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Amaryllidaceae alkaloids of haemanthamine structural type and their semisynthetic derivatives as potential drugs in the treatment of Alzheimer's disease.
Peřinová, Rozálie ; Cahlíková, Lucie (advisor) ; Lapčík, Oldřich (referee) ; Mučaji, Pavel (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmacognosy and Pharmaceutical Botany Candidate: Ing. Rozálie Peřinová Supervisor: prof. Ing. Lucie Cahlíková, Ph.D. Title of doctoral thesis: Amaryllidaceae alkaloids of haemanthamine structural type and their semisynthetic derivatives as potential drugs in the treatment of Alzheimer's disease. To deepen the knowledge about the Amaryllidaceae alkaloid haemanthamine, which was isolated at our workplace as part of previous phytochemical studies, derivatives of this alkaloid were synthesized. First, series of aliphatic (3-12) and aromatic ester derivatives (13-66) were prepared, and then, to compare the structure-activity relationship, ether derivatives (67-80) were prepared from the most active substituents. All synthesized compounds were identified using the following structural analysis methods: NMR, HPLC/MS, and HRMS, including testing physical properties such as optical rotatability. After structure confirmation, all derivatives were subjected to screening studies for their inhibitory potential against hAChE and hBuChE. The selected derivatives were tested for their inhibitory potential against another enzyme, GSK-3β, which plays a significant role in the pathogenesis of AD. In cooperation with the Faculty of Medicine in...
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Alkaloids of Zephyranthes citrina (Amaryllidaceae): isolation, determination of structure, biological activity
Čejdová, Aneta ; Vrabec, Rudolf (advisor) ; Cahlíková, Lucie (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmacognosy and Pharmaceutical Botany Candidate: Aneta Čejdová Title of diploma thesis: Alkaloids of Zephyranthes citrina (Amaryllidaceae): isolation, determination of structure, biological activity Key words: Amaryllidaceae, alkaloids, Zephyranthes citrina, biological activity, isolation From the selected alkaloidal fractions obtained from the bulbs of Zephyranthes citrina, six different alkaloids were isolated by chromatographic methods. They were identified using standard analytical methods (NMR, MS, HRMS, and optical rotation). The obtained compounds belong to the lycorine structural type (lycorine, galanthine, 6-oxonarcissidine, narcissidine) and haemanthamine structural type (maritidine, zephyranine E). The alkaloid 6-oxonarcissidine has not been described in the literature yet. The inhibitory activity against human AChE and BuChE was measured for the isolated alkaloids. Lycorine, galanthine, narcissidine, and maritidine have already been measured in many studies before; therefore, the attention was focused on the two less-known alkaloids: zephyranine E and 6-oxonarcissidine. However, the resulting IC₅₀ values of both alkaloids against human AChE and BuChE were above 100 µM, which indicates their insignificant...
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Alkaloids of genus Narcissus: isolation, structural identification, biological activity
Šimková, Hana ; Cahlíková, Lucie (advisor) ; Opletal, Lubomír (referee)
Charles University, Faculty of Pharmacy in Hradec Králové, Department of Pharmaceutical Botany Author: Hana Šimková Supervisor: prof. Ing. Lucie Cahlíková, Ph.D. Title of diploma thesis: Alkaloids of genus Narcissus: isolation, structural identification, biological activity Key words: Narcissus, alkaloids, biological activity, Alzheimer's disease, cytotoxic activity The aim of the diploma thesis was an isolation of alkaloids with a focus on minor fractions. These fractions were obtained from the summary alkaloid extract of Narcissus pseudonarcissus cv. Carlton. The method of preparative TLC was used for the isolation of alkaloids. Three substances of alkaloid origin marked as Fj 3-4/kr, F 7/2-1, F 7/2-3 were isolated from the assigned fractions. These substances were identified as alkaloids of homolycorine type lycorenine, homolycorine and hippeastrine by using GC-MS, NMR and optical rotation. The results were also compared with data in the literature. These three alkaloids were tested for their inhibitory activity against AChE, BuChE, POP and GSK-3β. The inhibitory activity against AChE and BuChE was compared with the reference substances galanthamine (IC50 AChE = 1,71 ± 0,07 μM, IC50 BuChE = 42,3 ± 1,3 μM) and huperzine A (IC50 AChE = 0,033 ± 0,001 μM, IC50 BuChE> 1000 μM). The inhibitory...
