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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2012 |
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| Erschienen: |
2012 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:25 |
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| Enthalten in: |
Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine - 25(2012), 5 vom: 18. Okt., Seite 951-60 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Martins, Darliane A [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 25.01.2013 Date Revised 20.11.2014 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1007/s10534-012-9565-3 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM218499310 |
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| 100 | 1 | |a Martins, Darliane A |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Copper(II)-fluoroquinolone complexes with anti-Trypanosoma cruzi activity and DNA binding ability |
| 264 | 1 | |c 2012 | |
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| 500 | |a Date Completed 25.01.2013 | ||
| 500 | |a Date Revised 20.11.2014 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Fluoroquinolones |2 NLM | |
| 650 | 7 | |a Organometallic Compounds |2 NLM | |
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| 650 | 7 | |a Ofloxacin |2 NLM | |
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| 650 | 7 | |a sparfloxacin |2 NLM | |
| 650 | 7 | |a Q90AGA787L |2 NLM | |
| 700 | 1 | |a Gouvea, Ligiane R |e verfasserin |4 aut | |
| 700 | 1 | |a da Gama Jean Batista, Denise |e verfasserin |4 aut | |
| 700 | 1 | |a da Silva, Patrícia Bernardino |e verfasserin |4 aut | |
| 700 | 1 | |a Louro, Sonia R W |e verfasserin |4 aut | |
| 700 | 1 | |a de Nazaré C Soeiro, Maria |e verfasserin |4 aut | |
| 700 | 1 | |a Teixeira, Letícia R |e verfasserin |4 aut | |
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