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Antitumor activity of HPMA copolymer-bound gemcitabine conjugate potentiation by IAP inhibitors
Ivančík, Martin ; Kovář, Marek (advisor) ; Anděra, Ladislav (referee)
Cancer represents a significant global health challenge, with a substantially increasing incidence. There is a critical need for enhanced prevention, early detection, and improved therapeutic approaches to treat malignant diseases. While chemotherapy remains a standard treatment for many cancers, its efficacy is often limited by cytotoxic effects on healthy cells and numerous side toxicities. In response to these challenges, novel strategies such as combination therapies and drug delivery systems have emerged. In this project, we investigated the cytostatic and cytotoxic effects of two inhibitors of IAP (inhibitor of apoptosis) proteins, LCL-161 and AZD5582, and their potential to boost the anticancer activity of gemcitabine. These compounds were evaluated in five human cancer cell lines: pancreatic (PANC1, BxPC- 3, MiaPaca-2), prostatic (PC-3), and breast (MDA-MB-231) carcinomas. Both IAP inhibitors demonstrated anticancer activity as single agents, with the MiaPaca-2 and BxPC-3 cell lines showing the highest sensitivity. No correlation was observed between the expression levels of IAP genes (cIAP1, cIAP2, XIAP) and the sensitivity of cell lines to IAP inhibitors. However, four of five tested cell lines possessed a consistent pattern in the expression of these three genes. IAP inhibitors were able...
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Derivatives of Amaryllidaceae alkaloids as drugs
Ritomská, Aneta ; Cahlíková, Lucie (advisor) ; Kučerová, Marta (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Botany Candidate: Aneta Ritomská Supervisor: Assoc. Prof. Ing. Lucie Cahlíková, Ph.D. Title of diploma thesis: Derivatives of Amaryllidaceae Alkaloids as Drugs Plants of the family Amaryllidaceae belong to the widespread species. They contain a large amount of Amaryllidaceae alkaloids (AA) which are known for their biological activity. AA possess a broad spectrum of biological activities including an antiviral, antimalarial, antitumor, cholinesterase's inhibitory activity and others. An interesting AA is ambelline which occurs mainly in plants of the genus Crinum and Nerine. So far the biological activity of this compound has been studied only marginally. In the studies conducted, this substance appears to be less interesting. A series of aliphatic and aromatic derivatives of ambelline has been prepared in the framework of this thesis. Subsequently, their cholinesterase inhibitory activity and GSK-3β inhibitory activity were studied. Cytotoxic activity on a panel of selected tumor and resting cell lines was also screened. Of the prepared derivatives, LC-125 (3-methoxybenzoylambellin) had an interesting biological activity. This substance showed a promising activity in all biological studies. GSK-3β inhibitory...
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