Copper(II)-fluoroquinolone complexes with anti-Trypanosoma cruzi activity and DNA binding ability.
Copper(II) complexes of fluoroquinolone antibacterial agents levofloxacin (LEV) and sparfloxacin (SPAR), containing or not a nitrogen donor heterocyclic ligand, 2,2'-bipyridine (bipy) or 1,10-phenathroline (phen), were prepared and characterized. The complexes are of the type [CuCl(2)(H(2)O)(L)], [CuCl(bipy)(L)]Cl and [CuCl(2)(phen)(L)], where L = LEV or SPAR. The data suggest that LEV and SPAR act as zwitterionic bidentade ligands coordinated to Cu(II) through the carboxylate and ketone oxygen atoms. The electron paramagnetic resonance spectra of the [CuCl(bipy)(L)]Cl and [CuCl(2)(phen)(L)] complexes (L = LEV and SPAR) in aqueous and DMSO solutions indicate mixture of mononuclear and binuclear forms. The Cu(II) complexes, together with the corresponding ligands, were evaluated for their trypanocidal activity in vitro against Trypanosoma cruzi, the causative agent of Chagas disease. The assays performed against bloodstream trypomastigotes showed that all complexes were more active than their corresponding ligands. Complexes [CuCl(2)(phen)(LEV)] and [CuCl(2)(phen)(SPAR)] were revealed, among all studied compounds, to be the most active with IC(50) = 1.6 and 4.7 μM, respectively, both presenting a superior effect than benznidazole. The interactions of fluoroquinolones and their Cu(II) complexes with calf-thymus DNA were investigated. These compounds showed binding properties towards DNA, with moderated binding constants values, suggesting that this structure may represent a parasite target.
Departamento de Química, Universidade Federal de Minas Gerais, Belo Horizonte, MG, 31270-901, Brazil.
Darliane A
DA
Martins
Ligiane R
LR
Gouvea
Denise
D
da Gama Jean Batista
Patrícia Bernardino
PB
da Silva
Sonia R W
SR
Louro
Maria
M
de Nazaré C Soeiro
Letícia R
LR
Teixeira
D000818:Animals; D002417:Cattle; D003300:Copper / Q000378:metabolism / Q000494:pharmacology*; D004247:DNA / Q000187:drug effects / Q000378:metabolism; D004578:Electron Spin Resonance Spectroscopy; D024841:Fluoroquinolones / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D066298:In Vitro Techniques; D064704:Levofloxacin; D015242:Ofloxacin / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D009942:Organometallic Compounds / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D013056:Spectrophotometry, Ultraviolet; D014344:Trypanocidal Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D014349:Trypanosoma cruzi / Q000187:drug effects*
D024841:Fluoroquinolones; D009942:Organometallic Compounds; D014344:Trypanocidal Agents; D064704:Levofloxacin; D003300:Copper; D004247:DNA; C427203:calf thymus DNA; D015242:Ofloxacin; C061363:sparfloxacin