title: Deepening the Topology of the Translocator Protein Binding Site by Novel N,N-Dialkyl-2-arylindol-3-ylglyoxylamides.
abstract: As a continuation of our studies on 2-phenylindol-3-ylglyoxylamides as potent and selective translocator protein (TSPO) ligands, two subsets of novel derivatives, featuring hydrophilic group (OH, NH2, COOH) at the para-position of the pendent 2-phenyl ring (8-16) or different 2-aryl moieties, namely, 3-thienyl, p-biphenyl, 2-naphthyl (23-35), were synthesized and biologically evaluated, some of them showing Ki values in the subnanomolar range and the 2-naphthyl group performance being the best. The resulting SARs confirmed the key role played by interactions taking place between ligands and the lipophilic L1 pocket of the TSPO binding site. Docking simulations were performed on the most potent compound of the present series (29) exploiting the recently available 3D structures of TSPO bound to its standard ligand (PK11195). Our theoretical model was fully consistent with SARs of the newly investigated as well of the previously reported 2-phenylindol-3-ylglyoxylamide derivatives.
authors.affiliation: †Dipartimento di Farmacia, Università di Pisa, Via Bonanno 6, 56126 Pisa, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Barresi
authors.affiliation: ‡Dipartimento di Farmacia, Università di Napoli "Federico II", Via D. Montesano 49, 80131 Napoli, Italy.
authors.forename: Agostino
authors.initials: A
authors.lastname: Bruno
authors.affiliation: †Dipartimento di Farmacia, Università di Pisa, Via Bonanno 6, 56126 Pisa, Italy.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Taliani
authors.affiliation: §DiSTABiF, Seconda Università di Napoli, Via Vivaldi 43, 81100 Caserta, Italy.
authors.forename: Sandro
authors.initials: S
authors.lastname: Cosconati
authors.affiliation: †Dipartimento di Farmacia, Università di Pisa, Via Bonanno 6, 56126 Pisa, Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Da Pozzo
authors.affiliation: †Dipartimento di Farmacia, Università di Pisa, Via Bonanno 6, 56126 Pisa, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Salerno
authors.affiliation: †Dipartimento di Farmacia, Università di Pisa, Via Bonanno 6, 56126 Pisa, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Simorini
authors.affiliation: †Dipartimento di Farmacia, Università di Pisa, Via Bonanno 6, 56126 Pisa, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Daniele
authors.affiliation: †Dipartimento di Farmacia, Università di Pisa, Via Bonanno 6, 56126 Pisa, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Giacomelli
authors.affiliation: †Dipartimento di Farmacia, Università di Pisa, Via Bonanno 6, 56126 Pisa, Italy.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Marini
authors.affiliation: †Dipartimento di Farmacia, Università di Pisa, Via Bonanno 6, 56126 Pisa, Italy.
authors.forename: Concettina
authors.initials: C
authors.lastname: La Motta
authors.affiliation: ‡Dipartimento di Farmacia, Università di Napoli "Federico II", Via D. Montesano 49, 80131 Napoli, Italy.
authors.forename: Luciana
authors.initials: L
authors.lastname: Marinelli
authors.affiliation: ‡Dipartimento di Farmacia, Università di Napoli "Federico II", Via D. Montesano 49, 80131 Napoli, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Cosimelli
authors.affiliation: ‡Dipartimento di Farmacia, Università di Napoli "Federico II", Via D. Montesano 49, 80131 Napoli, Italy.
authors.forename: Ettore
authors.initials: E
authors.lastname: Novellino
authors.affiliation: ‡Dipartimento di Farmacia, Università di Napoli "Federico II", Via D. Montesano 49, 80131 Napoli, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Greco
authors.affiliation: †Dipartimento di Farmacia, Università di Pisa, Via Bonanno 6, 56126 Pisa, Italy.
authors.forename: Federico
authors.initials: F
authors.lastname: Da Settimo
authors.affiliation: †Dipartimento di Farmacia, Università di Pisa, Via Bonanno 6, 56126 Pisa, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Martini
mesh_terms: D000818:Animals; D001665:Binding Sites; D007211:Indoles / Q000737:chemistry / Q000494:pharmacology*; D051336:Mitochondrial Membranes / Q000378:metabolism; D051381:Rats; D018079:Receptors, GABA / Q000737:chemistry / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D007211:Indoles; D018079:Receptors, GABA; C499229:TSPO protein, human