Metabolism of the mitotic inhibitor BTB-1 by first phase biotransformation enzymes

Cancer is still one of the most common deaths in the world and therefore new drugs are needed to be developed to stop or slow down this disease. Recently, there has been a huge expansion in drug development. Cytostatics that are still widely used include a group of mitotic inhibitors aimed at inhibiting mitosis. A representative of a mitotic inhibitor is the small newly discovered molecule BTB-1. This molecule mediates reversible inhibition of the molecular motor Kif18A, which plays an important role in cell division. In the first part of this presented bachelor thesis, a suitable method for the determination of BTB-1 using high performance liquid chromatography was developed and subsequently its sensitivity was verified. Furthermore, a suitable extracting reagent was found. In the second part of the bachelor thesis, the metabolism of BTB-1 was studied by the microsomal system of non-premedicated rats and rats premedicated with various cytochrome P450 inducers. Subsequently, the time dependence of BTB-1 conversion was studied by the microsomal system of premedicated rats. The effect of different concentrations of BTB-1 on its metabolism was also studied using the microsomal system of premedicated rats. Furthermore, the metabolism of this new molecule was studied using cytosolar systems isolated...