ENRIZENRIZ] ricardoricardo] danieldaniel]
Synthesis, Dopaminergic profile and Molecular Dynamics Calculations of N-Aralkyl substituted 2-aminoindans
SEBASTIAN A. ANDUJAR, BIAGINA MIGLIORE DE ANGEL, JAIME E. CHARRIS, ANITA ISRAEL, HEBERTO SUÁREZ-ROCA, SIMON E. LÓPEZ, MARIA R. GARRIDO,CECIRE ROSALES. ELVIA CABRERA, FERNANDO D. SUVIRE, RICARDORICARDO] D.ENRIZENRIZ]. JORGE E. ANGEL-GUÍO.
BIOORGANIC & MEDICINAL CHEMISTRY.
Lugar: Amsterdam; Año: 2008 vol. 16 p. 3233 - 3233
Brain dopaminergic system has a crucial role in the etiology of several neuropsychiatric disorders, including Parkinson´s disease, depression and schizophrenia. Several dopaminergic drugs are used to treat these pathologies, but many problems are attributed to these therapies. Within this context, the search for new more efficient dopaminergic agents with less adverse effects represents a vast research field. The aim of the present study was to synthesize N-[2-(4,5-dihydroxyphenyl)-methyl-ethyl]-4,5-dihydroxy-2-aminoindan hydrobromide (3), planned to be a dopamine ligand, and to evaluate its dopaminergic action profile. This compound was assayed in two experimental models: stereotyped behavior (gnaw) and renal urinary response, after central administration. The pharmacological results showed that this compound 3 significantly blocked the apomorphine-induced stereotypy and dopamine-induced diuresis and natriuresis in rats. On the basis of the results, compound 3 demonstrated an inhibitory effect on dopaminergic-induced behavior and renal action. N-[2-(-methyl-ethyl)]-4,5-dihydroxy-2-aminoindan hydrobromide (4), was previously reported as an inotropic agent, and in the present work it was re-evaluated its possible central action on the behavior parameters such as stereotypy and dopamine-induced diuresis and natriuresis, in rats. Our results suggest that compound 4 produces an agonistic response, possibly through dopaminergic mechanisms. To better understand the experimental results we performed molecular dynamics simulations of two complexes: