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Study and mechanism of new-generation heterocyclic cytostatic with an emphasis on IL-6 andIL-8
Talianová, Veronika ; Jakubek, Milan (advisor) ; Mikula, Ivan (referee) ; Babula, Petr (referee)
EN The purpose of this study was to screen for novel synthetic inhibitors of interleukins IL-6 and IL-8, which are promising targets for cancer therapy. Small molecules are an attractive approach to inhibit these signalling pathways, which are known to be important for tumour cell growth and survival. The study aimed to discover new inhibitors of IL-6 and IL-8 signalling pathways by screening a small library of chemical derivatives, including π-expanded naphthalimide derivatives, Tröger's base, and pentamethinium derivatives. The structures of the compounds were designed based on in silico studies focusing on blocking the IL-6 and IL-8 signalling pathways. The study involved the use of various analytical and bioanalytical methods for the in vitro analysis of new potential anticancer drugs. The compounds were tested for cytotoxicity and their effect on cell growth using an MTT proliferation assay. Their antitumor activity was observed in NU/NU mice. The invasiveness of the cells was monitored using the wound healing assay. Live cell imaging was used to detect the distribution of the substances at the intracellular level. Other methods such as ELISA, microscale thermophoresis, and in silico predictions have been used to determine the selectivity of inhibitors of the signalling pathways IL-6 and IL-8....
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Drug repurposing for the inhibition of invasiveness and metastasis of cancer cells
Turchyna, Kateryna ; Brábek, Jan (advisor) ; Jakubek, Milan (referee)
Metastasis is the primary cause of death from cancer. Current lack of medicines for metastasis makes it a topical issue and encourages the global search for molecules that may potentially inhibit invasiveness of cancer cells, and thus prevent metastatic spread. Drug repurposing is a strategy of identifying new uses for approved drugs that are outside the scope of the original medical indication. The aim of this thesis is to summarize knowledge on the repurposing potential of selected groups of drugs with emphasis on molecular mechanisms of their action. In particular, the work is focused on selected antipsychotics, antidepressants, beta- blockers and statins, whose abilities to inhibit cancer invasiveness have been indicated.
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