title: Synthesis and Docking of Novel 3-Indolylpropyl Derivatives as New Polypharmacological Agents Displaying Affinity for 5-HT1AR/SERT.
abstract: A series of novel 3-indolylpropyl derivatives was synthesized and evaluated for their binding affinities at the serotonin-1A receptor subtype (5-HT1AR) and the 5-HT transporter (SERT). Compounds 11b and 14b exhibited the highest affinities at the 5-HT1AR (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.
authors.affiliation: Departamento de Química Orgánica y Fisicoquímica, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago, Chile.
authors.forename: Hernán
authors.initials: H
authors.lastname: Pessoa-Mahana
authors.affiliation: Departamento de Química Orgánica y Fisicoquímica, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago, Chile.
authors.forename: Paul
authors.initials: P
authors.lastname: Silva-Matus
authors.affiliation: Departamento de Farmacia, Facultad de Química, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: C David
authors.initials: CD
authors.lastname: Pessoa-Mahana
authors.affiliation: Departamento de Farmacia, Facultad de Química, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Hery
authors.initials: H
authors.lastname: Chung
authors.affiliation: Departamento de Ciencias Químicas y Recursos Naturales, Facultad de Ingeniería y Ciencias, Universidad de la Frontera, Temuco, Chile.
authors.forename: Patricio
authors.initials: P
authors.lastname: Iturriaga-Vásquez
authors.affiliation: Programa de Doctorado en Farmacología, Universidad de Chile, Santiago, Chile.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Quiroz
authors.affiliation: Centro de Bioinformática y Simulación Molecular, Facultad de Ingeniería, Universidad de Talca, Talca, Chile.
authors.forename: Patricia
authors.initials: P
authors.lastname: Möller-Acuña
authors.affiliation: Departamento de Química Inorgánica y Analítica, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago, Chile.
authors.forename: Gerald
authors.initials: G
authors.lastname: Zapata-Torres
authors.affiliation: Departamento de Química Orgánica y Fisicoquímica, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago, Chile.
authors.forename: Claudio
authors.initials: C
authors.lastname: Saitz-Barría
authors.affiliation: Instituto de Química de Recursos Naturales, Universidad de Talca, Talca, Chile.
authors.forename: Ramiro
authors.initials: R
authors.lastname: Araya-Maturana
authors.affiliation: Escuela de Medicina, Facultad de Ciencias Médicas, Universidad de Santiago de Chile, Santiago, Chile.|Facultad de Ciencias de la Salud, Universidad Autónoma de Chile, Talca, Chile.
authors.forename: Miguel
authors.initials: M
authors.lastname: Reyes-Parada
mesh_terms: D000928:Antidepressive Agents / Q000138:chemical synthesis / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D018490:Serotonin Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D000928:Antidepressive Agents; D007211:Indoles; D018490:Serotonin Agents; D050486:Serotonin Plasma Membrane Transport Proteins; D044282:Receptor, Serotonin, 5-HT1A
keywords: 5-Hydroxytryptamine 1A receptor; Docking; Indole; Piperazinylpropylindole derivatives; Serotonin transporter