Design of copper DNA intercalators with leishmanicidal activity.
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.
Navarro
Maribel
M
Centro de Química, Instituto Venezolano de Investigaciones Científicas, Carretera Panamericana, Altos de Pipe, KM 11, 1020-A, Caracas, Venezuela. mnavarro@ivic.ve
Cisneros-Fajardo
Efrén José
EJ
Sierralta
Aníbal
A
Fernández-Mestre
Mercedes
M
Silva
Pedro
P
Arrieche
Dwight
D
Marchán
Edgar
E
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
D007364:Intercalating Agents; D003300:Copper; D004247:DNA