Functionalized thiosemicarbazone clusters of copper(I) and silver(I)

Thiosemicarbazide and thiosemicarbazone complexes of copper have attracted particular attention over the past decade in the context of their wide spectrum of biological activity and applications as radiopharmaceuticals.(1,2) Thiosemicarbazones such as (LH)-H-2 (Figure 1) are known antitumor compounds, but their copper complexes show enhanced biological activities and are potent cytotoxic agents as well as inhibitors of DNA synthesis.(1) It is thought that the antitumor activity of the copper thiosemicarbazone complexes is due to their ability to inhibit DNA topoisomerase-II (topo-II), an enzyme that regulates the topology of DNA.(2) Very recently analogues of (LH)-H-2 have been successfully radiolabeled with Cu-64.(3) The resulting compounds showed high uptake in L1210 tumor line cells, which are known to express high levels of topo-II. It is possible that the cellular retention of these compounds involves intracellular reduction of the Cu(II) to a Cu(I) species that may or not be stable inside the cell(4,5).