title: DNA as molecular target of analogous palladium and platinum anti-Trypanosoma cruzi compounds: a comparative study.
abstract: In the search for drugs with anti-trypanosome activity, we had previously synthesized two series of platinum and palladium analogous compounds of the formula [M(II)Cl(2)(HL)], where HL were bioactive 5-nitrofuryl or 5-nitroacroleine thiosemicarbazone derivatives. In this work, we thoroughly characterized [M(II)Cl(2)(HL)] complexes interaction with DNA by using different techniques: gel electrophoresis, DNA viscosity measurements, circular dichroism (CD) and atomic force microscopy (AFM). Electrophoresis results showed that all complexes induced a withdrawal of DNA superhelicity demonstrated by a decrease in electrophoretic mobility of supercoiled DNA form. This effect on migration was dependent on dose but also on the nature of both the metal and the ligand. In general, the effect produced by palladium complexes was significantly more intense than that observed for the corresponding platinum analogs. Differences between palladium and platinum complexes were also observed in CD experiments. While palladium complexes induce evident calf thymus (CT)-DNA profile changes compatible with B-DNA to Z-DNA conformational transition, no clear effect was observed for platinum ones. Additionally, AFM studies showed that changes in the shape of plasmid DNA, like supercoiling, kinks and thickness increase resulted more intense for the former. In addition, either Pd or Pt complexes increased the viscosity of CT DNA solutions in a concentration dependent manner. Although the nature of DNA interaction of both series of analogous palladium and platinum complexes seemed to be similar, an explanation for the observed differential intensity of the effect could be related to the known kinetic stability differences between palladium and platinum compounds.
authors.affiliation: Cátedra de Química Inorgánica, Facultad de Química, UDELAR, Montevideo, Uruguay.
authors.forename: Marisol
authors.initials: M
authors.lastname: Vieites
authors.forename: Pablo
authors.initials: P
authors.lastname: Smircich
authors.forename: Mariana
authors.initials: M
authors.lastname: Pagano
authors.forename: Lucía
authors.initials: L
authors.lastname: Otero
authors.forename: Francielle Luane
authors.initials: FL
authors.lastname: Fischer
authors.forename: Hernán
authors.initials: H
authors.lastname: Terenzi
authors.forename: María José
authors.initials: MJ
authors.lastname: Prieto
authors.forename: Virtudes
authors.initials: V
authors.lastname: Moreno
authors.forename: Beatriz
authors.initials: B
authors.lastname: Garat
authors.forename: Dinorah
authors.initials: D
authors.lastname: Gambino
mesh_terms: D002942:Circular Dichroism; D056831:Coordination Complexes / Q000737:chemistry*; D004247:DNA / Q000737:chemistry*; D004278:DNA, Superhelical / Q000737:chemistry* / Q000648:ultrastructure; D004214:Distamycins / Q000737:chemistry; D018625:Microscopy, Atomic Force; D009690:Nucleic Acid Conformation; D010165:Palladium / Q000737:chemistry*; D010957:Plasmids; D010984:Platinum / Q000737:chemistry*; D014344:Trypanocidal Agents / Q000737:chemistry*; D014349:Trypanosoma cruzi; D014783:Viscosity
chemical_list: D056831:Coordination Complexes; D004278:DNA, Superhelical; D004214:Distamycins; D014344:Trypanocidal Agents; D010984:Platinum; D010165:Palladium; C030000:stallimycin; D004247:DNA; C427203:calf thymus DNA