RESUMO
This study reports elevated levels of bacterial lipopolysaccharides (LPSs) and cyclooxygenases (COX-1/2) in blood serum and cerebrospinal fluid (CSF) of Alzheimer's Disease (AD) and Mild Cognitive Impairment (MCI) patients compared to cognitively healthy individuals, indicating LPSs as promising biomarkers, especially in serum. LPSs, in both fluids, positively correlate with COX-1/2, Αß42 and tau and negatively with mental state. Furthermore, COX-2 is the main determinant of LPSs presence in serum, whereas COX-1 in CSF. These results underline the significance of microbial/ inflammatory involvement in dementia and offer novel perspectives on the roles of LPSs and COX in pathogenesis of AD.
Assuntos
Doença de Alzheimer/metabolismo , Proteínas de Bactérias/metabolismo , Disfunção Cognitiva/metabolismo , Lipopolissacarídeos/metabolismo , Prostaglandina-Endoperóxido Sintases/metabolismo , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
The cobalt(II) complexes with the quinolone antimicrobial agent enrofloxacin (Herx) in the presence of the nitrogen-donor heterocyclic ligands pyridine (py), 2,2'-bipyridylamine (bipyam), 1,10-phenanthroline (phen), 2,2'-bipyridine (bipy) or the oxygen-donor ligand N,N-dimethylformamide (DMF) were synthesized and characterized. The crystal structures of complexes [Co(erx)2(py)2]·MeOH·6H2O and [Co(erx)2(bipyam)]·4.5MeOH·1.25H2O were determined by X-ray crystallography. The deprotonated enrofloxacinato ligands are bidentately bound to cobalt(II) ion through the pyridone oxygen and a carboxylato oxygen. The antimicrobial activity of the complexes was tested against five different microorganisms (Escherichia coli XL1, Xanthomonas campestris ATCC 33013, Staphylococcus aureus ATCC 29213, Bacillus cereus ATCC 11778 and Bacillus subtilis ATCC 6633) and the complexes were more active than free Herx. The binding of the complexes to calf-thymus DNA (CT DNA) was monitored by spectroscopic techniques, viscosity measurements, cyclic voltammetry and by mobility shift experiments in agarose gel electrophoresis with CT DNA and plasmid DNA (pDNA). All complexes exhibited a preference for binding to the supercoiled structure of the pDNA. The ability of the complexes to displace ethidium bromide (EB) from the EB-DNA complex was also investigated. The experiments indicated intercalation as the most possible mode and the DNA-binding strength of the complexes were also calculated. The complexes bind to human or bovine serum albumin protein exhibiting relatively high binding constant values.
Assuntos
Antibacterianos/farmacologia , Cobalto/química , DNA/efeitos dos fármacos , Compostos Organometálicos/farmacologia , Animais , Antibacterianos/síntese química , Antibacterianos/química , Bacillus/efeitos dos fármacos , Bovinos , Relação Dose-Resposta a Droga , Escherichia coli/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Compostos Organometálicos/síntese química , Compostos Organometálicos/química , Plasmídeos/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Relação Estrutura-Atividade , Xanthomonas campestris/efeitos dos fármacosRESUMO
The reaction of MnCl2 with the quinolone antibacterial drug oxolinic acid (Hoxo) results to the formation of [KMn(oxo)3(MeOH)3]. Interaction of MnCl2 with the quinolone Hoxo or enrofloxacin (Herx) and the N,N'-donor heterocyclic ligand 1,10-phenanthroline (phen) results in the formation of metal complexes with the general formula [Mn(quinolonato)2(phen)]. The crystal structures of [KMn(oxo)3(MeOH)3] and [Mn(erx)2(phen)], exhibiting a 1D polymeric and a mononuclear structure, respectively, have been determined by X-ray crystallography. In these complexes, the deprotonated bidentate quinolonato ligands are coordinated to manganese(II) ion through the pyridone oxygen and a carboxylato oxygen. All complexes can act as potential antibacterial agents with [Mn(erx)2(phen)] exhibiting the most pronounced antimicrobial activity against five different microorganisms. Interaction of the complexes with calf-thymus DNA (CT DNA), studied by UV spectroscopy, has shown that they bind to CT DNA. Competitive study with ethidium bromide (EB) has shown that all complexes can displace the DNA-bound EB indicating their binding to DNA in strong competition with EB. Intercalative binding mode is proposed for the interaction of the complexes with CT DNA and has also been verified by DNA solution viscosity measurements and cyclic voltammetry. DNA electrophoretic mobility experiments suggest that [Mn(erx)2(phen)] binds strongly to supercoiled pDNA and to linearized pDNA possibly by an intercalative manner provoking double-stranded cleavage reflecting in a nuclease-like activity. The complexes exhibit good binding propensity to human or bovine serum albumin protein showing relatively high binding constant values. The binding constants of the complexes towards CT DNA and albumins have been compared to their corresponding zinc(II) and nickel(II) complexes.