Synthesis of novel blebbistatin derivatives as myosin inhibitors

Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Chemistry and Drug Control Student: Ngoc Lam Pham Supervisor: Assoc. Prof. RNDr. Veronika Opletalová, Ph.D. Thesis Title: Synthesis of novel blebbistatin derivatives as myosin inhibitors Myosins constitute a large and diverse superfamily of ATP-dependent motor proteins responsible for actin-based motility. Currently, based on phylogenetic analyses, myosins are classified into at least twenty four groups. The members of this superfamily are involved in several cell processes such as muscle contraction, cytokinesis, organelle transport, cell polarization and signal transduction. Thus, dysfunction and mutation of myosins can cause several diseases. Therefore, design of myosin inhibitors seems to be very attractive research field from the point of view of characterization of intracellular processes as well as development of novel targeted therapy against diseases implicating myosin dysfunction. Nowadays, one of the most well-known and widely used inhibitors of myosin is (S)-blebbistatin. This inhibitor of myosin II has many advantages, nevertheless it possesses also several limiting factors impeding the biological studies such as photosensitivity and low solubility in water. The aim of this Thesis was to..