|
|
Pyrazine derivatives as potential drugs III
Hošťálková, Anna ; Doležal, Martin (advisor) ; Kopecký, Kamil (referee)
Deriváty pyrazinu jako potanciální léčiva III. Tuberkulóza je problém v celosvětovém měřítku. Rostoucí počet nakažených lidí, vznik lékově rezistentních kmenů Mycobacterium tuberculosis a ko-infekce HIV vedly k naléhavé potřebě nových antituberkulotik. Tato diplomová práce referuje o současných léčivech používaných při léčbě tuberkulózy a některých nových potenciálních antituberkuloticích. Také bylo v rámci diplomové práce syntetizováno deset nových látek, derivátů anilidů kyseliny pyrazin-2-karboxylové, které byly charakterizovány jejich fyzikálními vlastnostmi a poté byla zkoušena jejich antimykobakteriální a antifungální aktivita in vitro. Abstract Pyrazine derivatives as potential drugs III. Tuberculosis is a health problem worldwide. The increasing number of infected people, emergence of drug resistant strains Mycobacterium tuberculosis and HIV co-infection have resulted in the urgent need for new antituberculosis drugs. This degree work reviews drugs used in current treatment for tuberculosis and some of new potential anti-tuberculosis drug candidates. Within the task of this work were also synthesized ten new compounds, derivatives of anilides of pyrazin-2-carboxylic acid, which were characterized by physical properties and then was assayed their antimycobacterial and antifungal activity in...
|
|
|
Isolation of alkaloids of the species Magnolia soulangeana Soul.-Bod. and study of their biological activity
Baková, Izabela ; Hošťálková, Anna (advisor) ; Opletal, Lubomír (referee)
Baková I.: Isolation of alkaloids of the species Magnolia soulangeana Soul.-Bod. and study of their biological activity. Diploma thesis, Charles University, Faculty of Pharmacy in Hradec Králové, Department of Pharmaceutical Botany and Ecology, Hradec Králové, 2017. Key words: Magnolia solulangeana, secondary metabolites, alkaloids, biological activity. Secondary metabolites of plants are responsible for various biological activities. Alkaloids were described as a potentially suitable for Alzheimer's disease therapy (AD) through their inhibition activities against cholinesterases. Nowadays, these substances are important medicine for AD, therefore a screening of herbal drugs is still a current topic. An alkaloid extract of Magnolia × soulangeana flowers was tested in a preliminary testing on anticholinesterase activity. Because of the promising results, it was chosen for an isolation and identification possible effective alkaloids. The extract was separated by a column chromatography using aluminium oxide and a step gradient elution. Alkaloids were isolated by a repeated preparative thin-layer chromatography. Individual alkaloids were identified by a structural analysis (NMR, MS) and then their optical activity was measured. Substances were tested for an inhibition activity against human...
|
|
|
Biological activity of plant metabolites XXXIV. Alkaloids from the herb of Glaucium flavum CRANTZ and their impact on human cholinesterases
Puzyrevská, Jana ; Hošťálková, Anna (advisor) ; Cahlíková, Lucie (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Botany and Ecology Candidate: Jana Puzyrevská Supervisor: PharmDr. Anna Hošťálková, Ph.D. Title of Thesis: Biological activity of plant metabolites XXXIV. Alkaloids from the herb of Glaucium flavum CRANTZ and their impact on human cholinesterases. Key words: Glaucium flavum Crantz, cataline, N-methyllaurotetanine, norchelidonine, protopine, AChE, BuChE. Alzheimer's disease, the most widespread neurodegenerative disease, causes decrease of cognitive functions and dementia. The most effective therapeutic approach is the application of central cholinesterase inhibitors, which alleviate cholinergic deficit in brain and thus improve memory. Currently, intensive investigation of new active compounds including natural substances is carried on. Within the preliminary testing, alkaloid extract from Glaucium flavum Crantz herb showed promising inhibition of human cholinesterases, so it was selected for further examination. The primary alkaloid extract was acquired from dried flowering herb by extraction with ethanol and subsequent liquid extraction at different pH. This extract was treated by preparative thin layer chromatography. The structure of alkaloids was determined by spectrometric methods (MS, NMR) and their optical...
