Cancer is a group of diseases in which abnormal cells grow and divide uncontrolled and may develop the ability to invade other parts of the body through blood and lymph systems. Several processes contributing to cell survival and tumor progression have been identified. These processes include the propagation of the cell cycle, over activation of signaling pathways, aberrant gene expression, avoidance of the immune system, inhibition of apoptosis, and resistance to radiation and chemotherapies.
Three projects are described in which compounds were designed and synthesized to target cancer cells by three different modes of action. [1] The synthesis of compounds capable of the inhibition of protein-protein interactions by the recruitment of a chaperone protein, FK506 binding protein (FKBP), was done by linking known target binding molecules to the specific ligand of FKBPs (SLF). [2] A library of molecules was synthesized for a SAR study of OU749’s inhibition of γ-Glutamyl Transpeptidase (GGT), an enzyme implicated in chemotherapy resistance. [3] Lastly several compounds were synthesized from an in silico screen of JMJD2A for the identification of a lead compound for the inhibition of histone demethylase enzymes. The synthesis of the compounds and biological results are reported.