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Amaryllidaceae alkaloids of genus Narcissus and their biological activity.
Al Mamun, Abdullah ; Cahlíková, Lucie (advisor) ; Mučaji, Pavel (referee) ; Strnad, Miroslav (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmacognosy and Pharmaceutical Botany Candidate: MSc. Abdullah Al Mamun Supervisor: Prof. Ing. Lucie Cahlíková, Ph.D. Title of Doctoral Thesis: Amaryllidaceae alkaloids of the genus Narcissus and their biological activity. Narcissus pseudonarcissus cv. Carlton has been chosen for the phytochemical investigation based on the screening study. An alkaloidal extract of 485 g has been obtained from 30 kg of fresh bulbs. Repeated liquid-liquid extraction gave 187 g of concentrated crude extract, which was separated by column chromatography (CC, Al2O3; 5800 g), followed by repetitive CC, preparative TLC, and crystallization. Thirteen previously described Amaryllidaceae alkaloids were obtained along with four novel compounds named carltonine A, B, C, and narciabduliine. All compounds were identified and characterized by spectrometric techniques (1D and 2D NMR, CD, and HRMS) and by comparison with data from the literature. Alkaloids isolated in sufficient amounts were used for further evaluation of their inhibition activity against human acetylcholinesterase (hAChE), butyrylcholinesterase (hBuChE) and prolyloligopeptidase (POP). Carltonine A and B demonstrated promising inhibition activity against the hBuChE enzyme with IC50 values of...
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Synthesis and evaluation of potential biologically active rhodanine derivatives and analogues
Šimková, Adéla ; Krátký, Martin (advisor) ; Matouš, Petr (referee)
The topic of this thesis is the synthesis of rhodanine derivatives and evaluation of their biological activity, particularly as potential cholinesterases inhibitors. This group of compounds is important for treatment of many diseases, e.g., Alzheimer's disease or myasthenia gravis. All synthetized compounds are based on structure of rhodanine (2-thioxothiazolidine- 4-one), which is an important heterocyclic compound with a wide spectrum of biological properties. Its structure can be modified in many ways, which can be used in the development of new drugs. Its derivatives have been shown to have, for example, anti-inflammatory, anticancer, antibacterial and antifungal activities, as well as inhibitory activity against several enzymes, e.g., cholinesterases. Seventeen compounds were synthesized in sufficient amount for characterisation and assessment of biological activity (7-93 %). Most of them are amides based on the structure of 2-thioxothiazolidine-4-one and thiazolidine-2,4-dione, that were prepared by carbodiimide- mediated coupling, other derivatives are based on the structure of 2-thioxothiazolidine-4-one and from 2,4-dioxothiazolidine-3-acetic acid. These compounds were prepared by Knoevenagel condensation in glacial acetic acid. All compounds were tested for their inhibitory activity...
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Amaryllidaceae alkaloids of montanine type and their derivatives as potential drugs.
Maafi, Negar ; Cahlíková, Lucie (advisor) ; Šmejkal, Karel (referee) ; Havlík, Jaroslav (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmacognosy and Pharmaceutical Botany Candidate: Negar Maafi Supervisor: Prof. Ing. Lucie Cahlíková, Ph.D. Title of Doctoral Thesis: Amaryllidaceae alkaloids of montanine type and their derivatives as potential drugs. Based on the knowledge of the biological activity of montanine-type alkaloids of Amaryllidaceae, these alkaloids were selected for the preparation of their semisynthetic derivatives to study the relationship between structure and the activity. Derivatives of montanine-type alkaloids were prepared using haemanthamine and montanine as starting substances. The montanine-type alkaloid 3-O- methylpancracine was prepared using intramolecular rearrangement of haemanthamine. Previously isolated montanine from bulbs of Hippeastrum x hybridum cv. Ferrari was used in synthesize of derivatives. In total, more than 80 aliphatic and aromatic derivatives of montanine and 3-O- methylpancracine have been prepared. All compounds were identified using 1D- and 2D-NMR, MS, HRMS, and so forth. The prepared derivatives were screened for a wide range of biological activities (inhibitory potential against hAChE/hBuChE, antimycobacterial, antibacterial and antifungal activity, cytotoxicity, and others). In the hAChE/hBuChE study, the...
