Different types of copper complexes with the quinolone antimicrobial drugs ofloxacin and norfloxacin: structure, DNA- and albumin-binding.
Three novel copper(II) complexes with the second-generation quinolone antibacterial agents norfloxacin (nfH) and ofloxacin (ofloH) have been synthesized resulting in the complexes [Cu(nfH)(phen)Cl]Cl·5H(2)O (1·5H(2)O), [Cu(nfH)(2)]Cl(2)·6H(2)O (2·6H(2)O) and [Cu(II)(ofloH)(2)][(Cu(I)Cl(2))(2)] (3), respectively. The crystal structures of the complexes have been determined by X-ray crystallography revealing that the quinolones act as bidentate ligands coordinated to Cu(II) atom through the pyridone oxygen and a carboxylato oxygen. UV study of the interaction of the quinolones and the complexes with calf-thymus DNA (CT DNA) has shown that they can bind to CT DNA with [Cu(II)(ofloxacin)(2)][(Cu(I)Cl(2))(2)] exhibiting the highest binding constant to CT DNA. The cyclic voltammograms of the complexes in the presence of CT DNA solution have shown that the interaction of the complexes with CT DNA is mainly through electrostatic binding. DNA solution viscosity measurements have shown that the interaction of the compounds with CT DNA by classical intercalation may be ruled out. Competitive studies with ethidium bromide (EB) indicate that the complexes can partially displace the DNA-bound EB suggesting low to moderate competition with EB. Norfloxacin, ofloxacin and their copper complexes exhibit good binding propensity to human or bovine serum albumin protein having relatively high binding constant values.
Faculty of Chemistry and Chemical Technology, University of Ljubljana, Aškerčeva 5, SI-1000 Ljubljana, Slovenia.
Petra
P
Živec
Franc
F
Perdih
Iztok
I
Turel
Gerald
G
Giester
George
G
Psomas
D000418:Albumins / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology; D002417:Cattle; D056831:Coordination Complexes / Q000737:chemistry* / Q000494:pharmacology; D003300:Copper / Q000737:chemistry*; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D004996:Ethidium / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D007364:Intercalating Agents / Q000737:chemistry* / Q000494:pharmacology; D008958:Models, Molecular; D009643:Norfloxacin / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000494:pharmacology; D015242:Ofloxacin / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000494:pharmacology; D011485:Protein Binding; D012709:Serum Albumin / Q000737:chemistry / Q000378:metabolism; D013050:Spectrometry, Fluorescence
D000418:Albumins; D000900:Anti-Bacterial Agents; D056831:Coordination Complexes; D007364:Intercalating Agents; D012709:Serum Albumin; C052890:ethidium-DNA complex; D003300:Copper; D004247:DNA; C427203:calf thymus DNA; D015242:Ofloxacin; D004996:Ethidium; D009643:Norfloxacin