Synthesis and characterization of [Au(dppz)(2)]Cl-3. DNA interaction studies and biological activity against Leishmania (L) mexicana

[Au(dppz)(2)]Cl-3 was synthesized by the reaction of HAuCl4 in excess of the dypirido[3,2-a: 2,3-c]phenazine (dppz) ligand. This complex was characterized by elemental analysis, fast atom bombardment (FAB) mass, NMR, UV-visible and IR spectroscopies. DNA-gold complex interactions were studied by spectroscopic titrations, viscosity measurements and electrophoretical assays. These studies showed that the gold complex interacts with DNA by intercalation mode. These observations, led us to carry out biological tests on cultures of promastigotes of Leishmania (L) mexicana. [Au(dppz)(2)]Cl-3 induced a dose dependent antiproliferative activity with minimal inhibitory concentration (MIC) of 3A nM and lethal doses LD26 of 17 nM for 48 h. These findings suggest that a very potent leishmanicidal activity could be associated to the cellular processes involving parasite DNA, constituting a new promising chemotherapeutic alternative in the search for definitive leishmaniasis cure. (c) 2006 Elsevier Inc. All rights reserved.