Cu(II) Propionyl-Thiazole Thiosemicarbazone Complexes: Crystal Structure, Inhibition of Human Topoisomerase IIα, and Activity against Breast Cancer Cells

Abstract

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].