Contribution to the SAR field of metallated and coordination complexes. Studies of the palladium and platinum derivatives with selected thiosemicarbazones as antitumoral drugs

This article reviews the chemical and antitumoral properties of thiosemicarbazone complex-based drugs containing platinum(II) or palladium(II). Tetranuclear orthometallated complexes are the preferentially formed by most of the selected TSCNs. The core of these complexes consists of a flexible eight-member ring of alternating M-S atoms, causing in some cases, formation of two different geometric isomers. The different isomers display different cytotoxic activity, which was significant especially with platinum derivatives. Moreover, they display cytotoxic activity in tumor cell lines resistant to cis-DDP; the analysis of the interaction with DNA indicates interhelical cross-link formation. Binuclear complexes of thiosemicarbazones are chloro-bridged complexes where no orthometallation occurs, but their cytotoxic testing shows activity against resistant cell lines. Mononuclear complexes, which show an analogous structure to cisplatin, have shown promising "in vitro" antitumor properties. In addition, the interaction with DNA indicates that they have an enhanced capacity to form DNA interstrand cross-links, by comparison with cis-DDR The final purpose is to evaluate the coordination chemistry of selected thiosemicarbazone complexes of palladium and platinum in order to provide guidance and determine structure and antitumor activity relationships for continuing studies of these systems. (C) 2003 Elsevier B.V. All rights reserved.