Interactions of selected gold(III) complexes with calf thymus DNA

DNA represents the primary target for platinum antitumor metal complexes an d is the probable target for newly developed cytotoxic gold(III) complexes. To test this hypothesis the reactions with calf thymus DNA of five represe ntative gold(III) complexes-namely [Au(en)(2)]Cl-3, [Au(dien)Cl]Cl-2, [Au(c yclam)](ClO4)(2)Cl, [Au(terpy)Cl]Cl-2 and [Au(phen)Cl-2]Cl-were analyzed in vitro through various physicochemical techniques including circular dichro ism, absorption spectroscopy, DNA melting, and ultradialysis, It is shown t hat all tested complexes interact with DNA and modify significantly its sol ution behavior. The solution conformation of DNA is affected to variable ex tents by the individual complexes as shown by CD titration experiments. Not ably, in all cases, the gold(III) chromophore is not largely perturbed by a ddition of calf thymus DNA ruling out occurrence of gold(III) reduction. Ul tradialysis experiments point out that the binding affinity of the various complexes for the DNA double helix is relatively low; in most cases the gol d(III)/DNA interaction is electrostatic in nature and reversible. The impli cations of these findings for the mechanism of action of antitumor gold(III ) complexes are discussed. (C) 2001 Academic Press.