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Eur J Med Chem ; 55: 67-73, 2012 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-22835721

RESUMEN

Quinolones are known for their antimicrobial and antitumor activities. Gold(III) compounds constitute an emerging class of biologically active substances, of special interest as potential anticancer agents. In this work three gold(III) complexes of the fluoroquinolones antimicrobial agents norfloxacin (NOR), levofloxacin (LEVO) and sparfloxacin (SPAR) were prepared and characterized with physicochemical and spectroscopic techniques. In these complexes, NOR, LEVO and SPAR act as bidentate neutral ligands bound to gold(III) through the nitrogen atoms of the piperazine ring, which is an unusual mode of coordination for this class of compounds. Two chloride ions occupy the remaining coordination sites. The cytotoxic activity of the fluoroquinolones and their gold(III) complexes was tested against the A20 (murine lymphoma), B16-F10 (murine melanoma) and K562 (human myeloid leukemia) tumor cell lines as well as the L919 (murine lung fibroblasts) and MCR-5 (human lung fibroblasts) normal cells lines. All complexes were more active than their corresponding free ligands. Complex [AuCl(2)(LEVO)]Cl was selected for DNA fragmentation and cell cycle analysis. Spectroscopic titration with calf-thymus DNA (CT DNA) showed that the complexes can bind weakly to CT DNA, probably by an external contact (electrostatic or groove binding). The complexes exhibit good binding propensity to bovine serum albumin (BSA) having relatively high binding constant values.


Asunto(s)
ADN/metabolismo , Fluoroquinolonas/química , Compuestos Orgánicos de Oro/metabolismo , Compuestos Orgánicos de Oro/farmacología , Albúmina Sérica Bovina/metabolismo , Animales , Antineoplásicos/química , Antineoplásicos/metabolismo , Antineoplásicos/farmacología , Transporte Biológico , Bovinos , Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Quelantes/química , Quelantes/metabolismo , Quelantes/farmacología , Fragmentación del ADN/efectos de los fármacos , Humanos , Concentración 50 Inhibidora , Ratones , Compuestos Orgánicos de Oro/química
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