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Synthesis,docking and pharmacological evaluation of novel homo- and hetero-bis 3-piperazinylpropylindole derivatives at SERT and 5-HT1A receptor |
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| Authors: | Hernán Pessoa-Mahana 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 |
| Affiliation: | 1. Departamento de Química Orgánica y Fisicoquímica, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Casilla 233, Santiago 1, Chile;2. Departamento de Química Orgánica, Facultad de Química, Pontificia Universidad Católica de Chile, Chile;3. Unidad de Gráfica Molecular, Departamento de Química Inorgánica y Analítica, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Casilla 233, Santiago 1, Chile;4. Departamento de Farmacia, Pontificia Universidad Católica de Chile, Casilla 306, Santiago 22, Chile;5. Departamento de Química. Facultad de Ciencias, Universidad de Chile, Chile;6. Escuela de Medicina, Facultad de Ciencias Médicas, Universidad de Santiago de Chile, Chile;7. Facultad de Ciencias de la Salud, Universidad Autónoma de Chile, Chile |
| 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: | Piperazinylpropylindole derivatives Serotonin transporter 5-Hydroxytryptamine 1A receptor Bivalent ligands Docking |
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