2. Academic Validation
  3. Synthesis, docking and pharmacological evaluation of novel homo- and hetero-bis 3-piperazinylpropylindole derivatives at SERT and 5-HT1A receptor

Synthesis, docking and pharmacological evaluation of novel homo- and hetero-bis 3-piperazinylpropylindole derivatives at SERT and 5-HT1A receptor

  • Bioorg Med Chem. 2013 Dec 15;21(24):7604-11. doi: 10.1016/j.bmc.2013.10.036.
Hernán Pessoa-Mahana 1,  Christian González-Lira,  Angélica Fierro,  Gerald Zapata-Torres,  C David Pessoa-Mahana,  Javiera Ortiz-Severin,  Patricio Iturriaga-Vásquez,  Miguel Reyes-Parada,  Paul Silva-Matus,  Claudio Saitz-Barría,  Ramiro Araya-Maturana
Affiliations

Affiliation

  • 1 Departamento de Química Orgánica y Fisicoquímica, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Casilla 233, Santiago 1, Chile. Electronic address: [email protected].
PMID: 24262884 DOI: 10.1016/j.bmc.2013.10.036
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.

Keywords

5-Hydroxytryptamine 1A receptor; Bivalent ligands; Docking; Piperazinylpropylindole derivatives; Serotonin transporter.

Figures