RESUMEN
Two analogues of tolcapone where the nitrocatechol group has been replaced by a 1-hydroxy-2(1H)-pyridinone have been designed and synthesised. These compounds are expected to have a dual mode of action both beneficial against Parkinson's disease: they are designed to be inhibitors of catechol O-methyl transferase, which contribute to the reduction of dopamine in the brain, and to protect neurons against oxidative damage. To assess whether these compounds are worthy of biological assessment to demonstrate these effects, measurement of their pKa and stability constants for Fe(III), in silico modelling of their potential to inhibit COMT and blood-brain barrier scoring were performed. These results demonstrate that the compounds may indeed have the desired properties, indicating they are indeed promising candidates for further evaluation.
Asunto(s)
Inhibidores de Catecol O-Metiltransferasa , Enfermedad de Parkinson , Benzofenonas , Catecol O-Metiltransferasa , Inhibidores de Catecol O-Metiltransferasa/farmacología , Catecoles/farmacología , Quelantes , Inhibidores Enzimáticos/farmacología , Compuestos Férricos , Humanos , Nitrofenoles , Enfermedad de Parkinson/tratamiento farmacológico , PiridonasRESUMEN
This work is devoted to the electrochemical characterization of 1,3-diethyl 2-(azulen-1-ylmethylene)propanedioate by cyclic voltammetry and differential pulse voltammetry. The redox processes are established, analyzed and assessed to the particular functional groups at which they take place. The complexation behavior towards lanthanide metal ions (Sm(3+), Eu(3+), Yb(3+), Tb(3+)) was studied by electrochemical methods and UV-Vis spectroscopy.