Biochemistry

Cytotoxic nucleoside and nucleotides analogs represent an important group of anticancer agents. However, their clinical use is limited by their adverse effects and primary or acquired resistance. The development of new nucleoside/nucleotide analogs aims to minimize these side effects and to improve their pharmacokinetic and pharmacodynamic properties. The objective of this thesis is to describe mechanisms underlying the cytostatic activity of selected newly developed nucleoside/nucleotide analogs with focus on apoptosis, cell cycle and intracellular metabolism of these compounds. Methodical approaches comprise quantitative PCR, immunoblotting, flow cytometry, fluorescence microscopy and spectral methods.