|
|
|
Alkaloids screening with a focus on potential drug discovery
Adamičková, Leona ; Opletal, Lubomír (advisor) ; Hošťálková, Anna (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Botany Candidate: Mgr. Leona Adamičková Supervisor: Prof. RNDr. Lubomír Opletal, CSc. Title of Rigorous Thesis: Alkaloids screening with a focus on potential drug discovery Key words: cholinesterase inhibition, Alzheimer disease, plant extract Within new anti-Alzheimer agent searching a screening of inhibition activity of various plants was performed. For this study plants used in traditional medicine were chosen and alkaloidal extracts were prepared and their potential to human cholinesterases inhibition was determined. For extraction bulbs of Fritillaria ussurensis, bulbs of F. cirrhosis, cortex and flowers of Magnolia officinalis, flowers of M. biondii, Nelumbo nucifera seeds, leaves and roots with rhizomes of Nuphar luteum, Papaver rheum roots, Laurus nobilis fruits and seeds of Ziziphus jujuba var. spinosa were used. The cholinesterase inhibitory activity was determined in vitro by modified Ellman's method. Extract of Fritillaria ussurensis bulbs was found to be the most potent inhibitor of BuChE with IC50 value of 11,63 ± 3,7 μg/mL. Extract of M. biondii inhibited both cholinesteras with IC50 values lower than 50 μg/mL. Among extracts with inhibition activity to BuChE pertain extracts of F. cirrhosa bulbs,...
|
|
|
Biological activity of plants secondary metabolites XXX. Basic search of selected taxons on anticholinesterase activity.
Karaščáková, Diana ; Opletal, Lubomír (advisor) ; Hošťálková, Anna (referee)
CHARLES UNIVERSITY Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Botany Candidate: Diana Karaščáková Supervisor: prof. RNDr. Lubomír Opletal, CSc. Title of diploma thesis: Biological activity of plants secondary metabolites XXX.; Basic search of selected taxons on anticholinesterase activity As part of the study of the biological activity of secondary metabolites, 7 taxa of higher plants were selected. The study deals with basic research of summary and alkaloid extracts prepared from morphological parts of plants Annona muricata (leaves), Leonotis leonurus (perch), Turnera diffusa (perch), Hamelia patens (perch), Uncaria guianensis (bark), Allamanda cathartica (perch) and Morinda citrifolia (leaves). To elucidate the presence of the major types of secondary metabolites, extracts were prepared and subjected to detection reactions by TLC using ten detection reagents. After detection by Dragendorff's reagent of ethyl acetate extracts, alkaloids were significantly present only in Annona muricata. Alkaloids were not detected in the bark of Uncaria guianensis. Using the Ellman method, the extracts were tested for potential inhibitory activity against human brain cholinesterases, using both recombinant enzymes. No significant active substances were present in any of the measured...
|
|
|
Natural substances and their biological activity.Screening of alkaloid plants for anticholinesterase effect
Valentová, Ivana ; Opletal, Lubomír (advisor) ; Hošťálková, Anna (referee)
1 ABSTRACT Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Botany Candidate: Mgr Ivana Valentová Supervisor: Prof. RNDr. Lubomír Opletal, CSc. Title of Rigorous Thesis: Natural substances and their biological activity. Screening of alkaloid plants on human cholinesterases inhibition Key words: cholinesterase inhibition, Alzheimer disease, plant extract Ten herbs were screened for cholinesterase inhibition activity within searching new anti-Alzheimer agent. These plants are traditionally used as rerbal remedies for various diseases and they could be sources of new potential natural compounds. For this reason, ethanolic and alkaloidal extracts plants were prepared and their ability to inhibit human cholinesterases inhibition was determined. For the extraction Papaver somniferum immature capsules, Euonymus europeus fruits, Papaver orientale leaves, Magnolia officinalis leaves, Lycopodium clavatum aerial parts, Laurus nobilis leaves, Fritillaria imperialis bulbs, Flueggea suffruticosa aerial parts, Uncaria tomentosa bark, and Evolvulus alsinoides aerial parts were chosen. For the determination of human cholinesterase inhibitory activity in vitro modified Ellman's method was used. Only two alkaloidal plant extracts could be considered as potential source of HuBuChE...
|
|
|
Study of Chemical Constituents of Taxons from Order Laurales and Ranunculales with Potential Neuroprotective Activity
Hošťálková, Anna ; Opletal, Lubomír (advisor) ; Kokoška, Ladislav (referee) ; Drašar, Pavel (referee)
Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Botany and Ecology Candidate: Mgr. Anna Hošťálková Supervisor: Prof. RNDr. Lubomír Opletal, CSc. Title of Doctoral Thesis: Study of chemical constituents of taxons from order Laurales and Ranunculales with potential neuroprotective activity. Key words: Berberis vulgaris, Peumus boldus, Hydrastis canadensis, isoquinoline alkaloids, acetylcholinesterase, butyrylcholinesterase, prolyl oligopeptidase. Commercial goldenseal extrakt, boldo leaves and barberry root bark were selected as sources of isoquinoline alkaloids for study of their biological activity. Mixtures of summary tertiary alkaloids were prepared by standard extraction and subsequently fractionated in aluminium oxide chromatography column using the step gradient elution with petrol, chloroform and ethanol. Repeated column chromatographies, preparative TLC and crystallizations led to the isolation of 28 isoquinoline alkaloids, 6 of them were identificated as new structures (some of them were propably artifacts). The chemical structures of isolated compounds were determined on the basis of spectrometric techniques (NMR, MS) and by comparison with literature. Isolated alkaloids in sufficient amount were tested on ability to inhibit human...
|
|
|
Biological aktivity of secondary plants metabolites X. Alkaloids of Vinca minor L.