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Derivatives of Amaryllidaceae alkaloids and their biological activity: Derivatives of maritidine
Moravcová, Markéta ; Cahlíková, Lucie (advisor) ; Kuneš, Jiří (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacognosy and Pharmaceutical Botany Candidate: Markéta Moravcová Supervisor: prof. Ing. Lucie Cahlíková, Ph.D. Title of diploma thesis: Derivatives of Amaryllidaceae alkaloids and their biological activity: derivatives of maritidine The object of this diploma thesis was the preparation a pilot series of semisynthetic derivatives and screenink of their biological activities. Ten aromatic esters of maritidine were prepared. The compounds were identified by LC-MS, HR-MS, NMR analysis, and optical rotation. All prepared analogues matridine were screened for in vitro inhibitory activity against hAChE and hBuChE. Most of the derivatives were inactive, only the 3-O-(4-ethylbenzoyl)maritidine derivative showed moderate activity against hBuChE with IC50 = 67.01 ± 3.12 μM. Two derivatives maritidine, 3-O-(3,5-dimethylbenzoyl)maritidine and 3-O-(3,5- dimethoxybenzoyl)maritidine, were tested for their antimycobacterial activity. The substances showed promising antimycobacterial activity against Mtb H37Ra strain (MICs = 7.81 and 15.625 µg/ml). These two derivatives maritidine were tested against different strains of microorganisms. 3-O-(3,5-dimethylbenzoyl)maritidine showed antimicrobial activity against Staphylococcus aureus (MIC =...
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Biological activity evaluation of substances of natural origin I.
Kupčíková, Júlia ; Suchánková, Daniela (advisor) ; Kučera, Tomáš (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacognosy and Pharmaceutical botany Candidate: Júlia Kupčíková Supervisor: PharmDr. Daniela Suchánková, Ph.D. Title of diploma thesis: Biological activity evaluation of substances of natural origin I. Alzheimer's disease (AD) is progressive neurodegenerative brain disorder characterized by memory loss and cognitive impairments. Manifestation of this disease is associated with decreased level of acetylcholine. Current treatment of AD is symptomatic and involves mainly restoring of acetylcholine levels through cholinesterase inhibition. Galanthamine, one of acetylcholinesterase inhibitors indicated for the treatment of AD belongs to Amaryllidaceae alkaloids. Therefore, other Amaryllidaceae alkaloids and their derivatives are prepared and studied for similar inhibitory properties. Amaryllidaceae alkaloid vittatine does not have cholinesterase inhibitory properties, but previous findings proved that some vittatine derivatives have potency to inhibit both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). Seven new semisynthetic derivatives of vittatine were prepared and studied for their inhibitory potential against both cholinesterases, using the Ellman's method. Significant BuChE inhibitory activity was...
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Structural modification of haemanthamine
Babcová, Jitka ; Cahlíková, Lucie (advisor) ; Kuneš, Jiří (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacognosy and Pharmaceutical Botany Candidate: Jitka Babcová Supervisor: prof. Ing. Lucie Cahlíková, Ph.D. Title of diploma thesis: Structural modification of haemanthamine The object of this diploma thesis was to prepare several derivates of alkaloid haemanthamine. Twelve aromatic esters of haemanthamine and two ethers were prepared. Compounds were identified by MS, NMR analysis and optical rotation and screened for their biological activities. Ten prepared derivates were screened for in vitro inhibitory activity againts hAChE and hBuChE. All derivates were considered inactive (IC50 ˃ 10 µM). Twelve derivates of haemanthamine were tested for thein antimycobacterial aktivity, using rifampicin as a standard. The most interesting antimycobacterial potencial against Mtb H37Ra strain has shown 11-O-(4-pentylbenzoyl)haemanthamine (MIC = 3,91 µg/ml), against M. aurum: 11-O-(4-tercbutyllbenzoyl)haemanthamine, 11-O-(1-naftoyl)haemanthamine a 11-O-(4-butylbenzoyl)haemanthamine (MICs = 7,81 µg/ml), against M. avium: 11-O-(4-pentylbenzoyl)haemanthamine, 11-O-(4-hexylbenzoyl)haemanthamine (MICs = 31,25 µg/ml), against M. kansasii: 11-O-(4-pentylbenzoyl)haemanthamine (MIC = 3,91 µg/ml), 11-O-(4-hexylbenzoyl)haemanthamine (MIC = 7,81...
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Alkaloids of Narcissus species cultivars and their biological activity III.
