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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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Derivatives of Amaryllidaceae alkaloids as potential drugs in the treatment of tumor diseases
Valachová, Iva ; Hulcová, 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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Alkaloids of Vinca minor (Apocynaceae) and their biological activities
Klátilová, Anežka ; Cahlíková, Lucie (advisor) ; Chlebek, Jakub (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical botany Candidate: Anežka Klátilová Supervisor: doc. Ing. Lucie Cahlíková Ph. D. Title of diploma thesis: Alcaloids of Vinca minor (Apocynaceae) and their biological activities The aim of this diploma thesis was to process the assigned fraction isolated from the Vinca minor L. plant and to isolate at least one alkaloid to test its biological activity. Using preparative TLC, the alkaloid was sequentially isolated from the fraction, which was then subjected to a structural analysis. NMR and EI-MS methods were used herein. Thanks to these analyzes, the alkaloid was identified as venoterpine. Furthermore, the alkaloid was prepared to test for biological activity. Thus, the isolated alkaloid was identified as venoterpine and tested for biological activity. The observed inhibitory concentration (IC50) to HuAChE and HuBuChe was more than 500 μM, indicating that venoterpine does not rank as a significant inhibitor of cholinesterase. Likewise, the value of cytotoxic activity, when this activity was found to be greater than 10 μM to colorectal cancer cells as well as to healthy cells, is not significant. Key words: Vinca minor, Apocynaceae, alkaloids, biological activities
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Synthesis of purine and pyrimidine derivatives with potential biological activities.
Jansa, Petr ; Holý, Antonín (advisor) ; Černý, Miloslav (referee) ; Rosenberg, Ivan (referee)
An extensive overview of the current state of the research in the field of the development of acyclic nucleoside phosphonates (ANPs) was elaborated, which quotes from 196 publications in abstracted journals. A new microwave-assisted methodology for the preparation of dialkyl haloalkylphosphonates was developed. Through strict control of the reaction temperatures in microwave reactor, it was possible to lower the amount of the reactants all the way to the ideal ratio of 1:1. With the use of a continuous-flow microwave reactor, it was possible to prepare the key building blocks for the subsequent syntheses of ANPs in large quantities (100 g), which significantly accelerates research in this area. The new method was patented and published. While studying various ANP prodrugs, a new highly effective methodology for the preparation of the diamides of ANPs was developed. The method starts directly from ANP diesters, which react with trimethylsilylbromide to form the corresponding bis(trimethylsilyl)esters of ANPs, which are well soluble in organic solvents and react smoothly during the subsequent introduction of aminoacid esters. Moreover, the reaction with trimethylsilylbromide protects the reactive groups present in the rest of the molecule and thus prevents undesired side reactions. Furthermore, using...
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