Šípková, Pavla ; Hošťálková, Anna (advisor) ; Chlebek, Jakub (referee)
Šípková, P.: Biological activity of secondary plants metabolites X. Alkaloids of Vinca minor L. Diploma thesis, Charles University, Faculty of Pharmacy in Hradec Králové, Department of Pharmaceutical Botany, Hradec Králové, 2019, 66 s. Key words: Apocynaceae, Vinca minor, alkaloids, isolation, biological activity, screening Alzheimer's disease is a progressive neurodegenerative disease. The number of affected patients is constantly increasing. This disease cannot be treated casually, therefore discovering and testing new substances that could potentially be used in a treatment is very important. The Vinca minor L. fraction after column chromatography was separated by flash chromatography. Isolation of the individual alkaloids was performed by preparative TLC. Based on NMR and MS analyses and comparison with literature, alkaloids were identified as vincarubine and (-)-vinoxine. Modified Ellman's method was used to test cholinesterase inhibitory activity of isolated alkaloids. Acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) are enzymes, that play a very important role in the pathofysiology of Alzheimer's diasease. (-)-Vinoxine showed relatively high activity against BuChE (IC50 = 24,61 ± 1,71 µM), inhibitory activity against AChE was insignificant (IC50 > 1000µM). Vincarubin did not...
|
|
|
Biological activity of plants secondary metabolites XXX. Basic search of selected taxons on anticholinesterase activity.
Karaščáková, Diana ; Opletal, Lubomír (advisor) ; Hošťálková, Anna (referee)
CHARLES UNIVERSITY Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Botany Candidate: Diana Karaščáková Supervisor: prof. RNDr. Lubomír Opletal, CSc. Title of diploma thesis: Biological activity of plants secondary metabolites XXX.; Basic search of selected taxons on anticholinesterase activity As part of the study of the biological activity of secondary metabolites, 7 taxa of higher plants were selected. The study deals with basic research of summary and alkaloid extracts prepared from morphological parts of plants Annona muricata (leaves), Leonotis leonurus (perch), Turnera diffusa (perch), Hamelia patens (perch), Uncaria guianensis (bark), Allamanda cathartica (perch) and Morinda citrifolia (leaves). To elucidate the presence of the major types of secondary metabolites, extracts were prepared and subjected to detection reactions by TLC using ten detection reagents. After detection by Dragendorff's reagent of ethyl acetate extracts, alkaloids were significantly present only in Annona muricata. Alkaloids were not detected in the bark of Uncaria guianensis. Using the Ellman method, the extracts were tested for potential inhibitory activity against human brain cholinesterases, using both recombinant enzymes. No significant active substances were present in any of the measured...
|
|
|
Vinca minor L. alkaloids and their biological activity (inhibition of human cholinesterases) V.
Vašíčková, Alžběta ; Chlebek, Jakub (advisor) ; Hošťálková, Anna (referee)
Vašíčková A.: Alkaloids of Vinca minor L. and their biological activity (inhibition of human cholinesterases) V. Diploma thesis, Charles University, Faculty of Pharmacy in Hradec Králové, Department of Pharmaceutical Botany, Hradec Králové 2020. From the selected fraction VM 215-258 were isolated 3 alkaloids by flash chromatography followed, preparative thin layer chromatography and crystallization. Their structure was determined by mass spectroscopy, NMR and optical rotation, and the obtained data were compared with those in literature. Strictamine and minovincinine belong to alkaloids previously isolated, the alkaloid AV-3 has not been isolated yet. These alkaloids were tested for their ability to inhibit human cholinesterases and their inhibitory activity was compared to standards galanthamine and physostigmine. Compound AV-3 showed mild inhibitory activity against BChE (IC50 μM > 86.3 ± 2.3), other alkaloids were considered inactive, their IC50 values against cholinesterases were > 100 μM. Key words: Vinca minor L. (Apocynaceae), vinca alkaloids, minovincinine, strictamine, Alzheimer's disease, acetylcholinesterase, butyrylcholinesterase.
|
guest ::