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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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Amaryllidaceae alkaloids as inspiration for preparation of selective butyrylcholinesterase inhibitors II
Králová, Kristýna ; Cahlíková, Lucie (advisor) ; Kučera, Tomáš (referee)
CHARLES UNIVERSITY FACULTY OF PHARMACY IN HRADEC KRÁLOVÉ DEPARTMENT OF PHARMACOGNOSY AND PHARMACEUTICAL BOTANY CANDIDATE: Kristýna Králová SUPERVISOR: prof. Ing. Lucie Cahlíková, Ph.D. CONSULTANT: Mgr. Filip Pidaný TITLE OF DIPLOMA THESIS: Amaryllidaceae alkaloids as inspiration of preparation of selective butyrylcholinesterase II Plants of the family Amaryllidaceae are an important source of biologically active substances, which are labeled as Amaryllidaceae alkaloids (AAs). These natural products show a wide range of biological characteristics, for which they are also intensively studied. Their significant biological effects include antiviral, antibacterial, antifungal, anti-inflammatory, antiparasitic, and cytotoxic activity. Their other important characteristic is the ability to inhibit both cholinesterases: acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). Inhibition of AChE is used in the therapy of Alzheimer's disease (AD). Currently, in the treatment of the symptoms of this disease, one AA, galanthamine, is used. Recently a new structural type of AAs, carltonins, have been isolated from the plant Narcissus pseudonarcissus cv. Carlton. These substances showed a significant inhibitory effect against BuChE and became the inspiration for the synthesis of selective BuChE inhibitors....
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Derivatives of Amaryllidaceae alkaloids as potential drugs in the treatment of tumor diseases
Valachová, Iva ; Suchánková, Daniela (advisor) ; Kučera, Tomáš (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacognosy Candidate: Iva Valachová Supervisor: Pharm.Dr. Daniela Hulcová, Ph.D. Title of diploma thesis: Derivatives of Amaryllidaceae alkaloids as potential drugs in the treatment of tumor diseases Twelve aromatic derivatives were prepared. The substitutions were performed on the hydroxyl group at C-3. This was acylated with differently substituted benzoyl chlorides affording the corresponding esters. Structural identification was performed by 1D- and 2D- NMR, ESI-HRMS spectroscopic techniques and optical rotation measurement. The yield of all reactions was more than 60 %. After converting these derivatives to hydrochlorides, their biological activity was tested. The Amaryllidaceae alkaloid vittaine itself exhibits cytotoxic activity and therefore its derivatives have been investigated in this respect. It has been tested against 9 cancerous and 1 non-cancerous cell lines. 3-O-(4-Chloro-3-nitrobenzoyl)vittatine showed the highest cytotoxic activity, unfortunatelly, it does not selectively affect only cancerous cells. Conversely, 3-O-(2-naphthoyl)vittatine has a selective effect on the HT-29 cancerous cell line (colorectal carcinoma) with a viability value of 32 ± 3 %, potentially being the subject of further studies of cytotoxicity...
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Amaryllidaceae alkaloids as inspiration for preparation of selective butyrylcholinesterase inhibitors I
Wisura, Matěj ; Cahlíková, Lucie (advisor) ; Kučerová, Marta (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Botany Candidate: Matěj Wisura Supervisor: prof. Ing. Lucie Cahlíková, Ph.D. Title of diploma thesis: Amaryllidaceae alkaloids as inspiration for preparation of selective butyrylcholinesterase inhibitors I The Amaryllidaceae family is considered to be very important source of biologicaly active natural compounds, alkaloids. These compounds are intensively studied because of their antiviral, antifungal, antiparasitic, antioxidative and antiinflammatory properties and especially for their ability to inhibit cholinesterases. This source is still not entirely depleted, which is proved by recent isolation of utterly new structural type of Amaryllidaceae alkaloids, carltonines, isolated form Narcissus pseudonarcissus cv. Carlton. Carltonines have shown promissing inhibitory activity of BuChE. Isolation of carltonines has become an inspiration for synthesis of highly selective BuChE inhibitors based on norbelladine structural type. This diploma thesis proceeds from pilot series of 20 compounds. During this study, another 21 compounds were prepared, expanding the portfolio and knowledge of structure-activity relationships within selective BuChE inhibitors group. Generated compounds were identified using NMR and ESI-HRMS....
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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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Amaryllidaceae alkaloids as inspiration for preparation of selective butyrylcholinesterase inhibitors I
Wisura, Matěj ; Cahlíková, Lucie (advisor) ; Kučerová, Marta (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Botany Candidate: Matěj Wisura Supervisor: prof. Ing. Lucie Cahlíková, Ph.D. Title of diploma thesis: Amaryllidaceae alkaloids as inspiration for preparation of selective butyrylcholinesterase inhibitors I The Amaryllidaceae family is considered to be very important source of biologicaly active natural compounds, alkaloids. These compounds are intensively studied because of their antiviral, antifungal, antiparasitic, antioxidative and antiinflammatory properties and especially for their ability to inhibit cholinesterases. This source is still not entirely depleted, which is proved by recent isolation of utterly new structural type of Amaryllidaceae alkaloids, carltonines, isolated form Narcissus pseudonarcissus cv. Carlton. Carltonines have shown promissing inhibitory activity of BuChE. Isolation of carltonines has become an inspiration for synthesis of highly selective BuChE inhibitors based on norbelladine structural type. This diploma thesis proceeds from pilot series of 20 compounds. During this study, another 21 compounds were prepared, expanding the portfolio and knowledge of structure-activity relationships within selective BuChE inhibitors group. Generated compounds were identified using NMR and ESI-HRMS....
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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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