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J Enzyme Inhib Med Chem ; 31(2): 302-13, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-25798685

RESUMEN

The synthesis, the antioxidative properties and the lipoxygenase (LOX) and acetylcholinesterase (AChE) inhibition of a number of 4-hydroxy-chalcones diversely substituted as well as of a series of bis-chalcones ether derivatives are reported. The chalcones derivatives were readily produced using a Claisen-Schmidt condensation in a ultra sound bath in good yields. The structures of the synthesized compounds were confirmed by spectral and elemental analysis. Their lipophilicity is experimentally determined by reversed-phase thin-layer chromatography method. Most of them are potent in vitro inhibitors of lipid peroxidation and of LOX. Compounds b2 and b3 were found to be the most potent LOX and AChE inhibitors among the tested derivatives with a significant anti-lipid peroxidation profile. The results led us to propose these enone derivatives as new multifunctional compounds against Alzheimer's disease. The results are discussed in terms of structural and physicochemical characteristics of the compounds. Moreover, the pharmacokinetic profile of these compounds was investigated using computational methods.


Asunto(s)
Chalconas/química , Chalconas/farmacología , Inhibidores de la Colinesterasa/farmacología , Inhibidores de la Lipooxigenasa/farmacología , Animales , Antioxidantes/química , Antioxidantes/farmacología , Células CACO-2 , Línea Celular , Chalconas/síntesis química , Técnicas de Química Sintética , Inhibidores de la Colinesterasa/síntesis química , Inhibidores de la Colinesterasa/química , Cromatografía en Capa Delgada , Citocromo P-450 CYP1A1/química , Citocromo P-450 CYP1A1/metabolismo , Citocromo P-450 CYP1A2/química , Citocromo P-450 CYP1A2/metabolismo , Citocromo P-450 CYP2D6/química , Citocromo P-450 CYP2D6/metabolismo , Evaluación Preclínica de Medicamentos/métodos , Glutatión/química , Humanos , Peroxidación de Lípido/efectos de los fármacos , Inhibidores de la Lipooxigenasa/síntesis química , Inhibidores de la Lipooxigenasa/química , Ratones , Simulación del Acoplamiento Molecular , Relación Estructura-Actividad
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