title: Design of copper DNA intercalators with leishmanicidal activity.
abstract: The complexes [Cu(dppz)(NO(3))]NO(3) (1), [Cu(dppz)(2)(NO(3))]NO(3) (2), [Cu(dpq)(NO(3))]NO(3) (3), and [Cu(dpq)(2)(NO(3))]NO(3) (4) were synthesized and characterized by elemental analysis, FAB-mass spectrometry, EPR, UV, and IR spectroscopies, and molar conductivity. DNA interaction studies showed that intercalation is an important way of interacting with DNA for these complexes. The biological activity of these copper complexes was evaluated on Leishmania braziliensis promastigotes, and the results showed leishmanicidal activity. Preliminary ultrastructural studies with the most active complex (2) at 1 h revealed parasite swelling and binucleated cells. This finding suggests that the leishmanicidal activity of the copper complexes could be associated with their interaction with the parasitic DNA.
authors.affiliation: Centro de Química, Instituto Venezolano de Investigaciones Científicas, Carretera Panamericana, Altos de Pipe, KM 11, 1020-A, Caracas, Venezuela. mnavarro@ivic.ve
authors.forename: Maribel
authors.initials: M
authors.lastname: Navarro
authors.forename: Efrén José
authors.initials: EJ
authors.lastname: Cisneros-Fajardo
authors.forename: Aníbal
authors.initials: A
authors.lastname: Sierralta
authors.forename: Mercedes
authors.initials: M
authors.lastname: Fernández-Mestre
authors.forename: Pedro
authors.initials: P
authors.lastname: Silva
authors.forename: Dwight
authors.initials: D
authors.lastname: Arrieche
authors.forename: Edgar
authors.initials: E
authors.lastname: Marchán
mesh_terms: D000818:Animals; D003300:Copper / Q000737:chemistry* / Q000378:metabolism; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D015195:Drug Design; D007364:Intercalating Agents / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D007892:Leishmania braziliensis / Q000187:drug effects* / Q000254:growth & development* / Q000378:metabolism
chemical_list: D007364:Intercalating Agents; D003300:Copper; D004247:DNA