Biologically active metabolites of plants. 10. Alkaloids of Fumaria officinalis L. and their biological activity

Šafratová M.: Biologicky aktivní metabolity rostlin 10. Alkaloidy Fumaria officinalis L. a jejich biologická aktivita. Univerzita Karlova v Praze, Farmaceutická fakulta v Hradci Králové, Katedra farmaceutické botaniky a ekologie, Hradec Králové, 2013. Diplomová práce. 70 s. Předmětem diplomové práce bylo zpracování výtřepku alkaloidů z Fumaria officinalis L. (Fumariaceae). Pomocí sloupcové chromatografie a následně preparativního TLC byly izolovány tři alkaloidy, které byly podrobeny strukturní analýze (MS a NMR). První látka byla identifikována jako isochinolinový alkaloid stylopin, druhým izolovaným alkaloidem byl sinaktin a třetím izolovaným alkaloidem byl fumarilin. Všechny tři alkaloidy již byly dříve z F. officinalis izolovány. U všech tří alkaloidů byla testována jejich inhibiční aktivita vůči lidské erytrocytární acetylcholinesteráze (HuAChE) a lidské sérové butyrylcholinesteráze (HuBuChE). U stylopinu byly stanovené hodnoty IC50 HuAChE ˂ 1000 µM a IC50 HuBuChE ˂ 1000 µM. Pro sinaktin byly naměřeny hodnoty IC50 HuAChE = 632 ± 22 µM a IC50 HuBuChE ˂ 1000 µM. Hodnoty fumarilinu byly IC50 HuAChE ˂ 1000 µM a IC50 HuBuChE = 330 ± 12 µM. V porovnání se standardy byly stylopin, sinaktin i fumarilin málo aktivní. Žádná z izolovaných látek se proto nejeví jako léčivo vhodné v terapii Alzheimerovy...Šafratová M.: Biologically active metabolites of plants 10. Alkaloids of Fumaria officinalis L. and their biological aktivity. Charles University in Prague, Faculty of Pharmacy in Hradec Králové. Department of Pharmaceutical Botany and Ecology, Hradec Králové, 2013. Diploma thesis. 70 s. The object of this diploma thesis was to process the pool of alkaloids from Fumaria officinalis L. (Fumariaceae). Using column chromatography and preparative TLC three alkaloids were isolated which have been subjected to structural analysis (MS, NMR). The first substance was identified as isoquinoline alkaloid stylopin, others isolated alkaloid was sinactin and third isolated alkaloid was fumarilin. All three alkaloids have been previously isolated from F. officinalis. For all three alkaloids were tested for their inhibitory activity against human erythrocyte acetylcholinesterase (HuAChE) and human serum butyrylcholinesterase (HuBuChE). For stylopine IC50 values were determined IC50 HuAChE ˂ 1000 µM and IC50 HuBuChE ˂ 1000 µM. For sinactine were measured IC50 HuAChE = 632 ± 22 µM and IC50 HuBuChE ˂ 1000 µM. Values for fumariline IC50 HuAChE ˂ 1000 µM and IC50 HuBuChE = 330 ± 12 µM. In comparison with standards were stylopine, sinactine and fumariline not very active. None of the isolated compounds are therefore...Department of Pharmaceutical Botany and EcologyKatedra farmaceutické botaniky a ekologieFaculty of Pharmacy in Hradec KrálovéFarmaceutická fakulta v Hradci Králov

Study of inhibition (toxicity) activity of alkaloids from selected plant species of Amaryllidaceae family on human enzyme systems (in vitro study) III

Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Botany and Ecology Candidate: Mgr. Marcela Šafratová Supervisor: Doc. Ing. Lucie Cahlíková PhD. Title of Doctoral Thesis: Study of inhibition (toxicity) activity of alkaloids from selected plant species of Amaryllidaceae family on human enzyme systems (in vitro study) III Key words: Narcissus poeticus cv. Pink Parasol, Amaryllidaceae, alkaloids, acetylcholinesterase, butyrylcholinesterase, prolyl oligopeptidase, cytotoxicity Bulbs of Narcissus poeticus. cv. Pink Parasol were selected as a source of Amaryllidaceae alkaloids for study of their biological activity. Concentrated alkaloid extract has been prepared were prepared by standard extraction and fractionated in aluminium oxide column chromatography column using step gradient elution with petrol, chloroform and ethanol. Column chromatography, vacuum liquid column chromatography, preparative TLC and crystallizations resulted in the isolation of 15 alkaloids, 2 of them were identified as new structures. The chemical structures of isolated compounds were determined on the basis of spectrometric techniques (NMR, MS, optical rotation) and by comparison with literature. Alkaloids isolated in sufficient amounts were tested on their inhibitory ability of human..

