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.
Laboratorio de Química de los Metales de Transición, Centro de Química, Instituto Venezolano de Investigaciones Cienti;ficas, Carretera Panamericana, Km 11, Altos de Pipe, 1020-A, Caracas, Venezuela.
Maribel
M
Navarro
Efrén J
EJ
Cisneros-Fajardo
Mercedes
M
Fernandez-Mestre
Dwight
D
Arrieche
Edgar
E
Marchan
D000818:Animals; D000981:Antiprotozoal Agents / Q000138:chemical synthesis / Q000494:pharmacology; D002417:Cattle; D003300:Copper / Q000737:chemistry*; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D007364:Intercalating Agents / Q000138:chemical synthesis / Q000378:metabolism; D007894:Leishmania mexicana / Q000166:cytology / Q000187:drug effects* / Q000648:ultrastructure; D008854:Microscopy, Electron; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000378:metabolism* / Q000494:pharmacology*; D021261:Parasitic Sensitivity Tests / Q000379:methods; D010619:Phenazines / Q000737:chemistry; D013057:Spectrum Analysis / Q000379:methods
C481080:(Cu(dppz)(2))BF(4); D000981:Antiprotozoal Agents; D007364:Intercalating Agents; D009942:Organometallic Compounds; D010619:Phenazines; D003300:Copper; D004247:DNA; C427203:calf thymus DNA