RESUMO

A series of novel 3-indolylpropyl derivatives was synthesized and evaluated for their binding affinities at the serotonin-1A receptor subtype (5-HT1A R) and the 5-HT transporter (SERT). Compounds 11b and 14b exhibited the highest affinities at the 5-HT1A R (Ki = 43 and 56 nM), whereas compounds 11c and 14a were the most potent analogs at the SERT (Ki = 34 and 17 nM). On the other hand, compounds 14b and 11d showed potent activity at both targets, displaying a profile that makes them promising leads for the search for novel potent ligands with a dual mechanism of action. Molecular docking studies in all the compounds unveiled relevant drug-target interactions, which allowed rationalizing the observed affinities.

Assuntos

Indóis/síntese química , Indóis/farmacologia , Simulação de Acoplamento Molecular , Receptor 5-HT1A de Serotonina/metabolismo , Serotoninérgicos/síntese química , Serotoninérgicos/farmacologia , Proteínas da Membrana Plasmática de Transporte de Serotonina/metabolismo , Antidepressivos/síntese química , Antidepressivos/farmacologia , Relação Dose-Resposta a Droga , Humanos , Indóis/química , Estrutura Molecular , Serotoninérgicos/química , Relação Estrutura-Atividade