title: Synthesis, antidepressant evaluation and docking studies of long-chain alkylnitroquipazines as serotonin transporter inhibitors.
abstract: Twelve alkyl analogues (1-12) of the high-affinity serotonin transporter (SERT) inhibitor 6-nitroquipazine (6-NQ) were synthesized and studied using in vitro radioligand competition binding assays to determine their binding affinity (Ki ). The putative antidepressant activity of five of the binders with the highest SERT binding affinities was studied by the forced swim and locomotor activity mouse tests. The three-dimensional (3D) structures of 8 and 9 were determined using NOE NMR technique. Flexible docking of the compounds was undertaken to illustrate the binding of the compounds in the SERT model. Our results showed that several of the 6-NQ analogues are high-affinity SERT inhibitors and indicated that the octyl (8), decyl (10) and dodecyl (12) 6-NQ analogues exhibit moderate antidepressant activity.
authors.affiliation: Medical Pharmacology and Toxicology, Department of Medical Biology, Faculty of Health Sciences, University of Tromsø, 9037 Tromsø, Norway.
authors.forename: Mari
authors.initials: M
authors.lastname: Gabrielsen
authors.forename: Karol
authors.initials: K
authors.lastname: Wołosewicz
authors.forename: Anna
authors.initials: A
authors.lastname: Zawadzka
authors.forename: Jerzy
authors.initials: J
authors.lastname: Kossakowski
authors.forename: Gabriel
authors.initials: G
authors.lastname: Nowak
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Wolak
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Stachowicz
authors.forename: Agata
authors.initials: A
authors.lastname: Siwek
authors.forename: Aina W
authors.initials: AW
authors.lastname: Ravna
authors.forename: Irina
authors.initials: I
authors.lastname: Kufareva
authors.forename: Lech
authors.initials: L
authors.lastname: Kozerski
authors.forename: Elżbieta
authors.initials: E
authors.lastname: Bednarek
authors.forename: Jerzy
authors.initials: J
authors.lastname: Sitkowski
authors.forename: Wojciech
authors.initials: W
authors.lastname: Bocian
authors.forename: Ruben
authors.initials: R
authors.lastname: Abagyan
authors.forename: Andrzej J
authors.initials: AJ
authors.lastname: Bojarski
authors.forename: Ingebrigt
authors.initials: I
authors.lastname: Sylte
authors.forename: Zdzisław
authors.initials: Z
authors.lastname: Chilmonczyk
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001665:Binding Sites; D008297:Male; D051379:Mice; D062105:Molecular Docking Simulation; D009043:Motor Activity / Q000187:drug effects; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011814:Quipazine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D044282:Receptor, Serotonin, 5-HT1A / Q000737:chemistry / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins / Q000737:chemistry* / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000928:Antidepressive Agents; D011814:Quipazine; D044282:Receptor, Serotonin, 5-HT1A; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; C031227:6-nitroquipazine