Identification of the Substitutes on α‐(N)‐Heterocyclic Thiosemicarbazones that Interact with Human Topoisomerase‐II‐α with Nuclear Magnetic Resonance

Abstract

Topoisomerase IIα (TopoIIα) is an essential enzyme for cell proliferation. Cancer cells are rapidly dividing cells. Thus, TopoIIα is a primary target for many anticancer drugs. Thiosemicarbazones (TSCs) have been known to possess anticancer activity by inhibiting topoisomerase‐II. Recent studies of our lab found the structure‐activity relationship of TSCs and their inhibition on TopoIIα. Our results suggest that the metal ion of TSC metal complexes and the terminal nitrogen side chain play important roles in increasing TopoIIα‐mediated cleavage complexes. The direct interaction between TSCs and TopoIIα remains unknown. It is hypothesized by our lab that the metal ions and the terminal nitrogen side chains interact with TopoIIα directly. This hypothesis is being tested by studying the interaction of 2‐acetylthiazole (ATZ) TSC, 2‐acetyl‐4‐methylthiazole (AMT) TSC, and benzoylpyridine (BZP) TSC metal complexes with TopoIIα by saturation transfer difference nuclear magnetic resonance (STD‐NMR) and diffusion ordered spectroscopy nuclear magnetic resonance (DOSY‐NMR). Recent STD‐NMR experiments suggest that the aliphatic region of 2‐acetylthiazole (ATZ) TSC and benzoylpyridine (BZP) TSC interact with TopoIIα.Support or Funding InformationThis research is supported by the Faculty Research Grant (XJ) and the NSF MRI project (1531870).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.