Artículo de revista
Synthesis and Docking of Novel 3-Indolylpropyl Derivatives as New Polypharmacological Agents Displaying Affinity for 5-HT1AR/SERT
Fecha
2017Registro en:
Archiv der Pharmazie volumen: 350 Número: 1 jan 2017
15214184
03656233
10.1002/ardp.201600271
Autor
Pessoa Mahana, Hernán
Silva Matus, Paul Eduardo
Pessoa Mahana, Carlos David
Chung, Hery
Iturriaga-Vásquez, Patricio
Quiroz, Gabriel
Möller-Acuña, Patricia
Zapata Torres, Gerald
Saitz Barría, Claudio
Araya Maturana, Ramiro
Reyes Parada, Miguel
Institución
Resumen
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.