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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 the Amaryllidaceae family as potential drugs in therapy of diseases of affluence
Breiterová, Kateřina ; Cahlíková, Lucie (advisor) ; Lapčík, Oldřich (referee) ; Nagy, Milan (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Botany Candidate: Mgr. Kateřina Breiterová Supervisor: Assoc. prof. Ing. Lucie Cahlíková PhD. Title of Doctoral Thesis: Alkaloids of the Amaryllidaceae family as potential drugs in therapy of diseases of affluence Key words: alkaloids, Amaryllidaceae, analogues, AChE, BuChE, POP, GSK-3β, cell cycle progression, apoptosis Narcissus cv. Professor Einstein was chosen based on results of previous screening studies for detailed phytochemical work for the purpose of isolation of the widest range of AmA. From 34,3 kg of fresh bulbs was obtained 31,7 g of purified alkaloidal extract, which was processed using column chromatography with stepwise elution by light petrol, chloroform and ethanol in different ratios to almost 500 fractions. These fractions were fused into 27 subfractions, which were processed by preparative TLC, vacuum column chromatography and crystallization. Finally, 25 pure alkaloids were isolated. All compounds were identified by GC-MS, ESI-MS, NMR, optical rotation and literature. One compound was identified as a new unpublished alkaloid of lycorine structure type. All alkaloids isolated in sufficient amount were tested for their biological activities associated with Alzheimer's disease (inhibition of...
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