... Ksi^dz, co jesc nie mogi 29 -- JAN KOCHANOWSKI -- Na zdrowie 30 -- Do Baltazera 31 -- Do doktora Montana ... ... Dydyňski] -- Šwietny byt 177 -- [ANONIM] -- Bajka medyczno-farma ceutyczna 178 -- EGO-ISTA [pseud.] -- Typ ...
Wyd. 1. 399 s. : il. ; 20 cm.
- MeSH
- lékařství v literatuře MeSH
- Publikační typ
- beletrie MeSH
- vtip a humor MeSH
- Konspekt
- Polská literatura
- NLK Obory
- lékařství
- humanitní vědy a umění