Author(s)

Edward C. Lisic^1*, Victoria G. Rand¹, Lana Ngo¹, Patrick Kent², Jeffrey Rice², Deidra Gerlach³, Elizabeth T. Papish³, Xiaohua Jiang¹

¹Department of Chemistry, Tennessee Technological University, Cookeville, TN, USA.
²Department of Chemical Engineering, Tennessee Technological University, Cookeville, TN, USA.
³Department of Chemistry, The University of Alabama, Tuscaloosa, Alabama, USA.

Two new thiosemicarbazone ligands, 2-propionylthiazole ethylthiosemicarbazone (PTZ-ETSC), and 2-propionylthiazole tert-butylthiosemicarbazone (PTZ-tBTSC), along with their two copper(II) complexes, [Cu(PTZ-ETSC)Cl] and [Cu(PTZ-tBTSC)Cl], are reported here for the first time. Once characterized by NMR and MS, these mono-anionic tridentate ligands were reacted with Cu²⁺ to form the square planar metal complexes [Cu(PTZ-ETSC)Cl] and [Cu(PTZ-tBTSC)Cl]. The x-ray crystal structure of the [Cu(PTZ-tBTSC)Cl] complex shows that the complex adopts a square planar arrangement around the copper(II) ion, but forms a sulfur-bridged dimer in the solid state. Both of the copper complexes displayed strong inhibition of human topoisomerase IIα at activities between 2-4 μM for [Cu(PTZ-ETSC)Cl], and between 8-10 μM for the [Cu(PTZ-tBTSC)Cl] complex. The EC50 values for the MDA-MB-231 breast cancer cell line were 82.6 μM for (PTZ-ETSC), 17.9 μM for [Cu(PTZ- ETSC)Cl], 97.8 μM for (PTZ-tBTSC), and 1.41 μM for [Cu(PTZ-tBTSC)Cl]. The EC50 values for the MCF7 breast cancer cell lines were 9.36 μM for (PTZ-ETSC), 0.13 μM for [Cu(PTZ-ETSC)Cl], 0.333 μM for (PTZ-tBTSC), and 0.093 μM for [Cu(PTZ-tBTSC)Cl].

Topoisomerase, Breast Cancer, Thiosemicarbazones

C. Lisic, E. , G. Rand, V. , Ngo, L. , Kent, P. , Rice, J. , Gerlach, D. , Papish, E. and Jiang, X. (2018) Cu(II) Propionyl-Thiazole Thiosemicarbazone Complexes: Crystal Structure, Inhibition of Human Topoisomerase IIα, and Activity against Breast Cancer Cells. Open Journal of Medicinal Chemistry, 8, 30-46. doi: 10.4236/ojmc.2018.82004.