Digital Commons Network^™

Discovery Of Piperlongumine Derivatives As Anti-Leukemic And Anti-Prostate Cancer Agents, Yi Liao

Wayne State University Dissertations

Piperlongumine (PL) is an electrophilic anti-cancer natural product. Through non-covalent or covalent interactions with cellular targets, PL inactivates multiple oncogenic pathways and suppresses key components of cellular anti-oxidant/anti-electrophile defense systems. These actions result in pleiotropic anticancer effects and are expected to be effective to heterogeneous acute myeloid leukemia (AML) and prostate cancer (PCa). We applied two approaches to enhance the anticancer potency of PL: 1) To design PL-histone deacetylase inhibitor hybrid drugs (PL-HDACis; e.g., 1-58), and 2) To dimerize PL pharmacophore to generate a dimeric PL (DiPL) warhead that is suitable for further conjugation (e.g., 5-17). Both 1-58 and 5-17 …