Kahovcová, Anna ; Hradiská Breiterová, Kateřina (advisor) ; Suchánková, Daniela (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department: Department of Pharmacognosy and Pharmaceutical Botany Author: Kahovcová Anna Supervisor: PharmDr. Kateřina Hradiská Breiterová, PhD. Title of thesis: Alkaloids of Narcissus species cultivars and their biological activity III. Key words: Narcissus, alkaloids, biological activity, Alzheimer's disease, cytotoxicity The most important aim of this diploma thesis was to prepare summary alkaloid extracts from bulbs of the genus Narcissus L., specifically from seven cultivars Narcissus cv. MONDRAGON, RIP VAN WINKLE, SAGITTA, CHEERFULNESS, DOUBLE FASHION, PRECOCIOUS and FLOWER DRIFT, which were labeled as AL-458, AL-575, AL-443, AL-466, AL-549, AL-545 a AL-546. Samples were subsequently prepared for GC-MS analysis and screening determination of biological activities, namely the ability to inhibit human cholinesterases hAChE and hBuChE and cytotoxicity from these extracts. Using GC-MS analysis a total of 20 alkaloids were identified by comparing their mass spektra with the literature or the NIST library. Identified alkaloids include lycorine, lycoramine, lycoraminone, anhydrolycorine, pankracine, caranine, O-acetyllycorine, pluvine, norpluvine, assoanine, haemanthamine, galanthine, incartine, O-methylpseudolycorine, hippeastrine,...
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Amaryllidaceae alkaloids of genus Narcissus and their biological activity.
Al Mamun, Abdullah ; Cahlíková, Lucie (advisor) ; Mučaji, Pavel (referee) ; Strnad, Miroslav (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmacognosy and Pharmaceutical Botany Candidate: MSc. Abdullah Al Mamun Supervisor: Prof. Ing. Lucie Cahlíková, Ph.D. Title of Doctoral Thesis: Amaryllidaceae alkaloids of the genus Narcissus and their biological activity. Narcissus pseudonarcissus cv. Carlton has been chosen for the phytochemical investigation based on the screening study. An alkaloidal extract of 485 g has been obtained from 30 kg of fresh bulbs. Repeated liquid-liquid extraction gave 187 g of concentrated crude extract, which was separated by column chromatography (CC, Al2O3; 5800 g), followed by repetitive CC, preparative TLC, and crystallization. Thirteen previously described Amaryllidaceae alkaloids were obtained along with four novel compounds named carltonine A, B, C, and narciabduliine. All compounds were identified and characterized by spectrometric techniques (1D and 2D NMR, CD, and HRMS) and by comparison with data from the literature. Alkaloids isolated in sufficient amounts were used for further evaluation of their inhibition activity against human acetylcholinesterase (hAChE), butyrylcholinesterase (hBuChE) and prolyloligopeptidase (POP). Carltonine A and B demonstrated promising inhibition activity against the hBuChE enzyme with IC50 values of...
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Alkaloids of the family Amaryllidaceae and their biological activity 1.
Klímová, Kamila ; Cahlíková, Lucie (advisor) ; Siatka, Tomáš (referee)
Mišáková K: Alkaloids of the Amaryllidaceae family and their biological activity 1. Diploma thesis, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Department of Pharmaceutical Botany and Ecology, Hradec Králové, 2014, 63 p. The aim of the diploma thesis was a preparation of alkaloidal extract from Nerine Bowdenii to izolation of 2 pure alkaloids by column and thin layer chromatography. Subsequently these two alkaloids were subjected to structural MS and NMR analysis and tested for biological activity against human cholinesterases (HuAChE and HuBuChE) and for antioxidant and cytotoxic activity. Isolated substances were identified as ambelline and undulatine alkaloids, which have been already described previously in this plant. In the test for determining cholinesterase inhibitory activity of ambelline and undulatine the following values were measured; for ambelline: IC50, HuAChE = 169 ± 7 μM a IC50, HuBuChE = 985 ± 25 μM, for undulatine: IC50, HuAChE = 23,52 ± 1,19 μM a IC50, HuBuChE > 1000 μM. Galanthamin (IC50, HuAChE = 1,71 ± 0,007 μM, IC50, HuBuChE = 42,30± 1,30 μM), huperzin A (IC50, HuAChE = 0,033 ± 0,001 μM, IC50, HuBuChE > 1000 μM) and eserin (IC50, HuAChE = 0,063 ± 0,001 μM, IC50, HuBuChE = 0,130 ± 0,004 μM) were used like a positive controls. In the test for...
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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...
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