Synthesis, characterization, DNA binding study and biological activity against Leishmania mexicana of [Cu(dppz)2]BF4.

[Cu(dppz)(2)]BF(4) complex has been synthesized by the reaction of [Cu(CH(3)CN)(4)]BF(4) and dipyrido[3,2-A:2',3'-c]phenazine (dppz) in a molar ratio of 1:2. The compound was characterized by fast atom bombardment mass spectrometry, 1H nuclear magnetic resonance, UV-Vis and IR spectroscopies. Absorption and viscometric studies carried out on the interaction of [Cu(dppz)(2)]BF(4) complex with calf thymus DNA suggested that the complex binds by intercalation. No covalent binding was observed. Additionally, the results obtained from electrophoresis showed nuclease activity. The biological activity of the complex was tested in vitro on Leishmania mexicana promastigote cultures. A leishmanicidal effect (LD(30)) was observed in 48 h at concentration of 41 nM. Preliminary studies of the ultrastructure of L. mexicana treated with a sublethal dose of the complex (IC(7)=4.1 nM) for 48 h showed an induction of cytoplasm disorganization, vacuolization and binucleated cells. These findings suggest that the leishmanicidal activity of the title complex could be associated with its interaction with the parasitic DNA.

New silver polypyridyl complexes: synthesis, characterization and biological activity on Leishmania mexicana.

Leishmania parasites are the causal agents of leishmaniasis that currently threatens 350 million people in 88 different countries, in the absence of an effective drug. In order to continue the development of transition metal complexes with planar ligands that show interactions with DNA and activity against Leishmania parasites, the synthesis of the complexes [Ag(dpq)2]NO3 (1) and [Ag(dppz)2]NO3 (2), which were obtained by the reaction of silver nitrate with dpq and dppz, respectively, in a 1:2 molar ratio is reported. These complexes were characterized by elemental analysis and 1H-NMR, IR, and UV-vis spectroscopies. The most probable structure for these complexes is tetrahedral, with two molecules of ligand coordinated to the silver atom and a nitrate as a counter ion. Affinity studies of DNA vs. bovine albumin were carried out, and a strong interaction of the complexes with DNA was observed. Bioassays were undertaken in vitro on promastigotes of Leishmania (L.) mexicana exposed to the silver complexes for 48 h. At 10 micromol/L complex 2 induced a leishmanicidal effect (LD23), whilst complex 1 reduced the parasites growth rate by 55% (LD55). These findings suggest that biological activity could be associated with the interaction of the complexes with the parasitic DNA.