title: Atypical fluoroquinolone gold(III) chelates as potential anticancer agents: relevance of DNA and protein interactions for their mechanism of action.
abstract: 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.
authors: Departamento de Química, Universidade Federal de Minas Gerais, Av. Antonio Carlos 6627, 31270-901 Belo Horizonte (MG), Brazil.
authors: Ligiane R
authors: LR
authors: Gouvea
authors: Luciene S
authors: LS
authors: Garcia
authors: Daniela R
authors: DR
authors: Lachter
authors: Paula Roberta
authors: PR
authors: Nunes
authors: Flávia
authors: F
authors: de Castro Pereira
authors: Elisângela P
authors: EP
authors: Silveira-Lacerda
authors: Sônia R W
authors: SR
authors: Louro
authors: Paulo Jorge S
authors: PJ
authors: Barbeira
authors: Letícia R
authors: LR
authors: Teixeira
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D001692:Biological Transport; D002417:Cattle; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002614:Chelating Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D004247:DNA / Q000378:metabolism*; D053938:DNA Fragmentation / Q000187:drug effects; D024841:Fluoroquinolones / Q000737:chemistry*; D006801:Humans; D020128:Inhibitory Concentration 50; D051379:Mice; D050607:Organogold Compounds / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D012710:Serum Albumin, Bovine / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D002614:Chelating Agents; D024841:Fluoroquinolones; D050607:Organogold Compounds; D012710:Serum Albumin, Bovine; D004247:DNA