Role of Metalation in the Topoisomerase Ilα Inhibition and Antiproliferation Activity of a Series of α-Heterocyclic-N4-Substituted Thiosemicarbazones and Their Cu(II) Complexes

The topoisomerase-Il alpha inhibition and antiproliferative activity of alpha-heterocyclic thiosemicarbazones and their corresponding copper(II) complexes have been investigated. The Cu-II(thiosemicarbazonato)Cl complexes were shown to catalytically inhibit topoisomerase-Il alpha at concentrations (0.3-7.2 mu M) over an order of magnitude lower than their corresponding thiosemicarbazone ligands alone. The copper complexes were also shown to inhibit the proliferation of breast cancer cells expressing high levels of topoisomerase-Il alpha (SK-BR-3) at lower concentrations than cells expressing lower levels of the enzyme (MCF-7).