Synthesis and Docking of Novel 3-Indolylpropyl Derivatives as New Polypharmacological Agents Displaying Affinity for 5-HT1AR/SERT

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Date
2017
DOI
10.1002/ardp.201600271

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Author
Pessoa-Mahana H.
Silva-Matus P.
Pessoa-Mahana C.D.
Chung H.
Iturriaga-Vásquez P.
Quiroz G.
Möller-Acuña P.
Zapata-Torres G.
Saitz-Barría C.
Araya-Maturana R.
Reyes-Parada M.
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. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
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