Síntese e avaliação da atividade anticolinesterásica de benzotiazin-4-onas derivadas da 4-(2-aminoetil)morfolina, da 1-(3-aminopropil)piperidina e da 1-(2-aminoetil)piperidina

Abstract

The present study assessed the inhibitory activity of acetylcholinesterase (AChE) of nineteen benzothiazin-4-one. To obtain benzotiazinonas reactions were used "one-pot" between an aliphatic amine (4-(2-aminoethyl)morpholine, 1-(3- aminopropyl)piperidine, 1-(2-aminoethyl)piperidine), aliphatic aldehydes (valeraldehyde) or aromatic (benzaldehyde, 4-nitrobenzaldehyde, 4-fluorbenzaldeído, 4-methoxybenzaldehyde, 4-methylbenzaldehyde and 4-metilsulfonilbenzaldeído) and thiosalicylic acid by conventional thermal heating. The novel compounds were synthesized efficiently with moderate to good yields (43-93%) were identified and characterized by gas chromatography coupled with mass spectrometry and nuclear magnetic resonance H1 and C13 NMR and GC-MS. Furthermore, the anticholinesterasic activity in vitro in cerebral cortex and hippocampus were evaluated in all of the compounds. Among the molecules that best results were significant with respect to the potential of AChE inhibition, are the compounds 5Ba (2-butyl-3-(3-(piperidin-1-yl)propyl)-2,3-dihydro-4H-benzo[e] [1,3]thiazin-4-one) which showed inhibitory effect at a concentration from 10 μM in the cerebral cortex and from 100 μM in hippocampus and compound 5Bd (2- (4- nitrophenyl) 3- (3- (piperidin-1-yl) propyl) -2,3-dihydro-4H-benzo[e][1,3]thiazin-4-one), which also showed inhibitory effects in the concentration of from 10 μM in the cerebral cortex and from 50 μM in the hippocampus when groups compared to controls (water and methanol) (P <0.05). Moreover, the cytotoxicity of seven compounds were evaluated in cell lines MCR-5 strain of human fibroblast using the sulforhodamine B test for 24h. It is important to note that 5Ba and 5Bd compounds showed a good therapeutic window due to the absence of cytotoxicity at the concentration of 100 μM, considerably greater than that found active concentration.