Synthesis and Docking of Novel 3-Indolylpropyl Derivatives as New Polypharmacological Agents Displaying Affinity for...

A series of novel 3-indolylpropyl derivatives was synthesized and evaluated for their binding affinities at the serotonin-1A receptor subtype (5-HT_1A R) and the 5-HT transporter (SERT). Compounds 11b and 14b exhibited the highest affinities at the 5-HT_1A R (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.