Synthesis and Docking of Novel 3-Indolylpropyl Derivatives as New Polypharmacological Agents Displaying Affinity for 5-HT_1AR/SERT

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• 作者：Herná ; n Pessoa-Mahana ; Paul Silva-Matus ; C. David Pessoa-Mahana ; Hery Chung ; Patricio Iturriaga-Vá ; squez ; Gabriel Quiroz ; Patricia Mö ; ller-Acuñ ; a ; Gerald Zapata-Torres ; Claudio Saitz-Barr&iacute ; a ; Ramiro Araya-Maturana and Miguel Reyes-Parada
• 刊名：Archiv der Pharmazie
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：350
• 期：1
• 全文大小：1809K
• ISSN：1521-4184

文摘

A series of novel 3-indolylpropyl derivatives was synthesized and evaluated for their binding affinities at the serotonin-1A receptor subtype (5-HT_1AR) and the 5-HT transporter (SERT). Compounds 11b and 14b exhibited the highest affinities at the 5-HT_1AR (K_i = 43 and 56 nM), whereas compounds 11c and 14a were the most potent analogs at the SERT (K_i = 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.