Synthesis and characterization of [Au(dppz)2]Cl3. DNA interaction studies and biological activity against Leishmania (L) mexicana.
[Au(dppz)(2)]Cl(3) was synthesized by the reaction of HAuCl(4) 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 3.4nM and lethal doses LD(26) of 17nM for 48h. 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.
Navarro
Maribel
M
Centro de Química, Instituto Venezolano de Investigaciones Científicas (IVIC), Carretera Panamericana KM.11, Altos de Pipe. Apartado 21827, Caracas 1020 A, Venezuela. mnavarro@ivic.ve
Hernández
Clara
C
Colmenares
Ibis
I
Hernández
Paola
P
Fernández
Mercedes
M
Sierraalta
Anibal
A
Marchán
Edgar
E
D000818:Animals; D002417:Cattle; D004247:DNA / Q000187:drug effects*; D017612:Gold Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D007894:Leishmania mexicana / Q000187:drug effects*; D013057:Spectrum Analysis / Q000379:methods
D017612:Gold Compounds; D004247:DNA