Biologically active metabolites of plants. 10. Alkaloids of Fumaria officinalis L. and their biological activity

Šafratová M.: Biologically active metabolites of plants 10. Alkaloids of Fumaria officinalis L. and their biological aktivity. Charles University in Prague, Faculty of Pharmacy in Hradec Králové. Department of Pharmaceutical Botany and Ecology, Hradec Králové, 2013. Diploma thesis. 70 s. The object of this diploma thesis was to process the pool of alkaloids from Fumaria officinalis L. (Fumariaceae). Using column chromatography and preparative TLC three alkaloids were isolated which have been subjected to structural analysis (MS, NMR). The first substance was identified as isoquinoline alkaloid stylopin, others isolated alkaloid was sinactin and third isolated alkaloid was fumarilin. All three alkaloids have been previously isolated from F. officinalis. For all three alkaloids were tested for their inhibitory activity against human erythrocyte acetylcholinesterase (HuAChE) and human serum butyrylcholinesterase (HuBuChE). For stylopine IC50 values were determined IC50 HuAChE ˂ 1000 µM and IC50 HuBuChE ˂ 1000 µM. For sinactine were measured IC50 HuAChE = 632 ± 22 µM and IC50 HuBuChE ˂ 1000 µM. Values for fumariline IC50 HuAChE ˂ 1000 µM and IC50 HuBuChE = 330 ± 12 µM. In comparison with standards were stylopine, sinactine and fumariline not very active. None of the isolated compounds are therefore..

Biologically active metabolites of plants. 10. Alkaloids of Fumaria officinalis L. and their biological activity

Šafratová M.: Biologically active metabolites of plants 10. Alkaloids of Fumaria officinalis L. and their biological aktivity. Charles University in Prague, Faculty of Pharmacy in Hradec Králové. Department of Pharmaceutical Botany and Ecology, Hradec Králové, 2013. Diploma thesis. 70 s. The object of this diploma thesis was to process the pool of alkaloids from Fumaria officinalis L. (Fumariaceae). Using column chromatography and preparative TLC three alkaloids were isolated which have been subjected to structural analysis (MS, NMR). The first substance was identified as isoquinoline alkaloid stylopin, others isolated alkaloid was sinactin and third isolated alkaloid was fumarilin. All three alkaloids have been previously isolated from F. officinalis. For all three alkaloids were tested for their inhibitory activity against human erythrocyte acetylcholinesterase (HuAChE) and human serum butyrylcholinesterase (HuBuChE). For stylopine IC50 values were determined IC50 HuAChE ˂ 1000 µM and IC50 HuBuChE ˂ 1000 µM. For sinactine were measured IC50 HuAChE = 632 ± 22 µM and IC50 HuBuChE ˂ 1000 µM. Values for fumariline IC50 HuAChE ˂ 1000 µM and IC50 HuBuChE = 330 ± 12 µM. In comparison with standards were stylopine, sinactine and fumariline not very active. None of the isolated compounds are therefore..

Study of inhibition (toxicity) activity of alkaloids from selected plant species of Amaryllidaceae family on human enzyme systems (in vitro study) III

Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Botany and Ecology Candidate: Mgr. Marcela Šafratová Supervisor: Doc. Ing. Lucie Cahlíková PhD. Title of Doctoral Thesis: Study of inhibition (toxicity) activity of alkaloids from selected plant species of Amaryllidaceae family on human enzyme systems (in vitro study) III Key words: Narcissus poeticus cv. Pink Parasol, Amaryllidaceae, alkaloids, acetylcholinesterase, butyrylcholinesterase, prolyl oligopeptidase, cytotoxicity Bulbs of Narcissus poeticus. cv. Pink Parasol were selected as a source of Amaryllidaceae alkaloids for study of their biological activity. Concentrated alkaloid extract has been prepared were prepared by standard extraction and fractionated in aluminium oxide column chromatography column using step gradient elution with petrol, chloroform and ethanol. Column chromatography, vacuum liquid column chromatography, preparative TLC and crystallizations resulted in the isolation of 15 alkaloids, 2 of them were identified as new structures. The chemical structures of isolated compounds were determined on the basis of spectrometric techniques (NMR, MS, optical rotation) and by comparison with literature. Alkaloids isolated in sufficient amounts were tested on their inhibitory ability of human..

Cytotoxic activities of Amaryllidaceae alkaloids against gastrointestinal cancer cells

The treatment of many diseases is highly dependent on natural products and natural products can also be used as design templates for future anticancer drugs. Thirteen Amaryllidaceae alkaloids possessing α-crinane, β-crinane, galantamine, lycorine and tazettine-type skeleton have been isolated in our laboratory, and their cytotoxicity against p53-mutated gastrointestinal cancer cells were evaluated. At the same time, healthy small intestine cells were used to determine overall toxicity against noncancerous cells. In this study, we demonstrated that haemanthamine, haemanthidine and lycorine showed strong cytotoxicity against p53-mutated Caco-2 and HT-29 colorectal adenocarcinoma cells as quantified in terms of IC50 values. We for the first time observed approximately 20 times higher IC50values against normal intestine epithelial cells FHs-74 Int after haemanthamine and lycorine treatment when compared with Caco-2 and HT-29 cancer cells. In conclusion, our data indicate that α-C2 bridged haemanthamine may be perspective anticancer drug candidate for further semisynthetic modification and structure-activity relationship study

Amaryllidaceae Alkaloids as Potential Glycogen Synthase Kinase-3β Inhibitors

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)}

Amaryllidaceae Alkaloids from Clivia miniata (Lindl.) Bosse (Amaryllidaceae): Isolation, Structural Elucidation, and Biological Activity

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

Amaryllidaceae Alkaloids of Belladine-Type from Narcissus pseudonarcissus cv. Carlton as New Selective Inhibitors of Butyrylcholinesterase

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