Gold(III) compounds as potential antitumor agents: cytotoxicity and DNA binding properties of some selected polyamine-gold(III) complexes

Three gold(III) -polyamine complexes of different structure - ( [Au(en)(2)]Cl-3, [AuCl( dien) ]Cl-2 and [Au(cyclam) ] (ClO4)(2)Cl) - were synthesized and tested for cytotoxic properties against a human tumor cell line (A2780) either sensitive (A2780/S) or resistant (A2780/R) to cisplatin. Significant cytotoxic activities were found for both [AuCl(dien) ] Cl-2 and [Au(en)(2)]Cl-3, whereas [ Au(cyclam) [ (ClO4)(2)Cl was poorly cytotoxic. The stability of these gold(III) complexes under physiological conditions was investigated through absorption spectroscopy; their ability to bind DNA, the presumed final target for the cytotoxic action, and modify its conformation was studied through atomic absorption and circular dichroism spectroscopies. Attempts are made to define preliminary structure-function relationships for cytotoxic gold(III) complexes. (C) 1998 Elsevier Science S.A. All rights reserved.