RESUMO
A series of 6-cyclic aliphatic amino-7-nitro-3,4-dihydroquinoline-2(1H)-ones were prepared and tested for platelet aggregation inhibitory effect, cardiotonic activity and chronotropic activity. These compounds appeared to show selective inhibitory activity against platelet aggregation. Among them, 6-(4-ethoxycarbonylpiperidino)-7-nitro-3,4-dihydroquinoline-2(1H)-one (22f) showed the most potent inhibitory activity and high selectivity. A divergent synthetic route to 6-cyclic aliphatic amino-7-nitro-3,4-dihydroquinoline-2(1H)-one derivatives has also been investigated.
Assuntos
Nitrocompostos/síntese química , Nitrocompostos/farmacologia , Inibidores da Agregação Plaquetária/síntese química , Agregação Plaquetária/efeitos dos fármacos , Quinolonas/síntese química , Quinolonas/farmacologia , Acetilação , Animais , Cardiotônicos/síntese química , Cardiotônicos/farmacologia , Cobaias , Átrios do Coração/efeitos dos fármacos , Técnicas In Vitro , Indicadores e Reagentes , Espectroscopia de Ressonância Magnética , Contração Miocárdica/efeitos dos fármacos , Inibidores da Agregação Plaquetária/farmacologia , Coelhos , Relação Estrutura-AtividadeRESUMO
Vascular endothelial growth factor (VEGF) has recently been shown to be involved in the pathogenesis of proliferative diabetic retinopathy. However, its involvement in the development of the early phase of diabetic retinopathy is not fully understood. In this study we investigated the retinal VEGF mRNA level in spontaneously diabetic Otsuka Long-Evans Tokushima fatty (OLETF) rats, a model of non-insulin-dependent diabetes, without overt retinopathy, using quantitative reverse-transcription polymerase chain reaction. The retinal VEGF mRNA level was 2.2 times higher (p < 0.0005) in OLETF rats than in control rats at the age of 60 weeks. Moreover, their retinal mRNA level was positively correlated with serum concentration of advanced glycation end products (AGEs) but not to serum glucose concentration. Furthermore, the peak latency of the oscillatory potentials in the electroretinogram, one of the most sensitive markers for the early phase of diabetic retinopathy, was significantly prolonged in OLETF rats (p < 0.05), being also correlated with the serum AGE concentration. The results thus suggest that AGEs, which are formed acceleratedly in diabetic conditions, are involved in the development of the early phase of diabetic retinopathy probably through the induction of retinal VEGF mRNAs.
