title: Synthesis, docking and pharmacological evaluation of novel homo- and hetero-bis 3-piperazinylpropylindole derivatives at SERT and 5-HT1A receptor.
abstract: A series of 3-(3-(4-(3-(1H-indol-3-yl)propyl)piperazin-1-yl)propyl)-1H-indole derivatives (3a-d and 5a-f) as homo- and hetero-bis-ligands, were synthesized and evaluated for in vitro affinity at the serotonin transporter (SERT) and the 5-HT1A receptor. Compounds 5b and 5f showed nanomolar affinities for both targets. The experimental data were rationalized according to results obtained from docking experiments. These findings are in agreement with our proposal that bis-indole derivatives can bind both targets, and might serve as leads in the quest of ligands endowed with a dual mechanism of action.
authors.affiliation: Departamento de Química Orgánica y Fisicoquímica, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Casilla 233, Santiago 1, Chile. Electronic address: hpessoa@ciq.uchile.cl.
authors.forename: Hernán
authors.initials: H
authors.lastname: Pessoa-Mahana
authors.forename: Christian
authors.initials: C
authors.lastname: González-Lira
authors.forename: Angélica
authors.initials: A
authors.lastname: Fierro
authors.forename: Gerald
authors.initials: G
authors.lastname: Zapata-Torres
authors.forename: C David
authors.initials: CD
authors.lastname: Pessoa-Mahana
authors.forename: Javiera
authors.initials: J
authors.lastname: Ortiz-Severin
authors.forename: Patricio
authors.initials: P
authors.lastname: Iturriaga-Vásquez
authors.forename: Miguel
authors.initials: M
authors.lastname: Reyes-Parada
authors.forename: Paul
authors.initials: P
authors.lastname: Silva-Matus
authors.forename: Claudio
authors.initials: C
authors.lastname: Saitz-Barría
authors.forename: Ramiro
authors.initials: R
authors.lastname: Araya-Maturana
mesh_terms: D004305:Dose-Response Relationship, Drug; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D010879:Piperazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D007211:Indoles; D010879:Piperazines; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D044282:Receptor, Serotonin, 5-HT1A
keywords: 5-Hydroxytryptamine 1A receptor; Bivalent ligands; Docking; Piperazinylpropylindole derivatives; Serotonin transporter